A condition of decreased oxygen content at the cellular level.
Relatively complete absence of oxygen in one or more tissues.
A reduction in brain oxygen supply due to ANOXEMIA (a reduced amount of oxygen being carried in the blood by HEMOGLOBIN), or to a restriction of the blood supply to the brain, or both. Severe hypoxia is referred to as anoxia, and is a relatively common cause of injury to the central nervous system. Prolonged brain anoxia may lead to BRAIN DEATH or a PERSISTENT VEGETATIVE STATE. Histologically, this condition is characterized by neuronal loss which is most prominent in the HIPPOCAMPUS; GLOBUS PALLIDUS; CEREBELLUM; and inferior olives.
Deficient oxygenation of FETAL BLOOD.
Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.
An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.
A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.
The fleshy or dry ripened ovary of a plant, enclosing the seed or seeds.
The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346)
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
One of the BIOLOGICAL SCIENCE DISCIPLINES concerned with the origin, structure, development, growth, function, genetics, and reproduction of animals, plants, and microorganisms.
The dormant state in which some warm-blooded animal species pass the winter. It is characterized by narcosis and by sharp reduction in body temperature and metabolic activity and by a depression of vital signs.
Abnormally low BODY TEMPERATURE that is intentionally induced in warm-blooded animals by artificial means. In humans, mild or moderate hypothermia has been used to reduce tissue damages, particularly after cardiac or spinal cord injuries and during subsequent surgeries.
Lower than normal body temperature, especially in warm-blooded animals.
A technique to arrest the flow of blood by lowering BODY TEMPERATURE to about 20 degrees Centigrade, usually achieved by infusing chilled perfusate. The technique provides a bloodless surgical field for complex surgeries.
A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.
The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature.
The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle.
Pathologic deposition of calcium salts in tissues.
A pathological constriction that can occur above (supravalvular stenosis), below (subvalvular stenosis), or at the AORTIC VALVE. It is characterized by restricted outflow from the LEFT VENTRICLE into the AORTA.
Pathological conditions involving any of the various HEART VALVES and the associated structures (PAPILLARY MUSCLES and CHORDAE TENDINEAE).
A natural high-viscosity mucopolysaccharide with alternating beta (1-3) glucuronide and beta (1-4) glucosaminidic bonds. It is found in the UMBILICAL CORD, in VITREOUS BODY and in SYNOVIAL FLUID. A high urinary level is found in PROGERIA.
The development of bony substance in normally soft structures.
Pathological condition characterized by the backflow of blood from the ASCENDING AORTA back into the LEFT VENTRICLE, leading to regurgitation. It is caused by diseases of the AORTIC VALVE or its surrounding tissue (aortic root).
The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.
The quantity of volume or surface area of a CELL NUCLEUS.
Tumors or cancer of the COLON.
A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis.
The degree of replication of the chromosome set in the karyotype.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
A hapten capable of eliciting both antibody formation and delayed hypersensitivity when bound to aromatic amino acids, polypeptides or proteins. It is used as an immunologic research tool.
A basic helix-loop-helix transcription factor that plays a role in APOPTOSIS. It is composed of two subunits: ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR and HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
An increased reactivity to specific antigens mediated not by antibodies but by cells.
A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.
Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.
Infections with bacteria of the genus PSEUDOMONAS.
Persistent abnormal dilatation of the bronchi.
An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)
Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)
Tumors or cancer of the MOUTH.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA.
An intermediate compound in the metabolism of carbohydrates, proteins, and fats. In thiamine deficiency, its oxidation is retarded and it accumulates in the tissues, especially in nervous structures. (From Stedman, 26th ed)
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
A metabolic process that converts GLUCOSE into two molecules of PYRUVIC ACID through a series of enzymatic reactions. Energy generated by this process is conserved in two molecules of ATP. Glycolysis is the universal catabolic pathway for glucose, free glucose, or glucose derived from complex CARBOHYDRATES, such as GLYCOGEN and STARCH.
Recombinases that insert exogenous DNA into the host genome. Examples include proteins encoded by the POL GENE of RETROVIRIDAE and also by temperate BACTERIOPHAGES, the best known being BACTERIOPHAGE LAMBDA.
A family of structurally-related angiogenic proteins of approximately 70 kDa in size. They have high specificity for members of the TIE RECEPTOR FAMILY.
An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC
Cytokine-induced cell adhesion molecule present on activated endothelial cells, tissue macrophages, dendritic cells, bone marrow fibroblasts, myoblasts, and myotubes. It is important for the recruitment of leukocytes to sites of inflammation. (From Pigott & Power, The Adhesion Molecule FactsBook, 1993, p154)
Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.
Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.

Induction of serotonin transporter by hypoxia in pulmonary vascular smooth muscle cells. Relationship with the mitogenic action of serotonin. (1/5029)

-The increased delivery of serotonin (5-hydroxytryptamine, 5-HT) to the lung aggravates the development of hypoxia-induced pulmonary hypertension in rats, possibly through stimulation of the proliferation of pulmonary artery smooth muscle cells (PA-SMCs). In cultured rat PA-SMCs, 5-HT (10(-8) to 10(-6) mol/L) induced DNA synthesis and potentiated the mitogenic effect of platelet-derived growth factor-BB (10 ng/mL). This effect was dependent on the 5-HT transporter (5-HTT), since it was prevented by the 5-HTT inhibitors fluoxetine (10(-6) mol/L) and paroxetine (10(-7) mol/L), but it was unaltered by ketanserin (10(-6) mol/L), a 5-HT2A receptor antagonist. In PA-SMCs exposed to hypoxia, the levels of 5-HTT mRNA (measured by competitive reverse transcriptase-polymerase chain reaction) increased by 240% within 2 hours, followed by a 3-fold increase in the uptake of [3H]5-HT at 24 hours. Cotransfection of the cells with a construct of human 5-HTT promoter-luciferase gene reporter and of pCMV-beta-galactosidase gene allowed the demonstration that exposure of cells to hypoxia produced a 5.5-fold increase in luciferase activity, with no change in beta-galactosidase activity. The increased expression of 5-HTT in hypoxic cells was associated with a greater mitogenic response to 5-HT (10(-8) to 10(-6) mol/L) in the absence as well as in the presence of platelet-derived growth factor-BB. 5-HTT expression assessed by quantitative reverse transcriptase-polymerase chain reaction and in situ hybridization in the lungs was found to predominate in the media of pulmonary artery, in which a marked increase was noted in rats that had been exposed to hypoxia for 15 days. These data show that in vitro and in vivo exposure to hypoxia induces, via a transcriptional mechanism, 5-HTT expression in PA-SMCs, and that this effect contributes to the stimulatory action of 5-HT on PA-SMC proliferation. In vivo expression of 5-HTT by PA-SMC may play a key role in serotonin-mediated pulmonary vascular remodeling.  (+info)

Ischemic tolerance in murine cortical cell culture: critical role for NMDA receptors. (2/5029)

Murine cortical cultures containing both neurons and glia (days in vitro 13-15) were exposed to periods of oxygen-glucose deprivation (5-30 min) too brief to induce neuronal death. Cultures "preconditioned" by sublethal oxygen-glucose deprivation exhibited 30-50% less neuronal death than controls when exposed to a 45-55 min period of oxygen-glucose deprivation 24 hr later. This preconditioning-induced neuroprotection was specific in that neuronal death induced by exposure to excitotoxins or to staurosporine was not attenuated. Neuroprotection was lost if the time between the preconditioning and severe insult were decreased to 7 hr or increased to 72 hr and was blocked if the NMDA antagonist 100 microM 3-((D)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid was applied during the preconditioning insult. This was true even if the duration of preconditioning was increased as far as possible (while still remaining sublethal). A similar preconditioning effect was also produced by sublethal exposure to high K+, glutamate, or NMDA but not to kainate or trans-1-aminocyclopentane-1, 3-dicarboxylic acid.  (+info)

Role of hypoxia-induced Bax translocation and cytochrome c release in reoxygenation injury. (3/5029)

We investigated mechanisms of cell death during hypoxia/reoxygenation of cultured kidney cells. During glucose-free hypoxia, cell ATP levels declined steeply resulting in the translocation of Bax from cytosol to mitochondria. Concurrently, there was cytochrome c release and caspase activation. Cells that leaked cytochrome c underwent apoptosis after reoxygenation. ATP depletion induced by a mitochondrial uncoupler resulted in similar alterations even in the presence of oxygen. Moreover, inclusion of glucose during hypoxia prevented protein translocations and reoxygenation injury by maintaining intracellular ATP. Thus, ATP depletion, rather than hypoxia per se, was the cause of protein translocations. Overexpression of Bcl-2 prevented cytochrome c release and reoxygenation injury without ameliorating ATP depletion or Bax translocation. On the other hand, caspase inhibitors did not prevent protein translocations, but inhibited apoptosis during reoxygenation. Nevertheless, they could not confer long-term viability, since mitochondria had been damaged. Omission of glucose during reoxygenation resulted in continued failure of ATP production, and cell death with necrotic morphology. In contrast, cells expressing Bcl-2 had functional mitochondria and remained viable during reoxygenation even without glucose. Therefore, Bax translocation during hypoxia is a molecular trigger for cell death during reoxygenation. If ATP is available during reoxygenation, apoptosis develops; otherwise, death occurs by necrosis. By preserving mitochondrial integrity, BCL-2 prevents both forms of cell death and ensures cell viability.  (+info)

150-kDa oxygen-regulated protein (ORP150) suppresses hypoxia-induced apoptotic cell death. (4/5029)

To determine the contribution of 150-kDa oxygen-regulated protein (ORP150) to cellular processes underlying adaptation to hypoxia, a cell line stably transfected to overexpress ORP150 antisense RNA was created. In human embryonic kidney (HEK) cells stably overexpressing ORP150 antisense RNA, ORP150 antigen and transcripts were suppressed to low levels in normoxia and hypoxia, whereas wild-type cells showed induction of ORP150 with oxygen deprivation. Inhibition of ORP150 in antisense transfectants was selective, as hypoxia-mediated enhancement of glucose-regulated protein (GRP) 78 and GRP94 was maintained. However, antisense ORP150 transfectants displayed reduced viability when subjected to hypoxia, compared with wild-type and sense-transfected HEK cells. In contrast, diminished levels of ORP150 had no effect on cytotoxicity induced by other stimuli, including oxygen-free radicals and sodium arsenate. Although cellular ATP content was similar in hypoxia, compared with ORP150 antisense transfectants and wild-type HEK cells, suppression of ORP150 expression was associated with accelerated apoptosis. Hypoxia-mediated cell death in antisense HEK transfectants did not cause an increase in caspase activity or in cytoplasmic cytochrome c antigen. A well recognized inducer of apoptosis in HEK cells, staurosporine, caused increased caspase activity and cytoplasmic cytochrome c levels in both wild-type and antisense cells. These data indicate that ORP150 has an important cytoprotective role in hypoxia-induced cellular perturbation and that ORP150-associated inhibition of apoptosis may involve mechanisms distinct from those triggered by other apoptotic stimuli.  (+info)

Regulation of the hypoxia-inducible transcription factor 1alpha by the ubiquitin-proteasome pathway. (5/5029)

HIF-1alpha (hypoxia-inducible factor 1alpha) is a basic-helix-loop-helix PAS (Per/Arnt/Sim) transcription factor that, under hypoxic conditions, dimerizes with a partner factor, the basic-helix-loop-helix/PAS protein Arnt, to recognize hypoxia-responsive elements of target genes. It has recently been demonstrated that HIF-1alpha protein but not mRNA levels are dramatically up-regulated in response to hypoxia. Here we show that inhibitors of 26 S proteasome activity produced a dramatic accumulation of endogenous as well as transfected HIF-1alpha protein under normoxic conditions, whereas the levels of Arnt protein were not affected. HIF-1alpha was polyubiquitinated in vivo under normoxic conditions, indicating rapid degradation via the ubiquitin-proteasome pathway. This degradation process appeared to target a region within the C terminus of HIF-1alpha. Importantly, HIF-1alpha ubiquitination was drastically decreased under hypoxic conditions. Up-regulation of HIF-1alpha protein by proteasome inhibitors did not result in transcriptional activation of reporter genes, indicating either the requirement of additional regulatory steps to induce functional activity of HIF-1alpha or the inability of polyubiquitinated forms of HIF-1alpha to mediate hypoxic signal transduction. In support of both these notions, we demonstrate that HIF-1alpha showed hypoxia-dependent translocation from the cytoplasm to the nucleus and that this regulatory mechanism was severely impaired in the presence of proteasome inhibitors. Taken together, these data demonstrate that the mechanism of hypoxia-dependent activation of HIF-1alpha is a complex multistep process and that stabilization of HIF-1alpha protein levels is not sufficient to generate a functional form.  (+info)

Regulation of interleukin-8 expression by reduced oxygen pressure in human glioblastoma. (6/5029)

Oxygen deprivation is an important biological feature of tumor growth. We previously showed that in glioma, anoxia increases expression of IL-8, a chemokine and angiogenic factor. Here, we analysed for the first time the biochemical mechanisms inducing the IL-8 gene upon anoxia in glioma cells, and showed that they differ from those inducing the VEGF gene. Both genes are induced in biologically and genetically heterogenous glioblastoma cell lines (LN-229, LN-Z308, U87MG, T98G), whereas, in gliosarcoma cells (D247MG), only the VEGF gene is induced. The kinetics of IL-8 and VEGF mRNA inductions differ in these cells and reoxygenation experiments showed that the induction is due to the anoxic stress per se. Furthermore, in LN-229 and LN-Z308 cell lines actinomycin D, DRB and nuclear run-on experiments showed that anoxia stimulates increased transcription of both genes. Electromobility shift assays show increased protein binding to the AP-1 site on the IL-8 promoter following anoxia treatment. Finally, in situ hybridization on glioblastoma sections shows that the in vivo expression patterns of IL-8 and VEGF genes overlap, but are not identical. Since intratumoral augmentation of IL-8 and VEGF secretion, following microenvironmental decreases in oxygen pressure, may promote angiogenesis, further definition of these pathways is essential to appropriately target them for antitumoral therapy.  (+info)

Plasmalogens as endogenous antioxidants: somatic cell mutants reveal the importance of the vinyl ether. (7/5029)

Exposure of plasmalogen-deficient variants of the murine cell line RAW 264.7 to short-term (0-100 min) treatment with electron transport inhibitors antimycin A or cyanide (chemical hypoxia) resulted in a more rapid loss of viability than in the parent strain. Results suggested that plasmalogen-deficient cells were more sensitive to reactive oxygen species (ROS) generated during chemical hypoxia; the mutants could be rescued from chemical hypoxia by using the antioxidant Trolox, an alpha-tocopherol analogue, and they were more sensitive to ROS generation by plumbagin or by rose bengal treatment coupled with irradiation. In addition, the use of buffers containing 2H2O greatly enhanced the cytotoxic effect of chemical hypoxia, suggesting the involvement of singlet oxygen. We used the unique enzymic deficiencies displayed by the mutants to differentially restore either plasmenylethanolamine (the major plasmalogen species normally found in this cell line) or its biosynthetic precursor, plasmanylethanolamine. Restoration of plasmenylethanolamine, which contains the vinyl ether, resulted in wild-type-like resistance to chemical hypoxia and ROS generators, whereas increasing levels of its precursor, which bears the saturated ether, had no effect on cell survival. These findings identify the vinyl ether double bond as a crucial element in cellular protection under these conditions and support the hypothesis that plasmalogens, through the vinyl ether, act as antioxidants to protect cells against ROS. These phospholipids might protect cells from ROS-mediated damage during events such as chemical hypoxia.  (+info)

VEGF deprivation-induced apoptosis is a component of programmed capillary regression. (8/5029)

The pupillary membrane (PM) is a transient ocular capillary network, which can serve as a model system in which to study the mechanism of capillary regression. Previous work has shown that there is a tight correlation between the cessation of blood flow in a capillary segment and the appearance of apoptotic capillary cells throughout the segment. This pattern of cell death is referred to as synchronous apoptosis (Lang, R. A., Lustig, M., Francois, F., Sellinger, M. and Plesken, H. (1994) Development 120, 3395-3404; Meeson, A., Palmer, M., Calfon, M. and Lang, R. A. (1996) Development 122, 3929-3938). In the present study, we have investigated whether the cause of synchronous apoptosis might be a segmental deficiency of either oxygen or a survival factor. Labeling with the compound EF5 in a normal PM indicated no segmental hypoxia; this argued that oxygen deprivation was unlikely to be the cause of synchronous apoptosis. When rat plasma was used as a source of survival factors in an in vitro PM explant assay, inhibition of vascular endothelial growth factor (VEGF) all but eliminated the activity of plasma in suppressing apoptosis. This argued that VEGF was an important plasma survival factor. Furthermore, inhibition of VEGF in vivo using fusion proteins of the human Flk-1/KDR receptor resulted in a significantly increased number of capillaries showing synchronous apoptosis. This provides evidence that VEGF is necessary for endothelial cell survival in this system and in addition, that VEGF deprivation mediated by flow cessation is a component of synchronous apoptosis.  (+info)

TY - JOUR. T1 - Hypoxia inducible factor-1α inactivation unveils a link between tumor cell metabolism and hypoxia-induced cell death. AU - Favaro, Elena. AU - Nardo, Giorgia. AU - Persano, Luca. AU - Masiero, Massimo. AU - Moserle, Lidia. AU - Zamarchi, Rita. AU - Rossi, Elisabetta. AU - Esposito, Giovanni. AU - Plebani, Mario. AU - Sattler, Ulrike. AU - Mann, Thomas. AU - Mueller-Klieser, Wolfgang. AU - Ciminale, Vincenzo. AU - Amadori, Alberto. AU - Indraccolo, Stefano. PY - 2008/10. Y1 - 2008/10. N2 - Hypoxia and the acquisition of a glycolytic phenotype are intrinsic features of the tumor microenvironment. The hypoxia inducible factor-1α (HIF-1α) pathway is activated under hypoxic conditions and orchestrates a complex transcriptional program that enhances cell survival. Although the consequences of HIF-1α inactivation in cancer cells have been widely investigated, only a few studies have addressed the role of HIF-1α in the survival of cancer cells endowed with different glycolytic ...
Disulfiram causes selective hypoxic cancer cell toxicity and radio-chemo-sensitization via redox cycling of copper. Free Radic Biol Med. 2020 Feb 04;: Authors: Falls-Hubert KC, Butler AL, Gui K, Anderson M, Li M, Stolwijk JM, Rodman SN, Solst SR, Tomanek-Chalkley A, Searby CC, Sheffield VC, Sandfort V, Schmidt H, McCormick M, Wels BR, Allen BG, Buettner GR, Schultz MK, Spitz DR Ab...
Cell hypoxia is a serious condition in which cells dont have enough oxygen. If not quickly treated, cell hypoxia can lead to...
Intratumoral hypoxia (low oxygen concentration or pO2) occurs when oxygen consumption exceeds its delivery by the vascular system. Hypoxia is associated with adverse patient outcome in many human cancers and this association is hypothesized to be due to a combination of treatment resistance and aggressive tumor biology.. The study of hypoxia is also important as new cancer drugs are being developed that are specifically active on cancer cells in area of tumors with lower oxygen levels.. his study involves administering the hypoxia probe pimonidazole hydrochloride to patients prior to resection of pancreatic adenocarcinoma to evaluate the extent, molecular context and clinical relevance of hypoxia in clinical pancreatic cancer samples and the subsequently derived primary xenograft tumors.. We propose accrual of patients over a 5-year period to evaluate hypoxia within 100 clinical tumor specimens and corresponding primary xenograft tumours where available. The complementary techniques of ...
Hypoxic tumour cells can be directly targeted using pro-drugs that are metabolically reduced to cytotoxic agents in cells at low oxygen tensions [39, 40]. The use of hypoxia-activated cytotoxins to treat metastatic disease is supported by the detection of hypoxic cells in metastatic tumour foci in a number of pre-clinical tumour models. Some groups have shown that micrometastases smaller than approximately 1 mm3 can be hypoxic [41-46], while other groups have found hypoxic tumour cells develop in metastases as they grow larger than 2 to 3 mm2 in diameter [47]. Clinical data regarding the hypoxic fraction of metastatic tumours are lacking, due in large part to infrequent biopsying and subsequent immunohistochemical analysis of hypoxic cells in tumour metastases. It is worth noting, however, that relatively large clinical metastases can contain hypoxic tumour cells as evidenced by uptake of the radiolabeled hypoxia marker 18F-EF5 assessed by positron emission tomography (PET) [48]. Taken together, ...
TY - JOUR. T1 - Nox4 mediates hypoxia-stimulated myofibroblast differentiation in nasal polyp-derived fibroblasts. AU - Moon, You Mi. AU - Kang, Hee Joon. AU - Cho, Jung Sun. AU - Park, Il Ho. AU - Lee, Heung Man. PY - 2012/11/1. Y1 - 2012/11/1. N2 - Background: Chronic hypoxia is associated with remodeling in various organs. Reactive oxygen species (ROS) derived from NADPH oxidases (Nox), and transforming growth factor-β1 (TGF-β1) have been implicated in the pathogenesis of hypoxia-induced remodeling. The aims of this study were to determine in hypoxia-stimulated nasal polyp-derived fibroblasts (NPDF) the effect of hypoxia on the differentiation of myofibroblasts, the role of ROS, the major Nox homolog mediating myofibroblast differentiation, and the role of TGF-β1. Methods: Eight primary cultures of NPDF were established from nasal polyps, which were incubated under hypoxic conditions. Reverse transcription polymerase chain reaction for αSMA, Nox1, Nox3, Nox4, Nox5, and fibronectin mRNA ...
HighlightsMiR-503 suppresses hypoxia-induced proliferation, migration and angiogenesis of endothelial progenitor cells.MiR-503 directly targets to Apelin via its 3′-UTR region in EPCs.Increased expression of Apelin promotes EPC growth, migration and angiogenesis under hypoxia.ABSTRACTEndothelial pro
Tissue hypoxia is frequently found under various pathophysiological conditions, such as circulatory failure, myocardial infarction and cerebral ischemia (Garin et al., 2005; Li and Jackson, 2002; McCord, 1985; Michiels, 2004). Owing to the high incidence and clinical relevance of tissue hypoxia and ischemia-reperfusion injury, an understanding of the hypoxia-associated cellular and molecular mechanisms is essential for the development of new and effective strategies to reduce ischemia-reperfusion- and tissue-hypoxia-mediated cell damage.. An elegant and straightforward method for the investigation of hypoxia-associated mechanisms is the use of cell culture systems. So far, different in vitro models (e.g. hypoxic chambers, chemical or enzymatic generation of hypoxia) have been employed to induce hypoxic conditions in cultures of cell lines and primary cells and to evaluate the effects as well as underlying mechanisms of in vitro hypoxia. Unfortunately, all of the currently described models have ...
One of the hallmarks of cancer treatment is the frequent ability to achieve remission which is inevitably followed by relapse. This behavior is typical of nearly every common human cancer and strongly implies that within an individual patient, tumor cells are not homogeneous in their treatment sensitivities. Numerous mechanisms of resistance have been demonstrated, including the presence of drug resistance transporters, mutated or amplified drug targets, altered drug metabolism, altered DNA repair, overexpression of antiapoptotic genes, inactivity of proapoptotic gene products, and noncell autonomous features of tumor growth in vivo, such as the presence of hypoxia in solid tumors (36). Disordered tumor cell perfusion and resulting hypoxia may be particularly important as features conferring tumor inhomogeneity which may contribute to relapse following tumor shrinkage during therapy. Studies of solid tumor cells have suggested that through induction of apoptosis, hypoxia may select for cells ...
Intratumoral hypoxia is associated with poor prognosis, regardless of the mode of therapy. Cancer cells survive this condition through activating several adaptive signaling pathways, including the integrated stress response (ISR) and autophagy. Activating transcription factor 4 (ATF4) is the major transcriptional mediator of the ISR, which we have shown to be involved in autophagy regulation to protect cells from severe hypoxia. Here we demonstrate that ATF4 orchestrates a program of BH3-only protein expression in severe hypoxia. We find that the BH3-only proteins HRK, PUMA, and NOXA are transcriptionally induced in severe hypoxia and that their expression is abrogated by RNA interference against ATF4. In particular, we show that the BH3-only protein harakiri (HRK) is transactivated by ATF4 in severe hypoxia through direct binding of ATF4 to the promoter region. Furthermore, we demonstrate through siRNA knockdown that HRK induces autophagy and promotes cancer cell survival in severe hypoxia.
Intratumoral hypoxia is associated with poor prognosis, regardless of the mode of therapy. Cancer cells survive this condition through activating several adaptive signaling pathways, including the integrated stress response (ISR) and autophagy. Activating transcription factor 4 (ATF4) is the major transcriptional mediator of the ISR, which we have shown to be involved in autophagy regulation to protect cells from severe hypoxia. Here we demonstrate that ATF4 orchestrates a program of BH3-only protein expression in severe hypoxia. We find that the BH3-only proteins HRK, PUMA, and NOXA are transcriptionally induced in severe hypoxia and that their expression is abrogated by RNA interference against ATF4. In particular, we show that the BH3-only protein harakiri (HRK) is transactivated by ATF4 in severe hypoxia through direct binding of ATF4 to the promoter region. Furthermore, we demonstrate through siRNA knockdown that HRK induces autophagy and promotes cancer cell survival in severe hypoxia.
Hypoxia is a characteristic feature of locally advanced solid tumors resulting from an imbalance between oxygen (O(2)) supply and consumption. Major causative factors of tumor hypoxia are abnormal structure and function of the microvessels supplying the tumor, increased diffusion distances between the nutritive blood vessels and the tumor cells, and reduced O(2) transport capacity of the blood due to the presence of disease- or treatment-related anemia. Tumor hypoxia is a therapeutic concern since it can reduce the effectiveness of radiotherapy, some O(2)-dependent cytotoxic agents, and photodynamic therapy. Tumor hypoxia can also negatively impact therapeutic outcome by inducing changes in the proteome and genome of neoplastic cells that further survival and malignant progression by enabling the cells to overcome nutritive deprivation or to escape their hostile environment. The selection and clonal expansion of these favorably altered cells further aggravate tumor hypoxia and support a vicious circle
In this report, we found that p16 inhibits breast cancer cell proliferation and migration, but has no apparent effect on cell adhesion. Interestingly, p16 shows much higher inhibition on cell migration in hypoxia than in normoxia. In addition, a parallel inhibition of HIF-1α transactivation by p16 was observed along with the p16-mediated inhibition of hypoxia-induced migration. As hypoxia promotes metastatic process and stimulates HIF-1α activation, these combined results imply a particular aspect of the metastatic process (such as migration) may be contributed, at least in part, by HIF-1α; and that p16 can effectively inhibit that aspect by inactivating HIF-1α. Noticeably, this study is the first report to our knowledge demonstrating that p16 inhibits hypoxia-induced cell migration in breast cancer cells, in parallel with its inhibition of HIF-1a transactivation activity. This study suggests that p16s ability to suppress tumor metastasis may be partially resulted from p16s inhibition on ...
Sigma-Aldrich offers abstracts and full-text articles by [Peter DelNero, Maureen Lane, Scott S Verbridge, Brian Kwee, Pouneh Kermani, Barbara Hempstead, Abraham Stroock, Claudia Fischbach].
The signal transduction events that modulate the expression of HIF-1α, as well as the subsequent expression of VEGF and other HIF-1-regulated genes, are currently under intensive scrutiny. The results of the present study confirm and extend the earlier report that rapamycin inhibits both the stabilization of HIF-1α and the transcriptional activity of HIF-1 in hypoxic cancer cells (50). Furthermore, we provide genetic evidence to support the conclusion that the rapamycin target protein, mTOR, functions as a positive regulator of HIF-1 activation by hypoxia or the hypoxia-mimetic agent, CoCl2.. A synthesis of the available data indicates that at least two integrated signaling pathways promote the accumulation of HIF-1α in mammalian cells. The first pathway is triggered by hypoxia or CoCl2 and involves the inhibition of a family of PHDs that modify Pro-564 and Pro-402 of HIF-1α (5, 21, 22, 27, 41). The second pathway is triggered by polypeptide growth factors or oncogenic mutations (e.g., PTEN ...
Background Expression of intrinsic markers of tumour hypoxia and angiogenesis are important predictors of radiotherapeutic, and possibly surgical, outcome in several cancers. Extent of tumour hypoxia in localised prostate cancer is comparable to that in other cancers, but few data exist on the association of extent of tumour hypoxia with treatment outcome. We aimed to study the predictive value of intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer, both in patients treated with radiotherapy and in those treated surgically. Methods We applied a new, needle biopsy tissue microarray (TMA) technique to study diagnostic samples from men with localised, previously untreated prostate cancer treated in two randomised controlled trials of radiotherapy-dose escalation. Multivariate analysis by Cox proportional hazards was done to assess the association between clinical outcome, in terms of biochemical control, and immunohistochemical staining of hypoxia inducible factor-1 ...
Tumour cells exploit both genetic and adaptive means to survive and proliferate in hypoxic microenvironments, resulting in the outgrowth of more aggressive tumour cell clones. Direct measurements of tumour oxygenation, and surrogate markers of the hypoxic response in tumours (for instance, hypoxia inducible factor-1alpha, carbonic anhydrase 9 and glucose transporter-1) are well-established prognostic markers in solid cancers. However, individual markers do not fully capture the complex, dynamic and heterogeneous hypoxic response in cancer. To overcome this, expression profiling has been employed to identify hypoxia signatures in cohorts or models of human cancer. Several of these hypoxia signatures have demonstrated prognostic significance in independent cancer datasets. Nevertheless, individual hypoxia markers have been shown to predict the benefit from hypoxia-modifying or anti-angiogenic therapies. This review aims to discuss the clinical impact of translational work on hypoxia markers and to explore
Based on cDNA microarray results, integrin-linked kinase (ILK) emerged as an interesting candidate in hypoxia-mediated survival mechanisms employed by cancer cells. This notion was confirmed here by the following observations: the 5 promoter region of the ilk gene contains hypoxia responsive elements (HRE) that bind hypoxia-inducible factor (HIF) transcription factor complexes and drive HRE-luciferase gene expression in reporter assays; ILK protein and kinase activity are induced following hypoxia; downstream targets of ILK signaling are induced following hypoxia treatment; inhibition of ILK leads to increased apoptosis; and HIF and ILK are co-localized within human cancer tissues. The identification of ILK as a player in hypoxia survival signaling employed by cancer cells further validates ILK as a unique target for cancer therapy ...
Hypoxia is present in most solid tumors and is clinically correlated with increased metastasis and poor patient survival. While studies have demonstrated the role of hypoxia and hypoxia-regulated proteins in cancer progression, no attempts have been made to identify hypoxia-regulated proteins using quantitative proteomics combined with MALDI-mass spectrometry imaging (MALDI-MSI). Here we present a comprehensive hypoxic proteome study and are the first to investigate changes in situ using tumor samples. In vitro quantitative mass spectrometry analysis of the hypoxic proteome was performed on breast cancer cells using stable isotope labeling with amino acids in cell culture (SILAC). MS analyses were performed on laser-capture microdissected samples isolated from normoxic and hypoxic regions from tumors derived from the same cells used in vitro. MALDI-MSI was used in combination to investigate hypoxia-regulated protein localization within tumor sections. Here we identified more than 100 proteins, ...
In 1923, Dr. Warburg had observed that tumors acidified the Ringer solution when 13 mM glucose was added, which was identified as being due to lactate. When glucose is the only source of nutrient, it can serve for both biosynthesis and energy production. However, a series of studies revealed that the cancer cell consumes glucose for biosynthesis through fermentation, not for energy supply, under physiological conditions. Recently, a new observation was made that there is a metabolic symbiosis in which glycolytic and oxidative tumor cells mutually regulate their energy metabolism. Hypoxic cancer cells use glucose for glycolytic metabolism and release lactate which is used by oxygenated cancer cells. This study challenged the Warburg effect, because Warburg claimed that fermentation by irreversible damaging of mitochondria is a fundamental cause of cancer. However, recent studies revealed that mitochondria in cancer cell show active function of oxidative phosphorylation although TCA cycle is ...
The phenotypic change of cancer cells in the hypoxic tumour microenvironment promotes aggressive cancer progression (1). Understanding the molecular mechanisms underlying hypoxia-mediated cancer cell state transition will pave the way to develop treatment strategies. Epigenetic modifications to mediate transcriptional alteration are crucial for cellular state transitions (16). Accordingly, attempts have been made to characterize the functional implication of epigenetic modifications, including lysine demethylase-mediated chromatin alterations in hypoxia-mediated transcriptional modulation (17). In this context, the present study demonstrated the functional involvement of KDM3A in the hypoxia-induced metastatic potential of breast cancer cells through increased invasion. Mechanistically, KDM3A, the expression of which is increased by HIF-1 under hypoxic conditions, is recruited to remove the transcriptionally repressive histone modification marker H3K9me2 from the promoter of SNAI2, which encodes ...
Solid tumors contain regions of hypoxia, and tumor hypoxia is an important determinant of clinical prognosis (1-3, 34). Although mechanisms by which severe hypoxia renders tumor cells resistant to radiotherapy and chemotherapy have been defined, it is likely that cellular hypoxia has other important consequences. Recent attention has focused on alterations in gene expression and the possibility that these may induce significant changes such as enhanced angiogenic and metastatic behavior (4, 35, 36).. To determine whether the oxygen-regulated transcription factor HIF-1 is activated in solid tumors, we grew tumor xenografts from Hepa-1 cells that were wild type, defective (c4), and revertant (Rc4) for HIF-1β/ARNT. To provide an assay for the activation of HIF-1-dependent gene expression in the tumors, we first analyzed the expression of GLUT3 mRNA. Hepa-1 cells in normoxic culture express this gene at a low level that is strongly induced by hypoxia (21). In hypoxic tissue culture, induction was ...
Hypoxia, however, induces p53 to mutate: The less oxygen, the more mutations in the p53 gene, so cancer cells are not killed; instead, they proliferate. A team led by Wafik El-Deiry, MD, PhD, Associate Professor, Departments of Medicine, Genetics, and Pharmacology with the Abramson Cancer Center of the University of Pennsylvania, discovered a gene related to p53 called Bnip3L that can also cause cell death. The gene is turned on by p53 and a second transcription factor called hypoxia inducible factor, or HIF. The team silenced Bnip3L in cells with normal p53 and exposed cells to low oxygen conditions. In cell culture and in an animal model with implanted tumor cells, the researchers showed that tumors with silenced Bnip3L grew more aggressively in low oxygen conditions than cells and tumors with intact Bnip3L. El-Deiry and first author Peiwen Fei, MD, PhD, a post-doctoral fellow, report their findings in the December issue of Cancer Cell ...
Accumulating evidence suggests that dysregulation of hypoxia-regulated transcriptional mechanisms is involved in development of chronic kidney diseases (CKD). However, it remains unclear how hypoxia-induced transcription factors (HIFs) and subsequent biological processes contribute to CKD developmen …
Tumor growth, progression and response to the hypoxic tumor microenvironment (TME) involve the action of hypoxia inducible transcription factors, HIF1 and HIF2. HIF is a heterodimeric transcription factor containing an inducible HIFalpha subunit and a constitutively expressed HIFbeta subunit. The signaling pathways operational in macrophages regulating hypoxia induced HIFalpha stabilization remain the subject of intense investigation. Here it was discovered that the PTEN/PI3K/AKT signaling axis controls hypoxia induced HIF1alpha (HIF1A) and HIF2alpha (EPAS1) stability in macrophages. Using genetic mouse models and pan-PI3 kinase as well as isoform specific inhibitors, inhibition of the PI3K/AKT pathway blocked the accumulation of HIFalpha protein and its primary transcriptional target VEGF in response to hypoxia. Moreover, blocking the PI3K/AKT signaling axis promoted the hypoxic degradation of HIFalpha via the 26S proteasome. Mechanistically, a macrophage dominant PI3K isoform (p110gamma) ...
Application of advanced intravital imaging facilitates dynamic monitoring of pathway activity upon therapeutic inhibition. Here, we assess resistance to therapeutic inhibition of the PI3K pathway within the hypoxic microenvironment of pancreatic ductal adenocarcinoma (PDAC) and identify a phenomenon whereby pronounced hypoxia-induced resistance is observed for three clinically relevant inhibitors. To address this clinical problem, we have mapped tumor hypoxia by both immunofluorescence and phosphorescence lifetime imaging of oxygen-sensitive nanoparticles and demonstrate that these hypoxic regions move transiently around the tumor. To overlay this microenvironmental information with drug response, we applied a FRET biosensor for Akt activity, which is a key effector of the PI3K pathway. Performing dual intravital imaging of drug response in different tumor compartments, we demonstrate an improved drug response to a combination therapy using the dual mTORC1/2 inhibitor AZD2014 with the ...
TY - JOUR. T1 - Nucleus accumbens-associated protein-1 promotes glycolysis and survival of hypoxic tumor cells via the HDAC4-HIF-1α axis. AU - Zhang, Y.. AU - Ren, Y. J.. AU - Guo, L. C.. AU - Ji, C.. AU - Hu, J.. AU - Zhang, H. H.. AU - Xu, Q. H.. AU - Zhu, W. D.. AU - Ming, Z. J.. AU - Yuan, Y. S.. AU - Ren, X.. AU - Song, J.. AU - Yang, J. M.. PY - 2017/7/20. Y1 - 2017/7/20. N2 - Nucleus accumbens-associated protein-1 (NAC1), a nuclear factor of the BTB/POZ gene family, has emerging roles in cancer. In this study, we identified the NAC1-HDAC4-HIF-1α axis as an important pathway in regulating glycolysis and hypoxic adaptation in tumor cells. We show that nuclear NAC1 binds to histone deacetylase type 4 (HDAC4), hindering phosphorylation of HDAC4 at Ser 246 and preventing its nuclear export that leads to cytoplasmic degradation of the deacetylase. Accumulation of HDAC4 in the nuclei results in an attenuation of HIF-1α acetylation, enhancing the stabilization and transcriptional activity of ...
Cullin-RING ubiquitin ligases are the largest Ubiquitin ligase family in eukaryotes and are multi-protein complexes. In these complexes, the Cullin protein serves as a scaffold to connect two functional modules of the ligases, the catalytic subunit and substrate-binding subunit. KLHL20 is a substrate-binding subunit of Cullin3 (Cul3) ubiquitin ligase. Recent studies have identified a number of substrates of KLHL20-based ubiquitin ligase. Through ubiquitination of these substrates, KLHL20 elicits diverse cellular functions, some of which are associated with human diseases. Furthermore, the functions, subcellular localizations, and expression of KLHL20 are regulated by several physiological and stressed signals, which allow KLHL20 to preferentially act on certain substrates to response to these signals. Here, we provide a summary of the functions and regulations of KLHL20 in several physiological processes and stress responses and its disease implications.
Weve previously discovered that hypoxia stimulates proliferation of vascular fibroblasts through Gi-mediated activation of ERK1/2. will also be noticed upon blockade of MKP-1 activation. Due to the parallel suppressive activities of PKC and MKP-1 on ERK1/2 phosphorylation and proliferation, the part of PKC in the rules of MKP-1 manifestation was examined. PKC attenuation decreases MKP-1 manifestation, whereas PKC overexpression raises MKP-1 levels. To conclude, our outcomes indicate for the very first time that hypoxia activates PKC, which functions as a terminator of ERK1/2 activation through the rules of downstream focus on, MKP-1 expression and therefore acts to limit hypoxia-induced proliferation of fibroblasts. Intro Fibroblast proliferation can be associated with different types of vascular illnesses (Sartore 2001 ), different fibrotic circumstances (Atamas, 2002 ) and tumor (Bhowmick 2004 ). Hypoxia may be the essential contributor towards the pathophysiological circumstances of these ...
Hypoxia plays an important role in tumour recurrence among head and neck cancer patients. The identification and quantification of hypoxic regions are therefore an essential aspect of disease management. Several predictive assays for tumour oxygenation status have been developed in the past with varying degrees of success. To date, functional imaging techniques employing positron emission tomography (PET) have been shown to be an important tool for both pretreatment assessment and tumour response evaluation during therapy. Hypoxia-specific PET markers have been implemented in several clinics to quantify hypoxic tumour subvolumes for dose painting and personalized treatment planning and delivery. Several new radiotracers are under investigation. PET-derived functional parameters and tracer pharmacokinetics serve as valuable input data for computational models aiming at simulating or interpreting PET acquired data, for the purposes of input into treatment planning or radio/chemotherapy response prediction
Hsp90α is a molecular chaperone protein involved in the structural maturation of oncogenic signaling proteins. Hsp90 was recently identified as an anticancer target; various studies are ongoing to find ways for managing cancer through Hsp90α. However, this approach is limited by reported side-effects. Hypoxia is a hallmark of solid tumors, including those of breast cancer and the extent of tumor hypoxia is associated with resistance to treatment and poor prognosis. One of the major signaling pathways in cancer cells, the Jak2/STAT5b pathway, has been found to be closely correlated with hypoxia. The objective of this study was to investigate the role of Jak2/STAT5b in the regulation of Hsp90α expression so that Hsp90α targeting can be achieved indirectly by modulating the Jak2/STAT5b pathway. We examined the role of the Jak2/STAT5b pathway in the expression of Hsp90α under hypoxic conditions by immunoblotting, reporter gene assays, EMSA and RNA interference analysis. With the help of in vivo ...
Hypoxia triggers a proangiogenic pathway involving cancer cell microvesicles and PAR-2-mediated heparin-binding EGF signaling in endothelial cells.: Highly mali
Abstract : Inefficient immune response is a major glitch during tumor growth and progression. Chaotic and leaky blood vessels created in the process of angiogenesis allow tumor cells to escape and extricate anti-cancer immunity. Proangiogenic characteristics of hypoxic tumor microenvironment maintained by low oxygen tension attract endothelial progenitor cells, drive expansion of cancer stem cells, and deviantly differentiate monocyte descendants. Such cellular milieu further boosts immune tolerance and eventually appoint immunity for cancer advantage. Blood vessel normalization strategies that equilibrate oxygen levels within tumor and fix abnormal vasculature bring exciting promises to future anticancer therapies especially when combined with conventional chemotherapy. Recently, a new group of microRNAs (miRs) engaged in angiogenesis, called angiomiRs and hypoxamiRs, emerged as new therapeutic targets in cancer. Some of those miRs were found to efficiently regulate cancer immunity and their ...
Metastasis is a major cancer-related cause of death. Recent studies have described metastasis pathways. However, the exact contribution of each pathway remains unclear. Another key feature of a tumor is the presence of hypoxic areas caused by a lack of oxygen at the center of the tumor. Hypoxia leads to the expression of pro-metastatic genes as well as the repression of anti-metastatic genes. As many Affymetrix datasets about metastasis and hypoxia are publicly available and not fully exploited, this study proposes to re-analyze these datasets to extract new information about the metastatic phenotype induced by hypoxia in different cancer cell lines. Affymetrix datasets about metastasis and/or hypoxia were downloaded from GEO and ArrayExpress. AffyProbeMiner and GCRMA packages were used for pre-processing and the Window Welch t test was used for processing. Three approaches of meta-analysis were eventually used for the selection of genes of interest. Three complementary approaches were used, that
PURPOSE: The Cancer Imaging Program of the National Cancer Institute convened a workshop to assess the current status of hypoxia imaging, to assess what is known about the biology of hypoxia as it relates to cancer and cancer therapy, and to define clinical scenarios in which in vivo hypoxia imaging could prove valuable. RESULTS: Hypoxia, or low oxygenation, has emerged as an important factor in tumor biology and response to cancer treatment. It has been correlated with angiogenesis, tumor aggressiveness, local recurrence, and metastasis, and it appears to be a prognostic factor for several cancers, including those of the cervix, head and neck, prostate, pancreas, and brain. The relationship between tumor oxygenation and response to radiation therapy has been well established, but hypoxia also affects and is affected by some chemotherapeutic agents. Although hypoxia is an important aspect of tumor physiology and response to treatment, the lack of simple and efficient methods to measure and image
Adenoviruses in which HIFs regulate gene expression have been used to target hypoxic tumor cells in human tumor xenografts and in clinical trials but these had to be injected directly into primary tumors and at very high viral titres of adenovirus. Moreover, this approach fails to target metastatic tumors growing at distant sites (23-26).. Our finding that macrophages accumulate in hypoxic areas of human prostate tumors and human prostate tumor xenografts prompted us to develop a means of using these cells to deliver therapeutic adenovirus to these sites and via a systemic route permitting the targeting of primary tumors and their metastases. As hypoxia also exists in diseased tissues other than tumors (27) and mild hypoxia can exist in healthy tissues (28), we added a further degree of tumor targeting by placing the exogenous gene (e.g., GFP) in the virus or the further replication of the virus itself when released by macrophages-under the control of prostate-specific promoters.. We found ...
Rapidly growing tumors and tumor metastases are exposed to ongoing hypoxic conditions in the tissue microenvironment. Hypoxia, in turn, has a profound influence on tumor pathophysiology. The survival of the tumor and its aggressiveness depend on its ability to respond quickly to hypoxia cues. Cells undergo a variety of biological responses when placed under hypoxic conditions, including activation of signaling pathways that regulate proliferation, angiogenesis, and death (1-3). Cancer cells have adapted these pathways, allowing tumors to survive and even grow under hypoxic conditions (2). Although tissue hypoxia is a well-documented phenomenon, our understanding of the response of tumor cells to hypoxia is far from being complete. The response to hypoxia may be divided into two mechanisms: the first one sensing the level of oxygen and the second one activating the hypoxia-induced genes, some of which contribute to tumor angiogenesis. A large body of evidence accumulated with regard to the role ...
A decrease in oxygen availability (hypoxia) can be encountered in solid tumors and has been associated with a poor outcome. Hypoxia can affect the function of m...
Insufficient supply of oxygen to target tissues. Since most cells in the body rely on oxidative metabolism for the majority of their energetic needs, an inadequate supply of oxygen will cause a drop in cellular functions and will eventually cause them to die. Hypoxia co-occurs with inflammation both as a cause and as a consequence. Hypoxic injury to cells can trigger the inflammatory response, and inflammation can create parenchymal hypoxia trough accumulation of oxygen-consuming leukocytes and fluid in the surrounding ECM. Hypoxia is also a signal for macrophage-activation, which might be part of the reason why inflammatory processes tends to create such an environment around the affected tissues. Cells that dontget enough oxygen switch on a different set of metabolic programs to meet their needs, which leaves molecular traces in the affected tissues. The most studied of these is hypoxia inducible factor 1-alpha (HIF-1a), which is considered a master regulator that orchestrates the cellular ...
Cells are able to sense and respond to oxygen deprivation (hypoxia) by modifying their metabolism to cope with low oxygen levels. The evolutionarily conserved hypoxia response plays a crucial role for survival under changing environmental conditions, as well as in diseases, including cancer, ischemia, and stroke. In Drosophila larvae, hypoxia induces tracheal growth and branching, resembling angiogenic responses induced by hypoxic tumor cells. We use hypoxia-induced tracheal growth as a paradigm to address the interrelation between cellular metabolism and gas exchange. ...
The proteins HIF-1a and CD24 have both been implicated in the aggressive characteristics of hypoxic cancers. University of Colorado Cancer Center study shows that HIF-1a drives CD24 overexpression, and that CD24 then drives aggressive tumor features.
R(2)* maps from BOLD-MRI have high sensitivity but low specificity for defining intraprostatic tumor hypoxia. This together with the negative predictive value of 70% when combined with blood volume information makes BOLD-MRI a potential noninvasive technique for mapping prostatic tumor hypoxia.
Hypoxia. An apathogical condition in which the body as a whole (generalised) hypoxia) or a region of the body (tissue hypoxia) is deprived of an adequate oxygen
Hypoxia is a condition in which the body does not have enough oxygen supply. When there is low oxygen content in the blood, it is called hypoxia. Know the causes, symptoms, treatment, complications of hypoxia.
Differential effects of Th1 versus Th2 cytokines in combination with hypoxia on HIFs and angiogenesis in RA. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Maintenance of oxygen and extracellular matrix (ECM) homeostases is crucial for normal development and physiology, and several pathologies are associated with hypoxia or ECM abnormalities.
A tidepool crustaceans ability to survive oxygen deprivation though it lacks a key set of genes raises the possibility that animals might have more ways of dealing with hypoxic environments than had been thought.
The aim of the present study was to investigate the influence of fixation delay and the perioperative ischemia on hypoxia inducible factor (HIF)-1α gene expression, HIF-1α protein expression, and immunohistochemical (IHC) expression of HIF-1α, GLUT-1, Bcl-2, and Ki-67 in colorectal cancer. The study included 25 surgically removed colorectal tumors. Three ...
Lung cells experience hypoxia during development, during travel to high altitude, and in acute and chronic lung diseases. The functional responses evoked by hypoxia are diverse and generally act to protect the cells from hypoxic injury, although some lung cell responses are counterproductive because they degrade normal function of the organ. The cellular O(2) sensor responsible for many of these responses involves the mitochondrial electron transport chain. Under hypoxic conditions, increased release of reactive oxygen species from the inner mitochondrial membrane to the intermembrane space leads to the activation of transcription factors, including hypoxia-inducible factor, activation of hypoxic pulmonary vasoconstriction, activation of AMP-dependent protein kinase, and internalization of the membrane Na,K-ATPase from the basolateral membrane of alveolar epithelial cells. Although the specific targets of reactive oxygen species signals are not fully understood, this signaling pathway is ...
Title: Hypoxia Inducible Factor-1 as a Therapeutic Target in Cerebral Ischemia. VOLUME: 4 ISSUE: 3. Author(s):Penelope Aguilera, Edgar Vazquez-Contreras, Carlos Daniel Gomez-Martínez and Maria Elena Chanez Cardenas. Affiliation:Laboratorio de Patologia Vascular Cerebral, Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez. Av Insurgentes Sur 3877, Mexico D.F. 14269, Mexico.. Keywords:Hypoxia inducible factor, ischemic preconditioning, prolyl hydroxylase, cerebral ischemia. Abstract: Cerebral ischemia is the third leading cause of death in industrialized countries and an important health system problem with no efficient treatment to date. The reduction in oxygen and glucose supply triggers a cascade of events such as excitotoxicity, oxidative stress, inflammation, apoptosis, and an adjustment of the gene expression program. The hypoxia inducible factor-1 (HIF-1) is a transcription factor that mediates the adaptive responses to the reduction in oxygen availability. HIF-1 ...
Hypoxia-specific upregulation of calpain activity and gene expression in pulmonary artery endothelial cells.: The effects of exposure to hypoxia on the catalyti
Gene therapy techniques were used to insert a peptide into cultures of human cancer cells that blocked their ability to use the enzyme Hypoxia-inducible factor-1, a heterodimeric transcription factor that enables cell survival under low oxygen conditions by altering the transcription of over 300 genes. Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival, and progression of tumors. There is significant evidence that inhibition of HIF-1 would be beneficial for cancer therapy, since tumor cells must thrive in a microenvironment characterized by lack of oxygen. In previous work, investigators at the University of Southampton (United Kingdom) discovered a cyclic hexapeptide (cyclo-CLLFVY) that inhibited the HIF-1alpha/HIF-1beta protein-protein interaction in vitro and prevented HIF-1-mediated hypoxia-response signaling in cells. This cyclic peptide was
INTRODUCTION: Hypoxia and T-helper cell 1 (Th1) cytokine-driven inflammation are key features of rheumatoid arthritis (RA) and contribute to disease pathogenesis by promoting angiogenesis. The objective of our study was to characterise the angiogenic gene signature of RA fibroblast-like synoviocytes (FLS) in response to hypoxia, as well as Th1 and T-helper cell 2 (Th2) cytokines, and in particular to dissect out effects of combined hypoxia and cytokines on hypoxia inducible transcription factors (HIFs) and angiogenesis. METHODS: Human angiogenesis PCR arrays were used to screen cDNA from RA FLS exposed to hypoxia (1% oxygen) or dimethyloxalylglycine, which stabilises HIFs. The involvement of HIF isoforms in generating the angiogenic signature of RA FLS stimulated with hypoxia and/or cytokines was investigated using a DNA-binding assay and RNA interference. The angiogenic potential of conditioned media from hypoxia-treated and/or cytokine-treated RA FLS was measured using an in vitro endothelial-based
Hypoxic condition is known to influence the cell survivability by inhibiting its metabolism and growth. Till date, no information is available on how the mammary epithelial cells (MECs) of dairy species respond to chemically induced hypoxia. This study was therefore planned to assess the transcriptional responsiveness of mammary epithelial cells (MECs) of riverine buffaloes- the major dairy species of India to chemically induced hypoxic condition. Initially, the primary MECs culture from buffalo mammary gland tissue was established and thereafter different doses of CoCl2 (50 μM, 100 μM and 250 μM) were evaluated for inducing hypoxia in MECs under culture condition. The 250 μM of CoCl2 was selected and cells were grown for 48 h before assessing the expression of HIF-1α and its target genes in treated (hypoxic) as well as in control (normoxic) cells. The mRNA expression of all studied genes viz; HIF-1α, GLUT-1, GLUT-8, HK2, JAK2 and STAT5 was found to be significantly induced in hypoxic ...
HIF1A (Hypoxia-Inducible-Factor 1A) expression in solid tumors is relevant to establish resistance to therapeutic approaches. The use of compounds direct against hypoxia signaling and HIF1A does not show clinical efficiency because of changeable oxygen concentrations in solid tumor areas. The identification of HIF1A targets expressed in both normoxia and hypoxia and of HIF1A/hypoxia signatures might meliorate the prognostic stratification and therapeutic successes in patients with high-risk solid tumors. In this study, we conducted a combined analysis of RNA expression and DNA methylation of neuroblastoma cells silenced or unsilenced for HIF1A expression, grown in normoxia and hypoxia conditions. The analysis of pathways highlights HIF-1 (heterodimeric transcription factor 1) activity in normoxia in metabolic process and HIF-1 activity in hypoxia in neuronal differentiation process. HIF1A driven transcriptional response in hypoxia depends on epigenetic control at DNA methylation status of gene
Hypoxia-induced autophagy via the RAGE-KRAS-HIF1α pathway is a survival mechanism in pancreatic tumor cells. (a and b) Indicated Panc02 cells were treated with
Objective: Regulated promoter system consented to tightly controlled gene expression is desirable for safe and efficacious overexpression of therapeutic transgenes. Combined with skeletal myoblast (SkMs) transplantation, we report the efficacy of hypoxia-regulated VEGF gene delivery for myocardial repair during acute phase cardiomyopathy.. Methods and Results. A hypoxia-regulated VEGF plasmid (pHRE-VEGF) was developed by inserting 5 copies of hypoxia response elements (HRE). At optimal transfection conditions, flowcytometry revealed that ~30% SkMs were transfected for the gene overexpression using polyethyleneimine nanoparticles. Peak VEGF expression was significantly higher in pHRE-VEGF transfected SkMs (VEGFSkMs) grown under hypoxia (151.34±8.59 ng/ml) as compared with normoxia (16.92±2.74 ng/ml). The efficacy of our hypoxia-regulated gene expression system was assessed in a rabbit model of ischemic cardiomyopathy, developed by permanent coronary artery ligation. The animals were grouped ...
Although tumor progression involves genetic and epigenetic alterations to normal cellular biology, the underlying mechanisms of these changes remain obscure. Numerous studies have shown that hypoxia-inducible factor 1α (HIF-1α) is overexpressed in many human cancers and up-regulates a host of hypoxia-responsive genes for cancer growth and survival. We recently identified an alternative mechanism of HIF-1α function that induces genetic alterations by suppressing DNA repair. Here, we show that long-term hypoxia, which mimics the tumor microenvironment, drives a perpetual epithelial-mesenchymal transition (EMT) through up-regulation of the zinc finger E-box binding homeobox protein ZEB2, whereas short-term hypoxia induces a reversible EMT that requires the transcription factor Twist1. Moreover, we show that the perpetual EMT driven by chronic hypoxia depends on HIF-1α induction of genetic alterations rather than its canonical transcriptional activator function. These mesenchymal tumor cells not ...
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Introduction: Intratumoral hypoxia is a hallmark of solid tumor formation and a negative predictor of patient survival. Adaptation to hypoxia is mainly achieved by the transcription factor HIF-1a, which is upregulated in a diverse range of human and experimental tumors and their metastases. HIF-1a target genes have been implicated in the induction of invasion and metastasis. However, HIF-1as tumor-supporting action depends on cell type and microenvironment and the precise role of HIF-1a for the pathogenesis of neuroendocrine tumors (NET) is largely unknown ...
Background Inflamed environments are typically hypercellular, rich in pro-inflammatory cytokines, and profoundly hypoxic. While the effects of hypoxia on neutrophil longevity and function have been widely studied, little is known about the consequences of this stimulus on eosinophils. Objective We sought to investigate the effects of hypoxia on several key aspects of eosinophil biology, namely secretion, survival, and their sensitivity to glucocorticosteroids (GCS), agents that normally induce eosinophil apoptosis. Methods Eosinophils derived from patients with asthma/atopy or healthy controls were incubated under normoxia and hypoxia, with or without glucocorticoids. Activation was measured by flow cytometry, ELISA of cultured supernatants, and F-actin staining; apoptosis and efferocytosis by morphology and flow cytometry; and GCS efficacy by apoptosis assays and qPCR. Results Hypoxic incubation (3 kPa) caused (i) stabilization of HIF-2α and up-regulation of hypoxia-regulated genes including ...
Poorly oxygenated ( hypoxic) tumors are frequently more aggressive compared to corresponding tumors that are better oxygenated. Adaptation to hypoxia is primarily mediated by two closely related hypoxia inducible transcription factor complexes, HIF-1 and HIF-2, which become stabilized and activated at low oxygen levels. Whether HIF-1 and HIF-2 have different roles in tumorigenesis is an open question and an issue we discuss. With focus on HIF-2, we summarize reported phenotypical changes of HIF genetic models and HIF expression patterns during normal development, in adult non - malignant tissues and in tumors. We further address the much - discussed subject of target gene preferences between HIF-1 and HIF-2, given that both transcription factors bind to the same DNA motif. Finally, we also discuss the observations that the oxygen - sensitive HIF-2 alpha subunit is accumulated and active under non - hypoxic conditions as exemplified by HIF-2 alpha expressing tumor macrophages and neuroblastoma ...
Research at the University of Liverpool has explained how cells behave when placed in a low oxygen environment, a development that could have implications for cancer patients and other serious illnesses.
Tumor bicycling hypoxia is a well-recognized sensation in pet and individual good tumors now. in glioblastoma cells concomitant MK-0679 with reduced replies to doxorubicin and BCNU. Nevertheless, knockdown inhibited these results. Moreover, immunofluorescence movement and imaging cytometric evaluation for ABCB1, HIF-1 activation, and Hoechst 3342 in glioblastoma uncovered extremely localized ABCB1 appearance predominantly in possibly bicycling hypoxic areas with HIF-1 activation and bloodstream perfusion in the solid tumor microenvironment. The cycling hypoxic tumor cells produced from glioblastoma xenografts exhibited higher ABCB1 appearance, P-glycoprotein function, and chemoresistance, weighed against persistent hypoxic and normoxic cells. Tumor-bearing mice that received YC-1, an HIF-1 inhibitor, exhibited suppressed tumor microenvironment-induced induction and improved survival price in BCNU chemotherapy. Bicycling hypoxia plays an essential function in tumor microenvironment-mediated ...
Hypoxia can be a significant problem in the management of many solid tumors (3) . Hypoxia-inducible factor 1α, which is overexpressed in response to hypoxia, is the primary transcription factor mediating a number of physiological and biological changes that include aerobic glycolysis and slowing of proliferation (39) . This study was prompted by the greater degree of variation in FMISO and FDG uptake in several tumor types seen on PET scanning. Whereas it is reasonable to anticipate that hypoxia results in increased glycolysis, the results in our study indicate that there can be a wide variation in these two phenomena.. We analyzed the uptake patterns of these two tracers (FMISO and FDG) in two different ways: (a) global measures (HV and SUVmax); and (b) pixel analysis (SUV and T:Bmax) using all of the pixels in the delineated tumor. Visual interpretation of these graphs showed different correlation between the global uptake of the two tracers for the various tumor types. However, because the ...
Tumor hypoxia has been shown to affect the biological behavior and therapeutic resistance of a number of human malignancies. Therefore, evaluation of tumor hypoxia and characterization of mechanisms involved in cellular responses to conditions of reduced oxygenation are of considerable clinical relevance. Here we report on statistically significant HIF-1α colocalization with the nitroimidazole hypoxia marker EF5 in human cervical carcinoma xenografts and similarities in their spatial tissue distribution in relationship to tumor blood vessels. Summarized, our results indicate that HIF-1α is an intrinsic marker for tissue hypoxia.. Hypoxia has been found to induce the expression of the transcription factor HIF-1 (13) . HIF-1 has been found to stimulate the expression of a variety of genes involved in oxygen transport and maintenance of cellular energy equilibrium (14) . Recent work by Jewell et al. (10) has shown that cellular HIF-1α levels rise almost instantaneously in response to conditions ...
The hypoxia inducible factor-1 (HIF-1), a heterodimer composed of HIF-1alpha and HIF-1beta, is activated in response to low oxygen tension and serves as the master regulator for cells to adapt to hypoxia. HIF-1 is usually considered to be regulated via degradation of its a-subunit. Recent findings, however, point to the existence of alternative mechanisms of HIF-1 regulation which appear to be important for down-regulating HIF-1 under prolonged and severe oxygen depletion. The aims of my Ph.D. thesis, therefore, were to further elucidate mechanisms involved in such down-regulation of HIF-1. The first part of the thesis addresses the impact of the severity and duration of oxygen depletion on HIF-1alpha protein accumulation and HIF-1 transcriptional activity. A special focus was put on the influence of the transcription factor p53 on HIF-1. I found that p53 only accumulates under prolonged anoxia (but not hypoxia), thus limiting its influence on HIF-1 to severe hypoxic conditions. At low ...
The hypoxia inducible factor-1 (HIF-1), a heterodimer composed of HIF-1alpha and HIF-1beta, is activated in response to low oxygen tension and serves as the master regulator for cells to adapt to hypoxia. HIF-1 is usually considered to be regulated via degradation of its a-subunit. Recent findings, however, point to the existence of alternative mechanisms of HIF-1 regulation which appear to be important for down-regulating HIF-1 under prolonged and severe oxygen depletion. The aims of my Ph.D. thesis, therefore, were to further elucidate mechanisms involved in such down-regulation of HIF-1. The first part of the thesis addresses the impact of the severity and duration of oxygen depletion on HIF-1alpha protein accumulation and HIF-1 transcriptional activity. A special focus was put on the influence of the transcription factor p53 on HIF-1. I found that p53 only accumulates under prolonged anoxia (but not hypoxia), thus limiting its influence on HIF-1 to severe hypoxic conditions. At low ...
mDC development from monocytic precursors recruited at sites of inflammation and infection occurs in the setting of low pO2.5,6 The impact of the hypoxic microenvironment on DC maturation process is still controversial. This study characterizes the transcriptional profile of mDCs generated from human monocytes under chronic hypoxic conditions similar to those present in diseased tissues, demonstrating that H-mDCs are functionally reprogrammed through the differential expression of a large number of genes involved in innate and adaptive immunity. Furthermore, we define a new subpopulation of hypoxic mDCs characterized by the CD1a+/CD83+/TREM-1+ phenotype.. Divergent effects of hypoxia on DC maturation were reported in previous studies based on the expression of maturation markers, costimulatory molecules, chemokine receptors, and T cell-priming ability. Mancino et al showed that acute hypoxia impaired iDC phenotypic and functional maturation in response to lipopolysaccharide,14 whereas Rama et ...
in Experimental Cell Research (2001), 265(1), 114-24. Hypoxia is an important pathophysiological stress that occurs during blood vessel injuries and tumor growth. It is now well documented that hypoxia leads to the activation of several transcription factors ... [more ▼]. Hypoxia is an important pathophysiological stress that occurs during blood vessel injuries and tumor growth. It is now well documented that hypoxia leads to the activation of several transcription factors which participate in the adaptive response of the cells to hypoxia. Among these transcription factors, AP-1 is rapidly activated by hypoxia and triggers bFGF, VEGF, and tyrosine hydroxylase gene expression. However, the mechanisms of AP-1 activation by hypoxia are not well understood. In this report, we studied the events leading to AP-1 activation in hypoxia. We found that c-jun protein accumulates in hypoxic HepG2 cells. This overexpression is concomitant with c-jun phosphorylation and JNK activation. Moreover, we showed ...
A2A and A2B extracellular adenosine receptors. There are four different adenosine receptors: A1, A2A, A2B, and A3 (25). The high-affinity A1 receptor and the low-affinity A3 receptor are Gi protein coupled. The cAMP-elevating Gs protein-coupled A2 receptors are subdivided into high-affinity A2AR and low-affinity A2BR. Adenosine receptors are known to be immunosuppressive. The CD8+ and CD4+ T cells, including antitumor CD8+ and human T cells, predominantly express A2AR and A2BR (12, 14, 26). The cAMP-elevating signaling through A2AR results in inhibition of TCR-triggered effector functions, including proliferation, expansion, and secretion by T cells of such important antitumor cytokines as IFN-γ and tumor necrosis factor-α (14, 22).. Tumor hypoxia and accumulation of extracellular adenosine. Many solid tumors are characterized by an insufficient oxygen supply and transient or chronic hypoxia in some microenvironments (27). Tumor hypoxia may contribute to the propagation of oncogenic signals in ...
so that they are sensitive to hopoxia level. but Extreme hypoxia eventually causes failure of brain stem functions. The brainstem is a part of the brain most resistant to the effects of hypoxia, and only malfunctions and fails at degrees of hypoxia causing failure of the rest of the brain. Extreme hypoxia causes failure of all cerebral cortex functions, as well as brainstem malfunction so inducing loss of consciousness, together with abnormal breathing. Even more extreme hypoxia causes failure of all brainstem functions, causing loss of consciousness and cessation of breathing, resulting in anoxia, subsequent irreversible brainstem damage and death. I hope this helped you ...
The major new finding in the present study is that STAT3 activation protects cardiomyocytes against ROS caused by H/R through the upregulation of the MnSOD gene and its enzyme activity.. Endotoxin and cytokines such as tumor necrosis factor-α, interleukin-1β, and interluekin-6 are known to induce MnSOD, and several studies have confirmed the cardioprotective role of MnSOD.14-16 In view of the transcriptional regulation, 3 interferon-γ activation site motifs (TTCCTCTAA, TTCCTCAA, and TTACATCAA) that are bound with activated STAT3 were identified in the region spanning from -2505 to -1104 in the MnSOD promoter region.17,18 This suggests that LIF induce MnSOD mRNA expression mainly via the STAT3 binding cis-element in cardiac myocytes. It remains to be identified which motifs of the 3 discussed above are the most important for the induction of the MnSOD gene.. To clarify the role of MnSOD in H/R, we used an antisense strategy to suppress MnSOD induction.7 The responses to the pretreatment with ...
Positron Emission Tomography (PET) with fluorine-18 fluoromisonidazole (FMISO) has been used for several years as a non invasive imaging technique to study tumor hypoxia. Several experimental and clinical studies have indicated that FMISO uptake of tissues is correlated with tissue oxygen tension and that FMSO PET allows non-invasive differentiation between hypoxic and normoxic tumors. Currently, FMISO-PET represents the best characterized and validated noninvasive hypoxia imaging technique. Nevertheless, clinical studies have also shown the limitations of FMISO PET. Accumulation of FMISO in hypoxic tumors is relatively low, resulting in a low contrast between hypoxic tumors and surrounding normal tissues. In addition, imaging needs to be started relatively late after tracer injection (about 3 hours post-injection), when a significant percentage of the fluorine-18 label has already decayed and the count statistics of the PET images are relatively low. Because of these limitations, FMISO PET is ...
Hypoxia is a near universal feature of solid tumors and is associated with advanced stage and poor prognosis in a range of adult tumor types. Less is known about the significance of hypoxia in pediatric tumor types, although studies are emerging to suggest that hypoxia leads to the same drug resistance in childhood cancer cells that has been reported in adult tumor types (7-9). Data also suggest that hypoxia is a feature of neuroblastoma and contributes to poor prognosis and drug resistance (14, 15). Thus therapeutic strategies that target hypoxic areas of tumor, and are able to re-sensitize hypoxic tumor cells to clinically relevant cytotoxic agents would be of considerable interest in the treatment of this poor prognosis tumor.. Activity of the orally bioavailable ABT-737 analog, ABT-263, against neuroblastoma xenografts in the pediatric preclinical testing panel was limited (26), and in agreement with this we found that all 6 neuroblastoma cell lines studied were relatively resistant to ...
Hypoxia inducible factor-1 (HIF-1) is a key regulator in hypoxia. It has been suggested to be a critical regulator of neurological outcomes following ischemic s...
The fate of tumors depends both on the cancer cells intrinsic characteristics and on the environmental conditions where the tumors reside and grow. Engineered in vitro models have led to significant advances in cancer research, allowing the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. Here we present a biomimetic cancer model based on a collagen matrix synthesized through a biologically inspired process. We compared in this environment the responses of two breast tumor lineages characterized by different molecular patterns and opposite clinical behaviors: MCF-7 that belong to the luminal A subtype connected to an indolent course, and basal-like MDA-MB-231 connected to high-grade and aggressive disease. Cancer cells in the biomimetic matrix recreate a hypoxic environment that affects their growth dynamics and phenotypic features. Hypoxia induces apoptosis and the selection of aggressive cells that acquire expression
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
Inflammation is a primary response to injury and or infection, allowing the body to eliminate pathogens and/or damaged tissue and to initiate repair processes. Low oxygen levels, or hypoxia, is a key feature of inflamed tissue and is due to damage to the local vasculature and increased oxygen consumption by pathogens and infiltrating immune cells. In addition to being a feature of inflammation, hypoxia also induces and regulates the inflammatory response by inducing the release of inflammatory cytokines, directing immune cell infiltration, and tuning the responses of the immune cells themselves. These effects are largely mediated by a family of hypoxia-inducible transcription factors (HIFs), which serve as the master regulators of cellular responses to inadequate oxygenation and HIFs and their regulatory factors are now emerging as therapeutic targets in a number of disease states. Reviews in this series discuss the roles of hypoxia and HIFs in the regulation of inflammatory pathways, immune ...
HIF-3 alpha (hypoxia-inducible factor 3-alpha/ HIF3A) represents an isoform of HIF-alpha subunits which heterodimerize with stable beta subunit (HIF-beta) for the regulation of HIF target genes through binding to hypoxia response elements/HRE in the promoter regions.
TY - JOUR. T1 - Methylene blue-induced neuronal protective mechanism against hypoxia-reoxygenation stress. AU - Ryou, M. G.. AU - Choudhury, G. R.. AU - Li, W.. AU - Winters, A.. AU - Yuan, F.. AU - Liu, R.. AU - Yang, S. H.. PY - 2015/8/1. Y1 - 2015/8/1. N2 - Brain ischemia and reperfusion (I/R) injury occurs in various pathological conditions, but there is no effective treatment currently available in clinical practice. Methylene blue (MB) is a century-old drug with a newly discovered protective function in the ischemic stroke model. In the current investigation we studied the MB-induced neuroprotective mechanism focusing on stabilization and activation of hypoxia-inducible factor-1α (HIF-1α) in an in vitro oxygen and glucose deprivation (OGD)-reoxygenation model. Methods: HT22 cells were exposed to OGD (0.1% O2, 6h) and reoxygenation (21% O2, 24h). Cell viability was determined with the calcein AM assay. The dynamic change of intracellular O2 concentration was monitored by fluorescence ...
The tumor immune response is in a dynamic balance between antitumor mechanisms, which serve to decrease cancer growth, and the protumor inflammatory response, which increases immune tolerance, cell survival, and proliferation. Hypoxia and expression of HIF-1α and HIF-2α are characteristic features of all solid tumors. HIF signaling serves as a major adaptive mechanism in tumor growth in a hypoxic microenvironment. HIFs represent a critical signaling node in the switch to protumorigenic inflammatory responses through recruitment of protumor immune cells and altered immune cell effector functions to suppress antitumor immune responses and promote tumor growth through direct growth-promoting cytokine production, angiogenesis, and ROS production. Modulating HIF function will be an important mechanism to dampen the tumor-promoting inflammatory response and inhibit cancer growth.. ...
Apaziquone, also known as EO9, EOquin, is an indolequinone bioreductive prodrug and analog of mitomycin C with potential antineoplastic and radiosensitization activities. Apaziquone is converted to active metabolites in hypoxic cells by intracellular reductases, which are present in greater amounts in hypoxic tumor cells. The active metabolites alkylate DNA, resulting in apoptotic cell death. This agent displays activity towards both hypoxic solid tumors, which exhibits higher expression of cytochrome P450 reductase, and well-oxygenated malignant cells that overexpress the bioreductive enzyme NQO1 (NAD(P)H: quinone oxidoreductase). Apaziquone may selectively sensitize hypoxic tumor cells to radiocytotoxicity.
Hypoxia increases the proliferation of hCMPCs. hCMPCs were cultured under normoxic and hypoxic conditions for the indicated time intervals. An increase in the n
Previous studies have demonstrated the cardioprotective role of resveratrol (Res). However, the underlying molecular mechanisms involved in the protective
Of all the Hallmarks of Cancer defined by Hanahan and Weinberg, the ability to proliferate indefinitely is often considered to be the most central to cancers core features. Sustaining Growth and Resisting Cell Death enable cancer cells to override signaling that ensures normal tissues homeostasis of numbers and size. Previous chapters in our mini-series on Hypoxia and the Hallmarks of Cancer have showcased Avoiding Immune Destruction and Tumor Promoting Inflammation and Genome Instability and Mutation and Enabling Replicative Immortality as well as Inducing Angiogenesis and Activating Invasion and Metastasis.. In part four of our mini-series describing Hypoxia and the Hallmarks of Cancer, we look more closely at how researchers are using the HypOxystation to delineate the Hallmarks Sustaining Growth and Resisting Cell Death. The HypOxystation creates a cell culture environment that mimics authentic conditions for cancer research with regard to oxygen, CO2, temperature, and humidity. ...
... but observations in human hepatocellular carcinoma cells indicate that c-Fos is a mediator of c-myc-induced cell death and ... genes associated with hypoxia; and angiogenesis; which makes its dysregulation an important factor for cancer development. It ... as observed in a human T-cell leukaemia cell line. Another possible mechanism of c-Fos involvement in tumour suppression could ... Cell. Biol. 19 (11): 7589-99. doi:10.1128/MCB.19.11.7589. PMC 84780. PMID 10523647. Yang X, Chen Y, Gabuzda D (September 1999 ...
doi:10.1016/j.cell.2016.07.002. PMC 5036969. PMID 27471965. Brown JM (2007). "Tumor hypoxia in cancer therapy". Methods in ... Among different cell types, neurons are particularly sensitive to MFN2 defects: to work properly, these cells need functional ... phenotype in cancer cells. MDR cancer cells have a much more aggressive behaviour and they are very invasive with a better ... Cell. 130 (3): 548-62. doi:10.1016/j.cell.2007.06.026. PMID 17693261. S2CID 1138255. Filadi R, Pendin D, Pizzo P (February 2018 ...
1 Hypoxia miR-26 is involved in responses to low oxygen levels and has been shown to suppress cell apoptosis in a hypoxia ... cell line LoVo cells, compared with other three colorectal cell lines SW480, HT29 and Caco-2. Overexpression of miR-26b ... "Human embryonic stem cells and metastatic colorectal cancer cells shared the common endogenous human microRNA-26b". J Cell Mol ... 2007). "A microRNA signature of hypoxia". Mol Cell Biol. 27 (5): 1859-67. doi:10.1128/MCB.01395-06. PMC 1820461. PMID 17194750 ...
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cell body. Биологический процесс. • response to hypoxia. • toll-like receptor signaling pathway. • response to molecule of ... microglial cell activation involved in immune response. • positive regulation of leukocyte migration. • cell surface pattern ... negative regulation of cell proliferation. • response to toxic substance. • positive regulation of Wnt signaling pathway. • ... cell surface. • Toll-like receptor 1-Toll-like receptor 2 protein complex. • Toll-like receptor 2-Toll-like receptor 6 protein ...
It therefore, causes nutrient and hypoxic stress (or a state of hypoxia). In this regard, cancer cells and stromal cells can ... In addition to cell-autonomous changes that drive a cancer cell to proliferate and contribute to tumorigenesis, it has also ... doi:10.1016/j.cell.2011.02.013. PMID 21376230. Cairns, Rob A.; Harris, Isaac S.; Mak, Tak W. (2011). "Regulation of cancer cell ... CS1 maint: discouraged parameter (link) Semenza, G.L. (2012). "Hypoxia-inducible factors in physiology and medicine". Cell. 148 ...
... hypoxia and Akt-induced stem cell factor; ROS generated via pharmacologic activation of the mitochondrial potassium-sensitive ... "A selective epsilon-protein kinase C antagonist inhibits protection of cardiac myocytes from hypoxia-induced cell death". The ... Implications in cytoprotection against hypoxia induced cell apoptosis". Cellular Signalling. 26 (9): 1909-17. doi:10.1016/j. ... "Protein kinase C-epsilon protects MCF-7 cells from TNF-mediated cell death by inhibiting Bax translocation". Apoptosis. 12 (10 ...
Semenza, Gregg (February 2012). "Hypoxia-Inducible Factors in Physiology and Medicine". Cell. 148 (3): 399-408. doi:10.1016/j. ... Additional related processes included the formation and differentiation of B cells, T cells, endothelial cells, endoderm, and ... HIF, or hypoxia-inducible factors, are responsible for the mediation of hypoxia effects within the body. In addition, HIFs ... Predicted associated biological processes of the gene include regulation of the cell cycle, cell proliferation, apoptosis, and ...
"Hypoxia-regulated catecholamine secretion in chromaffin cells". Cell and Tissue Research. 372 (2): 433-441. doi:10.1007/s00441- ... In response to fetal hypoxia, catecholamines can maintain glucose levels, but also naturally increases during gestation. ...
... suppresses hypoxia-induced apoptotic cell death". J Biol Chem. 274 (10): 6397-404. doi:10.1074/jbc.274.10.6397. PMID 10037731 ... in HeLa cells". Cell. Physiol. Biochem. 17 (1-2): 89-96. doi:10.1159/000091467. PMID 16543725. Takeuchi S (2007). "Molecular ... Hypoxia up-regulated protein 1 is a protein that in humans is encoded by the HYOU1 gene. The protein encoded by this gene ... "Entrez Gene: HYOU1 hypoxia up-regulated 1". Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap ...
Schipani E (2006). "Hypoxia and HIF-1 alpha in chondrogenesis". Seminars in Cell & Developmental Biology. 16 (4-5): 539-46. doi ... Furthermore, cell culture experiments with VHL -/- cells have shown that the addition of pVHL can induce a mesenchymal to ... Another theory holds that although in all cells loss of VHL leads to activation of HIF, in most cells this leads to no ... Secondly, the link to Cyclin D1 (as mentioned above) is only seen in renal cells. Finally, many cells in the kidney normally ...
In white blood cells such as macrophages, dendritic cells, lymphocytes, eosinophils, and mast cells, purinergic signalling ... Hypoxia-inducible factors also influence adenosine signalling. In the central nervous system (CNS), ATP is released from ... Generally speaking, all cells have the ability to release nucleotides. In neuronal and neuroendocrinal cells, this mostly ... It involves the activation of purinergic receptors in the cell and/or in nearby cells, thereby regulating cellular functions. ...
Mechanisms of cell survival in hypoxia and hypothermia. 2001: Frederick William Henry Beamish, Burapha University. Axioms and ...
"Hypoxia-regulated carbonic anhydrase-9 (CA9) relates to poor vascularization and resistance of squamous cell head and neck ... CA IX is overexpressed in many types of cancer including clear cell renal cell carcinoma (RCC) as well as carcinomas of the ... It is over-expressed in VHL mutated clear cell renal cell carcinoma (ccRCC) and hypoxic solid tumors, but is low-expressed in ... a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer". Journal of ...
"Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche". Cancer ... Secreted LOX is responsible for the invasive properties of hypoxic cancer cells through focal adhesion kinase activity and cell ... In contrast, LOX inhibition prevents CD11b+ cell recruitment and metastatic growth. In cells lacking TGF-β receptors, a ... non-small cell lung cancer, and colorectal cancer. LOX expression was also detected in megakaryocytes, or bone marrow cells ...
... a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer". Journal of ... It is over-expressed in VHL mutated clear-cell renal cell carcinoma (ccRCC) and hypoxic solid tumors, but is low-expressed in ... response to hypoxia. • bicarbonate transport. • morphogenesis of an epithelium. • one-carbon metabolic process. • secretion. • ... cell projection. • nucleus. • membrane. • basolateral plasma membrane. • microvillus membrane. • integral component of membrane ...
Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer Cell, 26: 605-22, 2014 Jain, RK. ...
"Cell therapy for neonatal hypoxia-ischemia and cerebral palsy". Annals of Neurology. 71 (5): 589-600. doi:10.1002/ana.22670. ... Stem cell therapy, and other cell-based therapies are being studied as a treatment. A potential treatment for some forms of ... has been studied under the theory that improving oxygen availability to damaged brain cells can reactivate some of them to ...
"PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome". Cell Stem Cell. 2 (6): 576-83. doi: ... Nelson DA, Tan TT, Rabson AB, Anderson D, Degenhardt K, White E (September 2004). "Hypoxia and defective apoptosis drive ... PUMA inducers target cancer or tumor cells, while PUMA inhibitors can be targeted to normal, healthy cells to help alleviate ... Cell. 123 (4): 641-53. doi:10.1016/j.cell.2005.09.029. PMID 16286009. S2CID 13472437. Overview of all the structural ...
"Iron regulation and the cell cycle: identification of an iron-responsive element in the 3'-untranslated region of human cell ... Amar J. Majmundar; Waihay J. Wong & M. Celeste Simon (October 2010). "Hypoxia-inducible factors and the response to hypoxic ... CDC14A encodes a dual-specificity phosphatase implicated in cell cycle control and also interacts with interphase centrosomes. ... Mayka Sanchez; Bruno Galy; Martina U. Muckenthaler & Matthias W. Hentze (May 2007). "Iron-regulatory proteins limit hypoxia- ...
In most cells, HIF1A gene is constitutively expressed in low levels under normoxic conditions, however, under hypoxia, HIF1A ... Schipani E (2006). "Hypoxia and HIF-1 alpha in chondrogenesis". Seminars in Cell & Developmental Biology. 16 (4-5): 539-46. doi ... Hypoxia promotes apoptosis in both normal and tumor cells. However, hypoxic conditions in tumor microenvironment especially, ... While research efforts to develop therapeutic drugs to target hypoxia-associated tumor cells have been ongoing for many years, ...
During this stage, the state of hypoperfusion causes hypoxia. Due to the lack of oxygen, the cells perform lactic acid ... Because cells can only produce adenosine at a rate of about 2% of the cell's total need per hour, even restoring oxygen is ... Brain damage and cell death are occurring, and death will occur imminently. One of the primary reasons that shock is ... Due to the decreased perfusion of the cells in the body, sodium ions build up within the intracellular space while potassium ...
As expected, such cells were also highly vulnerable to stress, and ceased to be viable at elevated temperature ranges. Although ... doi:10.1016/b978-0-12-805421-5.00003-3. ISBN 978-0-12-805421-5. Majmundar AJ, Wong WJ, Simon MC (October 2010). "Hypoxia- ... The Cell Stress Response (Report). Simon Fraser University. Hofer H, East ML (1998-01-01). Møller AP, Milinski M, Slater PJ ( ... Early research has suggested that cells which are better able to synthesize stress proteins and do so at the appropriate time ...
This is an example of histotoxic hypoxia. The most hazardous compound is hydrogen cyanide, which is a gas and kills by ... As a result, the electron transport chain is disrupted, meaning that the cell can no longer aerobically produce ATP for energy ... the fourth complex of the electron transport chain found in the inner membrane of the mitochondria of eukaryotic cells. It ...
Hypoxia[edit]. Hypoxia stimulates hypoxia-inducible factor-1 alpha (HIF-1α) to be produced, which initiates the hypoxic ... in sarcoma cells and oral cancer cells. BHLHE41 also suppresses cytochrome P450 2D6 (CYP2D6) in hepatocellular carcinoma cells ... cell nucleus. Biological process. • cell differentiation. • regulation of transcription, DNA-templated. • rhythmic process. • ... Zhang Y, Zhang Y, Gu W, Sun B (2014). "TH1/TH2 cell differentiation and molecular signals". T Helper Cell Differentiation and ...
Hypoxia[edit]. Hypoxia stimulates hypoxia-inducible factor-1 alpha (HIF-1α) to be produced, which initiates the hypoxic ... in sarcoma cells and oral cancer cells. BHLHE41 also suppresses cytochrome P450 2D6 (CYP2D6) in hepatocellular carcinoma cells ... and metastasis in sarcoma cells and hepatocellular carcinoma cells.[34] It has been shown that the normal tissue adjacent to ... cell differentiation. • regulation of transcription, DNA-templated. • rhythmic process. • negative regulation of transcription ...
There are about 24,000 oxidative DNA adducts per cell in young rats and 66,000 adducts per cell in old rats. Likewise, any ... Oxidative stress also plays a role in the ischemic cascade due to oxygen reperfusion injury following hypoxia. This cascade ... Cells. 32 (1): 1-5. doi:10.1007/s10059-011-1021-7. PMC 3887656. PMID 21424583. Galano JM, Mas E, Barden A, Mori TA, Signorini C ... Cell Biol. 39 (1): 44-84. doi:10.1016/j.biocel.2006.07.001. PMID 16978905. Bonomini F, Tengattini S, Fabiano A, Bianchi R, ...
These cells have also been demonstrated to be hypoxia-resistant. Bone marrow contains different cell populations, which exhibit ... These cell populations are endothelial progenitor cells, hematopoietic stem cells and mesenchymal stem cells. Adipose tissue ... Further to cell and necessary relevant growth factor selection, cell delivery is an important issue. Indeed, the intracoronary ... However, cardiac remodelling remains limited due to limited cell residency, impact of mechanical forces onto cell survival and ...
"Methane biogenesis during sodium azide-induced chemical hypoxia in rats". American Journal of Physiology. Cell Physiology. 304 ... The beta cells of the pancreas in type 1 diabetes produce an excess of the gas, leading to the death of these cells and to a ... There is a theory that, in some nerve cell synapses, when long-term memories are being laid down, the receiving cell makes ... These attributes make nitric oxide ideal for a transient paracrine (between adjacent cells) and autocrine (within a single cell ...
"A Glucose-Triptolide Conjugate Selectively Targets Cancer Cells under Hypoxia". iScience. 23 (9). doi:10.1016/j.isci. ... Cell. Biol. 10 (6): 2570-2581. doi:10.1128/MCB.10.6.2570. PMC 360615. PMID 2111438. Weeda G, van Ham RC, Vermeulen W, Bootsma D ... Cell. Biol. 16 (5): 2044-2055. doi:10.1128/MCB.16.5.2044. PMC 231191. PMID 8628270. Iyer N, Reagan MS, Wu KJ, Canagarajah B, ... Cell. Biol. 29 (5): 1276-90. doi:10.1128/MCB.01229-08. PMC 2643825. PMID 19114557. Takeda N, Shibuya M, Maru Y (January 1999 ...
ventricular cardiac muscle cell development. · cellular response to hypoxia. · positive regulation of cell aging. ... M phase of mitotic cell cycle. · mitotic prophase. · mitotic anaphase. · mitotic cell cycle. · apoptotic process. · cellular ... Halaschek-Wiener J, Brooks-Wilson A. Progeria of stem cells: stem cell exhaustion in Hutchinson-Gilford progeria syndrome. J. ... J. Cell. Sci. October 2000, 113 (19): 3473-84. PMID 10984438.. *^ Dreuillet C, Tillit J, Kress M, Ernoult-Lange M. In vivo and ...
It also contains pacemaker cells and nonpacemaker cells that initiate spontaneous breathing. Research is being conducted on the ... Investigation of the respiratory response to Acute intermittent hypoxia (AIH), repeated episodes of hypoxia, reveals connection ... since intermittent hypoxia causes an increase in persistent frequency after ongoing hypoxia.The respiratory system is regulated ... Hypoxia results in gasping due to the increased dependence on the sodium current and the overlap in networks between the ...
response to hypoxia. • regulation of transcription, DNA-templated. • response to oxidative stress. • cell-cell adhesion. • ... cadherin binding involved in cell-cell adhesion. • actin binding. • muscle alpha-actinin binding. ... Pitx2 pathway mediating cell-type-specific proliferation during development.". Cell. 111 (5): 673-85. PMID 12464179. doi: ... Vallenius T، Mäkelä TP (2003). "Clik1: a novel kinase targeted to actin stress fibers by the CLP-36 PDZ-LIM protein.". J. Cell ...
Anaplastic cells have lost total control of their normal functions and many have deteriorated cell structures. Anaplastic cells ... Arterial and venous hypoxia, or the deprivation of adequate oxygen supply to certain areas of the brain, occurs when a tumor ... Necrotic cells send the wrong chemical signals which prevent phagocytes from disposing of the dead cells, leading to a buildup ... Glial cells such as Schwann cells in the periphery or, within the cord itself, oligodendrocytes, wrap themselves around the ...
... also has neuroprotective properties in its demonstrated anti-hypoxia or anti-ischemia effects; there is a ... in neuronal cells as well as in synaptic vesicles; extracellular levels also increase which results in increased monoamine ...
Isenberg, S. J.; McRee, W. E.; Jedrzynski, M. S.; Gange, S. N.; Gange, S. L. (1987-01-01). "Effects of sickle cell anemia on ... Isenberg, S. J.; McRee, W. E.; Jedrzynski, M. S. (1986-10-01). "Conjunctival hypoxia in diabetes mellitus". Investigative ... "Vascular changes in the bulbar conjunctiva associated with sickle-cell disease: some observations on fine structure" ...
Gerald Karp (19 October 2009). Cell and Molecular Biology: Concepts and Experiments. John Wiley and Sons. pp. 14-. ISBN 978-0- ... Toxic effects from anatoxin-a progress very rapidly because it acts directly on the nerve cells (neurons) as a neurotoxin. The ... It acts on the voltage-gated sodium channels of nerve cells, preventing normal cellular function and leading to paralysis. The ... As a result, the muscle cells contract permanently, the communication between the brain and the muscles is disrupted and ...
If a lumbar puncture is performed, it will show normal cerebral spinal fluid and cell counts but an increase in pressure.[7] In ... Hypoxia increases extracellular fluid, which passes through the vasogenic endothelium in the brain. The leaking may be caused ... Another theory about the cause of HACE is that hypoxia may induce nitrous oxide synthase.[24] Vasodilation is caused by the ... Patients with HACE have an elevated white blood cell count, but otherwise their blood count and biochemistry are normal. ...
Prolonged hypoxia induces neuronal cell death via apoptosis, resulting in a hypoxic brain injury.[1][2] ... For other uses, see hypoxia (disambiguation).. Cerebral hypoxia is a form of hypoxia (reduced supply of oxygen), specifically ... Anemia and carbon monoxide poisoning are common causes of hypemic hypoxia.. *Ischemic hypoxia ( or "stagnant hypoxia") - ... Nov 2001). "Hypoxia induces apoptosis via two independent pathways in Jurkat cells: differential regulation by glucose". ...
T suppressor cells - T4 cell - T4 cells (T-helper cells) - T8 cells - Tanner staging - TAT - TB - template - TeachAIDS - ... hypoxia IEdit. idiopathic - idiopathic thrombocytopenia purpura - IHS - immune complex - immune deficiency/immunodeficiency - ... B-cell lymphoma - B cells - B lymphocytes (B cells) - bactericidal - bacteriostatic - bacterium - baculovirus - baseline - ... cells - CDC National Prevention Information Network (CDC-NPIN) - cell lines - cell-mediated immunity (CMI) - cellular immunity ...
57:51-9. Tang PS, Mura M, Seth R, Liu M. (2008) Acute lung injury and cell death: how many ways can cells die? Am J Physiol 294 ... the vasoconstrictive response to hypoxia, thereby mismatching ventilation with perfusion. Gas exchange is affected by increases ... There are two types of alveolar epithelial cells - Type 1 pneumocytes represent 90% of the cell surface area, and are easily ... Furthermore, when phosgene hydrolyzes it forms hydrochloric acid, which can damage the cell surface and cause cell death in the ...
The gut mucosal cells do not get enough nourishment from arterial blood supply to stay healthy, especially in very premature ... Intrauterine hypoxia. *Infant respiratory distress syndrome. *Transient tachypnea of the newborn. *Meconium aspiration syndrome ...
... distributes readily in high concentrations into immune cells, has antimicrobial and natural killer cell activities, ... Hypoxia-inducible factor-proline dioxygenase enzymes (isoforms: EGLN1, EGLN2, and EGLN3)[95][96] ... Cell. 132 (6): 1039-48. doi:10.1016/j.cell.2008.01.042. PMID 18358815. Lay summary - Science Daily (March 21, 2008).. ... Plant and Cell Physiology. 45 (9): 1271-1279. doi:10.1093/pcp/pch152. PMID 15509850.. ...
Mechanism of cell death[edit]. Cells that undergo an extreme amount of stress experience cell death either through apoptosis or ... These metabolic stresses include hypoxia, nutrient deprivation, and an increase in proliferation. These stresses activate ... "Cannabisin B induces autophagic cell death by inhibiting the AKT/mTOR pathway and S phase cell cycle arrest in HepG2 cells". ... Tavassoly, Iman (2015). Dynamics of Cell Fate Decision Mediated by the Interplay of Autophagy and Apoptosis in Cancer Cells. ...
2002) „From erythropoietin to oxygen: hypoxia-inducible factor hydroxylases and the hypoxia signal pathway". Blood Purification ... 2007) „Does erythropoietin have a dark side? Epo signaling and cancer cells". Science's STKE 2007 (395), pe38. o. DOI:10.1126/ ... 2012) „The effect of erythropoietin on normal and neoplastic cells". Biologics 6, 163-89. o. DOI:10.2147/BTT.S32281. PMID ... 1996) „Erythropoietin production by interstitial cells of hypoxic monkey kidneys". British Journal of Haematology 95 (1), 27-32 ...
Mechanism of cell death[edit]. Cells that undergo an extreme amount of stress experience cell death either through apoptosis or ... These metabolic stresses include hypoxia, nutrient deprivation, and an increase in proliferation. These stresses activate ... Mizushima N, Komatsu M (November 2011). "Autophagy: renovation of cells and tissues". Cell. 147 (4): 728-41. doi:10.1016/j.cell ... Tavassoly I (2015). Dynamics of Cell Fate Decision Mediated by the Interplay of Autophagy and Apoptosis in Cancer Cells. ...
Targeting double-stranded breaks increases the probability that cells will undergo cell death. Cancer cells are generally less ... Solid tumors can outgrow their blood supply, causing a low-oxygen state known as hypoxia. Oxygen is a potent radiosensitizer, ... Fractionation allows normal cells time to recover, while tumor cells are generally less efficient in repair between fractions. ... Single-strand DNA damage is then passed on through cell division; damage to the cancer cells' DNA accumulates, causing them to ...
... live in all of the oceans, particularly in tropical and warm subtropical waters. They are commonly found in the epipelagic zone, the top layer of the ocean to a depth of about 200 m (656 ft). Numerous morphological features give flying fish the ability to leap above the surface of the ocean. One such feature is fully broadened neural arches, which act as insertion sites for connective tissues and ligaments in a fish's skeleton. Fully broadened neural arches act as more stable and sturdier sites for these connections, creating a strong link between the vertebral column and cranium.[10] This ultimately allows a rigid and sturdy vertebral column (body) that is beneficial in flight. Having a rigid body during glided flight gives the flying fish aerodynamic advantages, increasing its speed and improving its aim.[10] Furthermore, flying fish have developed vertebral columns and ossified caudal complexes.[11] These features provide the majority of strength to the flying fish, allowing them ...
Ketogenic diets have also been shown to have some neuroprotective effects in models of Parkinson's disease and hypoxia as well. ... Proper myelination is critical for carrying electrical signals, or data, from one nerve cell to the next. When myelin becomes ... MAP kinase is imperative for numerous physiological changes including regulation of cell division and differentiation, thus, ... which further leads to secondary cell damage and death. Additionally, oxidative stress may be responsible for loss of striatal ...
Automaticity refers to a cardiac muscle cell firing off an impulse on its own. Every cardiac cell has this potential: if it ... Conditions that increase automaticity include sympathetic nervous system stimulation and hypoxia. The resulting heart rhythm ... Every cardiac cell is able to transmit impulses in every direction, but will only do so once within a short period of time. ... Fatty acids play an important role in the life and death of cardiac cells because they are essential fuels for mechanical and ...
PANIC does not apply to cells that can be recharged with redox materials. These galvanic or voltaic cells, such as fuel cells, ... An abnormal redox state can develop in a variety of deleterious situations, such as hypoxia, shock, and sepsis. Redox mechanism ... For a redox reaction that takes place in a cell, the potential difference is: E0. cell = E0. cathode - E0. anode. However, the ... The summary equation for cell respiration is: C6H12O6 + 6 O2 → 6 CO2 + 6 H2O. The process of cell respiration also depends ...
Rh blood type incompatibility can cause the mother's immune system to attack the baby's red blood cells.[1] ... incidents involving hypoxia to the brain (such as near drowning), and encephalitis or meningitis.[59] ... including stem cell therapy.[1] However, more research is required to determine if it is effective and safe.[1] ... hypoxia of the brain (thrombotic events, placental conditions), birth trauma during labor and delivery, and complications ...
Mast cell tryptase levels may be elevated if the attack was due to an acute allergic (anaphylactic) reaction. When the patient ... Abdominal attacks have also been known to cause a significant increase in the patient's white blood cell count, usually in the ... Bradykinin is released by various cell types in response to numerous different stimuli; it is also a pain mediator. Dampening ... Hypoxia/Asphyxia. *Barotrauma *Aerosinusitis. *Decompression sickness. *High altitude *Altitude sickness. *Chronic mountain ...
Journal of Cell Biology. 1965, 27 (3): 505-17. PMC 2106769. PMID 5885427. doi:10.1083/jcb.27.3.505.. ... Latent hypoxia(英语:Latent hypoxia). *List of diving hazards and precautions(英语:List of diving hazards and precautions) ... The effect of oxygen at high pressure on the histology of the central nervous system and sympathetic and endocrine cells. Acta ...
Possible causes of widespread brain damage include birth hypoxia, prolonged hypoxia (shortage of oxygen), poisoning by ... Brain damage, which is the destruction or degeneration of brain cells, is a common occurrence in those who experience a head ...
Presence in nonerythroid cells[edit]. Some nonerythroid cells (i.e., cells other than the red blood cell line) contain ... therefore preventing its release at the tissue and inducing a level of hypoxia in extreme cases.[81] ... mesangial cells in the kidney, endometrial cells, cervical cells and vaginal epithelial cells.[11] In these tissues, ... Other cells that contain haemoglobin include the A9 dopaminergic neurons in the substantia nigra, macrophages, alveolar cells, ...
The osteoblast cell is derived from the Mesenchymal Stem Cell (MSC) which can also differentiate into a chondrocyte.[23] The ... A reduction in A1 expression appears to prevent hypoxia-induced ventriculomegaly and loss of white matter, which raises the ... It allows for the inhibition of growth in human melanoma cells. Specific antagonists include MRS1191, MRS1523 and MRE3008F20, ... cell signalling involved in the stimulation of the A2B receptor directs the route of differentiation to osteoblast, rather than ...
... which are cell-cell adhesion molecules found in desmosomes). Underlying cancer or irreversible system impairment, seen in acute ... which may occur in response to hypoxia or ectopic EPO production/altered catabolism. Erythrocytosis is common in regions of the ... In contrast, these phenomena are mediated by humoral factors (such as hormones or cytokines) secreted by tumor cells or by an ... In this scenario, the body may produce antibodies to fight off the tumor by directly binding and destroying the tumor cell. ...
Cell studies[edit]. Crocin and crocetin may provide neuroprotection in rats by reducing the production of various neurotoxic ... Gainer, J (2008). "Trans-sodium crocetinate for treating hypoxia/ischemia". Expert Opinion on Investigational Drugs. 17 (6): ... "Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells". European Journal of Pharmacology. 648 (1-3): ... is an experimental drug that increases the movement of oxygen from red blood cells into hypoxic (oxygen-starved) tissues.[8] ...
2 diffuses through membranes in the lungs and into red blood cells. Hemoglobin binds O. 2, changing color from bluish red to ... Hypoxia (environmental) for O. 2 depletion in aquatic ecology. *Ocean deoxygenation. *Hypoxia (medical), a lack of oxygen ...
If not quickly treated, cell hypoxia can lead to... ... Cell hypoxia is a serious condition in which cells dont have ... Injury and illnesses can initiate cell hypoxia. Treating cell hypoxia entails replacing oxygen, fluids and nutrition. ... Cell hypoxia also alters cellular calcium supplies required for proper membrane function and the release of neurotransmitters ... Treating and managing hypoxia involve general care measures. Supplemental oxygen and intravenous fluids prevent further cell ...
t = 480 s) Bulk polymerized part of the cell is revealed. (t = 540 s) The cell attains its hypoxia shape (cell d in Movie S1). ... 1996) Vascular cell adhesion molecule-1 is involved in mediating hypoxia-induced sickle red blood cell adherence to endothelium ... Hypoxia Enhances Sickle Cell Adherence.. Normoxic individual sickle cells show pronounced morphological heterogeneity, and this ... Adherence of ISCs Under Hypoxia.. Sickle cell blood samples contain a subpopulation of abnormally dense cells compared with ...
Percentage of dead cells versus total cells with hypoxia treatment alone or in combination with 10% PRC (mean ± SD, ). versus ... However, hypoxia (0.1% O2) significantly induced cell death from 1.6% under normoxia to 7.5% under hypoxia 48 h after treatment ... Primary human tenocytes were exposed to total hypoxia (0.1% O2) for 1, 4, 8, 16, 24, and 48 h. The cells were harvested in cell ... Percentage of apoptotic cells versus total cells (mean ± SE, ; versus 10% FCS alone; versus 1% FCS alone; ns not significant ...
The objective of this article is to discuss the role of HIFs in the function of innate and adaptive immune cells in hypoxia, ... A characteristic feature of immune cells is their ability to infiltrate and operate in tissues with low level of nutrients and ... HIFs are key mediators of the cellular response to hypoxia, but they are also associated with pathological stress such as ... and the adaptation to inadequate tissue oxygenation is regulated by hypoxia-inducible factors (HIFs). ...
YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression.. Shi Y1,2, Fan S3, Wu M4, Zuo Z5, Li X5, Jiang L1, ... Indicated cell extracts were probed with indicated antibodies. n Overlap of m6A-seq peaks in A549 cells with RIP-seq for YTHDF1 ... After 72 h treatment under hypoxia condition, indicated cells are stained with Annexin V/PI, and the percentage of apoptotic ... d, e Effect of DDP and/or AKR1C1 inhibitor BPS on cell viabilities of indicated A549 cell lines (d), which were further ...
Myeloid cell infiltration on its own can contribute to O2 deprivation at these sites. In response to hypoxia, myeloid cells ... Hypoxia and hypoxia-inducible factors. In many of the pathological situations described above (5, 7, 8, 12, 16, 17), HIFs are ... Hypoxia-inducible factors: key regulators of myeloid cells during inflammation. Nan Lin and M. Celeste Simon Abramson Family ... Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell. 2010;40(2):294-309.. View this article via: PubMed ...
They have discovered the hairy gene, that has a survival switch that helps cells and tissues to survive a low-oxygen ... This research has implications for people suffering from diseases that involve hypoxia or tissue that has been oxygen deprived. ... Scientists have examined fruit flies to discover cells that can survival low-levels of oxygen or hypoxia. ... Depriving Cells of Oxygen: Hypoxia. Hypoxia is a condition whereby cells and tissues become severely deprived of oxygen. In ...
Cellular responses to oxygen levels are monitored, in part, by the transcriptional activity of the hypoxia inducible factors ( ... HIFs). Under hypoxia, HIFs regulate a variety of pro-angiogenic and pro-glycolysis pathw … ... Hypoxia inducible factors in cancer stem cells Br J Cancer. 2010 Mar 2;102(5):789-95. doi: 10.1038/sj.bjc.6605551. Epub 2010 ... Under hypoxia, HIFs regulate a variety of pro-angiogenic and pro-glycolysis pathways. In solid cancers, regions of hypoxia are ...
Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells.. Facciabene A1, Peng X, Hagemann IS, Balint K, ... Here we show that tumour hypoxia promotes the recruitment of regulatory T (T(reg)) cells through induction of expression of the ... However, a direct link between tumour hypoxia and tolerance through the recruitment of regulatory cells has not been ... Hypoxia, a condition that is known to drive angiogenesis in tumours, results in the release of damage-associated pattern ...
Hypoxia increases the Aldefluor+ stem cell population in breast cancer cell lines in vitro. MDA-MB-231, SUM159, and MCF-7 cells ... C) The percentage of Aldefluor+ cells increased under hypoxia in untransfected cells and cells transfected with either control ... 2008) Notch signaling regulates mammary stem cell function and luminal cell-fate commitment. Cell Stem Cell 3:429-441. ... cells following hypoxia treatment, luciferase activity was increased by approximately twofold in GFP− cells following hypoxia ...
... but also alter many of their functions in response to hypoxia to either facilitate or suppress inflammation. Hypoxia stabilizes ... Hypoxia is a prominent characteristic of many acute or chronic inflammatory diseases, and exerts significant influence on their ... and these O2-sensitive transcription factors are key regulators of inflammatory responses in myeloid cells. In this review, we ...
Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory ... Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their ... Small hypoxia-primed mesenchymal stem cells attenuate graft-versus-host disease Leukemia. 2018 Dec;32(12):2672-2684. doi: ... Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their ...
... and hypoxia induced-chemoresistance in T-cell non-Hodgkins lymphoma (T-NHL), as well as the underlying... ... 2f) in hypoxia, but not in normoxia in Jurkat cells. Similar results were also observed in Hut-78 cells (Fig. 2g-j). ... Hypoxia triggers expression of AEG-1, LC3-II and Beclin-1 in T-NHL cells. To understand the effects of hypoxia on AEG-1 ... Effect of hypoxia on AEG-1 and autophagy markers in T-NHL cells. Hut-78 and Jurkat cells were incubated under normoxia or ...
Y. Jiang, W. Zhang, K. Kondo et al., "Gene expression profiling in a renal cell carcinoma cell line: dissecting VHL and hypoxia ... Identification of Multiple Hypoxia Signatures in Neuroblastoma Cell Lines by -. Regularization and Data Reduction. Paolo Fardin ... J.-T. Chi, Z. Wang, D. S. A. Nuyten et al., "Gene expression programs in response to hypoxia: cell type specificity and ... A. Jögi, I. Øra, H. Nilsson et al., "Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural ...
Double KO mice of Vegf and hypoxia inducible factor-1α (Hif-1α) showed increased life span and suppressed tumor growth due to ... These changes of adhesion molecules were not observed in the primary culture of the tumor cells under hypoxic conditions. Thus ... but is not directly caused by acute hypoxia. ... Cell culture. Cells were cultured in a humidified atmosphere of ... S5a). The cells in CTOS shared similar morphology with the original tumor cells and the cells stained positive for insulin ( ...
Mechanisms of cell survival in hypoxia and hypothermia Message Subject (Your Name) has sent you a message from Journal of ... Semenza, G. L. (1999). Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu. Rev. Cell Dev. Biol. 15, 551 ... However, many cells and tissues exhibit a whole host of adaptive molecular-level responses to sustainable levels of hypoxia, as ... Ionic integrity of cells during hypothermia. To understand why many mammalian tissues and cells are so cold-sensitive, we must ...
Abstract 3401: Hypoxia, Inflammatory Cells, and Hyaluronan Homeostasis in Aortic Valve Calcification. Jerome G Saltarrelli, ... Conclusions: Mature and immature nodules within CAVD demonstrate evidence for hypoxia-, matrix-, and inflammatory cell-driven ... Abstract 3401: Hypoxia, Inflammatory Cells, and Hyaluronan Homeostasis in Aortic Valve Calcification ... Abstract 3401: Hypoxia, Inflammatory Cells, and Hyaluronan Homeostasis in Aortic Valve Calcification ...
Actin Hypoxia In Cell ELISA Kit (IR) (ab125300). Please let us know if you have used this product in your publication ... Cell Biology. Epigenetics. Metabolism. Developmental Biology. By research area. Immunology. Microbiology. Neuroscience. Signal ... Cell and tissue imaging tools. Cellular and biochemical assays. By product type. Proteins and Peptides. Proteomics tools. ...
Two TAPP (MRP3 and Trp1) were down-regulated by hypoxia in glioma cell lines. Growing the glioma cells under hypoxia for 13 ... The antigens expressed by hypoxic tumor cells may be a better source of starting tumor material for loading dendritic cells for ... Intracranial xenografts grown in nude mice derived from U251 cells that had been cultured under neurosphere stem cell ... Whsc2-specific cytotoxic T lymphocytes killed the hypoxic U251 glioma cells better than normoxic glioma cells. ...
Recently, it was suggested that hypoxia increased the size of the cancer stem-cell (CSC) subpopulations and promoted the ... However, candidate hypoxia-regulated mediators specifically relevant to the stemness-related functions of colorectal CSCs have ... Through various in vitro studies, we found that hypoxia-induced Wnt/β-catenin signaling increased the occurrence of CSC-like ... phenotypes and the level of Id2 expression in colorectal-cancer cells. Importantly, the levels of hypoxia-induced CSC-sphere ...
Recently, great effort has been invested towards elucidating the interplay between hypoxia-induced autophagy and cancer cell ... Recently, great effort has been invested towards elucidating the interplay between hypoxia-induced autophagy and cancer cell ... Hypoxia adaptation requires coordination of intricate pathways and mechanisms such as hypoxia-inducible factors (HIFs), the ... Hypoxia adaptation requires coordination of intricate pathways and mechanisms such as hypoxia-inducible factors (HIFs), the ...
Treatment of HCT-116 and Caco-2 colon cancer cells with the hypoxia mimic CoCl2 induced the formation of cells with larger cell ... the pharmacological induction of hypoxia in colon cancer cells causes the formation of PGCCs, the expansion of a cell ... Cytometric analysis showed that CoCl2 treatment induced G2 cell cycle arrest and the generation of a polyploid cell ... Generation of PGCCs also contributed to expansion of a cell subpopulation with cancer stem cells (CSCs) characteristics, as ...
C, Hypoxia- and TCR/CD3 stimulation-dependent expression of HIF-1α protein in T cells. PHA-activated T cells were incubated in ... A, Hypoxia and TCR/CD3 stimulation repress AICD in peripheral T cells. PHA-preactivated human peripheral T cells maintained in ... D, Synthetic AM peptides mimic the effect of hypoxia in protection of T cells against AICD. PHA-activated T cells with TCR/CD3 ... Hypoxia affects cytokine production and proliferative responses by human peripheral mononuclear cells. J. Cell. Physiol. 173: ...
S44 Pseudomonas aeruginosa induces neutrophil cell death which is reversed by hypoxia ... S44 Pseudomonas aeruginosa induces neutrophil cell death which is reversed by hypoxia ... Neutrophils have a unique ability to survive and function in such hypoxic environments, a response regulated by the hypoxia- ... Furthermore, we postulated that the killing effects of these bacteria are reversed in hypoxia. ...
Cell, Tumor, and Stem Cell Biology Xanthine Oxidase-Dependent Regulation of Hypoxia-Inducible Factor in Cancer Cells. Corinne E ... 43) who found that ROS production was increased in PC12 cells during hypoxia but was not the cause of the hypoxia-driven ... Consequently, the initial GSH/GSSH ratio is 2-fold higher in D54-MG cells compared with U251-MG cells. When cells were treated ... Xanthine Oxidase-Dependent Regulation of Hypoxia-Inducible Factor in Cancer Cells. Corinne E. Griguer, Claudia R. Oliva, Eric E ...
B, patient 5. High binding cells are admixed with dead cells (black areas within regions of bright binding represent dead cells ... Detection of Hypoxia in Human Squamous Cell Carcinoma by EF5 Binding. Sydney M. Evans, Stephen Hahn, Deirdre R. Pook, W. ... Detection of Hypoxia in Human Squamous Cell Carcinoma by EF5 Binding. Sydney M. Evans, Stephen Hahn, Deirdre R. Pook, W. ... Detection of Hypoxia in Human Squamous Cell Carcinoma by EF5 Binding. Sydney M. Evans, Stephen Hahn, Deirdre R. Pook, W. ...
... the idea being that two types of unusual cells could form synapse and provide a model for studies o ... to chemical stimuli with and without PC-12 cells in co-culture instead of glomus is not known- ... Cell Hypoxia. Coculture Techniques. Ganglia, Sensory / cytology*. Intracellular Space / drug effects, metabolism. Neurons / ... Calcium sensitivity of petrosal ganglion neurons (PGNs) to chemical stimuli with and without PC-12 cells in co-culture instead ...
2009) Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 15, 501-513.. *CrossRef , ... 2010) Regulation of the HIF-1alpha level is essential for hematopoietic stem cells. Cell Stem Cell 7, 391-402.. *CrossRef , ... Cell Stem Cell, 2017, 21, 1, 18. CrossRef. *4. Tim S Cliff, Stephen Dalton, Metabolic switching and cell fate decisions: ... a critical review of sphere-formation as an assay for stem cells. Cell Stem Cell 8, 486-498.. *CrossRef , ...
Hypoxia-inducible factor 1 alpha-activated angiopoietin-like protein 4 contributes to tumor metastasis via vascular cell ... Hypoxia-inducible factor 1 alpha-activated angiopoietin-like protein 4 contributes to tumor metastasis via vascular cell ... Dongjun Luo, Zhongxia Wang, Junyi Wu, Chunping Jiang, Junhua Wu, The Role of Hypoxia Inducible Factor-1 in Hepatocellular ...
Identification of Serum Markers For Tumor Hypoxia in Non-Small Cell Lung Cancers. The safety and scientific validity of this ... Carcinoma, Non-Small-Cell Lung. Hypoxia. Respiratory Tract Neoplasms. Thoracic Neoplasms. Neoplasms by Site. Neoplasms. Lung ... Identification of Serum Markers For Tumor Hypoxia in Non-Small Cell Lung Cancers. ... The purpose of the study is to identify a surrogate serum marker for tumor hypoxia in patients with lung cancers. ...
  • Total hypoxia caused significant tenocyte apoptosis. (hindawi.com)
  • Hypoxia caused sustained upregulation of several proapoptotic proteins known to mediate hypoxia-induced apoptosis, such as Bnip3 and Nix, but others were unchanged although they were reportedly hypoxia-sensitive in other cell types. (hindawi.com)
  • Additionally, the proliferation and apoptosis of Hut-78 cells exposed to different concentration of Adriamycin (ADM) in normoxia and hypoxia were evaluated by MTT and Annexin-V FITC/PI staining assay. (springer.com)
  • Hypoxia induced proliferation and reduced apoptosis of Hut-78 cells exposed to ADM. (springer.com)
  • AEG-1 overexpression further increased proliferation and decreased apoptosis of Hut-78 cells exposed to ADM in hypoxia. (springer.com)
  • Moreover, overexpression of AEG-1 significantly inversed 3-MA induced-changes in cell proliferation and apoptosis of Hut-78 cells exposed to ADM in hypoxia. (springer.com)
  • Double KO mice of Vegf and hypoxia inducible factor-1α ( Hif-1α ) showed increased life span and suppressed tumor growth due to increased apoptosis. (nature.com)
  • The apoptosis of retinal ganglion cells (RGCs) is a hallmark of several optic neuropathies. (spandidos-publications.com)
  • It was observed that overexpression of miR-137 markedly aggravated hypoxia-induced cell apoptosis, whereas inhibition of miR-137 effectively protected RGCs against hypoxia-induced apoptosis. (spandidos-publications.com)
  • Hypoxia induced Notch1 expression and signaling activation, while blocking Notch signaling significantly aggravated hypoxia-induced cell apoptosis. (spandidos-publications.com)
  • Hypoxia is the critical pathological factor for several optic neuropathies, and hypoxia-induced apoptosis of RGCs results in progressive vision loss ( 4 - 6 ). (spandidos-publications.com)
  • thus, protecting RGCs against hypoxia-evoked cell apoptosis is crucial for treating hypoxia-induced retinal diseases. (spandidos-publications.com)
  • The Notch signaling pathway plays an important role in various cellular processes, including cell proliferation and apoptosis, and is involved in numerous pathological processes ( 8 , 9 ). (spandidos-publications.com)
  • The Notch signaling pathway is extensively involved in regulating cell proliferation, apoptosis and differentiation through crosstalk with other signaling pathways ( 16 ). (spandidos-publications.com)
  • However, the role of Notch signaling in hypoxia-induced cell apoptosis of RGCs has not been extensively investigated. (spandidos-publications.com)
  • Thus, miRNAs are involved in the regulation of a wide range of cellular processes, such as stress response, cell survival and apoptosis ( 22 ). (spandidos-publications.com)
  • Under normal conditions, the thickness of the vascular wall is maintained at an optimal level by a fine balance between proliferation and apoptosis of the resident cell types. (ersjournals.com)
  • Preeclampsia is often accompanied by hypoxia of the placenta and this condition induces apoptosis in trophoblastic cells. (medsci.org)
  • The aim of this study was to characterize global changes of apoptosis-related proteins induced by hypoxia in trophoblastic cells so as to clarify the mechanism of hypoxia-induced apoptosis by using the PoweBlot, an antibody-based Western array. (medsci.org)
  • Hypoxia induced apoptosis accompanied by increased expression of Bcl-x, Caspase-3 and -9, Hsp70, PTEN, and Bag-1. (medsci.org)
  • Hypoxia-induced apoptosis was increased with the transfection of a bag-1 antisense oligonucleotide. (medsci.org)
  • Both mitochondrial and stress-activated apoptosis pathways played important roles in the hypoxia induced cell death of trophoblastic cells. (medsci.org)
  • Ishioka Si, Ezaka Y, Umemura K, Hayashi T, Endo T, Saito T. Proteomic analysis of mechanisms of hypoxia-induced apoptosis in trophoblastic cells. (medsci.org)
  • The present study investigates the ability of DAF to protect primary cultured neuronal cells subjected to sodium cyanide (NaCN)-induced hypoxia from degeneration and apoptosis. (harvard.edu)
  • Treatment of hypoxic cells with 200 ng/ml of recombinant human DAF resulted in attenuation of neuronal apoptosis and exerted significant protection against neuronal dendritic spine loss and plateau depolarization reduction. (harvard.edu)
  • Conclusion: DAF was found to reduce neuronal cell death and apoptosis in NaCN induced hypoxia. (harvard.edu)
  • Treatment response was evaluated with cell viability, apoptosis, oxidative stress, and summarized with IC50. (diva-portal.org)
  • TUNEL assay was used to detect cell apoptosis after UV-irradiation. (molvis.org)
  • We have shown that hypoxia preconditioning provides generalized protection to corneal stromal cells against induced apoptosis in vitro and in an ex vivo cornea model. (molvis.org)
  • CONCLUSIONS: The action of NGAL against hypoxia/reoxygenation injury was due to inhibiting the apoptosis via inhibition of the expression of the genes of proapoptotic proteins Bax, Bcl-2, and caspase-3. (biomedsearch.com)
  • Hypoxia induces G 0 /G 1 arrest in primary fibroblasts but triggers apoptosis in oncogene-transformed derivatives. (asm.org)
  • Studies of solid tumor cells have suggested that through induction of apoptosis, hypoxia may select for cells with defective apoptotic regulators such as p53 ( 19 ). (asm.org)
  • Hypoxia may also induce apoptosis in tumor cells ( 49 , 58 ) and has recently been implicated in the selection for p53-deficient tumor cells with a diminished apoptotic potential in central (hypoxic) areas of solid tumors ( 19 ). (asm.org)
  • In the injured mouse tissue, renal-infiltrating CD4 + and CD8 + T cells express hypoxia-inducible factor-1 (HIF-1), which alters their cellular metabolism and prevents their apoptosis in hypoxia. (sciencemag.org)
  • Participants will have the opportunity of participating in an optional biopsy procedure for the purposes of further studying contemporaneous tumour tissue (contemporaneous with the EF5-PET) for markers of hypoxia, apoptosis, angiogenesis etc. (knowcancer.com)
  • The cell viability and apoptosis were respectively analyzed by cell counting kit-8 (CCK-8) assay and flow cytometry. (portlandpress.com)
  • Astorvastatin reduced the HIF-1α protein expression in hypoxia-induced PC3 cells, and induced apoptosis of both control and hypoxia-induced cells with and without irradiation. (portlandpress.com)
  • Radioresistance of prostate cancer may be mainly due to hypoxia in the center of tumors, which could induce a G 2 /M cell cycle arrest, inhibit apoptosis, and reduce the number of senescent cells [ 6 ]. (portlandpress.com)
  • It could promote radiosensitivity and apoptosis in PC3 prostate cancer cells [ 12 ]. (portlandpress.com)
  • Cell apoptosis was determined by Hoechst staining FC assay. (medscimonit.com)
  • Our findings indicate that resveratrol induces apoptosis via HIF-1α/ROS/p53 signaling in prostate cancer cells and may be a useful therapeutic agent against prostate cancer. (medscimonit.com)
  • Furthermore, cancer cells exposed to hypoxic conditions are notoriously known to be more resistant to apoptosis induced by radiation and chemotherapy drugs, and a variety of mechanisms have been suggested to affect the treatment sensitivity ( 9 - 12 ). (asm.org)
  • FTO upregulation repressed apoptosis of H/R-treated myocardial cells. (springer.com)
  • Mhrt overexpression reduced apoptosis of H/R-treated myocardial cells. (springer.com)
  • Cell apoptosis was evaluated using flow cytometry and protein analysis of cleaved caspase 3 (cle-caspase 3). (springer.com)
  • Our data showed that hypoxia enhanced apoptosis andNF-κB signaling pathway, which was alleviated by Res treatment. (springer.com)
  • Furthermore, miR-30d-5p depletion inhibited the proliferation, reduced apoptosis and decreased the expression of cle-caspase 3 in H9c2 cells with hypoxia treatment. (springer.com)
  • Interestingly, the rescue-of-function experiments further indicated that knockdown of SIRT1 attenuated the effect of miR-30d-5p depletion on proliferation, apoptosis NF-κB signaling pathway inH9c2 cells with hypoxia treatment. (springer.com)
  • In addition, the suppression of NF-κB signaling pathway increased cell viability while decreased cell apoptosis in hypoxia-mediatedH9c2 cells. (springer.com)
  • Our data suggested Res mayprotectH9c2 cells against hypoxia-induced apoptosis through miR-30d-5p/SIRT1/NF-κB axis. (springer.com)
  • Chen CJ, Yu W, Fu YC, Wang X, Li JL and Wang W 2009 Resveratrol protects cardiomyocytes from hypoxia-induced apoptosis through the SIRT1-FoxO1 pathway. (springer.com)
  • This study suggests that p16's ability to suppress tumor metastasis may be partially resulted from p16's inhibition on cell migration, in addition to its known functions on inhibition of cell proliferation, angiogenesis and induction of apoptosis. (jcancer.org)
  • Minocycline directly targets the mitochondrial proteins and impedes the release of factors responsible for cell death which could either be caspase-dependent (Smac/Diablo, cytochrome c (cyt c)) or caspase independent (apoptosis-inducing factor) [6]. (termedia.pl)
  • Fas cell surface death receptor (FAS)-mediated apoptosis in spinal cord injury is reported to require mitochondrial signalling and the inhibition of FAS ligand (FASL) protects the cells from undergoing apoptosis [13]. (termedia.pl)
  • Mounting evidence suggests that the stabilization of HIF-1α following neuronal damage protects the hypoxic cells from apoptosis [15, 16]. (termedia.pl)
  • In this study, we hypothesised that minocycline modulates mitochondrial cell death via mechanisms interlinking HIF-1α stabilization and FASL-mediated apoptosis. (termedia.pl)
  • Both features of apoptosis and necrosis can be found in this cell death pattern and were termed as LPPCN. (jcancer.org)
  • Hypoxia inducible factor-1α (HIF-1α) is a key oxygen-regulated transcriptional activator, playing a fundamental role in the adaptation of tumor cells to hypoxia by upregulating the transcription of target genes related to multiple biological processes, including cell survival, proliferation, angiogenesis and anti-apoptosis.Significant HIF1A expression has been noted in most solid tumors studied, which include cancers of the gastric and colon. (wikipedia.org)
  • Hypoxia occurs naturally at high-altitudes and pathologically in hypoxic solid tumors. (nih.gov)
  • Because tumors are characterized by hypoxic environments, we used a novel in vitro noninvasive magnetic resonance imaging assay to examine the influence of invasive MDA-MB-231 breast cancer cells on the invasion and migration of human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) under normoxic and hypoxic conditions. (nih.gov)
  • Hypoxia is a common characteristic in solid tumors (Zhang et al. (springer.com)
  • 2012 ). Hypoxia in the tumor microenvironment is the major cause of drug resistance in cancer chemotherapy (Cosse & Michiels, 2008 ), but the mechanism by which hypoxia induces drug resistance in tumors is unclear. (springer.com)
  • The RIP1-Tag2 transgenic mouse model overexpresses SV40 T antigen under the control of the insulin promoter, resulting in development of islet cell tumors 4 . (nature.com)
  • Hypoxia, a feature common to most solid tumors, is known to regulate many aspects of tumorigenesis. (nature.com)
  • Localization and quantitation of 2-nitroimidazole drug binding in low pO 2 tumors is a technique that can allow the assessment of hypoxia as a predictive assay. (aacrjournals.org)
  • These studies demonstrate substantial heterogeneity of in situ binding between and within individual squamous cell tumors. (aacrjournals.org)
  • A number of studies reported that hypoxia-inducible factor-1 (HIF-1) is the central mediator of adaptive responses to hypoxia in tumors. (scielo.br)
  • Although the ability of tumors to survive during hypoxia is a crucial determinant of therapeutic response and tumor progression, the cellular mechanisms by which tumor cells respond to, and survive during, hypoxia are poorly understood. (biologists.org)
  • Hypoxia may influence tumor biology in paradoxically opposing ways: it is lethal as a direct stress trigger, yet hypoxic zones in solid tumors harbor viable cells which are particularly resistant to treatment and contribute importantly to disease relapse. (asm.org)
  • Numerous mechanisms of resistance have been demonstrated, including the presence of drug resistance transporters, mutated or amplified drug targets, altered drug metabolism, altered DNA repair, overexpression of antiapoptotic genes, inactivity of proapoptotic gene products, and noncell autonomous features of tumor growth in vivo, such as the presence of hypoxia in solid tumors ( 36 ). (asm.org)
  • Hypoxia, a hallmark of malignant tumors, often correlates with increasing tumor aggressiveness and poor treatment outcomes. (ca.gov)
  • We aimed to evaluate the feasibility of using streptavidin-biotin-based pretargeting for positron emission tomography (PET) imaging of hypoxia-inducible factor (HIF)-1-active tumors. (nii.ac.jp)
  • Tumors are complex tissues in which transformed cells communicate with the surrounding microenvironment and evolve traits promoting their own survival and malignancy. (urotoday.com)
  • On a tumor-by-tumor basis, 5 of 7 head and neck and 7 of 13 cervix tumors showed no overlap between metallothionein and hypoxia at the microregional level. (aacrjournals.org)
  • Hypoxic cells in human tumors tend to be in regions immunostaining for involucrin, and it seems possible that differentiation of hypoxic cells in squamous cell carcinomas might affect metallothionein I and II expression. (aacrjournals.org)
  • Even when, for example, melanoma tumors do express antigens that can be recognized by T cells and despite the massive influx of tumor antigen-specific T cells to the tumor site, the incidence of complete tumor destruction is very low ( 5 ). (aacrjournals.org)
  • The long sought after explanation of the coexistence of tumors and antitumor immune cells in a cancer patient or in a mouse ("Hellstrom Paradox") has been a challenging problem to solve ( 6 ). (aacrjournals.org)
  • Why do antitumor T cells fail to completely and reliably destroy tumors in vivo even when the ability to recognize tumors is not the limiting factor and there are large numbers of antitumor T cells present ( 5 ) or when very high numbers of highly lytic antitumor T cells are injected in a cancer patient or into tumor-bearing mice ( 7 )? (aacrjournals.org)
  • Adoptively transferred mesenchymal stem cells ( MSCs) home to solid tumors. (uni-muenchen.de)
  • One of the characteristic features of solid tumors is hypoxia. (uni-muenchen.de)
  • Our results demonstrate the potential of using tumor hypoxia-based approaches to drive radioiodide therapy in non-thyroidal tumors. (uni-muenchen.de)
  • Hypoxia is a feature of solid tumors. (asm.org)
  • Hypoxia is a condition commonly occurring in most solid tumors. (asm.org)
  • One general characteristic of fast-growing solid tumors including breast cancer is the development of intratumoral hypoxia, whose existence correlates with a more malignant tumor phenotype and worse diagnosis. (jcancer.org)
  • Highly aggressive tumors are exposed to hypoxia and increased tumor interstitial fluid pressure (IFP) conditions which is resistant to blood supply. (jcancer.org)
  • Hypoxic microenvironements in solid tumors are a result of available oxygen being consumed within 70 to 150 μm of tumour vasculature by rapidly proliferating tumor cells thus limiting the amount of oxygen available to diffuse further into the tumor tissue. (wikipedia.org)
  • During cancer progression, tumor cells acquire comprehensive metabolic reprogramming, and tissue hypoxia is a prominent feature of solid tumors leading to cell metabolism adaptive changes. (wikipedia.org)
  • Having an increased level of GLUT1, in the case of hypoxic tumors, increases the flux of glucose into the cells allowing for a higher rate of glycolysis and thus greater risks of metastasis (as elaborated upon below). (wikipedia.org)
  • This evidence of the stimulatory effects of hypoxia on tumorigenesis prompted us to investigate the underlying mechanisms by which hypoxia regulates the tumorigenic properties of CSCs in colorectal cancers. (nature.com)
  • This study demonstrates that minocycline protects retinal pigment epithelial cells in culture from the effects of hypoxia. (arvojournals.org)
  • In the present article, the authors have reviewed the evidence from the many in vitro studies of hypoxia on pulmonary vascular cell proliferation and function but have concentrated on the controversy surrounding the reported effects of hypoxia on SMC proliferation. (ersjournals.com)
  • However, the effects of hypoxia on the differentiation and self-renewal of MMSCs have been unclear. (thefreelibrary.com)
  • To test this hypothesis, we used hypoxic culture of isolated MMSCs to address the effects of hypoxia on development of the kidney. (thefreelibrary.com)
  • Methods and Results: We used a novel, redox-sensitive, ratiometric fluorescent protein sensor (RoGFP) to assess the effects of hypoxia on redox signaling in cultured PASMCs and SASMCs. (luriechildrens.org)
  • Functional genome analysis revealed substantial effects of hypoxia on immune response, transcriptional regulation, protein modification, cell growth and proliferation, and cell metabolism. (jrheum.org)
  • dominant negative RhoB or manumycin, a farnesyltransferase inhibitor that targets the vascular function of RhoB, inhibited the effects of hypoxia. (diva-portal.org)
  • Polymerization and adhesion, dynamic processes that are hallmarks of sickle cell disease (SCD), have thus far been studied in vitro only separately. (pnas.org)
  • We find that tenocytes respond to hypoxia in vitro by activating classical HIF-1 α -driven pathways. (hindawi.com)
  • In vitro studies revealed that hypoxia-driven stem/progenitor cell enrichment is primarily mediated by hypoxia-inducible factor 1α. (pnas.org)
  • We further show that the Akt/β-catenin cancer stem cell regulatory pathway is activated in breast cancer cells under hypoxic conditions in vitro and in sunitinib-treated mouse xenografts. (pnas.org)
  • Through various in vitro studies, we found that hypoxia-induced Wnt/β-catenin signaling increased the occurrence of CSC-like phenotypes and the level of Id2 expression in colorectal-cancer cells. (nature.com)
  • We further demonstrated, for the first time, that the degree of hypoxia-induced CSC-sphere formation (CD44 + subpopulation) in vitro and of tumor metastasis/dissemination in vivo were markedly suppressed by knocking down Id2 expression. (nature.com)
  • Recent in vitro evidence indicated that hypoxia, defined as reduced oxygen tension, strongly promoted poor patient survival, therapeutic resistance and an aggressive tumor phenotype 1 . (nature.com)
  • Although hypoxic pulmonary vascular remodelling is associated with medial hypertrophy, many in vitro studies have found that hypoxia does not lead to a direct increase in smooth muscle cell proliferation. (ersjournals.com)
  • The present authors reviewed data from in vitro studies and also considered whether hypoxia could act on adjacent cells such as fibroblasts and endothelial cells to trigger smooth muscle cell proliferation. (ersjournals.com)
  • The present article reviews the data from in vitro studies of hypoxia on the three cellular components of the pulmonary vascular wall, namely endothelial cells, smooth muscle cells and fibroblasts. (ersjournals.com)
  • In vitro studies have demonstrated that hypoxia has direct effects on cell proliferation in some, but not all, cell preparations 10 - 12 . (ersjournals.com)
  • Models of in vitro hypoxic cell culture of bladder cancer, bladder cancer cells with low HIF-1α expression and HIF-1α RNA interference (RNAi) expression vector were established. (scielo.br)
  • The pattern of metabolic gene expression iii seen in vitro was unaffected when LNCaP cells were grown as subcaspular and muscle xenografts in immunodeficient mice, though xenografts did exhibit indications of an hypoxic response (elevated VEGF mRNA). (queensu.ca)
  • To examine mechanisms underlying growth-survival decisions during hypoxia, we have compared genetically related transformed and untransformed fibroblast cells in vitro for proliferation, survival, clonogenicity, cell cycle, and p53 expression. (asm.org)
  • However, it has been shown that hypoxia stimulates ureteric bud branching in vitro [3]. (thefreelibrary.com)
  • In this study we examined the in vitro transmembrane migration of hMSC permanently cultured in hypoxia in response to various cytokines. (7thspace.com)
  • Using glioblastoma multiforme (GBM) as a model tumor, we evaluated the ability of CXCR4-overexpressing hADSCs to target tumor hypoxia in vitro using a 2D migration assay and a 3D collagen hydrogel model. (ca.gov)
  • Numerous studies have investigated the differentiation of MSCs into various types of cells in vitro and their application to numerous fields. (eurekaselect.com)
  • Effects of in vitro low oxygen tension preconditioning of adipose stromal cells on their in vivo chondrogenic potential: application in cartilage tissue repair. (eurekaselect.com)
  • Here, we conditionally inactivated the hypoxia-responsive transcription factor hypoxia-inducible factor-1α (HIF-1α) in murine NPCs to determine its role in proliferation, survival, and dopaminergic differentiation in vitro as well as survival of murine dopaminergic neurons in vivo . (jneurosci.org)
  • Such use of genomic information paved the way for the development of in vitro assays that measure T cell release of IFN-γ, which improved the specificity and possibly sensitivity of TB immunodiagnosis ( 5 ). (jimmunol.org)
  • In vitro, both were induced by hypoxia in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. (mit.edu)
  • Finally, inhibition of lipid storage reduced protection against reactive oxygen species toxicity, decreased the survival of cells subjected to hypoxia-reoxygenation in vitro, and strongly impaired tumorigenesis in vivo. (mit.edu)
  • The majority of hypoxic cells in squamous cell carcinomas do not express metallothionein protein, although metallothionein is induced by hypoxia in human tumor cells in vitro . (aacrjournals.org)
  • This finding was unexpected on the basis of in vitro and glioma data and has led us to test the result in squamous cell carcinomas by examining a second oxygen-regulated protein, MT, which is regulated by a hypoxia-sensitive transcription factor very different from that for VEGF. (aacrjournals.org)
  • (22 , 23) have shown that MT-I and MT-IIa can be induced by hypoxia and that induction in vitro is regulated by metal transcription factor-1. (aacrjournals.org)
  • What is it in the tumor microenvironment in vivo that prevents tumor destruction by the tumor-specific and highly lytic in vitro antitumor CD8 + T cells? (aacrjournals.org)
  • In vitro and in vivo studies have shown that tumor hypoxia is associated with an increased likelihood of local recurrence and distant metastasis, as well as resistance to radiation therapy and various types of chemotherapy ( 3 ). (snmjournals.org)
  • We claim that the model, the first of its kind, enables researchers to rapidly and reversibly induce hypoxic conditions in vitro without unwanted interference of the hypoxia-inducing agent on the cultured cells. (biologists.org)
  • Finally, C57BL/6J mouse red blood cells were incubated in vitro with 13 C 1 -aspartate or 13 C 5 -adenosine under normoxic or hypoxic conditions, with or without deoxycoformycin, a purine deaminase inhibitor. (haematologica.org)
  • Hypoxia in vitro and in vivo decreased purine oxidation and enhanced purine salvage reactions in human and mouse red blood cells, which was partly explained by decreased adenosine monophosphate deaminase activity. (haematologica.org)
  • In conclusion, hypoxanthine is an in vitro metabolic marker of the red blood cell storage lesion that negatively correlates with post-transfusion recovery in vivo . (haematologica.org)
  • Additionally, pulmonary vascular cells have been reported to proliferate in response to hypoxia in vitro [ 6 - 8 ]. (oncotarget.com)
  • Oxygen concentration is one of the most crucial environmental conditions for cell proliferation and differentiation both in vitro and in vivo. (semanticscholar.org)
  • We show that YTHDF1 deficiency inhibits NSCLC cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. (nih.gov)
  • Hypoxia has been shown to promote adipose tissue-derived stem cells proliferation and maintenance of pluripotency, but the influence of hypoxia on their smooth myogenic differentiation remains unexplored. (mdpi.com)
  • Vascular remodelling is characterised largely by fibroblast, smooth muscle and endothelial cell proliferation, which results in lumen obliteration. (ersjournals.com)
  • It is possible that hypoxia is sensed by fibroblasts, endothelial cells, or both, and relayed to adjacent pulmonary artery smooth muscle cells by intercellular signalling, causing proliferation. (ersjournals.com)
  • Proliferation of adventitial fibroblasts increases within hours of hypoxic exposure 4 , but, a few days after exposure (to hypoxia), thickening of the medial layer (hypertrophy and hyperplasia) begins to develop 5 . (ersjournals.com)
  • It is accepted that hypoxia is a cause of pulmonary vascular cell proliferation and vascular remodelling, but the mechanisms remain unclear. (ersjournals.com)
  • METHODS: The effect of NGAL on the proliferation of HK-2 cell lines was analyzed with a MTT colorimetric assay. (biomedsearch.com)
  • Many studies have indicated that hypoxia influences development of the embryo by regulating the differentiation and self-renewal (including the maintenance of stemness and proliferation) of stem cells. (thefreelibrary.com)
  • Oxygen tension is critical for proliferation of human and murine midbrain-derived neural precursor cells (mNPCs). (jneurosci.org)
  • It is necessary to understand the mechanisms governing cell proliferation, dopaminergic differentiation, and senescence of NPCs to facilitate clinical therapies ( Sharpless and DePinho, 2004 ). (jneurosci.org)
  • Hypoxia in wounded tissues is caused in part by the vascular damage and decreased blood supply, but also, in a large part, by the O 2 consumption of the cells in the wound that are metabolically activated for migration, proliferation, and wound healing ( Tandara and Mustoe, 2004 ). (aspetjournals.org)
  • The proliferation of prostate cancer cells was determined by CCK-8 assay. (medscimonit.com)
  • Physiological oxygen levels, pathophysiological hypoxia, and the induction of HIF have considerable effects on CD3+ T cell survival and function, i.e., cytokine secretion and proliferation 4 , 5 , 13 - 15 . (jrheum.org)
  • Notably, RhoB was specifically required for hypoxia-induced factor-1 alpha stabilization and for hypoxia- and platelet-derived growth factor-induced cell proliferation and migration. (diva-portal.org)
  • MTT assay was performed to evaluate the cell proliferation. (springer.com)
  • In the present study the MCF-7 human breast cancer cell was exposed to various oxygen concentrations and thus varying levels of chronic hypoxia, and the associated cellular respiration and proliferation were investigated. (uio.no)
  • We found that p16 inhibits breast cancer cell proliferation and migration, but has no apparent effect on cell adhesion. (jcancer.org)
  • Our findings revealed that the absence of NOD2 exacerbated hypoxia-induced PASMC proliferation, pulmonary hypertension and vascular remodeling, but had no effect on PASMC migration or contractility. (oncotarget.com)
  • In vivo studies have indicated that hypoxia increases the wall thickness of pulmonary blood vessels by promoting pulmonary artery smooth muscle cell (PASMC) proliferation [ 4 , 5 ]. (oncotarget.com)
  • While the induction of PI3K and Akt signaling is important for cells to grow, proliferate, migrate and survive [ 9 ], this pathway can also stimulate cellular proliferation in response to hypoxia. (oncotarget.com)
  • Indeed, Akt activation has been observed during the remodeling of blood vessels and the proliferation of PASMCs following vascular injury and hypoxia [ 10 ], and has been reported to stabilize hypoxia-inducible factor-1 alpha (HIF-1α) [ 11 ]. (oncotarget.com)
  • Importantly, upregulation of miR-503 suppressed the proliferation, migration and capillary-like tube formation of EPCs induced by hypoxia. (ovid.com)
  • In order to support continuous growth and proliferation in challenging hypoxic environments, cancer cells are found to alter their metabolism. (wikipedia.org)
  • We proposed that tumour hypoxia induces the expression of chemotactic factors that promote tolerance. (nih.gov)
  • In some organs, such as the lung, nervous system and heart, hypoxia induces the differentiation of stem cells into mature cells [6-8]. (thefreelibrary.com)
  • conversely, coculture of the mesenchyme with cells expressing Wnt4 induces tubulogenesis in organ culture [17, 18]. (thefreelibrary.com)
  • Objective: This study tested the hypothesis that hypoxia induces redox changes that differ among subcellular compartments in pulmonary (PASMCs) and systemic (SASMCs) smooth muscle cells. (luriechildrens.org)
  • Like other stresses, the deprivation of adequate oxygen (known as hypoxia) induces a rapid cascade of changes in transcription and translation-or does it? (plantcell.org)
  • 1 Hypoxia stabilizes the transcription factor Hif-1 and thereby induces and promotes the expression of several genes containing hypoxia responsive elements in their regulatory region: proangiogenic factors like vascular endothelial growth factor (VEGF) or stromal-cell derived factor-1α (SDF-1α, CXCL12), 2 vasoconstrictors like endothelin-1 as well as inflammation-associated genes such as inducible NO synthase 3 and Cox2. (ahajournals.org)
  • EPO has strong organ-protective effects in the heart, the brain, and the kidney, it promotes reendothelialization, 6 and induces the mobilization of endothelial progenitor cells (EPCs). (ahajournals.org)
  • Although hypoxia induces angiogenesis for tissue remodeling during wound healing, it may also affect the healing response of parenchymal cells. (aspetjournals.org)
  • Hypoxia stimulates tumor malignant progression and induces HIF-1α. (jcancer.org)
  • However, during hypoxia, this process is inhibited, such that HIF-1α accumulates, dimerizes with HIF-1β and induces hypoxia-specific gene expression [ 14 ]. (oncotarget.com)
  • Oxygen deprivation on the cellular level is called cell hypoxia . (wisegeek.com)
  • Depending on the extent of the depletion, cells may chemically signal systemic mechanisms which attempt to compensate for the lack of energy and oxygen. (wisegeek.com)
  • Treating cell hypoxia entails replacing oxygen, fluids and nutrition. (wisegeek.com)
  • Without an adequate oxygen supply, electron transport within the cell does not function properly. (wisegeek.com)
  • Cells emit chemical signals which encourage blood flow in an attempt at getting more oxygen. (wisegeek.com)
  • Outward signs of hypoxia can include increased respiration rates as the body strives to replace oxygen. (wisegeek.com)
  • Hypoxia is caused by any circumstance that interferes with oxygen access, including blunt force trauma, fluid loss, and tissue damage from prolonged applied pressure. (wisegeek.com)
  • Illnesses impeding normal blood flow or reducing oxygen intake also contribute to cell hypoxia. (wisegeek.com)
  • Scientists speculate that oxygen-starved cells and the processes that follow, may create environments that encourage cancerous tumor growth. (wisegeek.com)
  • Supplemental oxygen and intravenous fluids prevent further cell damage and encourage cell replication by ensuring adequate blood flow and oxygen supplies. (wisegeek.com)
  • However tendons are relatively avascular and not considered to have high oxygen requirements and the vulnerability of tendon cells to hypoxia is unclear. (hindawi.com)
  • A characteristic feature of immune cells is their ability to infiltrate and operate in tissues with low level of nutrients and oxygen. (mdpi.com)
  • One feature of inflammation sites is low oxygen (O 2 ) tension, termed "hypoxia. (jci.org)
  • Scientists have uncovered a critical genetic switch that helps cells to survive when they are deprived of oxygen. (brighthub.com)
  • Although the work was carried out in fruit flies there could be an immediate application in humans where cells and tissues have been deprived of oxygen because of disease. (brighthub.com)
  • Hypoxia is a condition whereby cells and tissues become severely deprived of oxygen. (brighthub.com)
  • Researchers from the University of California, San Diego School of Medicine, have identified a genetic switch in fruit flies that enables cells to survive low oxygen levels. (brighthub.com)
  • By doing this it allows the cells to become resistant to a low oxygen environment, they are somehow able to conserve power. (brighthub.com)
  • By knowing more about what happens in hypoxic cells in fruit flies, it's hoped that the knowledge can be applied to help human cells and tissue survive in low oxygen conditions caused by disease. (brighthub.com)
  • Cellular responses to oxygen levels are monitored, in part, by the transcriptional activity of the hypoxia inducible factors (HIFs). (nih.gov)
  • Local oxygen (O 2 ) concentrations can directly affect the differentiation or self-renewal capacity of stem cells. (nature.com)
  • Low oxygen availability, a condition known as hypoxia, is a common feature of various pathologies including stroke, ischemic heart disease, and cancer. (frontiersin.org)
  • Insufficient oxygen availability or hypoxia, represents a common feature of several pathologic as well as physiologic processes. (frontiersin.org)
  • To cope with oxygen deprivation, cells respond by adjusting their metabolic and bioenergetic demands through a number of oxygen-sensing pathways including the hypoxia-inducible factors (HIFs) family of transcription factors -dependent and -independent responses. (frontiersin.org)
  • It should be noted that during traffic through different compartments of the body, T cells are likely to encounter significant differences in oxygen tension, i.e. ∼100 mm of Hg (14% O 2 ) in arterial blood and 40 mm of Hg (5-6% O 2 ) or less in the tissue interstitium ( 9 ). (jimmunol.org)
  • Neutrophils have a unique ability to survive and function in such hypoxic environments, a response regulated by the hypoxia-inducible transcription factor (HIF)/hydroxylase oxygen sensing pathway. (bmj.com)
  • We showed that CoCl 2 increased xanthine oxidase (XO)-derived reactive oxygen species (ROS), which causes accumulation of HIF1-α protein in U251-MG cells. (aacrjournals.org)
  • The former method measures DNA damage in single cells obtained by fine needle aspirate immediately after an oxygen-sensitive damaging process. (aacrjournals.org)
  • Oxygen concentrations of 2%, 5%, 10%, and 20% were used during differentiation of adipose tissue-derived stem cells. (mdpi.com)
  • Hypoxia influences differentiation of smooth muscle cells from adipose stem cells and 5% oxygen was the optimal condition to generate smooth muscle cells that contract from adipose stem cells. (mdpi.com)
  • Cell growth curves with and without minocycline were constructed for cells cultured in an hypoxic chamber (2% oxygen) and results compared to culture in normoxic conditions over a period of 8 days. (arvojournals.org)
  • However, it is unclear how these microenvironmental conditions interact to promote neovascularization, due in part to a lack of comprehensive, unbiased data sets describing tumor cell gene expression as a function of oxygen levels within three-dimensional (3D) culture. (sigmaaldrich.com)
  • Here, we utilized alginate-based, oxygen-controlled 3D tumor models to study the interdependence of culture context and the hypoxia response. (sigmaaldrich.com)
  • Cancer cells have the ability to survive when oxygen is limiting, and upregulate the pathway of fatty acid synthesis, owing in part to alterations in their metabolism. (queensu.ca)
  • LNCaP cells had a more oxidative phenotype based on oxygen consumption, lactate production, enzyme assays, and mRNA levels. (queensu.ca)
  • While DU145 and PC3 cells were more glycolytic, they were unresponsive to dichloroacetate (DCA), and dinitrophenol (DNP), stimulators of oxygen consumption. (queensu.ca)
  • This finding is supported by decreased oxygen consumption, increased lactate production, and a reduction in the activity of the oxidative enzymes CS and COX in the clonally selected LNCaP-luc cell line. (queensu.ca)
  • Buckler, K.J., Williams, B.A., and Honore, E. (2000) An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemo receptor cells. (springer.com)
  • The primary features of tumor physiology that lead to hypoxia are limited arteriolar supply and arteriolar deoxygenation ( 8 ), relatively low vascular density and disorderly vascular architecture ( 46 ), oxygen consumption rates that are out of balance with oxygen supply ( 47 ), and an unstable blood supply ( 29 ). (asm.org)
  • Endothelial cells (ECs) are the primary sensors of variations in blood oxygen concentrations. (sigmaaldrich.com)
  • They use the hypoxia-sensitive stabilization of the hypoxia-inducible factor-1α (HIF-1α) transcription factor to engage specific transcriptional programs in response to oxygen changes. (sigmaaldrich.com)
  • Because the effect of hypoxia on development of the kidney is controversial, understanding the kidney's responses to oxygen deprivation is critical. (thefreelibrary.com)
  • HIF-1 turns on genes that help cells survive when oxygen is low, such as during a heart attack or stroke. (bio-medicine.org)
  • Engineering human cells to lack this enzyme and subjecting them to low oxygen, the scientists found the cells unable to rid themselves of COX4-1. (bio-medicine.org)
  • PET imaging of hypoxia-inducible factor-1-active tumor cells with pretargeted oxygen-dependent degradable streptavidin and a novel [18]F-labeled biotin derivative. (nii.ac.jp)
  • 2 , 5 , 6 A common feature of inflamed tissues is represented by hypoxia, a condition of low partial oxygen pressure (pO 2 , 0-20 mmHg), which arises as a result of dysfunctional vascular network and diminished O 2 supply and affects the phenotype and functions of every cell exposed to it. (bloodjournal.org)
  • Briefly, transcriptional activation is mediated primarily by the hypoxia-inducible factor-1 (HIF-1), a heterodimer of the constitutive HIF-1β subunit and an oxygen-sensitive α-subunit (HIF-1α/-2α). (bloodjournal.org)
  • Rationale: Recent studies have implicated mitochondrial reactive oxygen species (ROS) in regulating hypoxic pulmonary vasoconstriction (HPV), but controversy exists regarding whether hypoxia increases or decreases ROS generation. (luriechildrens.org)
  • The objective was to discover whether the oxygen-regulated protein, metallothionein, is expressed in the hypoxic cells of squamous cell carcinomas. (aacrjournals.org)
  • While hypoxia and high temperatures do not typically co-occur in the environment, the accumulation of mRNAs for chaperones like HSPs and other reactive oxygen species-protecting proteins may offer a protective barrier during extended hypoxia and reaeration (itself causing a burst of reactive oxygen species throughout the plant). (plantcell.org)
  • Therefore, and because of its invasive character, the oxygen electrode has not become a general clinical tool for measuring tumor hypoxia. (snmjournals.org)
  • Under hypoxic conditions, increased release of reactive oxygen species from the inner mitochondrial membrane to the intermembrane space leads to the activation of transcription factors, including hypoxia-inducible factor, activation of hypoxic pulmonary vasoconstriction, activation of AMP-dependent protein kinase, and internalization of the membrane Na,K-ATPase from the basolateral membrane of alveolar epithelial cells. (luriechildrens.org)
  • The role of hypoxia and reactive oxygen species (ROS) in mobilization and function of these cells is incompletely understood. (ahajournals.org)
  • Hypoxia (10% oxygen) induced the mobilization of EPCs in wild-type (WT) and Nox1 but not in Nox2 knockout (Nox2 y/− ) mice. (ahajournals.org)
  • The Hif-1 system is also used to measure the systemic oxygen supply and to control the formation of red blood cells. (ahajournals.org)
  • Wound healing and migration were significantly slower in hypoxic (1% oxygen) RPTC than normoxic (21% oxygen) cells. (aspetjournals.org)
  • Wound healing in tissues and organs is characterized by hypoxia, a condition of decreased availability of oxygen. (aspetjournals.org)
  • Complementary deoxyribonucleic acid microarray data from 36 mice subjected for 1, 2, or 4 weeks of their early life to normal atmospheric conditions (normoxia) or chronic intermittent (CIH) or constant (CCH) hypoxia were analyzed to extract organizational principles of the developing heart transcriptome and determine the integrated response to oxygen deprivation. (ad-astra.ro)
  • The choriocapillaris, Bruch's membrane, RPE, and photoreceptors function as one unit, with the choriocapillaris providing fuel for phototransduction, and Bruch's membrane and RPE cells filtering and regulating the reciprocal exchange of oxygen, nutrients, biomolecules, and metabolic waste products between the circulation and retina. (elifesciences.org)
  • We analyzed the extent to which hypoxia influences the transcriptome in the rheumatoid synovium according to a gene cluster reflecting adaptation to low oxygen levels. (jrheum.org)
  • It is known that these and other cells encounter pathologically low levels of oxygen, i.e., hypoxia, when executing their functions within the inflamed joint 3 . (jrheum.org)
  • Hypoxia can also be defined as a state in which the demand for oxygen exceeds the supply. (jrheum.org)
  • This is likely to occur in the inflamed synovium as a result of microvascular damage, microthrombotic vessel occlusion, or excessive oxygen demand from the dramatic influx of metabolically active inflammatory cells 6 . (jrheum.org)
  • A) Cells of sch9 mutant CCS3 and control strain CAF2-1 (wild type [wt]) were grown in liquid YPS for 4 h at 25°C. Cells were grown for 4 h in low oxygen (0.2% O 2 ) containing or not containing 6% CO 2 . (asm.org)
  • Studies of cultured endothelial cells (EC) demonstrated that hypoxia (1% oxygen) induced Cezanne via p38 MAP kinase-dependent transcriptional and post-transcriptional mechanisms. (ahajournals.org)
  • Administration of 200 U/ml superoxide dismutase (SOD) before hypoxia could partially prevent EC from such injuries, suggesting that the presence of oxygen free radicals may be one of the main factors involved in hypoxia-reoxygenation injury. (cnki.com.cn)
  • Serving as the primary modulators of hypoxic stress, hypoxia-inducible factors (HIFs) are rapidly induced in response to oxygen deprivation to regulate the expression of genes that facilitate adaptation to hypoxic conditions ( 2 , 3 ). (asm.org)
  • Hypoxia decreased oxygen consumption rates after five days of differentiation and after two days of normoxic recovery. (uwo.ca)
  • This coincided with a hypoxia-induced decrease in protein levels of the NDUFB8 subunit of complex I of the electron transport chain and decreases in mRNA levels of mitochondrial biogenesis transcription factors, both of which could contribute to the alterations observed in oxygen consumption rates. (uwo.ca)
  • Normoxic recovery supplemented with RSV did increase oxygen consumption rates, however this increase was not observed across all oxygen concentrations that were measured which may have be associated with the decreases in cell viability observed with RSV treatment. (uwo.ca)
  • Hypoxic cells exposed to acute irradiation are found, in general, to be more radioresistant than the equivalent well-oxygenized counterpart due to various cellular responses to low oxygen availability. (uio.no)
  • Hypoxanthine increased in stored red blood cell units as a function of oxygen levels. (haematologica.org)
  • In this work, we investigated the effects of lowered oxygen tension (20% and 5% O2) on the chondrogenesis and hypertrophy of articular chondrocytes (ACs), mesenchymal stem cells (MSCs) and their co-cultures with a 30:70 AC:MSC ratio. (rice.edu)
  • We conclude that the most promising cell source for cartilage engineering was co-cultures, as they have a potential to decrease the need for primary chondrocyte harvest and expansion while obtaining a stable highly chondrogenic phenotype independent of the oxygen tension in the cultures. (rice.edu)
  • However, under low oxygen tensions (hypoxia), HIF-1α becomes stabilized. (jcancer.org)
  • Oxygen Levels Regulate the Development of Human Cortical Radial Glia Cells. (semanticscholar.org)
  • Because lymphocytes are exposed to various oxygen tensions under pathophysiologic conditions, we hypothesize that hypoxia-inducible factors (HIFs) have roles in NKT cell activation, and thus determine the final outcome of renal IRI. (asnjournals.org)
  • Hypoxia-inducible factor-proline dioxygenase (EC, HIF hydroxylase) is an enzyme with systematic name hypoxia-inducible factor-L-proline, 2-oxoglutarate:oxygen oxidoreductase (4-hydroxylating). (wikipedia.org)
  • Hypoxia-inducible factor (HIF) is an evolutionarily conserved transcription factor that allows the cell to respond physiologically to low concentrations of oxygen. (wikipedia.org)
  • Tumor hypoxia is the situation where tumor cells have been deprived of oxygen. (wikipedia.org)
  • Furthermore, m 6 A modified mRNA binding protein YTHDF1, one of evolutionary positively selected genes for high-altitude adaptation is amplified in various cancers, including non-small cell lung cancer (NSCLC). (nih.gov)
  • They were on the lookout for changes in the basic genetics of the hypoxic fruit flies i.e. any genes that might be activated or suppressed during severe hypoxia. (brighthub.com)
  • Recruitment of HIF-1 α and HIF-2 α to common target genes is differentially regulated in neuroblastoma: HIF-2 α promotes an aggressive phenotype," Cancer Cell , vol. 10, no. 5, pp. 413-423, 2006. (hindawi.com)
  • Hypoxia modifies the transcriptome of primary human monocytes: modulation of novel immune-related genes and identification of CC-chemokine ligand 20 as a new hypoxia-inducible gene," Journal of Immunology , vol. 177, no. 3, pp. 1941-1955, 2006. (hindawi.com)
  • While most of the hypoxia-responsive genes rely on HIF-1α and HIF-2α heterodimerization with HIF-1β in the nucleus, little is known about HIF-3α regulation and function upon hypoxia. (frontiersin.org)
  • During chemical hypoxia induced by cobalt chloride (CoCl 2 ), hypoxia-inducible factor 1α (HIF1-α) mediates the induction of a variety of genes including erythropoietin and vascular endothelial growth factor. (aacrjournals.org)
  • 13 ) concluded that ROS are produced during exposure of cells to metals that mimic hypoxia but the formation of ROS was not involved in the activation of HIF1-α-dependent genes. (aacrjournals.org)
  • We also demonstrate that hypoxia leads to a significant induction in the activity of super-enhancers next to transcription factors and other genes implicated in angiogenesis, cell survival and adhesion, whereas super-enhancers near several negative regulators of angiogenesis were repressed. (frontiersin.org)
  • HIF-1 can adapt to hypoxia by regulating the expression of various target genes and involves in the process of tumor growth, invasion and metastasis ( 3 ). (scielo.br)
  • HIF-1α is the major transcription factor that controls the expression of hypoxia-regulated genes. (molvis.org)
  • Finally, we bring evidence that silencing TTP expression enhances hypoxia-induced increase in HIF-1α protein levels with a concomitant increase in the levels of the carbonic anhydrase enzyme CA IX, thus suggesting that TTP physiologically controls the expression of a panel of HIF-1α target genes. (sigmaaldrich.com)
  • We analyzed the fold induction of the 100 most highly induced genes at 7 d of hypoxia, as well as transcript abundance, peptide-binding prediction (ProPred) adjusted for population-specific MHC class II allele frequency, and by literature search. (jimmunol.org)
  • In this study, we identified by gene expression profiling a significant cluster of genes coding for immune-related cell surface receptors strongly up-regulated by hypoxia in monocyte-derived mDCs and characterized one of such receptors, TREM-1, as a new hypoxia-inducible gene in mDCs. (bloodjournal.org)
  • α-Subunits are post-translationally stabilized under hypoxia and translocate to the nucleus where they dimerize with HIF-1β transactivating the hypoxia responsive element (HRE) present in the promoter of many O 2 -sensitive genes. (bloodjournal.org)
  • We reported that monocyte differentiation into iDCs under chronic hypoxia promotes the onset of a unique migratory phenotype by differentially modulating the expression profile of chemokines/receptors and genes involved in cell adhesion and tissue remodeling. (bloodjournal.org)
  • Hypoxia-inducible transcription factors (HIFs) 1 are central mediators of cellular adaptation to hypoxia that control the expression of genes involved in anaerobic metabolism, intracellular pH, angiogenesis, and cell growth and survival ( 1 ). (mcponline.org)
  • The authors then (1) performed clustering analysis to reduce data complexity and identify common regulatory themes (see figure ) and (2) focused on hypoxia-responsive genes ( HRGs ) and ribosomal protein genes ( RPs ). (plantcell.org)
  • Some genes (such as hypoxia-responsive genes [ HRGs ]) are actively transcribed and translated, whereas mRNAs for ribosomal protein genes ( RPs ) tend to accumulate in the nucleus and are therefore not translated. (plantcell.org)
  • Hypoxia also stimulates the association of RNA polymerase II with the promoters of heat-stress-responsive genes. (plantcell.org)
  • On average, the expression of each heart gene was tied to the expression of about 20% of other genes in normoxia but to only 8% in CCH and 9% in CIH, indicating a strong decoupling effect of hypoxia. (ad-astra.ro)
  • Therefore, in order to ensure adaptation and functional integrity, immune cells need to respond to these hypoxic conditions by coordinated expression of numerous genes, such as vascular endothelial growth factor ( VEGF ) 7 , glucose transporter 1 ( GLUT-1 ) 8 , and phosphoglycerate kinase 1 ( PGK-1 ) 9 , 10 . (jrheum.org)
  • A key factor in this process is the hypoxia-inducible factor-1 (HIF-1), which regulates transcription of many hypoxia-activated genes (e.g. (jrheum.org)
  • Hypoxia-reoxygenation had minimal effects on pro-inflammatory signalling in unmanipulated EC but significantly enhanced Lys-63 polyubiquitination of TRAF6, activation of NF-κB and expression of inflammatory genes following silencing of Cezanne. (ahajournals.org)
  • Transcriptomal analyses showed that Sch9 regulates most genes solely under hypoxia and in the presence of elevated CO 2 . (asm.org)
  • In this environment, Sch9 downregulates genes encoding cell wall proteins and nutrient transporters, while under normoxia Sch9 and Tor1 coregulate a minor fraction of Sch9-regulated genes, e.g., by inducing glycolytic genes. (asm.org)
  • Under hypoxic conditions, the hydroxylase activity of PHDs is inhibited, and stabilized HIF transcription factors can translocate to the nucleus and regulate the transcription of hypoxia-associated genes ( 3 - 5 ). (asm.org)
  • HIF-1 is a transcriptional activator for a group of genes that are responsible for promoting tumor cell angiogenesis and progression ( 1 , 2 ). (jcancer.org)
  • Recent data suggest that hypoxia-inducible factor (HIF-1), the master regulator of the hypoxic response, probably mediates many hypoxic effects either directly or indirectly via its target genes. (uzh.ch)
  • Calcified human aortic valves (n=14, mean age 65±15) were immunohistochemically stained for proteins involved in matrix remodeling, hypoxia, and cell differentiation. (ahajournals.org)
  • Effect of Hypoxia on the Differentiation and the Self-Renewal of Metanephrogenic Mesenchymal Stem Cells. (thefreelibrary.com)
  • Subsequently, the condensed cells undergo a mesenchymal-epithelial transition (MET), thus forming epithelial vesicles, and this is followed by sequential differentiation into functional nephrons [14, 15]. (thefreelibrary.com)
  • Thus, we hypothesized that hypoxia may regulate the differentiation and self-renewal of MMSCs by a Wnt4-dependent pathway. (thefreelibrary.com)
  • Hypoxic preconditioning, mesenchymal stem cell, differentiation. (eurekaselect.com)
  • Our findings indicate that HIF-1α promotes stem cell survival, growth, and dopaminergic differentiation, as well as survival of adult dopaminergic neurons. (jneurosci.org)
  • Recent studies have investigated hypoxia effects on DC differentiation, maturation, and functions. (bloodjournal.org)
  • In the hypoxia-containing sections, immunostaining for involucrin, a molecular marker for differentiation, overlapped with that for hypoxia in 82% of the cases. (aacrjournals.org)
  • Our findings underline that TRP-2 is a differentiation antigen, highlighting the importance to combine TRP-2 vaccination with other strategies targeting the aggressive undifferentiated hypoxia related subpopulation. (uzh.ch)
  • Using the C 2 C 12 mouse muscle myoblast cell line, I sought to investigate the hypothesis that differentiation under hypoxia impairs muscle mitochondrial respiratory function irreversibly. (uwo.ca)
  • Here we investigate hypoxia-induced changes in the Wnt/β-catenin signaling pathway, a key signaling cascade involved in OS pathogenesis. (nih.gov)
  • Hypoxia is a hallmark of inflamed, infected or damaged tissue, and the adaptation to inadequate tissue oxygenation is regulated by hypoxia-inducible factors (HIFs). (mdpi.com)
  • Moreover, the transcription factors hypoxia-inducible factors 1 and 2 alpha (HIF-1α and HIF-2α) have been linked to the stimulation of cancer stem cells (CSCs) in glioblastoma ( 9 ⇓ - 11 ). (pnas.org)
  • The expression and distribution of the hypoxia-inducible factors HIF-1 α and HIF-2 α in normal human tissues, cancers, and tumor-associated macrophages," American Journal of Pathology , vol. 157, no. 2, pp. 411-421, 2000. (hindawi.com)
  • Hypoxia inducible factor-1α (HIF-1α) is a transcription factor that regulates gene expression under hypoxic conditions 7 . (nature.com)
  • Hypoxia adaptation requires coordination of intricate pathways and mechanisms such as hypoxia-inducible factors (HIFs), the unfolded protein response (UPR), mTOR, and autophagy. (frontiersin.org)
  • We demonstrated in CD3-positive human T cells accumulating in inflammatory tissue expression of the hypoxia-inducible factor-1α (HIF-1α), indicating a role of hypoxia-mediated signals in regulation of T cell function. (jimmunol.org)
  • Cellular adaptation to hypoxic conditions involves a transcriptional response pathway mediated by the hypoxia-inducible factor (HIF)-1, a heterodimeric complex of the basic helix-loop-helix (bHLH) PAS (Per, Arnt, Sim) domain proteins HIF-1α and HIF-1β (Arnt) ( 11 , 12 , 13 ). (jimmunol.org)
  • In this study, we investigated the metabolic state of undifferentiated NSPCs in culture, and tested their relative reliance on oxidative versus glycolytic metabolism for survival, as well as their dependence on hypoxia inducible factor-1alpha (HIF-1α) expression for maintenance of metabolic phenotype. (wiley.com)
  • Inducible deletion of exon 1 of the Hif1a gene improved the ability of NSPCs to utilize pyruvate during glycolytic inhibition, but did not alter other parameters of metabolism, including their ability to withstand prolonged hypoxia. (wiley.com)
  • This study aimed to investigate the mechanism of hypoxia-inducible factor-1 alpha (HIF-1α) mediated hypoxia-induced permeability changes in bladder endothelial cells. (scielo.br)
  • This study determined whether the transcription factor HIF-1α (Hypoxia Inducible Factor) is responsible and whether this is promulgated by VEGF (Vascular Endothelial Growth Factor). (molvis.org)
  • Hypoxia-inducible factor-1α mRNA: a new target for destabilization by tristetraprolin in endothelial cells. (sigmaaldrich.com)
  • In 1992, Semenza's team had discovered a protein which they called HIF-1 (for hypoxia-inducible factor 1) that cells make in response to hypoxia. (bio-medicine.org)
  • Reducing renal hypoxia by inhibiting the hypoxia-inducible factor-1 (HIF-1) reduced T cell infiltration and kidney injury in lupus-prone mice, suggesting that targeting HIF-1 might be effective for treating lupus nephritis. (sciencemag.org)
  • In addition, the activated antitumor T cells in hypoxic tumor microenvironment could be inhibited by elevated levels of immunosuppressive hypoxia-inducible factor-1α. (aacrjournals.org)
  • Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors that play a key role in cellular adaptation to hypoxia. (mcponline.org)
  • Cells respond to hypoxia through alterations in gene expression, mediated most notably through the hypoxia-inducible factor (HIF) class of transcription factors. (nih.gov)
  • Furthermore, PD-L1 up-regulation under hypoxia was dependent on hypoxia-inducible factor-1α (HIF-1α) but not HIF-2α. (rupress.org)
  • Hypoxia-inducible factor-1α (HIF-1α) was induced during scratch-wound healing in normoxia, and the induction was more evident in hypoxia. (aspetjournals.org)
  • Under this condition, hypoxia contributes to the stimulation of the angiogenesis and tissue remodeling by activating a myriad of signaling pathways and inducing key transcription factors such as hypoxia-inducible factors (HIFs) ( Tandara and Mustoe, 2004 ). (aspetjournals.org)
  • Hypoxia-inducible factor-1α (HIF-1α) was detected in the rheumatoid synovium using immunohistochemistry. (jrheum.org)
  • To approach this aim, MDA-MB-231 and other breast cancer cells stably transfected with Tet-on inducible p16 were used to study the p16 effect on growth, adhesion and migration of the cancer cells. (jcancer.org)
  • the main mediator of the hypoxia response is hypoxia-inducible factor-1 (HIF-1) ( 1 ). (jcancer.org)
  • Zhang G, Zha J, Liu J, Di J. Minocycline impedes mitochondrial-dependent cell death and stabilizes expression of hypoxia inducible factor-1α in spinal cord injury. (termedia.pl)
  • However, the effect of minocycline on mitochondrial activity and hypoxia-inducible factor-1α (HIF-1α) regulation following traumatic spinal cord injury has not been studied. (termedia.pl)
  • Furthermore, hypoxia-inducible factor-1α expression and Akt phosphorylation were upregulated in PASMCs from NOD2-deficient mice exposed to hypoxia. (oncotarget.com)
  • Hypoxia inducible factor-1α (HIF-1α) is required for neural stem cell maintenance and vascular stability in the adult mouse SVZ. (semanticscholar.org)
  • This enzyme catalyses the following chemical reaction hypoxia-inducible factor-L-proline + 2-oxoglutarate + O2 ⇌ {\displaystyle \rightleftharpoons } hypoxia-inducible factor-trans-4-hydroxy-L-proline + succinate + CO2 Hypoxia-inducible factor-proline dioxygenase contains iron, and requires ascorbate. (wikipedia.org)
  • In humans, there are three isoforms of hypoxia-inducible factor-proline dioxygenase. (wikipedia.org)
  • Hypoxia-inducible factor prolyl hydroxylase inhibition: Robust new target or another big bust for stroke therapeutics? (wikipedia.org)
  • Thus, the invasive phenotype observed under angiogenesis inhibition requires Hif-1α , but is not directly caused by acute hypoxia. (nature.com)
  • Pandit, J.J. and Buckler, K.J. (2008) Halothane and sevoflurane exert different degree of inhibition on carotid body glomus cell hypoxic response. (springer.com)
  • We propose that tumor protection is to a large extent due to ( a ) inhibition of antitumor T cells by hypoxia-driven accumulation of extracellular adenosine in local tumor microenvironment and due to ( b ) T regulatory cell-produced extracellular adenosine. (aacrjournals.org)
  • The promising strategy may be in combining the anti-hypoxia-adenosinergic treatment that prevents inhibition of antitumor T cells by tumor-produced and T regulatory cell-produced adenosine with targeting of other negative regulators, such as CTL antigen-4 blockade. (aacrjournals.org)
  • Schema of the hypoxia-adenosinergic suppression of antitumor T-cell response ( A ) and suggested therapeutic approach to remove hypoxia/adenosine-mediated T-cell inhibition using antagonists of A2A and A2B adenosine receptors ( B ). (aacrjournals.org)
  • Atorvastatin could enhance radiosensitivity in hypoxia-induced prostate cancer cells, which may be related with inhibition of HIF-1α protein. (portlandpress.com)
  • In both cell lines we saw a dramatic right shift in the dose-response curve under hypoxic conditions, indicating that these cells were more resistant to doxorubicin-mediated growth inhibition (Figure 4A). (nih.gov)
  • Pharmacological inhibition of GSK3β resulted in β-catenin expression, accompanied by the suppression of wound healing and transwell cell migration. (aspetjournals.org)
  • Conversely, inhibition of β-catenin via dominant negative mutants or short hairpin RNA improved wound healing and transwell migration in hypoxic cells. (aspetjournals.org)
  • Importantly, p16 inhibits hypoxia-induced cell migration in breast cancer in parallel with its inhibition of HIF-1α transactivation activity. (jcancer.org)
  • Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. (nih.gov)
  • Hypoxia, a condition that is known to drive angiogenesis in tumours, results in the release of damage-associated pattern molecules, which can trigger the rejection of tumours by the immune system. (nih.gov)
  • Here we show that tumour hypoxia promotes the recruitment of regulatory T (T(reg)) cells through induction of expression of the chemokine CC-chemokine ligand 28 (CCL28), which, in turn, promotes tumour tolerance and angiogenesis. (nih.gov)
  • Treg-mediated angiogenesis and tolerance is programmed by hypoxia in the tumor microenvironment. (nih.gov)
  • 3D culture broadly regulates tumor cell hypoxia response and angiogenesis via pro-inflammatory pathways. (sigmaaldrich.com)
  • Taken together, our data suggest that pro-inflammatory pathways are critical regulators of tumor hypoxia response within 3D environments that ultimately impact tumor angiogenesis, potentially providing important therapeutic targets. (sigmaaldrich.com)
  • Many of these factors promote angiogenesis and wound healing and are thus critical for the response to local hypoxia and injury. (ahajournals.org)
  • p16, a tumor suppressor gene and cyclin D kinase inhibitor and a negative cell cycle regulator ( 5 , 6 ), was shown to be able to inhibit breast cancer angiogenesis and metastasis ( 7 ). (jcancer.org)
  • There are many reports showing hypoxia plays an important role in tumor angiogenesis and tumor progression, however, very few studies have been done to date with regard to analyzing how hypoxia specifically affects cell migration. (jcancer.org)
  • This study demonstrates that orderly cell death provided spatial structure for early angiogenesis in the hypoxic, high-IFP tumor microenvironment and the participation of linearly patterned programmed cell necrosis (LPPCN) in nascent melanoma angiogenesis. (jcancer.org)
  • Increased expression of Apelin promotes EPC growth, migration and angiogenesis under hypoxia. (ovid.com)
  • The extent of hypoxia strongly correlates to poor patient survival, therapeutic resistance and an aggressive tumour phenotype, but the full contribution of hypoxia and the HIFs to tumour biology is an area of active investigation. (nih.gov)
  • Cancer stem cells are critically dependant on the HIFs for survival, self-renewal, and tumour growth. (nih.gov)
  • Autophagy activation facilitates the removal of damaged cellular compartments and recycles components, thus promoting cell survival. (frontiersin.org)
  • Moreover, hypoxia repressed activation-induced cell death (AICD) by TCR/CD3 stimulation, resulting in an increased survival of the cells. (jimmunol.org)
  • Taken together, we propose that hypoxia is a critical determinant of survival of the activated T cells via the HIF-1α-AM cascade, defining a previously unknown mode of regulation of peripheral immunity. (jimmunol.org)
  • Based on cDNA microarray results, integrin-linked kinase (ILK) emerged as an interesting candidate in hypoxia-mediated survival mechanisms employed by cancer cells. (spandidos-publications.com)
  • The identification of ILK as a player in hypoxia survival signaling employed by cancer cells further validates ILK as a unique target for cancer therapy. (spandidos-publications.com)
  • Incubation with extracellular vesicle preparations containing extracellular RNA increased linc-RoR, HIF-1α expression and cell survival in recipient cells. (biologists.org)
  • Furthermore, this work identifies a mechanistic role for the extracellular transfer of linc-RoR in intercellular signaling to promote cell survival during hypoxic stress. (biologists.org)
  • The cell survival marker Bcl-2 was reduced by 58% while caspase-3 was activated. (jneurosci.org)
  • Hypoxia is an element intrinsic to most solid-tumor microenvironments, including that of OS, and is associated with resistance to therapy, poor survival, and a malignant phenotype. (nih.gov)
  • In radiotherapy of head and neck cancer (HNC) and non-small cell lung cancer (NSCLC), hypoxia is known to be an important prognostic factor for long-term survival and local tumor control. (snmjournals.org)
  • It was discovered that resveratrol suppresses cellular survival and migration and enhances cell death. (medscimonit.com)
  • Resveratrol suppressed cell survival and promoted cell death, but its effects were reversed after HIF-1α knockdown, suggesting that the effects of resveratrol in PC are mediated via HIF-1α. (medscimonit.com)
  • The analysis focused on the main regulators of translation and response to stress because of their role in the cardiac hypertrophy and cell survival in hypoxia. (ad-astra.ro)
  • Patients with a higher percentage of those cells have a less favourable tumor specific survival. (uzh.ch)
  • Adaptation to the hypoxic environment is critical for tumor cell survival and growth. (jcancer.org)
  • Traumatic spinal cord injury includes a complex pattern of pathophysiological processes out of which mitochondrial activity in cell survival and death holds a greater impact [5]. (termedia.pl)
  • Another important mitochondrial target gene is HIF-1α, and the expression of HIF-1α is time dependent, leading to cell death or cell survival following neuronal injury [14]. (termedia.pl)
  • We analyzed whole genome-based transcriptional profiles of Mycobacterium tuberculosis subjected to prolonged hypoxia to guide the discovery of novel potential Ags, by a combined bioinformatic and empirical approach. (jimmunol.org)
  • Notably, HIF-1 and HIF-2 are important transcriptional regulators in response to hypoxia. (oncotarget.com)
  • The direct effect of hypoxia under nonacidotic conditions is unique to transformed cells in that they override the hypoxic G 0 /G 1 arrest of primary cells. (asm.org)
  • Here, we used scratch-wound healing and transwell migration models to examine the effect of hypoxia in cultured renal proximal tubular cells (RPTC). (aspetjournals.org)
  • Ectopic expression of β-catenin in normoxic cells could also suppress wound healing, mimicking the effect of hypoxia. (aspetjournals.org)
  • Further, the presence of hypoxia in tumours may present challenges for therapy because of the promotion of CSC phenotypes even upon successful killing of CSCs. (nih.gov)
  • In the presence of hypoxia halothane also increased channel activity (3 fold) while isoflurane again only had weak effects ( p = 0.004). (springer.com)
  • The presence of hypoxia may also be involved in the development of a more aggressive phenotype and contribute to metastasis ( 6 , 45 ). (asm.org)
  • Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype," Proceedings of the National Academy of Sciences of the United States of America , vol. 99, no. 10, pp. 7021-7026, 2002. (hindawi.com)
  • Recently, it was suggested that hypoxia increased the size of the cancer stem-cell (CSC) subpopulations and promoted the acquisition of a CSC-like phenotype. (nature.com)
  • Importantly, it has also been reported that hypoxia increased the size of CSC subpopulations and promoted the acquisition of a CSC-like phenotype 5 , thereby aggravating the patient's prognosis. (nature.com)
  • Recently, we have described specific bioenergetic markers associated with the metabolic phenotype of several human and mouse glioma cell lines. (aacrjournals.org)
  • The D54-MG and GL261 glioma cell lines displayed an oxidative phosphorylation-dependent phenotype and, alternatively, U251-MG and U87-MG glioma cells exhibited a glycolytic-dependent phenotype with functional oxidative phosphorylation ( 19 ). (aacrjournals.org)
  • This study investigated the phenotype and contractility of adipose-derived stem cells differentiated toward the smooth myogenic lineage under hypoxic conditions. (mdpi.com)
  • When LNCaP cells were subjected to high passage, with and without clonal selection, the derived lines acquired a dysfunctional oxidative phenotype, becoming more glycolytic. (queensu.ca)
  • Changes in the local environment likely shape the phenotype and function of renal-infiltrating T cells in lupus and other autoimmune illnesses. (sciencemag.org)
  • A common feature at pathologic sites is represented by hypoxia, a condition of low pO 2 , which creates a unique microenvironment affecting cell phenotype and behavior. (bloodjournal.org)
  • Electron accumulation also interferes with the activity of the sodium- potassium pump, allowing potassium to flood into extra cellular spaces and sodium and water to enter the cell, in turn causing cellular edema and possible rupture. (wisegeek.com)
  • Cell hypoxia also alters cellular calcium supplies required for proper membrane function and the release of neurotransmitters within the cell. (wisegeek.com)
  • Providing oral or intravenous nutrition assists cells in acquiring the nutrients necessary for cellular function. (wisegeek.com)
  • Cultured human tenocytes were exposed to hypoxia and the cellular response detected using QPCR, Western blotting, viability, and ELISA assays. (hindawi.com)
  • HIFs are key mediators of the cellular response to hypoxia, but they are also associated with pathological stress such as inflammation, bacteriological infection or cancer. (mdpi.com)
  • Macrophages and neutrophils are major cellular components of innate immunity and contribute not only to O 2 deprivation at the site of inflammation, but also alter many of their functions in response to hypoxia to either facilitate or suppress inflammation. (jci.org)
  • The rise in free cytosolic intracellular Ca 2+ concentration results in the activation of Ca 2+ -dependent phospholipases and proteases that further hasten the rate of membrane depolarisation, leading to uncontrolled cellular swelling and, ultimately, to cell necrosis ( Hochachka, 1986 ) ( Fig.1 ). (biologists.org)
  • The pulmonary vascular wall consists of three layers: adventitia, media and intima, whose cellular components are fibroblasts, smooth muscle cells (SMC) and endothelial cells (EC), respectively. (ersjournals.com)
  • The vesicles can contribute to cell-to-cell communication and modulate cellular activities in recipient cells by transfer of their content. (biologists.org)
  • Together, these results validate polymeric nanoparticle-induced CXCR4-overexpressing hADSCs as a potent cellular vehicle for targeting tumor hypoxia, which may be broadly useful for enhancing drug delivery to various cancer types. (ca.gov)
  • Now, an experimental model of this chronic hypoxia reveals that those cellular alterations have behavioral consequences. (medicalxpress.com)
  • Dependence of cellular morphologies on hypoxia and CO 2 . (asm.org)
  • The aim of the study was to establish a model that is suitable for the investigation of cellular and molecular effects associated with transient and long-term hypoxia and to gain insights into hypoxia-mediated mechanisms employing a neuronal culture system. (biologists.org)
  • Employing neuronal IMR-32 cells, we showed that 3 hours of hypoxia led to morphological signs of cellular damage and significantly increased levels of lactate dehydrogenase (a biochemical marker of cell damage). (biologists.org)
  • In summary, we present a novel framework for investigating hypoxia-mediated mechanisms at the cellular level. (biologists.org)
  • An understanding of the hypoxia-associated cellular and molecular mechanisms is essential for the development of new and effective strategies to reduce ischemia-reperfusion injury and hypoxia-mediated cell damage, leading to an improved clinical outcome and reduced mortality. (biologists.org)
  • A fraction of 3H-valine was added to the growth medium of the cells, and as the valine was incorporated into the cellular proteins, the radioactive decay irradiated the cell from within. (uio.no)
  • The walls of pulmonary blood vessels can undergo cellular and histological alterations due to sustained hypoxia. (oncotarget.com)
  • Here, we present quantitative results of the simultaneous and synergistic effects of adhesion and polymerization of deoxygenated sickle hemoglobin (HbS) in the human red blood cell (RBC) on the mechanisms underlying vasoocclusive pain crisis. (pnas.org)
  • Thus, the counter-activation of tolerance mechanisms at the site of tumour hypoxia would be a crucial condition for maintaining the immunological escape of tumours. (nih.gov)
  • This study was to examine the link between astrocyte elevated gene-1 (AEG-1) and hypoxia induced-chemoresistance in T-cell non-Hodgkin's lymphoma (T-NHL), as well as the underlying molecular mechanisms. (springer.com)
  • A prevailing experimental approach has been to probe tissues from natural models of hypoxia-tolerant and cold-tolerant vertebrates to look for common mechanisms of defence against O 2 lack and hypothermia. (biologists.org)
  • Although novel types of selective autophagy have been identified, including mitophagy, pexophagy, lipophagy, ERphagy and nucleophagy among others, their potential interface with hypoxia response mechanisms remains poorly understood. (frontiersin.org)
  • Therefore, a deeper understanding of the molecular crosstalk between hypoxia response mechanisms and autophagy could provide important insights with relevance to cancer and hypoxia-related pathologies. (frontiersin.org)
  • EPCs are known to contribute to vascular repair, although the exact mechanisms of the action of these cells are still under controversial discussion. (ahajournals.org)
  • Nevertheless, the underlying mechanisms causing cell damage are still not fully understood, which is at least partially due to the lack of cell culture systems for the induction of rapid and transient hypoxic conditions. (biologists.org)
  • The system could help to further unravel hypoxia-associated mechanisms that are clinically relevant in various tissues and organs. (biologists.org)
  • BACKGROUND: To uncover the protective role of Vildagliptin in hypoxia-reoxygenation (H/R)-induced injury of cardiac microvascular endothelial cells (CMECs) and the pharmacological mechanisms. (minervamedica.it)
  • This review discusses current knowledge of physiological cell-specific regulation of barrier function, their responses to hypoxia as well as consequences of hypoxic- and HIF-1-mediated mechanisms on barrier integrity during select brain diseases. (uzh.ch)
  • Both mechanisms interrupt the binding between B-cell lymphoma 2 (BCL2) and BCL2 associated X protein (BAX), which leads to the oligomerization of BAX and eventually permeabilization of the mitochondrial membrane [17]. (termedia.pl)
  • Activation of PGI through proposed HIF-1 induced mechanisms results in increased conversion of glucose 6-phosphate to fructose 6-phosphate and also contributes to cell motility and invasion during cancer metastasis. (wikipedia.org)
  • Normal human tenocytes expressed all isoforms of the hypoxia-induced vascular growth factor VEGF except VEGF-D. Hypoxia markedly upregulated VEGF-A mRNA, followed by increased VEGF protein secretion. (hindawi.com)
  • 0.05) linking chondrogenic and osteogenic markers (S100, BMP-2) with markers for brown adipocytes (uncoupling protein-1, PPARgamma co-activator 1alpha) and hypoxia (HIF-1alpha). (ahajournals.org)
  • Most of the cells in the stably transfected HIF-1α RNAi expression vector pcDNA6.2-GW/EmGFP-miR-siHIF-1α expressed green fluorescence protein (GFP) under fluorescence microscope. (scielo.br)
  • The protein profile of a 92-biomarker panel was analyzed on cells treated with 0 or 0.1 mu M doxorubicin during 6 or 72 h, under normoxia or hypoxia. (diva-portal.org)
  • These three commonly used cell lines have critically different responses to chemotherapy and hypoxia, which was reflected in their different protein expression profile. (diva-portal.org)
  • Our previous study showed that the expression of NGAL mRNA and protein can be induced by hypoxia/reoxygenation. (biomedsearch.com)
  • To restrict expression of a therapeutic gene to hypoxic Muller cells, we constructed a hybrid promoter using conserved domains of the human glial fibrillary acidic protein (GFAP) gene promoter and several hypoxia-responsive elements (HRE) and aerobically silenced elements (HRSE). (arvojournals.org)
  • In addition, it was revealed that resveratrol elevated ROS concentration and expression of biomarker of cell death Bax, while inhibiting Bcl2, an anti-apoptotic protein, and reinforcing expression of p53. (medscimonit.com)
  • RhoB, a protein homologous to RhoA and activated by hypoxia, regulates neoplastic growth and vasoconstriction but its role in the regulation of pulmonary vascular function is not known. (diva-portal.org)
  • Specifically, hypoxia-induced downregulation of PHLPP is partially rescued in TSC2 or 4E-BP1 knockdown cells as the result of elevated mTOR activity and protein synthesis. (asm.org)
  • Previous studies have shown that hypoxia inhibits mTOR and cap-dependent protein translation via a TSC2-dependent mechanism upon the induction of REDD1 ( 6 , 7 ). (asm.org)
  • mTOR is an evolutionarily conserved serine/threonine protein kinase that functions in two distinct complexes, mTORC1 and mTORC2, in cells. (asm.org)
  • RSV did increase some skeletal muscle markers of mitochondrial biogenesis, but did not increase protein levels of the subunit NDUFB8 of complex I. Hypoxia alters mitochondrial biogenesis and skeletal muscle respiratory function and may induce permanent changes in mitochondrial respiration of differentiating skeletal muscle cells. (uwo.ca)
  • Expression of nucleotide-binding oligomerization domain protein 2 (NOD2) is upregulated in pulmonary artery smooth muscle cells (PASMCs) during hypoxia. (oncotarget.com)
  • Gene expression programs in response to hypoxia: cell type specificity and prognostic significance in human cancers," PLoS Medicine , vol. 3, no. 3, pp. 395-409, 2006. (hindawi.com)
  • Microarray gene expression analysis of tumor cells cultured in 2D versus 3D under ambient or hypoxic conditions revealed striking interdependence between culture dimensionality and hypoxia response, which was mediated in part by pro-inflammatory signaling pathways. (sigmaaldrich.com)
  • I compared the metabolic phenotypes of the prostate cancer cell lines LNCaP, DU145, and PC3 assessing energy metabolism, and metabolic gene expression. (queensu.ca)
  • Altogether, these data reveal a new role for TTP in the control of gene expression during the response of endothelial cell to hypoxia. (sigmaaldrich.com)
  • This data set is far from having revealed all of its secrets and provides the basis for a global comparative analysis of gene expression in response to hypoxia. (plantcell.org)
  • EPO-induced STAT5-dependent reporter gene expression was absent in Nox2-deficient cells. (ahajournals.org)
  • HIF is a family of transcription factors that are induced by hypoxia to regulate gene expression ( Semenza, 2007 ). (aspetjournals.org)
  • and that hypoxia directly affects differential gene expression in human T cells with up to 4.8% modulation of the transcriptome. (jrheum.org)
  • While our previous studies showed that p16 downregulates VEGF gene expression and neutralizes HIF-1α transactivation activity, it is not known whether p16 directly affects one or more aspects of malignant progression such as adhesion and migration of breast cancer cells in order to suppress metastasis. (jcancer.org)
  • We used glioma cells with oxidative phosphorylation-dependent (D54-MG) and glycolytic-dependent (U251-MG) phenotypes to monitor HIF1-α regulation in association with redox responsiveness to CoCl 2 treatment. (aacrjournals.org)
  • Our findings reveal that XO-derived ROS is a novel and critical component of HIF1-α regulation in U251-MG cells, pointing toward a more general role of this transcription factor in tumor progression. (aacrjournals.org)
  • Notch signaling has been implicated in the regulation of an increasing number of stem cells in several different tissues ( 14 ). (spandidos-publications.com)
  • In particular, interleukin-8 (IL-8) emerged as a major player in the microenvironmental regulation of the hypoxia program. (sigmaaldrich.com)
  • Results: When compared to controls, hypoxic cells had fewer dendritic spines, reduced plateau depolarization accompanied by increased apoptotic activity and accumulation of MAC, as well as up-regulation of C3, C3a and C3aR, enhancement of C3a-C3aR engagement, and elevated caspase and Src activity. (harvard.edu)
  • The authors documented all possible checkpoints of gene regulation fully and collected samples from 7-d-old Arabidopsis ( Arabidopsis thaliana ) seedlings grown in long days and subjected to 2 or 9 h of hypoxia starting at dusk. (plantcell.org)
  • Multi-Scale Analysis of Nuclear Regulation in Response to Hypoxia. (plantcell.org)
  • Down regulation of Wnt signaling mitigates hypoxia-induced chemoresistance in human osteosarcoma cells. (nih.gov)
  • Hypoxia caused a rapid, dramatic, and selective up-regulation of PD-L1 on splenic MDSCs in tumor-bearing mice. (rupress.org)
  • Blockade of PD-L1 under hypoxia enhanced MDSC-mediated T cell activation and was accompanied by the down-regulation of MDSCs IL-6 and IL-10. (rupress.org)
  • Findings suggest that HIF-1α is an important factor in the increase of bladder cancer cell permeability. (scielo.br)
  • However, protection of cortical neurons [ 15 , 16 ], pancreatic cancer cells [ 16 ], and retinal photoreceptors require HIF-1α, which is generally associated with upregulation of protective growth factors such as VEGF (vascular endothelial growth factor) and EPO (erythropoietin). (molvis.org)
  • Use of culture geometry to control hypoxia-induced vascular endothelial growth factor secretion from adipose-derived stem cells: optimizing a cell-based approach to drive vascular growth. (eurekaselect.com)
  • The path to prevent potential inflammatory pathologies due to autoimmunity in responding patients has been shown by the demonstration of clinically detectable antitumor immunity without toxicity in metastatic melanoma patients that have been periodically infused with anti-CTLA-4 antibodies after treatment with granulocyte-macrophage colony-stimulating factor-secreting autologous tumor cells ( 3 ). (aacrjournals.org)
  • Expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular endothelial growth factor (VEGF) in rat brain tissue was evaluated by immunohistochemical methods and western blot assays. (termedia.pl)
  • We demonstrate that hypoxia regulates the nascent transcription of ~1800 lncRNAs. (frontiersin.org)
  • Recently, great effort has been invested toward elucidating the interplay between hypoxia-induced autophagy and cancer cell metabolism. (frontiersin.org)
  • These observations raised the possibility that the heterogeneity in glucose metabolism might identify an important biological marker of glioma cells that is critical for their progression and adaptation to hypoxic conditions. (aacrjournals.org)
  • Hypoxia occurs in human atherosclerotic lesions and has multiple adverse effects on endothelial cell metabolism. (frontiersin.org)
  • The results stress the importance of environmental conditions on Sch9 function and establish a novel response circuitry to both hypoxia and CO 2 in C. albicans , which suppresses hypha formation but also allows efficient nutrient uptake, metabolism, and virulence. (asm.org)
  • A particular change in metabolism, historically known as the Warburg effect results in high rates of glycolysis in both normoxic and hypoxic cancer cells. (wikipedia.org)
  • Under hypoxia, HIFs regulate a variety of pro-angiogenic and pro-glycolysis pathways. (nih.gov)
  • From the experiments shown here, we concluded that ROS were indeed generated in D54-MG cells exposed to CoCl 2 but it was unlikely that ROS participated in the hypoxic signal transduction pathways in this cell type. (aacrjournals.org)
  • Hypoxia preconditioning can be anti-apoptotic either by HIF-1α dependent or independent pathways. (molvis.org)
  • HIF-1-dependent gene-regulated pathways were also up-regulated in renal-infiltrating T cells in human lupus nephritis. (sciencemag.org)
  • Dendritic cells (DCs) are a heterogeneous group of professional antigen-presenting cells involved in the initiation and amplification of innate and adaptive immunity, which develop through different hematopoietic pathways. (bloodjournal.org)
  • 6 - 9 Activation of gene transcription is the primary mechanism by which mammalian cells respond to decreased pO 2 , and the underlying molecular pathways have been elucidated in detail and extensively reviewed. (bloodjournal.org)
  • 7 , 8 , 10 HIF-1 expression and activity are tightly regulated by various cofactors and transcription factors, and HIF-independent pathways mediating gene induction by hypoxia have also been described. (bloodjournal.org)
  • We demonstrate that administration of antiangiogenic agents such as the VEGF receptor tyrosine kinase inhibitor sunitinib and the anti-VEGF antibody bevacizumab increases the CSC population in breast cancer xenografts as a consequence of the generation of tumor hypoxia. (pnas.org)
  • Since VEGF is induced by hypoxia, can be HIF-1α dependent, and is often protective, we examined the changes in transcription of VEGF and its receptors after 4 h of hypoxia preconditioning. (molvis.org)
  • VEGF and its receptors Flt-1 and Flk-1 are up-regulated after hypoxia preconditioning. (molvis.org)
  • However, the transcription and translation of VEGF were paradoxically increased by siHIF-1α, suggesting that VEGF expression in stromal cells is not down-stream of HIF-1α. (molvis.org)
  • These findings demonstrate that hypoxia preconditioning protection in corneal stromal cells requires HIF-1α, but that VEGF is not a component of the protection. (molvis.org)
  • From these microregional distributions, it was deduced that VEGF mRNA and HIF-1 are induced by hypoxia in human gliomas. (aacrjournals.org)
  • EPCs are bone marrow-derived mononuclear cells which are lineage negative and express the surface markers stem cell antigen (sca-1) or CD34 and endothelial markers like the VEGF-receptor 2 (flk-1 in mice). (ahajournals.org)
  • These data demonstrate the importance of hypoxia in lymphatic endothelial cell invasion and migration through extracellular matrix in the presence of cancer cells. (nih.gov)
  • Hypoxia is a prominent characteristic of many acute or chronic inflammatory diseases, and exerts significant influence on their progression. (jci.org)
  • Cell and molecular biological analyses suggest that chronic oxidative stress and inflammation are involved in the pathogenesis of AMD. (arvojournals.org)
  • Chronic hypoxia is a common cause of pulmonary hypertension and pulmonary vascular remodelling. (ersjournals.com)
  • Chronic hypoxia elicits expression of mitogens, growth factors and cytokines by fibroblasts and endothelial cells, and also the suppression of endothelial nitric oxide synthase. (ersjournals.com)
  • Pulmonary hypertension (PH) is a complication for those subjected to environmental hypoxia as a result of living at high altitude and for those suffering from chronic hypoxic lung diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis and asthma. (ersjournals.com)
  • Rationale and design of the Transendocardial Injection of Autologous Human Cells (bone marrow or mesenchymal) in Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction (TAC-HFT) trial: A randomized, double-blind, placebo-controlled study of safety and efficacy. (eurekaselect.com)
  • Chronic sublethal hypoxia is associated with locomotor miscoordination and long-term cerebellar learning deficits in a clinically relevant model of neonatal brain injury, according to a study led by Children's National Health System researchers published online Aug. 13, 2018, by Nature Communications . (medicalxpress.com)
  • Lung cells experience hypoxia during development, during travel to high altitude, and in acute and chronic lung diseases. (luriechildrens.org)
  • Objective: To determine the role of RhoB in pulmonary endothelial and smooth muscle cell responses to hypoxia and in pulmonary vascular remodeling in chronic hypoxia-induced pulmonary hypertension. (diva-portal.org)
  • RhoB deficiency in mice markedly attenuated development of chronic hypoxia-induced pulmonary hypertension, despite compensatory expression of RhoA in the lung. (diva-portal.org)
  • Conclusions: RhoB mediates adaptational changes to acute hypoxia in the vasculature, but its continual activation by chronic hypoxia can accentuate vascular remodeling to promote development of pulmonary hypertension. (diva-portal.org)
  • However, previous studies have indicated that chronic hypoxic cells are less tolerable to low dose-rate irradiation than well-oxygenized cells. (uio.no)
  • To investigate the involvement of NOD2 in the pulmonary vascular response to hypoxia, we subjected wild-type and NOD2-deficient mice to chronic normobaric hypoxic conditions. (oncotarget.com)
  • Pulmonary hypertension (PH) commonly occurs in populations that live at high altitudes and in individuals who experience chronic hypoxia due to pulmonary conditions. (oncotarget.com)
  • It can be induced by chronic hypoxia, high IFP and subsequent calcium influx. (jcancer.org)
  • The aim of this study was to investigate the effect and mechanism of chronic intermittent hypoxia (CIH) on cerebral injury using the ischemia-reperfusion rat model. (termedia.pl)
  • However, in certain lower vertebrates, neonates and diving mammals, hypoxia-induced membrane destabilisation of the kind seen in adult mammals is either slow to develop or does not occur at all as a result of adaptive decreases in membrane permeability (i.e. ion 'channel arrest') that dramatically reduce the energetic costs of ion-balancing ATPases ( Hochachka, 1986 ). (biologists.org)
  • It has been reported that foetal hypoxia decreases nephron numbers and kidney weight [2]. (thefreelibrary.com)
  • Analysing over 200 melanomas including primaries, partly matched metastases and patients' cell cultures we show that TRP-2 is correlated with Melan A expression and decreases with tumor progression. (uzh.ch)
  • Storage-dependent hypoxanthine accumulation is ameliorated by hypoxia-induced decreases in purine deamination reaction rates. (haematologica.org)
  • The objective of this article is to discuss the role of HIFs in the function of innate and adaptive immune cells in hypoxia, with a focus on how hypoxia modulates immunometabolism. (mdpi.com)
  • 1%) as found in the rheumatoid synovium modulates the transcriptome of human CD4+ T cells. (jrheum.org)
  • In rheumatoid arthritis (RA) synovial tissue samples, hypoxia modulates the transcription profile. (jrheum.org)
  • Severe hypoxia, a feature of joint inflammation, considerably modulates the transcriptome of cells found in the rheumatoid synovium. (jrheum.org)
  • The tissue-specific physiology of tendon is adjusted to extreme mechanical loading, which results in acute and repetitive reductions in blood perfusion and therefore a likely ability to tolerate transient hypoxia. (hindawi.com)
  • Upon tissue injury or pathogen invasion, local sentinel cells such as resident macrophages and mast cells respond to dilate blood vessels, increase vascular permeability, and recruit a variety of leukocytes to the site of inflammation. (jci.org)
  • During the acute phase of inflammatory responses, a major task of such recruited cells is the clearance of damaged tissue or pathogens. (jci.org)
  • In the setting of obesity, hypoxia develops as adipose tissue mass expands, initiating inflammatory responses. (jci.org)
  • In solid cancers, regions of hypoxia are commonly present throughout the tissue because of the chaotic vascular architecture and regions of necrosis. (nih.gov)
  • Introduction Neutrophils accumulate in the lungs of patients with bronchiectasis and cystic fibrosis, and the resulting inflammation causes tissue hypoxia. (bmj.com)
  • Smooth muscle differentiated adipose tissue-derived stem cells are a valuable resource for regeneration of gastrointestinal tissues, such as the gut and sphincters. (mdpi.com)
  • Among these, MALAT1, HYMAI, LOC730101, KIAA1656, and LOC339803 were found differentially expressed in human atherosclerotic lesions, compared to normal vascular tissue, and may thus serve as potential biomarkers for lesion hypoxia. (frontiersin.org)
  • The release of extracellular vesicles, such as exosomes, from cells in response to changes in the tissue environment provides a potential mechanism of intercellular signaling by which tissue responses to hypoxia could be coordinated. (biologists.org)
  • used lupus-prone mice and showed that the hypoxic environment associated with renal tissue injury modulated the activity of infiltrating T cells, promoting their effector function to cause tissue damage. (sciencemag.org)
  • however, how immune cells adapt to kidney's unique environment and contribute to tissue damage is unknown. (sciencemag.org)
  • Perturbation of these environmental adaptations by selective HIF-1 blockade inhibited infiltrating T cells and reversed tissue hypoxia and injury in murine models of lupus. (sciencemag.org)
  • The kidney is a primary target of damage in systemic lupus erythematosus (SLE, lupus), with deposition of pathogenic autoantibodies and subsequent T cell-mediated tissue injury ( 1 ). (sciencemag.org)
  • Yet, little is known about how the kidney environment contributes to the adaptation of infiltrating T cells with resultant tissue damage. (sciencemag.org)
  • Cancerous tissue protection from tumor-recognizing CD8 + and CD4 + T cells (antitumor T cells) limits the therapeutic potential of immunotherapies. (aacrjournals.org)
  • During ischemia-reperfusion, an in vivo condition of hypoxia, HIF family members are induced to regulate tissue repair and remodeling. (aspetjournals.org)
  • To answer these questions, we prepared synovial tissue samples from patients with RA and showed the influence of hypoxia on transcription profile compared to severe hypoxic cold ischemic synovial specimens (obtained post mortem) and to synovial tissue samples from patients with osteoarthritis (OA). (jrheum.org)
  • Ischemia-reperfusion injury and tissue hypoxia are of high clinical relevance because they are associated with various pathophysiological conditions such as myocardial infarction and stroke. (biologists.org)
  • Ischemia-reperfusion injury and tissue hypoxia are of high clinical relevance. (biologists.org)
  • Therapeutic approaches include transplantation of neural stem cells that have been expanded in an undifferentiated state ex vivo , and manipulation of endogenous NSPCs that are resident within the post-natal brain. (wiley.com)
  • Linc-RoR expression was increased in hypoxic regions within tumor cell xenografts in vivo . (biologists.org)
  • Impact of hypoxia and long-term cultivation on the genomic stability and mitochondrial performance of ex vivo expanded human stem/stromal cells. (eurekaselect.com)
  • Either they are not suitable for the clinically relevant rapid induction and/or termination of hypoxia (hypoxic chambers) or it is not possible to exclude potential side effects that are caused by the direct addition of hypoxia-inducing chemicals or enzymes to the culture medium and therefore to the cells within, which might impair the transferability of the results to the in vivo situation. (biologists.org)
  • HIF-2 α knockout promoted infiltration of NKT cells into ischemic kidneys and exacerbated IRI, which could be mitigated by in vivo NK1.1 + cell depletion or Fas ligand blockade. (asnjournals.org)
  • Western blot was also performed to analyze the expression of AEG-1, LC3-II, and Beclin-1 in T-NHL cells (Hut-78 and Jurkat cells) under normoxia and hypoxia. (springer.com)
  • Supernatants from wild-type and PHD-deficient P. aeruginosa were harvested at two hours and then co-cultured with neutrophils in normoxia and hypoxia. (bmj.com)
  • Hypoxia stabilizes HIF-αs in macrophages and neutrophils, and these O 2 -sensitive transcription factors are key regulators of inflammatory responses in myeloid cells. (jci.org)
  • Responses of T cells to hypoxia, therefore, may be essential not only for adaptation but also for their functional performance. (jimmunol.org)
  • Tumor cells regulate and adapt to the hypoxic environment by initiating a series of hypoxic adaptive responses. (scielo.br)
  • Pandit J.J., Winter V., Bayliss R., Buckler K.J. (2010) Differential Effects of Halothane and Isoflurane on Carotid Body Glomus Cell Intracellular Ca 2+ and Background K + Channel Responses to Hypoxia. (springer.com)
  • Although deregulated expression of many long noncoding RNA (lncRNA) occurs in human cancers, the contribution of such RNA to tumor responses to hypoxia are unknown. (biologists.org)
  • Dendritic cells (DCs) are a heterogeneous group of professional antigen-presenting cells functioning as sentinels of the immune system and playing a key role in the initiation and amplification of innate and adaptive immune responses. (bloodjournal.org)
  • 1 mDCs switch their chemokine receptor repertoire down-regulating inflammatory receptors and up-regulating those required for homing to secondary lymphoid organs, where they prime naive T cells triggering specific immune responses. (bloodjournal.org)
  • The functional responses evoked by hypoxia are diverse and generally act to protect the cells from hypoxic injury, although some lung cell responses are counterproductive because they degrade normal function of the organ. (luriechildrens.org)
  • Alterations in BBB stability that occur during injury have dire consequences on disease progression and it is clear that BBB cell-specific responses, positive or negative, must make a significant contribution to injury outcome. (uzh.ch)
  • Physiological responses of the organism may reduce IFP through induction of orderly cell death. (jcancer.org)
  • Here, we investigated the influence of hypoxia on immune checkpoint receptors (programmed death [PD]-1 and CTLA-4) and their respective ligands (PD-1 ligand 1 [PD-L1], PD-L2, CD80, and CD86) on MDSCs. (rupress.org)
  • The profile or the hypoxic cells (labeled H, indicated by heavy line) is compared to the shaded normoxic cells (labeled N, indicated by thin line). (plos.org)
  • The isotypic controls of the normoxic and hypoxic cells are superimposable and are shown as a single black shaded profile. (plos.org)
  • Similar to the DU145 and PC3 cells, NAO fluorescence indicates that the oxidative impairment in these LNCaP-derived lines may be due to a reduction in mitochondrial activity. (queensu.ca)
  • Taken together, our results reveal a hypoxia/HIF-2 α /adenosine A2A receptor axis that restricts NKT cell activation when confronted with oxidative stress and thus protects against renal IRI. (asnjournals.org)
  • Neuronal cell function, morphology and viability were investigated by measuring plateau depolarization potential, counting the number dendritic spines, and observing TUNEL and MTT assays. (harvard.edu)
  • Hypoxia decreased viability of HepG2 and SNU499. (diva-portal.org)
  • Tumor cell viability during hypoxia was reduced by small interfering RNA (siRNA) to linc-RoR. (biologists.org)
  • Moreover, when uncoupled from acidosis, hypoxia enhances tumor cell viability and clonogenicity relative to normoxia. (asm.org)
  • The viability of hypoxia-induced PC3 cells was inhibited by a higher dose of irradiation than control cells. (portlandpress.com)
  • The viability of hypoxia-induced PC3 cells were inhibited by astorvastatin with a higher concentration than control cells. (portlandpress.com)
  • Viability of cells after this time was assayed by a drop dilution test as for panel A. Strains tested were control strain CAF2-1, sch9 mutant CCS5, reconstituted sch9 mutant CCS4, rim15 mutant CCS6, tpk1 mutant IIHB6, and tpk2 mutant TPO7.4. (asm.org)
  • RSV treatment did not consistently reverse hypoxic alterations during normoxic recovery and negatively impacted cell viability indicating that RSV may not be a suitable pharmacological intervention for skeletal muscle cells which have differentiated under hypoxia. (uwo.ca)
  • The current experimental evidence suggests that CSCs are plastic cell states governed by microenvironmental conditions, such as hypoxia, that may be critical for the development of new therapies targeted to disrupt the microenvironment. (nih.gov)
  • In the later stages of atherosclerosis, plaque endothelial cells (ECs) are subject to an adverse microenvironment characterized by hypoxia and proinflammatory stimuli, greatly affecting their function as endothelial barrier ( 9 ). (frontiersin.org)
  • Hypoxia and inflammation are constant characteristics of prostate tumor microenvironment influencing both cancer stem cells and differentiated tumor cells. (urotoday.com)
  • However, malignant cells can create a self-protective, immunosuppressive tumor microenvironment that prevents tumor destruction by antitumor T cells ( 4 ). (aacrjournals.org)
  • Here, we discuss the available experimental evidence as well as hypothesize and propose ( Fig. 1 ) that the tumor protection from antitumor T cells is also due to hypoxia-adenosinergic immunosuppression in the local tumor microenvironment. (aacrjournals.org)
  • Tumor-infiltrating myeloid cells such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) form an important component of the hypoxic tumor microenvironment. (rupress.org)
  • A significant increase in the invasion and migration of HMVEC-dLy cells was detected in the presence of cancer cells, which further increased significantly under hypoxic conditions. (nih.gov)
  • In addition, blocking Akt signaling also significantly abrogated the protective effect of anti-miR-137 on hypoxia-induced cell injury. (spandidos-publications.com)
  • The expression of Bax/Bcl-2 ratio and caspase-3 were significantly higher in the hypoxia/reoxygenation compared with the control group. (biomedsearch.com)
  • Knockdown of endogenous expression of FABP3, FABP7, or Adipophilin (an essential LD structural component) significantly impaired LD formation under hypoxia. (mit.edu)
  • Using high-tech optical and physiological methods that allow researchers to turn neurons on and off and an advanced behavioral tool, the research team finds that Purkinje cells fire significantly less often after injury due to perinatal hypoxia. (medicalxpress.com)
  • Two weeks after experiencing hypoxia, the hypoxic group's locomotor performance remained significantly worse than the control group, and delays in learning could still be seen five weeks after hypoxia. (medicalxpress.com)
  • HIF-1α expression in PC3 cells was significantly increased after incubating with 5% O 2 for 24 h. (portlandpress.com)
  • This was not limited to MDSCs, as hypoxia also significantly increased the expression of PD-L1 on macrophages, dendritic cells, and tumor cells. (rupress.org)
  • Finally, neutralizing antibodies against IL-10 under hypoxia significantly abrogated the suppressive activity of MDSCs. (rupress.org)
  • Furthermore, we identify a TRP-2 negative, proliferative, hypoxia related cell subpopulation which is significantly associated with tumor thickness and diseases progression. (uzh.ch)
  • In addition, hypoxanthine levels negatively correlated with post-transfusion red blood cell recovery in mice and - preliminarily albeit significantly - in humans. (haematologica.org)
  • Reduced oxygenation, or hypoxia, is a characteristic of many brain diseases that significantly increases barrier permeability. (uzh.ch)
  • Hydrogen peroxide-induced Fas ligand expression on thymic wild-type NKT cells was significantly attenuated by CGS21680 treatment, but this effect was lost in HIF-2 α −/− NKT cells. (asnjournals.org)
  • Nonmalignant immortalized MCF-12A human mammary epithelial cells instead of cancer cells or chambers with HMVEC-dLy alone were used as controls for comparison. (nih.gov)
  • The development of the mammalian kidney is guided by reciprocal inductive interactions between the ureteric bud (UB, giving rise to the collecting duct system) and the metanephric mesenchyme (giving rise to all other renal epithelial cells) [13]. (thefreelibrary.com)
  • Uninterrupted blood flow and an intricate and architecturally optimized network of photoreceptors, interneurons, glia, and epithelial cells are required for vision. (elifesciences.org)
  • Similarly, ischemia induced Cezanne in the murine kidney in vascular EC, glomerular EC, podocytes and epithelial cells, and genetic deletion of Cezanne enhanced renal inflammation and injury in murine kidneys exposed to ischemia followed by reperfusion. (ahajournals.org)
  • Targeting Tumor Hypoxia Using Nanoparticle-engineered CXCR4-overexpressing Adipose-derived Stem Cells. (ca.gov)
  • Home › About CIRM › Our Publications › Grantee publications › Targeting Tumor Hypoxia Using Nanoparticle-engineered CXCR4-overexpressing Adipose-derived Stem Cells. (ca.gov)
  • To harness this mechanism for targeting tumor hypoxia, we developed polymeric nanoparticle-induced CXCR4-overexpressing human adipose-derived stem cells (hADSCs). (ca.gov)
  • For other cells such as cochlear spiral ganglion stem cells, human mesenchymal stem cells, and adipose-derived mesenchymal stem cells, hypoxia helps to maintain stemness to preserve the stem cell pool [9-11]. (thefreelibrary.com)
  • In rats, the metanephric kidney develops at embryonic day 12, and this is followed by the ingrowth of the UB into the metanephric blastema, inducing the metanephric mesenchymal stem cells (MMSCs) at the bud tips to condense around the UB tips. (thefreelibrary.com)
  • Upregulation of Wnt4, which mediates epithelialization of the metanephric mesenchyme, has been detected after exposure of mesenchymal stem cells to hypoxia [16]. (thefreelibrary.com)
  • Recent reports demonstrated the increased motility of human mesenchymal stem cells (hMSC) grown under hypoxic conditions compared to normoxic cells. (7thspace.com)
  • Mesenchymal Stem Cells (MSCs) are distributed in many parts of the human body, including the bone marrow, placenta, umbilical cord, fat, and nasal mucosa. (eurekaselect.com)
  • Telomere length analysis of human mesenchymal stem cells by quantitative PCR. (eurekaselect.com)
  • Multilineage potential of adult human mesenchymal stem cells. (eurekaselect.com)
  • Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. (eurekaselect.com)
  • Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. (eurekaselect.com)
  • 2017 MicroRNA-133 overexpression promotes the therapeutic efficacy of mesenchymal stem cells on acute myocardial infarction. (springer.com)
  • The increase in CSCs in response to hypoxia was mediated through HIF-1α through the activation of the Wnt pathway via Akt/β-catenin signaling. (pnas.org)
  • A successful immune response is achieved by rapid mobilization of circulating peripheral T cells and antigen-driven expansion of a certain fraction of the cells in situ. (jimmunol.org)
  • Subsequently, accumulated T cells may need to be cleared away to prevent a harmful over-response or for preservation of homeostasis within the T cell compartment of peripheral immunity. (jimmunol.org)
  • 18 ) have proposed that the integrity of the mitochondrial respiratory chain is not necessary for hypoxia response. (aacrjournals.org)
  • We recently reported that volatile anaesthetics directly depress the isolated glomus cell response to hypoxia, halothane more so than sevoflurane, in a manner mimicking the action of these agents on the human hypoxic ventilatory response. (springer.com)
  • We conclude that the effect of volatile anaesthetics on the glomus cell response to hypoxia is mediated at least in part by their effect on background K + channels, and that this plausibly explains their whole-body effect. (springer.com)
  • Pandit, J.J. (2002) The variable effect of low-dose volatile anaesthetics on the acute ventilatory response to hypoxia in humans: A quantitative review. (springer.com)
  • p53 is correspondingly upregulated in response to hypoxia-induced acidosis but downregulated during hypoxia without acidosis. (asm.org)
  • Compared to untransfected hADSCs, CXCR4-overexpressing hADSCs showed enhanced migration in response to hypoxia and penetrated the hypoxic core within tumor spheres. (ca.gov)
  • It's remarkable that the one-celled yeast also swap COX subunits in response to hypoxia, but because they lack HIF-1, they accomplish the swap in a completely different way," says Semenza. (bio-medicine.org)
  • In this study, we constructed a hypoxia-regulated, Muller cell-specific vector and tested its response to hypoxia. (arvojournals.org)
  • Aim of this review is to present the current knowledge regarding the crucial role, in prostate cancer progression, of a molecular network linking hypoxia, pro-inflammatory response and steroid receptors. (urotoday.com)
  • The need to eliminate negative regulators of immune response is well recognized ( 8 ), and the pioneering use of CTLA-4 blockade ( 2 , 3 ) or combined CTLA-4 blockade and Treg cells depletion ( 11 ) may have a synergistic effect in enabling the development of sufficient numbers of lethal and tumor-recognizing antitumor T cells. (aacrjournals.org)
  • Many also contained a DNA motif recognized by group VII ethylene response factors (ERFs), among them the hypoxia-responsive ERF HRE2. (plantcell.org)
  • Hypoxia results in chemoresistance of human OS cells to doxorubicin.A, Dose-response curves for the 143B and MNNG/HOS (mHOS) cell lines treated with increasing concentrations of doxorubicin under normoxic and hypoxic conditions (72 hour, 0.5% O2). (nih.gov)
  • B, Average half maximal inhibitory concentration (IC50) values were obtained from the dose-response curves and compared between normoxic and hypoxic conditions for the cell lines MNNG/HOS (mHOS), 143B, and a patient-derived OS cell line, 206-2. (nih.gov)
  • We also examined the response to doxorubicin treatment under hypoxia and normoxia in MNNG/HOS cells in the context of either HIF-1 or HIF-2 knockdown. (nih.gov)
  • Transplantation of bone marrow from Nox2 y/− mice into WT-mice blocked mobilization in response to hypoxia and EPO, whereas transplantation of WT bone marrow into Nox2 y/− mice restored mobilization. (ahajournals.org)
  • Chromatin immunoprecipitation and luciferase reporter assay revealed direct binding of HIF-1α to a transcriptionally active hypoxia-response element (HRE) in the PD-L1 proximal promoter. (rupress.org)
  • In this study, we tested the hypothesis that endothelial activation in response to hypoxia-reoxygenation can be influenced by Cezanne, a deubiquitinating enzyme that cleaves ubiquitin from specific modified proteins. (ahajournals.org)
  • Numerous studies have demonstrated that hypoxia plays a pivotal role in tumor progression and metastasis and is often associated with increased malignancy and poor prognosis ( 1 , 2 ). (asm.org)
  • HMVEC-dLy cells were labeled with a T(2) contrast agent (Feridex), and their invasion and migration through extracellular matrix under normoxic and hypoxic conditions were monitored using magnetic resonance imaging. (nih.gov)
  • HMVEC-dLy cells formed interconnecting strands extending toward the cancer cells under normoxic but not under hypoxic conditions. (nih.gov)
  • Comparison of HLA-Class I profiles of human glioma cells grown under hypoxic or normoxic conditions. (plos.org)
  • The U251, U87, T98G, LN18 or D54 glioma cells were either grown under normoxic or hypoxic conditions for 1 week. (plos.org)
  • A Mann Whitney U test showed that there was a significant difference in ARPE-19 growth between normoxic and hypoxic conditions when the culture media was supplemented with Minocycline at concentrations between 2μM and 10μM at all points of the cell growth curve. (arvojournals.org)
  • We also compared the level of GTP-bound RhoA in the cell extracts of Calpeptin activated Hypoxic and Normoxic hMSC. (7thspace.com)
  • Results: We found that hMSC cultured in hypoxia demonstrate markedly higher targeted migration activity compared to normoxic cells, particularly towards wound healing cytokines, including those found in ischemic and myocardial infarction. (7thspace.com)
  • Here we present a label- free electrochemical sensor to measure the EVs secretion levels of hypoxic and normoxic MCF-7 cells. (epfl.ch)
  • Designed label-free electrochemical sensors utilized for quanti cation of EVs secretion enhancement due to CoCl2-induced hypoxia and 1.23 fold increase with respect to normoxic conditions was found. (epfl.ch)
  • We cultured both MNNG/HOS cells and 143B cells under normoxic and hypoxic conditions for 72 hours in the presence of increasing concentrations of doxorubicin. (nih.gov)
  • Moreover, activation of HIF-1α with dimethyloxalylglycine in normoxic cells did not suppress wound healing, negating a major role of HIF-1α in wound healing in this model. (aspetjournals.org)
  • The α-subunit of HIF-1 (HIF-1α) is rapidly degraded under normoxic conditions and stabilized under hypoxia 11 . (jrheum.org)
  • Taken together, these data suggested that Wnt/β-catenin signaling mediated the hypoxia-induced self-renewal potential of colorectal-cancer CSCs through reactivating Id2 expression. (nature.com)
  • Like humans, most mammals possess little naturally evolved tolerance to severe hypoxia or hypothermia, and their excitable cells and tissues are normally debilitated by any prolonged exposure to either condition. (biologists.org)
  • IntroductionA feature which makes stem cells promising candidates for cell therapy is their ability to effectively migrate into damaged or diseased tissues. (7thspace.com)
  • Whether and how wound healing is affected by hypoxia in kidney cells and tissues is currently unknown. (aspetjournals.org)
  • The results suggest that GSK3β/β-catenin signaling may contribute to defective wound healing in hypoxic renal cells and tissues. (aspetjournals.org)
  • Mouse myocardial cells were exposed to hypoxia/reoxygenation (H/R). FTO and Mhrt were downregulated in heart tissues of HF mice. (springer.com)
  • Compared to wild-type mice, NOD2-deficient mice developed severe pulmonary hypertension with exaggerated elevation of right ventricular systolic pressure, profound right ventricular hypertrophy and striking vascular remodeling after exposure to hypoxia. (oncotarget.com)
  • Calcium sensitivity of petrosal ganglion neurons (PGNs) to chemical stimuli with and without PC-12 cells in co-culture instead of glomus is not known- the idea being that two types of unusual cells could form synapse and provide a model for studies of chemotransduction. (biomedsearch.com)
  • Unlike primary neurons, NSPCs from embryonic and adult mice survived prolonged hypoxia in culture. (wiley.com)
  • Retinal ganglion cells (RGCs) are important neurons in the retina that transmit visual signals from the retina to the brain ( 1 , 2 ). (spandidos-publications.com)
  • Nonbiased stereological cell counts of TH-positive neurons in SN of young adult HIF-1α CKO mice revealed a reduction of 31% compared with cre/wt mice (in which the wild- type Hif1a allele is expressed in parallel with the Cre recombinase allele). (jneurosci.org)
  • Muller cells represent the functional link between blood vessels and neurons. (arvojournals.org)
  • These essential tasks, Gallo says, are coordinated by Purkinje cells, large neurons located in the cerebellum that are elaborately branched like interlocking tree limbs and represent the only source of output for the entire cerebellar cortex. (medicalxpress.com)
  • A novel, immortal, and multipotent human neural stem cell line generating functional neurons and oligodendrocytes. (semanticscholar.org)
  • However, we observe that YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment. (nih.gov)
  • Incubation of Hut-78 and Jurkat cells in hypoxia obviously increased AEG-1, LC3-II and Beclin-1 expression. (springer.com)
  • Transcriptome of hypoxic immature dendritic cells: modulation of chemokine/receptor expression," Molecular Cancer Research , vol. 6, no. 2, pp. 175-185, 2008. (hindawi.com)
  • Importantly, the levels of hypoxia-induced CSC-sphere formation and Id2 expression were successfully attenuated by treatment with a Wnt/β-catenin-signaling inhibitor. (nature.com)
  • Real time reverse transcription polymerase chain reaction and immunofluorescence staining were used to detect the expression of smooth muscle cells-specific markers, including early marker smooth muscle alpha actin, middle markers calponin, caldesmon, and late marker smooth muscle myosin heavy chain. (mdpi.com)
  • Overall, the results of the present study demonstrated that miR-137 targets Notch1 expression, revealing a novel link between miR-137 and Notch signaling, and suggesting that a miR-137/Notch1 axis may serve as a potential molecular target for the treatment of hypoxia-induced retinal diseases. (spandidos-publications.com)
  • Interestingly, lncRNA expression is exquisitely cell type-specific and is often perturbed in disease states ( 5 , 6 ), suggesting functions in development, homeostasis and maintenance of cell identity. (frontiersin.org)
  • During hypoxia (0.5% O2), 5 μM cadmium chloride completely inhibited HIF-1α expression and reversed the protection by hypoxia preconditioning. (molvis.org)
  • HIF-1α siRNA (15 nM) reduced HIF-1α expression by 90% and produced a complete loss of protection provided by hypoxia preconditioning. (molvis.org)
  • RNA expression profiling identified several hypoxia-responsive lncRNAs, including the long intergenic noncoding RNA, regulator of reprogramming (linc-RoR), which is also increased in expression in malignant liver cancer cells. (biologists.org)
  • Exposure to hypoxia induced a 12-fold increase in expression in transfected primary mouse Muller cells and a 15-fold increase in the M10M1 Muller cell line. (arvojournals.org)
  • In the present study, we aim to investigate the effect of atorvastatin on HIF-1α expression and radiosensitivity in prostate cancer cells. (portlandpress.com)
  • We show that hypoxia results in increased expression and signaling activation of HIF proteins in human osteosarcoma cells. (nih.gov)
  • Methods and Results: Hypoxia increased expression and activity of RhoB in human pulmonary artery endothelial and smooth muscle cells, coincidental with activation of RhoA. (diva-portal.org)
  • We evaluated a hypoxia-based imaging and therapy strategy to target expression of the sodium iodide symporter ( NIS) gene to experimental hepatocellular carcinoma ( HCC) delivered by MSCs. (uni-muenchen.de)
  • MSCs engineered to express transgenes driven by a hypoxia-responsive promoter showed robust transgene induction under hypoxia as demonstrated by mCherry expression in tumor cell spheroid models, or radioiodide uptake using NIS. (uni-muenchen.de)
  • Here, we show that the expression of both PHLPP isoforms is negatively regulated by hypoxia/anoxia in colon cancer cells. (asm.org)
  • Interestingly, a hypoxia-induced decrease of PHLPP expression is attenuated by knocking down HIF1α but not HIF2α. (asm.org)
  • Taken together, we have identified hypoxia as a novel mechanism by which PHLPP is downregulated in colon cancer, and the expression of PHLPP may serve as a biomarker for better understanding of chemoresistance in cancer treatment. (asm.org)
  • Hypoxia increased the expression of miR-30d-5p while decreased the SIRT1expression, which was also attenuated by Res treatment. (springer.com)
  • Resveratrol (RSV) will increase expression of markers of mitochondrial biogenesis and reverse the hypoxia-induced depression of O 2 consumption rates. (uwo.ca)
  • Cells were cultured for six weeks within porous scaffolds, and their cellularity, cartilaginous matrix production (collagen II/I expression ratio, hydroxyproline and GAG content) and hypertrophy markers (collagen X expression, ALP activity, calcium accumulation) were analyzed. (rice.edu)
  • After two weeks, hypoxic culture conditions had expedited chondrogenesis with all cell types by increasing collagen II/I expression ratio and matrix synthesis by ∼2.5-11 and ∼1.5-3.0 fold, respectively. (rice.edu)
  • Moreover, hypoxia treatment enhanced the expression of Apelin in EPCs. (ovid.com)
  • In this study, we used Lck-Cre transgenic mice to specifically disrupt HIF-2 α in T/NKT cells and found that HIF-2 α knockout led to upregulated Fas ligand expression on peripheral NKT cells, but not on conventional T cells. (asnjournals.org)
  • Mechanistically, hypoxia-induced expression of adenosine A2A receptor in NKT cells and CGS21680-induced cAMP production in thymocytes were HIF-2 α -dependent. (asnjournals.org)
  • While naturally occurring hypoxia is indispensable for the early onset of mammalian embryonic development, it also contributes to the pathogenesis of several diseases such as stroke, heart failure, and cancer. (frontiersin.org)
  • Resistance to adverse environmental conditions, such as hypoxia, contributes to the reduced efficacy of anticancer therapies and tumor progression. (biologists.org)
  • however, it remains elusive how hypoxia-induced downregulation of translation contributes to tumor progression. (asm.org)
  • Antiapoptotic proteins Bcl2 and Bcl-xL were unchanged by hypoxia. (hindawi.com)
  • These proteins are often overexpressed in cancer cells, and HIF overexpression frequently correlates with poor prognosis, making HIF proteins promising therapeutic targets. (mcponline.org)
  • A layer of extracellular matrix proteins, Bruch's membrane, lies adjacent to the choriocapillaris, and a monolayer of retinal pigment epithelium (RPE) cells divides Bruch's membrane from the photoreceptors. (elifesciences.org)
  • We demonstrate that by generating intratumoral hypoxia in human breast cancer xenografts, the antiangiogenic agents sunitinib and bevacizumab increase the population of cancer stem cells. (pnas.org)
  • These studies demonstrate that hypoxia-driven cancer stem cell stimulation limits the effectiveness of antiangiogenic agents, and suggest that to improve patient outcome, these agents might have to be combined with cancer stem cell-targeting drugs. (pnas.org)
  • Mature and immature nodules within CAVD demonstrate evidence for hypoxia-, matrix-, and inflammatory cell-driven remodeling. (ahajournals.org)
  • We herein aimed to demonstrate that miR-137 acts as a hypoxia-responsive gene in RGCs that is downregulated under hypoxic conditions. (spandidos-publications.com)
  • Finally, the effects of AEG-1 on Hut-78 cells exposed to ADM in hypoxia were assessed by MTT and Annexin-V FITC/PI staining assay, and 3-MA (autophagy inhibitor) was further used to determine the underlying mechanism. (springer.com)
  • An apoptotic process termed activation-induced cell death (AICD) 3 triggered by repeated Ag challenge via the TCR/CD3 complex, is believed to be a mechanism for efficient elimination of activated T cells ( 1 , 2 ). (jimmunol.org)
  • It has been proposed ( 5 , 14 - 17 ) that hypoxia activates transcription via mitochondria-dependent signaling process involving increased ROS whereas CoCl 2 activates transcription by stimulating ROS generation via a mitochondria-independent mechanism. (aacrjournals.org)
  • YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression. (nih.gov)
  • We hypothesized that glioma cells would express one of at least two different metabolic phenotypes, possibly acquired through progression. (aacrjournals.org)
  • Resistance to therapy, and tumor progression, is increased by the ability of HCC cells to resist adverse environmental conditions, such as hypoxia. (biologists.org)
  • Hypoxia and Inflammation in prostate cancer progression. (urotoday.com)
  • Because p16 neutralizes effect of HIF-1α and attenuates tumor metastatic progression, we intended to investigate whether p16 directly affects one or more aspects of the malignant process such as adhesion and migration of breast cancer cells. (jcancer.org)
  • Neural stem/progenitor cells (NSPCs) are multipotent cells within the embryonic and adult brain that give rise to both neuronal and glial cell lineages. (wiley.com)
  • Neural stem/progenitor cells (NSPCs) are multipotent cells with self-renewing capabilities. (wiley.com)
  • Endothelial progenitor cells (EPCs, defined as sca-1 + flk-1 + lin − mononuclear blood cells) contribute to vascular repair. (ahajournals.org)
  • Endothelial progenitor cells (EPCs) are of great importance in the process of endogenous blood vessel repair to maintain endothelial integrity and have been applied in a wide range of models of ischemic diseases. (ovid.com)
  • Recent reports link resistance to conventional therapies and the metastatic potential to a stem-like tumour population, termed cancer stem cells (CSCs). (nih.gov)
  • These observations and those from normal stem cell biology provide a new mechanistic explanation for the contribution of hypoxia to malignancy. (nih.gov)
  • The therapeutic significance of understanding neural stem cell biology is also underscored by a potential link with CNS cancer stem cells, which share many properties with normal adult neural stem cells (Germano et al . (wiley.com)
  • A hypoxic environment represents the physiological growing conditions of embryonic stem cells. (thefreelibrary.com)
  • Signaling through the chemokine SDF-1alpha and its receptor CXCR4 plays a critical role in the homing of stem cells to ischemia for potential use as drug-delivery vehicles. (ca.gov)
  • Yield of human adipose-derived adult stem cells from liposuction aspirates. (eurekaselect.com)
  • Stem Cells Dev. (springer.com)
  • However, in mice Trp-2 was shown to be expressed in melanocyte stem cells of the hair follicle and therefore also considered as an indicator of stemness. (uzh.ch)
  • In mice it is expressed in differentiated melanocytes as well as in stem cells. (uzh.ch)
  • BACKGROUND Neural stem cells (NSCs) represent an optimal tool for studies and therapy of neurodegenerative diseases. (semanticscholar.org)
  • We recently established a v-myc immortalized human NSC (IhNSC) line, which retains stem properties comparable to parental cells. (semanticscholar.org)
  • Hypoxia or in situ normoxia: The stem cell paradigm. (semanticscholar.org)
  • Distribution of hematopoietic stem cells in the bone marrow according to regional hypoxia. (semanticscholar.org)
  • Wang Z, Lv H, Song S, Shen X, Yang L, Yu W. Emulsified Isoflurane Preconditioning Protects Isolated Rat Kupffer Cells against Hypoxia/Reoxygenation-Induced Injury. (medsci.org)
  • Fan X, Yang Y, Qi L. Vildagliptin protects hypoxia/reoxygenation-induced injury of cardiac microvascular endothelial cells. (minervamedica.it)