Cell Hypoxia: A condition of decreased oxygen content at the cellular level.Anoxia: Relatively complete absence of oxygen in one or more tissues.Hypoxia, Brain: 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.Fetal Hypoxia: Deficient oxygenation of FETAL BLOOD.Hypoxia-Inducible Factor 1, alpha Subunit: 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.Oxygen: 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.Basic Helix-Loop-Helix Transcription Factors: A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.Fruit: The fleshy or dry ripened ovary of a plant, enclosing the seed or seeds.Oxygen Consumption: 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)Reactive Oxygen Species: 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.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Kidney Medulla: The internal portion of the kidney, consisting of striated conical masses, the renal pyramids, whose bases are adjacent to the cortex and whose apices form prominent papillae projecting into the lumen of the minor calyces.Hypoxia-Inducible Factor 1: 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.BooksPublishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.Biology: One of the BIOLOGICAL SCIENCE DISCIPLINES concerned with the origin, structure, development, growth, function, genetics, and reproduction of animals, plants, and microorganisms.Hibernation: 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.Hypothermia, Induced: 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.Hypothermia: Lower than normal body temperature, especially in warm-blooded animals.Circulatory Arrest, Deep Hypothermia Induced: 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.Sarcoplasmic Reticulum: 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.Membrane Fluidity: 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.Erythropoiesis: The production of red blood cells (ERYTHROCYTES). In humans, erythrocytes are produced by the YOLK SAC in the first trimester; by the liver in the second trimester; by the BONE MARROW in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction.Erythropoietin: Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.Astrocytes: A class of large neuroglial (macroglial) cells in the central nervous system - the largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the BLOOD-BRAIN BARRIER. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with MICROGLIA) respond to injury.Anemia: A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.Cell Line, Tumor: A cell line derived from cultured tumor cells.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Proto-Oncogene Proteins c-bcl-2: Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.bcl-2-Associated X Protein: A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.Allergy and Immunology: A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder.Access to Information: Individual's rights to obtain and use information collected or generated by others.Journal Impact Factor: A quantitative measure of the frequency on average with which articles in a journal have been cited in a given period of time.Immune System Diseases: Disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-mediated, or both.Peer Review, Research: The evaluation by experts of the quality and pertinence of research or research proposals of other experts in the same field. Peer review is used by editors in deciding which submissions warrant publication, by granting agencies to determine which proposals should be funded, and by academic institutions in tenure decisions.Aortic Valve: The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle.Calcinosis: Pathologic deposition of calcium salts in tissues.Aortic Valve Stenosis: 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.Heart Valve Diseases: Pathological conditions involving any of the various HEART VALVES and the associated structures (PAPILLARY MUSCLES and CHORDAE TENDINEAE).Hyaluronic Acid: 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.Ossification, Heterotopic: The development of bony substance in normally soft structures.Aortic Valve Insufficiency: 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).Polyploidy: The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.Cell Nucleus Size: The quantity of volume or surface area of a CELL NUCLEUS.Colonic Neoplasms: Tumors or cancer of the COLON.Cobalt: 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.Ploidies: The degree of replication of the chromosome set in the karyotype.Cell Cycle: 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.

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)

... 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.
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
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 ...
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 ...
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) ...
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.
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 ...
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...
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.
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.
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 ...
... | eDoctorOnline.com. An informative article about hypoxia discussing the History of oxygen, Oxygen cascade, Oxygen transpor
... | eDoctorOnline.com. An informative article about hypoxia discussing the History of oxygen, Oxygen cascade, Oxygen transpor
The tumor microenvironment influences both therapeutic outcome and malignant progression. In particular, tumor hypoxia has been shown to be a prognostic indicat...
Hypoxia is a feature of most tumours, albeit with variable incidence and severity within a given patient population. It is a negative prognostic and predictive factor owing to its multiple contributions to chemoresistance, radioresistance, angiogenesis, vasculogenesis, invasiveness, metastasis, resi …
This work is divided into two parts. The first is the description of the regulation of the hypoxic response pathway via small molecule inhibitors. The hypoxia response pathway is a way in which cells sense and regulate ...
Solid tumors are characterized by the presence of both oxic and hypoxic regions. The hypoxic tumor microenvironment stimulates neo-angiogenesis, and tumor growth becomes linked to the availability of vasculature-supplied oxygen and nutrients. For this reason anti-angiogenics have been a major focus of cancer drug development efforts. Recent evidence also links hypoxia, DNA damage repair and pathological angiogenesis in both tumors and proliferative retinopathies [10, 24, 25]. While there have been some spectacular clinical successes with anti-angiogenics in cancer treatment, the overall and progression-free survival rates have been disappointing [26]. Among the factors contributing to this are adaptations of cancer cells in the hypoxic tumor microenvironment that allow them to proliferate and to become more invasive and resistant to chemo- and radio-therapy. Multiple studies have tried to correlate tumor tissue pO2, distance from blood vessels, and proliferation indices in attempts to derive a ...
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
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 ...
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 ...
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 ...
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 ...
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.. ...
Hypoxia increases the proliferation of hCMPCs. hCMPCs were cultured under normoxic and hypoxic conditions for the indicated time intervals. An increase in the n
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. ...
Ditching home oxygen sure sounds like a good idea most of the time. Its inconvenient and annoying.. Over 10 years, Ive cared for more than a thousand people with low oxygen level.. One of the most common questions I am asked is, "Can you recover from low oxygen levels?". The more chronic your condition, the more likely you will be to need oxygen therapy to live a normal life.. Amazing recovery from low oxygen levels is certainly a possibility, it just wont happen without consistent effort on your part. NOTHING is impossible.. Its understandable that your focus is getting your life back to normal. You dont want to drag oxygen tanks around. In fact, you might be inclined to sit at home and wait to get better. I want to encourage you to get out there and live your life WITH your oxygen tank if you need it! (You may NEED it even if you dont think you do!). Your LIFE will becomes your exercise program when you insure safe oxygen levels while you get out there and LIVE!. If you push through your ...
BMG LABTECH have developed a new gas ramping function that can fully manipulate the environment within a microplate reader, by mimicking in vitro hypoxia and ischaemia/reperfusion. Equipped with this unique feature, the CLARIOstar® with Atmospheric Control Unit (ACU) is the first plate reader that is able to rapidly return to physiological gas conditions upon active modification of oxygen (O2) and carbon dioxide (CO2) tensions within the reader, reproducing disease-specific settin
The low oxygen concentrations that prevail in many tumors enhance their propensity to metastasize to other tissues. Researchers at Ludwig-Maximilians-...
Acute and chronic hypoxia exists within the 3D microenvironment of solid tumors and drives therapy resistance, genetic instability and metastasis. Replicating cells exposed to either severe acute hypoxia (16 h with 0.02% O2) followed by reoxygenation or moderate chronic hypoxia (72 h with 0.2% O2) treatments had decreased RAD51 protein expression and homologous recombination (HR) function. As HR defects are synthetically lethal with poly(ADP‐ribose) polymerase 1 (PARP1) inhibition, we evaluated the sensitivity of HR‐defective hypoxic cells to PARP inhibition. Although PARP inhibition did not affect HR, we observed increased clonogenic killing in HR‐deficient hypoxic cells following inhibition or siRNA depletion of PARP1. PARP1−/− MEFs showed a proliferative disadvantage and a lack of cell adaption to hypoxia when compared to PARP1+/+ MEFs. PARP‐inhibited hypoxic cells accumulated H2AX and 53BP1 foci as a consequence of altered DNA replication firing leading to S phase‐specific cell ...
Almost any of the conditions discussed in the past few sections of this chapter can cause serious degrees of bodywide cellular hypoxia. Sometimes, oxygen
Everyone requires oxygen, including a fetus in its mothers womb. A new study indicates that oxygen deprivation during the fetal stage could increase the threat of birth defects.Know more.
Researchers have fresh insight into an evolutionarily ancient way that cells cope when oxygen levels decline, according to a new study in the October 7th issue of Cell Metabolism. In studies of cells taken from the lining ...
The results of the current study showed the molecular and functional activation of β-catenin by hypoxia in HCC and showed its contribution to hypoxia-induced metastatic phenotypes. The induction of EMT was one of the proinvasive mechanisms augmented by β-catenin during hypoxia. The coexpression of β-catenin and HIF-1α (a marker of hypoxia) in HCC was found to be correlated with metastases and poor prognosis in two independent cohorts of patients. These results confirm the importance of β-catenin in HCC under hypoxic conditions.. Hypoxia plays a critical role in tumor progression (1). Consistent with our previous report (17), it not only facilitated in vitro cell invasion in HCC but also resulted in peritoneal seeding and pulmonary metastasis in an in vivo HAL model. However, the growth of HCC cells and xenografts were suppressed by hypoxia. Further analysis revealed that this could be attributed to the arrest of cell proliferation rather than the induction of apoptosis (Supplementary Fig. ...
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Scientists have examined fruit flies to discover cells that can survival low-levels of oxygen or hypoxia. They have discovered the hairy gene, that has a survival switch that helps cells and tissues to survive a low-oxygen environment. This research has implications for people suffering from diseases that involve hypoxia or tissue that has been oxygen deprived.
Research may have implications for heart disease, stroke and cancer. Scientists at the Gladstone Institutes have identified a protein that kick-starts the response to low levels of oxygen, suggesting new lines of research relevant to a variety of potentially fatal disorders associated with diminished oxygen supply, including cancer, heart disease, stroke and other neurological conditions that affect millions of people worldwide.. In a paper being published today in Molecular Cell, the laboratory of Gladstone Associate Investigator Katerina Akassoglou, PhD, maps out the chain of events that take place during hypoxia. Hypoxia is a condition that can occur in people with diseases such as heart disease and stroke. It deprives tissues and organs of an adequate oxygen supply.. "This discovery provides a novel understanding of the steps by which cells normally respond to hypoxia, a fundamental biological process that is implicated in many medical conditions," said Dr. Akassoglou, whose research at ...
Supplementary MaterialsSupplementary Statistics. while treatment with particular inhibitors indicated that hypoxia upregulates HBEGF biosynthesis through anybody from the three analyzed MAPKs.2, 3 However, it had been unclear whether this MAPK pathway was functional or downstream of HBEGF shedding upstream. As a result, MMP2 was quantified in individual TB cells cultured at 2% O2 with particular inhibitors of ERK, jNK and p38. These inhibitors didnt impact the upregulation of MMP2 at low O2, recommending which the MAPKs function solely downstream of HBEGF signaling through the ERBB1/4 tyrosine kinases in individual TB cells, as indicated in Amount 9. Although both MMP2 and HBEGF post-transcriptionally are governed by O2, HBEGF upregulation by low O2 or CoCl2 was obstructed by reported that serum degrees of HSP70 are continuous throughout normal being pregnant, but upsurge in women with preeclampsia or preterm PRI-724 irreversible inhibition delivery significantly.49 Elevated circulating HSP70 ...
COMMD1 is the founding member of a family of 10 conserved factors present in most eukaryotic organisms. At the present time, very little is known about the functions of other family members, and we have a long-standing interest in identifying cellular functions for these factors and defining common molecular mechanisms of action for these molecules.. These studies have identified that besides its role in the NF-κB pathway, COMMD1 can regulate other critical cellular pathways. In particular, we have defined a role for this factor as a negative regulator of the hypoxia inducible factor (HIF), a transcriptional master regulator of the hypoxic response. As such, COMMD1 is involved in critical processes linked to HIF, such as tumor adaptation to hypoxia and the control of local invasion and metastasis. In the future, we are interested in using animal models to better define if COMMD1 can be a targetable molecule for the treatment of invasive cancer.. In addition, we have been investigating whether ...
The immunoreactivity of hypoxia inducible factor 1 alpha (HIF-1 alpha) has been considered a reliable indicator of the HIF-1 pathway activation in tissue hypoxia. However, HIF-1 alpha immunoreactivity has been evaluated ...
Methods and compositions relating to chimeric genes containing (i) a tissue-specific promoter and (ii) a hypoxia response enhancer element, both of which are operably linked to a selected gene, such a
The fact ventilation should just happen whenever sunlight are at of creating energy by means of Adenosine Triphosphate, or ATP. Hypoxia can cause tach...
Cutaneous brest cancer deposits show distinct growth patterns with different degrees of angiogenesis, hypoxia and fibrin deposition ...
Hypoxemia and/or hypoxia is a condition in which there is a deficiency of oxygen reaching the tissues. Know about the symptoms, causes, prevention and treatment.
Purpose: The purpose of this Web site is to provide members of the Hypoxia Advisory Panel (HAP) and the three HAP subgroups with access to the document references that are the most relevant to facilitate their research to address the charge to the Panel ...
BioSpherixs Animal A-Chambers and Gas Controllers provide highly reproducible conditions with O2, CO2, NO, CO, and O3, using Animal Isolation Chambers designed to provide controlled, isolated environments for animal modeling in the following areas:. ...
The tempo and extent of his mental status changes and hypoxia prompt you to place a definitive airway. Regarding optimization of his oxygenation and ventilation status, which of the following may be beneficial ...
b) all Iraqi petroleum and petroleum products, and interests therein, and proceeds, obligations, or any financial instruments of any nature whatsoever arising from or related to the sale or marketing thereof, and interests therein, in which any foreign country or a national thereof has any interest, that are in the United States, that hereafter come within the United States, or that are or hereafter come within the possession or control of United Statespersons. ...
Purpose of Study This exploratory clinical study will investigate FMISO (fluoromisonidazole) in patients with (1) newly diagnosed primary malignant brain tumors (WHO [World Health Organization] Grade III or IV glial-based tumors) who have not had a complete surgical resection and by contrast MRI (Magnetic resonance imaging) have residual tumor > 1.0 cm in diameter and will be receiving radiotherapy or (2) newly diagnosed brain metastasis (> 1.0 cm in diameter who will be receiving radiotherapy. The ability to accurately assess tumor hypoxia and accurately determine the amount/degree of tumor hypoxia could potentially change patient management once validated as tumor hypoxia is known to be associated with a poor prognosis [Eyler 2008].
The inhibition of voltage-gated potassium channels (Kv) plays a significant role in the cerebral hypoxia-induced cell death. of cerebral hypoxia. In conclusion AA/15-LOX/15-HETE induces vasoconstriction by down-regulating Kv channels and Kv2.1/1.5 channels are the targets. Our study also suggests a therapeutic strategy to improve ischemic vascular occlusion by lowering 15-HETE level and preventing Kv channel down-regulation which makes 15-LOX as a new target for the treatment of cerebral hypoxia. Keywords: 15-lipoxygenase (15-LOX) 15 acid (15-HETE) hypoxia Kv1.5 Kv2.1 Introduction Cerebral vascular disease is MP470 one of diseases with high morbidity and mortality 75 of which is caused by ischemic cerebrovascular. Hypoxia-induced vascular constriction was an important pathogenesis which could lead to cell death in cerebral ischemia [1 2 However the underlying mechanism is still unknown and the treatment could not accomplish the desired effect. In recent years hypoxia inhibits voltage-gated ...
Studies investigating the oxygenation status and the development of hypoxia in microscopic tumors are sparse. The purpose of this study was to measure the extent of hypoxia in microscopic melanoma xenografts and to search for possible mechanisms leading to the development of hypoxia in these tumors. A-07, D-12, R-18, and U-25 human melanoma xenografts grown in dorsal window chambers or as flank tumors were used as preclinical tumor models. Morphologic and functional parameters of vascular networks were assessed with intravital microscopy, and the expression of angiogenesis-related genes was assessed with quantitative PCR. Microvessels, pericytes, and the extent of hypoxia were assessed by immunohistochemistry in microscopic tumors by using CD31, αSMA, and pimonidazole as markers, and the extent of radiobiological hypoxia was assessed in macroscopic flank tumors. Macroscopic R-18 and U-25 tumors showed extensive hypoxia, whereas macroscopic A-07 and D-12 tumors were less hypoxic. R-18 and U-25 tumors
Glioma growth is often accompanied by a hypoxic microenvironment favorable for the induction and maintenance of the glioma stem cell (GSC) phenotype. Due to the paucity of cell models of Isocitrate Dehydrogenase 1 mutant (IDH1mut) GSCs, biology under hypoxic conditions has not been sufficiently studied as compared to IDH1 wildtype (IDH1wt) GSCs. We therefore grew well-characterized IDH1mut (n = 4) and IDH1wt (n = 4) GSC lines under normoxic (20%) and hypoxic (1.5%) culture conditions and harvested mRNA after 72 h. Transcriptome analyses were performed and hypoxia regulated genes were further analyzed using the expression and clinical data of the lower grade glioma cohort of The Cancer Genome Atlas (LGG TCGA) in a confirmatory approach and to test for possible survival associations. Results show that global expression changes were more pronounced in IDH1wt than in IDH1mut GSCs. However, when focusing on known hypoxia-regulated gene sets, enrichment analyses showed a comparable regulation in both IDH1mut
Non-small-cell lung carcinoma (NSCLC) accounts for 85% of malignant lung tumors and is the leading cause of cancer deaths. Our group previously identified Tripartite Motif 14 (TRIM14) as a component of a prognostic multigene expression signature for NSCLC. Little is known about the function of TRIM14 protein in normal or disease states. We investigated the functional and prognostic role of TRIM14 in NSCLC using in vitro and in vivo perturbation model systems. Firstly, a pooled RNAi screen identified TRIM14 to effect cell proliferation/survival in NSCLC cells. Secondly, silencing of TRIM14 expression significantly enhanced tumor growth in NSCLC xenograft mouse models, while exogenous TRIM14 expression attenuated tumorigenesis. In addition, differences in apoptotic activity between TRIM14-deficient and control tumors suggests that TRIM14 tumor suppressor activity may depend on cell death signaling pathways. TRIM14-deficient cell lines showed both resistance to hypoxia-induced cell death and ...
Video articles in JoVE about hypoxia inducible factor 1 include Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis, Quantification of Neurovascular Protection Following Repetitive Hypoxic Preconditioning and Transient Middle Cerebral Artery Occlusion in Mice, Quantitative Analysis of Chromatin Proteomes in Disease, Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina, Anaerobic Growth and Maintenance of Mammalian Cell Lines, Isolation of Cerebral Capillaries from Fresh Human Brain Tissue, Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions, Induction of Hypoxia in Living Frog and Zebrafish Embryos, A Mouse Distraction Osteogenesis Model, Human Primary Trophoblast Cell Culture Model to Study the Protective Effects of Melatonin Against Hypoxia/reoxygenation-induced Disruption, Heterotopic Renal
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 ...
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. ...
... 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 ...
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. ...
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. ...
2000). "Hypoxia induces the expression of a 43-kDa protein (PROXY-1) in normal and malignant cells". Biochem. Biophys. Res. ... 2002). "Enhanced overexpression of an HIF-1/hypoxia-related protein in cancer cells". Environ. Health Perspect. 110 Suppl 5: ... 2002). "Enhanced expression of a novel protein in human cancer cells: a potential aid to cancer diagnosis". Cell Biol. Toxicol ... Cell Biol. 118 (5): 399-408. doi:10.1007/s00418-002-0460-9. PMID 12432451. Strausberg RL, Feingold EA, Grouse LH, et al. (2003 ...
"Mechanisms by which hypoxia augments Leydig cell viability and differentiated cell function in vitro". Digital Library and ... "Cell. 159 (2): 295-305. doi:10.1016/j.cell.2014.09.020. PMC 4206218 . PMID 25303526. Lay summary - SciGuru Science News.. ... The magnocellular neurosecretory cells that make oxytocin are adjacent to magnocellular neurosecretory cells that make ... The Leydig cells in some species have been shown to possess the biosynthetic machinery to manufacture testicular oxytocin de ...
Deng CX, Sieling F, Pan H, Cui J. Ultrasound-induced cell membrane porosity. Ultrasound Med Biol 2004 Apr;30(4):519-26. Li ML, ... Simultaneous molecular and hypoxia imaging of brain tumors in vivo using spectroscopic photoacoustic tomography. Proc IEEE 2008 ... Because of its real-time nature, micro-ultrasound can also guide micro-injections of drugs, stem cells, etc. into small animals ... Imaging modalities have long been crucial to the researcher in observing changes, either at the organ, tissue, cell, or ...
Activation of hypoxia-inducible factor-1 regulates human histidine decarboxylase expression.. Cell. Mol. Life Sci. 2009, 66 (7 ... Expression of non-mast cell histidine decarboxylase in tumor-associated microvessels in human esophageal squamous cell ... cell soma. 生物过程. · carboxylic acid metabolic process. · catecholamine biosynthetic process. · histamine metabolic process. · ... Detection of histidine decarboxylase mRNA in human vascular smooth muscle and endothelial cells.. Inflamm. Res. 2004, 53 (6): ...
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 ...
Targeting double-stranded breaks increases the probability that cells will undergo cell death. Cancer cells are generally less ... Harrison LB, Chadha M, Hill RJ, Hu K, Shasha D (2002). "Impact of tumor hypoxia and anemia on radiation therapy outcomes". The ... 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 ...
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 ...
... 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. PMC 84780 . PMID 10523647. Yang X, Chen Y, Gabuzda D (September 1999). "ERK MAP kinase links ...
response to hypoxia (en) positive regulation of cell proliferation (en) erythropoietin-mediated signaling pathway (en) ... response to hypoxia (en) negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress (en) ... negative regulation of myeloid cell apoptotic process (en) activation of protein kinase activity (en) embryo implantation (en) ... positive regulation of cell proliferation (en) regulation of transcription from RNA polymerase II promoter in response to ...
"Hypoxia increases corneal cell expression of CFTR leading to increased Pseudomonas aeruginosa binding, internalization, and ... Zhivov A, Stave J, Vollmar B, Guthoff R (January 2007). "In vivo confocal microscopic evaluation of langerhans cell density and ... A lens hindering passage of oxygen to the cornea causes corneal hypoxia which can result in serious complications, such as ... One group of researchers showed that corneal hypoxia exacerbated Pseudomonas binding to the corneal epithelium, internalization ...
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 ...
Cell. Biol. 17 (9): 4933-47. doi:10.1128/mcb.17.9.4933. PMC 232345 . PMID 9271372. Haase VH (2006). "Hypoxia-inducible factors ... Cell. Biol. 13 (4): 2504-14. PMC 359572 . PMID 8384309. Jiang BH, Rue E, Wang GL, Roe R, Semenza GL (1996). "Dimerization, DNA ... Cell. Biol. 24 (2): 608-16. doi:10.1128/mcb.24.2.608-616.2004. PMC 343817 . PMID 14701734. Moffett P, Reece M, Pelletier J ( ... Cell. Biol. 16 (10): 5865-75. PMC 231588 . PMID 8927054. Swanson HI, Yang Jh (1997). "Mapping the protein/DNA contact sites of ...
The resulting compound, TH-281, had a high HCR (hypoxia cytotoxicity ratio), a quantitative assessment of its hypoxia ... This renders cells unable to replicable their DNA and divide, leading to apoptosis. This investigational therapeutic approach ... In areas of hypoxia, evofosfamide becomes activated and converts to an alkylating cytotoxic agent resulting in DNA cross- ... The prodrug is activated only at very low levels of oxygen (hypoxia). Such levels are common in human solid tumors, a ...
It therefore, causes nutrient and hypoxic stress (or a state of hypoxia). In this regard, cancer cells and stromal cells can ... Semenza, G.L. (2012). "Hypoxia-inducible factors in physiology and medicine". Cell. 148 (3): 399-408. doi:10.1016/j.cell. ... 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 ...
... 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 ... "Lowered oxygen tension induces expression of the hypoxia marker MN/carbonic anhydrase IX in the absence of hypoxia-inducible ... "Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau ...
... 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: 399-408. "Home - EST - NCBI ... 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 ...
... 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 ...
Red blood cells will be less able to nurture organs with oxygen. Therefore, the probability for a hypoxia increases. ... Calcium will enter the cell and the cell membrane will be depolarised. Depolarisation of the membrane will result in the ... CGRP binding to its receptor will also promote mast cell degranulation and infiltration by neutrophils and other immune cells. ... The increase in immune cells and its inflammatory response is thought to be the main cause of the occurrence of migraine. Its ...
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 ...
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 ...
... such as programmed cell death, inflammation and/or stem cell modulation. Herein we analyze the role of hypoxia and ROS in the ... Modulation of neuronal stem cell differentiation by hypoxia and reactive oxygen species.. Vieira HL1, Alves PM, Vercelli A. ... in vitro neuronal differentiation from neural stem/precursor cells. In vivo, hypoxia promotes neurogenesis in embryos, newborns ... such as in cell replacement or in malignant cell proliferation. ... Therefore, manipulating hypoxia and ROS production represents a ...
Cancer stem cells (CSCs), also known as cancer initiating cells or tumor propagation cells, are neoplastic cells that could ... Hypoxia has been shown to help maintain multiple normal stem cell population but its roles in cancer stem cells were largely ... Hypoxia and hypoxia inducible factors in cancer stem cell maintenance.. Li Z1, Rich JN. ... The effects of hypoxia on cancer stem cells seem to be primarily mediated by HIFs, particularly HIF2α. HIF2α is highly ...
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 ...
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 ...
Cell-to-cell heterogeneity in gene transcription plays a central role in a variety of vital cell processes. To quantify gene ... Quantitative single-cell gene expression measurements of multiple genes in response to hypoxia treatment.. Zeng J1, Wang J, Gao ... We applied the method to cell populations exposed to hypoxia, quantifying expression levels of seven different genes spanning a ... The method features a two-step procedure consisting of a step to isolate RNA from a single mammalian cell, synthesize cDNA from ...
... 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 ...
... whether and how hypoxia regulates cancer cell differentiation and maintains cancer cell stemness. Here, we show that hypoxia ... Reduced oxygenation, or hypoxia, inhibits differentiation and facilitates stem cell maintenance. Hypoxia commonly occurs in ... Cells were cultured for 16 h at 1% (hypoxia, H) or 21% O2 (N). C, ChIP using @HIF-1α or @HIF-2α antibodies. BE(2)C cells were ... Hypoxia-regulated delta-like 1 homologue enhances cancer cell stemness and tumorigenicity.. Kim Y1, Lin Q, Zelterman D, Yun Z. ...
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 ...
... 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 ...
Systemic control of immune cell development by integrated carbon dioxide and hypoxia chemosensation in Drosophila.. Cho B1, ... Systemic control of immune cell development by integrated carbon dioxide and hypoxia chemosensation in Drosophila ... Systemic control of immune cell development by integrated carbon dioxide and hypoxia chemosensation in Drosophila ... Systemic control of immune cell development by integrated carbon dioxide and hypoxia chemosensation in Drosophila ...
The glial cell response is an essential component of hypoxia-induced erythropoiesis in mice. ... The glial cell response is an essential component of hypoxia-induced erythropoiesis in mice. ... To investigate the role of glial cells as a component of the systemic response to hypoxia, we created astrocyte-specific ... However, both neurons and astrocytes (the largest subpopulation of glial cells in the CNS) also express EPO following ischemic ...
In HepG2 cells that are strongly protected against cell death by hypoxia, hypoxia decreased the abundance of nearly all the pro ... Moreover, according to the cell lines, hypoxia differently influences cell death. The study of the effects of hypoxia on the ... BIM and NOXA are important mediators of etoposide-induced cell death in HepG2 cells and the hypoxia-induced modification of ... A better understanding of these cell-to-cell variations is crucial in order to overcome hypoxia-induced resistance and to ...
As a result of deprivation of oxygen (hypoxia) and nutrients, the growth and viability of cells is reduced. Hypoxia-inducible ... Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis.. Carmeliet P1, Dor Y, Herbert JM ... We find that hypoxia/hypoglycaemia-regulated genes involved in controlling the cell cycle are either HIF-1alpha-dependent ( ... cells, but not in ES cells with inactivated HIF-1alpha genes (HIF-1alpha-/-); however, a deficiency of HIF-1alpha does not ...
Oxygen-dependent expression of hypoxia-inducible factor-1alpha in renal medullary cells of rats.. Zou AP1, Yang ZZ, Li PL, ... Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that regulates the oxygen-dependent expression of a ... Increased abundance of HIF-1alpha mRNA in the renal medulla may represent an adaptive response of renal medullary cells to low ... This transcription factor may contribute to the abundant expression of many genes in renal medullary cells that function ...
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. ...
Hypoxia occurs naturally at high-altitudes and pathologically in hypoxic solid tumors. Here, we report that genes involved in ... YTHDF1 Links Hypoxia Adaptation and Non-Small Cell Lung Cancer Progression Nat Commun. 2019 Oct 25;10(1):4892. doi: 10.1038/ ... including non-small cell lung cancer (NSCLC). We show that YTHDF1 deficiency inhibits NSCLC cell proliferation and xenograft ... Hypoxia occurs naturally at high-altitudes and pathologically in hypoxic solid tumors. Here, we report that genes involved in ...
Inhibition of Caveolae Contributes to Propofol Preconditioning-Suppressed Microvesicles Release and Cell Injury by Hypoxia- ... Recent evidence has indicated EMVs and caveolae may have functional effects in cells undergoing H/R injury. Propofol, a widely ... EMVs released from H/R-treated cells caused a substantially increased mitochondrial and cellular damage to normal HUVECs after ... Endothelial microvesicles (EMVs), released after endothelial cell (EC) apoptosis or activation, may carry many adverse signals ...
Hypoxia made the cells more resistant to all drugs. Moreover, our results reveal that long time cell exposure to hypoxia ... Beyond the Limits of Oxygen: Effects of Hypoxia in a Hormone-Independent Prostate Cancer Cell Line. A. C. Mamede,1,2,3 A. M. ... The hypoxia effect on drug resistance to these drugs, as well as cell proliferation and migration, will be also analyzed. All ... Hypoxia can influence cellular resistance, proliferation, and migration. This study shows that hypoxia may be a key factor in ...
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 ...
  • 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)
  • Quantitative single-cell gene expression measurements of multiple genes in response to hypoxia treatment. (nih.gov)
  • We report an experimental technique based on the DNA-intercalating fluorescent dye SYBR green for quantitative expression level analysis of up to ten selected genes in single mammalian cells. (nih.gov)
  • We applied the method to cell populations exposed to hypoxia, quantifying expression levels of seven different genes spanning a wide dynamic range of expression in randomly picked single cells. (nih.gov)
  • In the experiment, 72 single Barrett's esophageal epithelial (CP-A) cells, 36 grown under normal physiological conditions (controls) and 36 exposed to hypoxia for 30 min, were randomly collected and used for measuring the expression levels of 28S rRNA, PRKAA1, GAPDH, Angptl4, MT3, PTGES, and VEGFA genes. (nih.gov)
  • 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)
  • 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)
  • To investigate the role of glial cells as a component of the systemic response to hypoxia, we created astrocyte-specific deletions of the murine genes encoding the hypoxia-inducible transcription factors HIF-1α and HIF-2α and their negative regulator von Hippel-Lindau (VHL) as well as astrocyte-specific deletion of the HIF target gene Vegf. (jci.org)
  • 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)
  • This transcription factor may contribute to the abundant expression of many genes in renal medullary cells that function normally under hypoxic conditions. (nih.gov)
  • 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)
  • To evaluate the effect of hypoxia-inducible factor-1alpha (HIF-1alpha) over-expression on the invasion-associated proteins in human prostate cancer cells, as HIF-1alpha is a transcriptional factor that could activate genes involved in the response to hypoxia, but might also enhance the invasive potency of prostate cancer cells. (nih.gov)
  • To conclude, the present study underlines the significance of NF- κ B and HIF-1 α and their target genes VEGF, IL-1 β , and MMP-1 in P. gingivalis and hypoxia induced periodontal inflammatory processes. (hindawi.com)
  • 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)
  • The expression of homologous recombination (HR) and non-homologous recombination (NHEJ) genes following gas hypoxia (0.2%) or exposure to HIF1alpha-inducing agent, CoCl2 (100 microM), was determined for normal diploid fibroblasts (GM05757) and the pre-malignant and malignant prostate cell lines, BPH-1, 22RV-1, DU145 and PC3. (nih.gov)
  • Hypoxia (48-72 h of 0.2% O2) decreased RNA expression of a number of HR-related genes (e.g. (nih.gov)
  • Hypoxia can down-regulate expression of DNA-dsb repair genes in both normal and cancer cells. (nih.gov)
  • The attenuation of HIF by PKG reflected a more fundamental inhibition of the hypoxic response, which was supported by the ability of PKG expression to block the hypoxia-induced activation of glycolytic genes including enolase and hexokinase 2. (aacrjournals.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)
  • Human NSCLC cell lines A549 and HCC2935 were exposed to hypoxia to investigate the expression of EMT-related genes and phenotypes. (sigmaaldrich.com)
  • 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)
  • Using bioinformatic analysis, hypoxiainducible factor (HIF)‑1α was identified as one of the target genes of miR‑18a, and based on the function of HIF‑1α in hypoxia, miR‑18a was predicted to regulate HIF‑1α expression. (spandidos-publications.com)
  • 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)
  • 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)
  • Depletion of mAKAP or disruption of its targeting to the perinuclear (in cardiomyocytes) region altered the stability of HIF-1 and transcriptional activation of genes associated with hypoxia. (wikipedia.org)
  • however, under hypoxia, HIF1A protein degradation is prevented and HIF1A levels accumulate to associate with HIF1B to exert transcriptional roles on target genes Enzymes prolyl hydroxylase (PHD) and HIF prolyl hydroxylase (HPH) are involved in specific post-translational modification of HIF1A proline residues (P402 and P564 within the ODD domain), which allows for VHL association with HIF1A. (wikipedia.org)
  • They form characteristic cell clusters in suspension culture that express a set of genes associated with pluripotency and can differentiate into endodermal, ectodermal and mesodermal cells both in vitro and in vivo. (wikipedia.org)
  • Stem cell markers are genes and their protein products used by scientists to isolate and identify stem cells. (wikipedia.org)
  • Below is a list of genes/protein products that can be used to identify various types of stem cells, or functional assays that do the same. (wikipedia.org)
  • HIF-1α is a ubiquitous, constitutively synthesized transcription factor responsible for upregulating the expression of genes involved in the cellular response to hypoxia. (wikipedia.org)
  • Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. (wikipedia.org)
  • The murine double minute (mdm2) oncogene, which codes for the Mdm2 protein, was originally cloned, along with two other genes (mdm1 and mdm3) from the transformed mouse cell line 3T3-DM. (wikipedia.org)
  • The expression 'pattern' of genes related to pluripotency in Muse cells was almost the same as that in ES and iPS cells, while the expression 'level' was much higher in ES and iPS cells and that in Muse cells. (wikipedia.org)
  • In contrast, genes related to cell cycle progression and tumorigenicity in Muse cells were at the same level as those in somatic cells, while the same genes were very high in ES and iPS cells. (wikipedia.org)
  • MTA3-NuRD complex and downstream targets have been shown to participate in primitive hematopoietic and angiogenesis in a zebrafish model system As a part of BCL6 corepressor complex, MTA3 regulates BCL6-dependent repression of target genes, including PRDM1, and modulates the differentiation of B-cells. (wikipedia.org)
  • The β-elemene - a traditional Chinese medicine, upregulates MTA3's expression in breast cancer cells The MTA3-NuRD complex represses Snail, a master regulator of epithelial-to-mesenchymal transition (EMT), Wnt4 expression in mammary epithelial cells, and BCL6-corepressor target genes The MTA3-NuRD complex interacts with GATA3 to regulate the expression of GATA3 downstream targets. (wikipedia.org)
  • Defects in its genes result in less control of cell growth and may cause tuberous sclerosis or tuberous sclerosis complex (TSC). (wikipedia.org)
  • When Ras is 'switched on' by incoming signals, it subsequently switches on other proteins, which ultimately turn on genes involved in cell growth, differentiation and survival. (wikipedia.org)
  • In 1982, activated and transforming human ras genes were discovered in human cancer cells by Geoffrey M. Cooper at Harvard, Mariano Barbacid and Stuart A. Aaronson at the NIH, Robert Weinberg at MIT, and Michael Wigler at Cold Spring Harbor Laboratory. (wikipedia.org)
  • This cascade transmits signals downstream and results in the transcription of genes involved in cell growth and division. (wikipedia.org)
  • Metallothioenein-1 and Metallothioenein-2 genes, which protect cells against cytotoxicity induced by toxic metals, are also direct targets of Nfe2l1. (wikipedia.org)
  • Brains of mice with conditional knockout of Nfe2l1 in neuronal cells showed decreased proteasome activity and accumulation of ubiquitin-conjugated proteins, and down regulation of genes encoding the 20S core and 19S regulatory sub-complexes of the 26S proteasome. (wikipedia.org)
  • Re-establishment of Nfe2l1 function in Nfe2l1 null cells rescued proteasome expression and function, indicating Nfe2l1 was necessary for induction of proteasome genes (bounce-back response) in response to proteasome inhibition. (wikipedia.org)
  • This compensatory up-regulation of proteasome genes in response to proteasome inhibition has also been demonstrated to be Nfe2l1-dependent in various other cell types. (wikipedia.org)
  • 2009 ) found that autophagy was a protective way to participate in HCC chemotherapy resistance under hypoxic conditions, and chemotherapy induced-cell death in hypoxia was less than that in normoxia. (springer.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)
  • While HD NK cell cytolytic abilities were markedly and significantly impaired under hypoxic conditions, haNK cells maintained killing capacity under hypoxic conditions. (nih.gov)
  • IL-2 has been previously implicated in serial killing and perforin regeneration and thus the endogenous IL-2 produced by haNK cells is likely a driver of the maintained killing capacity of haNK cells under hypoxic conditions. (nih.gov)
  • Excess BMP-2 is also linked with production of brown fat cells that stimulate hypoxic conditions in heterotopic ossification. (ahajournals.org)
  • The U251, U87, T98G, LN18 or D54 glioma cells were either grown under normoxic or hypoxic conditions for 1 week. (plos.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)
  • 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)
  • Based on a previous finding that endothelial cell-specific molecule-1 (ESM-1) is a potential serum marker for colorectal cancer (CRC), the aim of this study was to clarify the clinicopathological significance of ESM-1 expression in CRC, and to explore the correlation between ESM-1 and HIF-1α in the tumorigenesis of CRC related to hypoxic conditions. (nih.gov)
  • This study investigated the phenotype and contractility of adipose-derived stem cells differentiated toward the smooth myogenic lineage under hypoxic conditions. (mdpi.com)
  • 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)
  • The reduced levels of glycolytic enzymes in PKG-expressing cells relative to control cells was associated with reduced glycolysis, mitochondrial activity, and cellular ATP levels under hypoxic conditions. (aacrjournals.org)
  • Human choriocarcinoma cell line JAR was cultured for 24 hours under aerobic and hypoxic conditions. (medsci.org)
  • Recent reports demonstrated the increased motility of human mesenchymal stem cells (hMSC) grown under hypoxic conditions compared to normoxic cells. (7thspace.com)
  • In the present study, miR‑18a expression was revealed to be markedly downregulated under hypoxic conditions in MGC‑803 and HGC‑27 gastric carcinoma cell lines. (spandidos-publications.com)
  • We identified both common and unique gene expression signatures across different cells lines, with hypoxic conditions activating HIF1 signaling, whereas hydrostatic pressure resulted in restricted signatures of high clinical value. (aacrjournals.org)
  • Transferrin receptor (TfR1) and divalent metal transporter 1 (DMT1) are important proteins for cellular iron uptake, and both are regulated transcriptionally through the binding of hypoxia-inducible factor 1 (HIF-1) to hypoxia-responsive elements (HREs) under hypoxic conditions. (sigmaaldrich.com)
  • While HIF is mostly active in hypoxic conditions, VHL-defective renal carcinoma cells show constitutive activation of HIF even in oxygenated environments. (wikipedia.org)
  • In normal cells in hypoxic conditions, HIF1A is activated with little activation of HIF2A. (wikipedia.org)
  • DTCs were detected using immunocytochemistry, the level of tumor hypoxia using NMR spectroscopy, CD68, CD34, VEGF, and VEGFR-1 (Flt-1) expression using immunohistochemistry, and MMP-2 and MMP-9 activity using zymography. (hindawi.com)
  • We detected time-dependent additive effects of LPS-PG and hypoxia on NF- κ B and HIF-1 α activation in PDL cells followed by an upregulation of IL-1 β , MMP-1, and VEGF expression. (hindawi.com)
  • Induction of hypoxia was confirmed using HIF1alpha and VEGF expression in gas- and CoCl2-treated cultures. (nih.gov)
  • CXCR4 expression in tumor was positively correlated with hypoxia level and VEGF expression in tumor as well as OS. (hindawi.com)
  • Sevoflurane attenuate hypoxia-induced VEGF level in tongue squamous cell carcinoma cell by upregulating the DNA methylation states of the promoter region. (sigmaaldrich.com)
  • Results showed that sevoflurane attenuated the hypoxia-induced VEGF level without altering the HIF-1α after exposure for 24 and 72 h. (sigmaaldrich.com)
  • The attenuation effect of sevoflurane on hypoxia-induced VEGF level could be blocked by 5-Aza. (sigmaaldrich.com)
  • We concluded that sevoflurane attenuates hypoxia-induced VEGF level via DNA methylation of the promoter region in TSCC cell. (sigmaaldrich.com)
  • 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)
  • 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)
  • From these microregional distributions, it was deduced that VEGF mRNA and HIF-1 are induced by hypoxia in human gliomas. (aacrjournals.org)
  • For example, skin fibroblasts that were cultured in 3D collagen matrices at high densities generated hypoxia within the matrix core, which led to an upregulation of VEGF expression. (wikipedia.org)
  • VEGF, TSP-1) undergoes temporal changes in response to hypoxia which are not linear, due to habituation of the cellular response to stress stimulation. (wikipedia.org)
  • In addition, in the nasopharyngeal carcinoma cell line, miR-20a and miR-20b has been shown to target the 3' UTR of vascular endothelial growth factor (VEGF) and repress the expression of VEGF, which is an important angiogenic factor. (wikipedia.org)
  • The hypoxic environment stimulates muscle cells in the surrounding tissue to upregulate and secrete angiogenic cytokines, such as vascular endothelial growth factor (VEGF). (wikipedia.org)
  • VEGF expression is detected surrounding the nurse cell immediately after nurse cell formation, and the continued secretion of VEGF can maintain the constant state of hypoxia. (wikipedia.org)
  • ROCK1 acts as a negative regulator of VEGF endothelial cell activation and angiogensis. (wikipedia.org)
  • VEGF has been indicated to stimulate sprouting and tip branching in endothelial cells, leading to defective endothelial monolayers. (wikipedia.org)
  • Activity of VEGF-A, as its name implies, has been studied mostly on cells of the vascular endothelium, although it does have effects on a number of other cell types (e.g., stimulation monocyte/macrophage migration, neurons, cancer cells, kidney epithelial cells). (wikipedia.org)
  • In addition, inclusion or exclusion of exons 6 and 7 mediate interactions with heparan sulfate proteoglycans (HSPGs) and neuropilin co-receptors on the cell surface, enhancing their ability to bind and activate the VEGF receptors (VEGFRs). (wikipedia.org)
  • All members of the VEGF family stimulate cellular responses by binding to tyrosine kinase receptors (the VEGFRs) on the cell surface, causing them to dimerize and become activated through transphosphorylation, although to different sites, times, and extents. (wikipedia.org)
  • To quantify gene expression heterogeneity patterns among cells and to determine their biological significance, methods to measure gene expression levels at the single-cell level are highly needed. (nih.gov)
  • The results demonstrate that the method is sensitive enough to measure alterations in gene expression at the single-cell level, clearly showing heterogeneity within a cell population. (nih.gov)
  • We expect the advantages of this technique will facilitate further developments and advances in the field of single-cell gene expression profiling on a nanotechnological scale, and eventually as a tool for future point-of-care medical applications. (nih.gov)
  • 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)
  • 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)
  • I compared the metabolic phenotypes of the prostate cancer cell lines LNCaP, DU145, and PC3 assessing energy metabolism, and metabolic gene expression. (queensu.ca)
  • Gene expression analysis was performed by quantitative real-time PCR and cell phenotypes were studied by morphology assessment, scratch wound assay, and immunofluorescence. (sigmaaldrich.com)
  • 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)
  • In mammals, the hypoxia-dependent changes, on a gene expression level, are primarily mediated by the α-subunits of hypoxia-inducible transcription factors (HIFs). (spandidos-publications.com)
  • During malignant transformation, cells undergo stages of gene expression reprogramming and mutagenesis that alter their metabolic phenotype(s) ( 1 - 5 ). (frontiersin.org)
  • First, we studied how hypoxia with or without pressure influences cell biology and gene expression, using transcriptome profiling across a range of physiologically-relevant culturing conditions to mimic various tumor microenvironments found within the body. (aacrjournals.org)
  • Aside from this, intermittent hypoxia also alters overall nitric oxide production, concentration, and gene expression, which occurs due to cardiovascular adaptations to hypoxia. (wikipedia.org)
  • The GATA family of transcription factors, which contain zinc fingers in their DNA binding domain, have emerged as candidate regulators of gene expression in hematopoietic cells. (wikipedia.org)
  • A year later, Choi showed that blast cells derived from embryonic stem (ES) cells displayed common gene expression of both hematopoietic and endothelial precursors. (wikipedia.org)
  • These gene expression pattern and level may explain why Muse cells are pluripotent but without tumorigenic activity. (wikipedia.org)
  • Genomic and proteomic analyzes were done to determine the effect of hypoxia on the expression of factors important to NK cell function. (nih.gov)
  • 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)
  • The effect of hypoxia on small-conductance Ca 2+ -activated K + current was investigated in a study of adult rat adrenomedullary chromaffin cells (AMCs), which were maintained in short-term culture. (springer.com)
  • The nystatin-perforated, whole-cell patchclamp technique was used to study the effect of hypoxia with minimum perturbation of the intracellular milieu. (springer.com)
  • 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 . (thefreelibrary.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)
  • 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)
  • 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)
  • 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)
  • Here, we investigated in mice the mechanisms underlying CR-mediated protection against hypoxia in aged kidney, with a special focus on the role of the NAD-dependent deacetylase sirtuin 1 (Sirt1), which is linked to CR-related longevity in model organisms, on mitochondrial autophagy. (jci.org)
  • The protective actions of tanshinones on hypoxia-induced cell damages have been reported, although the mechanisms have not been fully elucidated. (hindawi.com)
  • Hypoxia causes changes of various cellular mechanisms related to mitochondrial dysfunction and oxidative stress [ 2 ]. (hindawi.com)
  • Understanding the relationship of these factors may help to interpret the mechanisms of cellular injury in hypoxia condition [ 9 , 10 ]. (hindawi.com)
  • Accumulating evidence suggests that dysregulation of hypoxia-regulated transcriptional mechanisms is involved in development of chronic kidney diseases (CKD). (nih.gov)
  • Together, these findings confirm the important role of Ssd in the chemoresistance of liver cancer, provide some data support for further understanding the molecular mechanisms of Ssd inhibition of malignant transformation of HCC cells, and provide a new perspective for the application of traditional Chinese medicine in the chemical resistance of liver cancer. (frontiersin.org)
  • Intermittent hypoxia-induced LTF has also been demonstrated in carotid denervated rats, suggesting that synaptic plasticity due to intermittent hypoxia also works through other mechanisms outside of carotid chemoafferents. (wikipedia.org)
  • 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)
  • The various processes involved in cellular stress responses serve the adaptive purpose of protecting a cell against unfavorable environmental conditions, both through short term mechanisms that minimize acute damage to the cell's overall integrity, and through longer term mechanisms which provide the cell a measure of resiliency against similar adverse conditions. (wikipedia.org)
  • In response to DNA damage NDRG1 translocates from the cytoplasm to the nucleus, where it may inhibit cell growth and promote DNA repair mechanisms. (wikipedia.org)
  • Other mechanisms include hypoxia-inducible factors, particularly HIF1. (wikipedia.org)
  • Recently, great effort has been invested toward elucidating the interplay between hypoxia-induced autophagy and cancer cell metabolism. (frontiersin.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)
  • The study of the tumor metabolism, also known as tumor metabolome describes the different characteristic metabolic changes in tumor cells. (wikipedia.org)
  • In addition to cell-autonomous changes that drive a cancer cell to proliferate and contribute to tumorigenesis, it has also been observed that alterations in whole-organism metabolism such as obesity are associated with heightened risks for a variety of cancers. (wikipedia.org)
  • Juveniles within nurse cells have an anaerobic or facultative anaerobic metabolism, but when they become activated, they adopt the aerobic metabolism characteristics of the adult. (wikipedia.org)
  • In the presence of higher glucose metabolism, and consequently increased relative levels of ATP, the KATP channels close, causing the membrane potential of the cell to depolarize, activating voltage-gated calcium channels, and thus promoting the calcium-dependent release of insulin. (wikipedia.org)
  • By phosphorylating glucose, HK3 effectively prevents glucose from leaving the cell and, thus, commits glucose to energy metabolism. (wikipedia.org)
  • Antiapoptotic proteins Bcl2 and Bcl-xL were unchanged by hypoxia. (hindawi.com)
  • Hypoxia has also been associated with the increased SUMOylation of multiple proteins, including GLI family proteins, which are key mediators of SHh signaling, and has become a promising target to develop drug-resistant drugs for cancer treatment. (frontiersin.org)
  • SUMOylation is required for hypoxia-dependent activation of GLI proteins. (frontiersin.org)
  • Nucleoside transporters (NTs) are a group of membrane transport proteins which transport nucleoside substrates including adenosine across the membranes of cells and/or vesicles. (wikipedia.org)
  • Stress proteins can exhibit widely varied functions within a cell- both during normal life processes and in response to stress. (wikipedia.org)
  • Because conditions such as high temperatures often cause proteins to denature, this mechanism enables cells to determine when they are subject to high temperature without the need of specialized thermosensitive proteins. (wikipedia.org)
  • Indeed, if a cell under normal (meaning unstressed) conditions has denatured proteins artificially injected into it, it will trigger a stress response. (wikipedia.org)
  • Early research has suggested that cells which are better able to synthesize stress proteins and do so at the appropriate time are better able to withstand damage caused by ischemia and reperfusion. (wikipedia.org)
  • Ras is a family of related proteins which is expressed in all animal cell lineages and organs. (wikipedia.org)
  • Ras is the prototypical member of the Ras superfamily of proteins, which are all related in 3D structure and regulate diverse cell behaviours. (wikipedia.org)
  • Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. (wikipedia.org)
  • Hypoxia is a prominent characteristic of many acute or chronic inflammatory diseases, and exerts significant influence on their progression. (jci.org)
  • Premature infants have chronic hypoxia, resulting in cognitive and motor neurodevelopmental handicaps caused by suboptimal neural stem cell (NSC) repair/recovery in neurogenic zones (including the subventricular and the subgranular zones). (nih.gov)
  • 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)
  • 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)
  • Now, an experimental model of this chronic hypoxia reveals that those cellular alterations have behavioral consequences. (medicalxpress.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)
  • Chronic hypoxia significantly reduced cell viability which accompanied with LDH release, increase in mitochondrial ROS, intracellular NO and calcium levels, decrease in superoxide dismutase (SOD) activity, and cellular ATP contents. (hindawi.com)
  • It has been established that chronic hypoxia is associated with cardiac dysfunctions in certain pathological conditions such as ischemia reperfusion, myocardial infarction (MI), and hypertrophy [ 1 ]. (hindawi.com)
  • And acute IH shows no evidence of the hippocampal cell death found in rats while chronic intermittent hypoxia exposure does Though intermittent hypoxia has been used for various therapeutic applications across a number of physiological system, there is a general consensus in what can be considered a safe and beneficial amount of intermittent hypoxia. (wikipedia.org)
  • In vivo, hypoxia promotes neurogenesis in embryos, newborns and adults, as well as in response to noxious stimuli such as ischemia. (nih.gov)
  • Cancer stem cells (CSCs), also known as cancer initiating cells or tumor propagation cells, are neoplastic cells that could self-renewal, differentiate as well as initiate tumor growth in vivo. (nih.gov)
  • SVZ BEC and NSC HIF-1α induction by hypoxia in vivo . (nih.gov)
  • 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)
  • Delivery of such hypoxia-induced factors in vivo has proved to be effective in supporting the vascularization, oxygenation and host-integration of subcutaneously-placed collagen implants. (wikipedia.org)
  • Though the concept of stem cell niche was prevailing in vertebrates, the first characterization of stem cell niche in vivo was worked out in Drosophila germinal development. (wikipedia.org)
  • By continuous intravital imaging in mice, researchers were able to explore the structure of the stem cell niche and to obtain the fate of individual stem cells (SCs) and their progeny over time in vivo. (wikipedia.org)
  • Differentiated airway epithelial cells can revert into stable and functional stem cells in vivo. (wikipedia.org)
  • Dexter observed that mesenchymal stromal cells could maintain early HSCs ex vivo, and both Lord and Gong showed that these cells localized to the endosteal margins in long bones. (wikipedia.org)
  • Muse cells do not undergo teratoma formation when transplanted into a host environment in vivo. (wikipedia.org)
  • These data highlight the role of the Sirt1-Foxo3 axis in cellular adaptation to hypoxia, delineate a molecular mechanism of the CR-mediated antiaging effect, and could potentially direct the design of new therapies for age- and hypoxia-related tissue damage. (jci.org)
  • The Influence of Hypoxia and pH on Bioluminescence Imaging of Luciferase-Transfected Tumor Cells and Xenografts," International Journal of Molecular Imaging , vol. 2013, Article ID 287697, 9 pages, 2013. (hindawi.com)
  • These cells named disseminated tumor cells (DTCs) cannot be detected by conventional cytological methods, but they may be found both by immunocytochemistry and molecular technologies. (hindawi.com)
  • Is carbonic anhydrase IX a validated target for molecular imaging of cancer and hypoxia? (wikipedia.org)
  • Cellular stress response is the wide range of molecular changes that cells undergo in response to environmental stressors, including extremes of temperature, exposure to toxins, and mechanical damage. (wikipedia.org)
  • Molecular Cell. (wikipedia.org)
  • Furthermore, there are vast developments in tissue engineering, which involve leveraging of technologies from biomaterials, molecular medicine, biochemistry, nanotechnology, genetic and biomedical engineering for regeneration and cell expansion targets to restructure and/or repair human organs. (wikipedia.org)
  • The researchers were able to identify the minimal conditions and factors that would be sufficient for starting the cascade of molecular and cellular processes to instruct pluripotent cells to organize the embryo. (wikipedia.org)
  • Imaging modalities have long been crucial to the researcher in observing changes, either at the organ, tissue, cell, or molecular level, in animals responding to physiological or environmental changes. (wikipedia.org)
  • Sir Peter John Ratcliffe FRS (born 14 May 1954) is a British doctor and cell and molecular biologist best known for his work on cellular reactions to hypoxia. (wikipedia.org)
  • We designed a system to study the influence of hypoxia, pressure, and native ECM conditions on cancer cell lines and primary cells, with the goal of creating culturing environments relevant for translational studies involving key immunotherapeutic targets. (aacrjournals.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-L PD-L2, CD80, and CD86) on MDSCs. (rupress.org)
  • 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)
  • In contrast, ROS accumulation, the endogenous gene response and cell death was limited in neuronal cells pre-incubated with 50 or 100, but not 10 microM of the phenolic antioxidant 3,3',5,5'-tetra-t-butyl-biphenyl-4,4'-diol (BP) prior to H/R injury. (nih.gov)
  • 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)
  • In neuronal and neuroendocrinal cells, this mostly occurs via regulated exocytosis. (wikipedia.org)
  • Neuroendocrine cells are cells that receive neuronal input (neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release message molecules (hormones) to the blood. (wikipedia.org)
  • Both agents strongly protected tenocytes from hypoxia-induced death over 48 h, suggesting possible efficacy in the acute postrupture tendon or integrating graft. (hindawi.com)
  • 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)
  • In contrast to HD NK cells, haNK cells are resistant to acute hypoxia. (nih.gov)
  • Increased circulating hematopoietic and endothelial progenitor cells in the early phase of acute myocardial infarction," Blood , vol. 105, no. 1, pp. 199-206, 2005. (hindawi.com)
  • Under voltage-clamp conditions, acute hypoxia ( P O2 ≅25 mmHg) suppressed the whole-cell outward currents of more than half the AMCs (24/46). (springer.com)
  • Among those affected, the majority develops cancer, most often acute myelogenous leukemia, and 90% develop bone marrow failure (the inability to produce blood cells) by age 40. (wikipedia.org)
  • citation needed] As FA is now known to affect DNA repair, specifically nonhomologous end joining, and given the current knowledge about dynamic cell division in the bone marrow, finding patients are more likely to develop bone marrow failure, myelodysplastic syndromes, and acute myeloid leukemia (AML) is not surprising. (wikipedia.org)
  • The body has different ways of coping with acute hypoxia. (wikipedia.org)
  • Meanwhile, HK3 was found to be repressed in acute myeloid leukemia (AML) blast cells and acute promyelocytic leukemia (APL) patients. (wikipedia.org)
  • 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)
  • However, it remains unclear how hypoxia-induced transcription factors (HIFs) and subsequent biological processes contribute to CKD development and progression. (nih.gov)
  • N 6 -methyladenosine (m 6 A) modification of mRNA plays a role in regulating embryonic stem cell pluripotency. (pnas.org)
  • Similarly, hypoxia also resulted in upregulation of VLDL-R mRNA in these cells (3.1-fold in macrophages and 5.1-fold in HCASMC, respectively). (ahajournals.org)
  • Transfection of HCASMC with siRNA against HIF-1α resulted in a 73±3.7% decrease in the hypoxia-induced increase of VLDL-R mRNA levels. (ahajournals.org)
  • Upregulation of asparagine synthetase mRNA was observed as well in these hamster cells. (wikipedia.org)
  • Other experiments demonstrated that quiescent rat thyroid cells entering S phase as a result of thyroid-stimulating hormone treatment was matched with a concurrent increase in asparagine synthetase mRNA content. (wikipedia.org)
  • MicroRNA-495 inhibits the level of MTA3 mRNA as well as the growth and migration of non-small cell lung cancer cells. (wikipedia.org)
  • Using fluorescence immunohistochemical techniques, we provide data on the presence, distribution, and levels of EF5 binding as a surrogate for hypoxia in human head and neck and uterine cervix squamous cell cancers (SCCs). (aacrjournals.org)
  • The initial observation that hypoxia was prognostically important in human cancer therapy came from studies in head and neck SCC 3 and uterine cervix SCC. (aacrjournals.org)
  • Human hepatoma cell lines were grown either in a normoxic or hypoxic condition. (nih.gov)
  • Comparison of HLA-Class I profiles of human glioma cells grown under hypoxic or normoxic conditions. (plos.org)
  • 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. (asm.org)
  • Surprisingly, accumulation of HIF-1α in human T cells required not only hypoxia but also TCR/CD3-mediated activation. (jimmunol.org)
  • The human ovarian cancer cell line, OC-MZ-6, used in this study was established (passaged between 100 and 300 times) from a patient with advanced serous cystadenocarcinomas of the ovary (provided by Dr. Georg Brunner, The University of Munster, Germany). (aacrjournals.org)
  • Recently, we have described specific bioenergetic markers associated with the metabolic phenotype of several human and mouse glioma cell lines. (aacrjournals.org)
  • In this study, we investigate the lncRNA profiles of human umbilical vein endothelial cells subjected to hypoxia using global run-on sequencing (GRO-Seq). (frontiersin.org)
  • 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)
  • Our results demonstrated that the regulated promoter construct was silenced by 91% in aerobic conditions in primary mouse Muller cells and 20% in the M10M1 human Muller cell line compared to unregulated promoter. (arvojournals.org)
  • Human CD34 + AC133 + VEGFR-2 + cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors," Experimental Hematology , vol. 35, no. 7, pp. 1109-1118, 2007. (hindawi.com)
  • Human hepatocellular carcinoma HepG2 cells are forced to oxidative phosphorylation (OXPHOS), when cultured in aglycemic conditions at galactose and glutamine. (frontiersin.org)
  • Renal cell carcinoma (RCC), the third most common malignancy of the genitourinary system, accounts for 2% to 3% of all human malignancies. (aacrjournals.org)
  • Breast cancer There is downregulation of miR-26a in breast cancer specimens and cell lines, and it has been shown to functionally antagonise human breast carcinogenesis. (wikipedia.org)
  • miR-26a is found to be downregulated in primary human Burkitt lymphoma and MYC-driven lymphoma cell lines. (wikipedia.org)
  • Hence, research has been focused on induced pluripotent stem cells (iPSCs) from somatic human tissue. (wikipedia.org)
  • For instance, multilineage-differentiating stress-enduring (Muse) cells are stress-tolerant adult human stem cells that can self-renew. (wikipedia.org)
  • hESCs can be generated by SCNT using dermal fibroblasts nuclei from both a middle-aged 35-year-old male and an elderly, 75-year-old male, suggesting that age-associated changes are not necessarily an impediment to SCNT-based nuclear reprogramming of human cells. (wikipedia.org)
  • however, later studies indicate that Naa11 is not expressed in the human cell lines HeLa and HEK293 or in cancerous tissues, and NAA11 transcripts were only detected in testicular and placental tissues. (wikipedia.org)
  • HIF-1α steady state accumulation was dependent on the amount of PHD silencing effected by siRNA in HeLa cells and a variety of other human cell lines. (wikipedia.org)
  • When another animal (perhaps a human) eats the infected meat, the larvae are released from the nurse cells in the meat (due to stomach pH), and migrate to the intestine, where they burrow into the intestinal mucosa, mature, and reproduce. (wikipedia.org)
  • Many human blood cells, such as red blood cells (RBCs), immune cells, and even platelets all originate from the same progenitor cell, the hematopoietic stem cell (HSC). (wikipedia.org)
  • Can be isolated as cells positive for SSEA-3, a well known human embryonic stem cell marker. (wikipedia.org)
  • Muse cells are identified as cells positive for SSEA-3+, a well-known marker for undifferentiated human ES cells. (wikipedia.org)
  • showed that human dermal fibroblast-derived Muse cells were efficiently differentiated into melanin-producing functional melanocytes by a cocktail of cytokines. (wikipedia.org)
  • This was shown in human Muse cells infused into animal models with fulminant hepatitis, partial hepatectomy, muscle degeneration, skin injury, stroke and spinal cord injury. (wikipedia.org)
  • Hela cells and human fibroblast-derived iPS cells showed high telomerase activity while Muse was at nearly the same level as that in somatic cells such as fibroblasts (these data are shown without running control for the telomerase activity, the comparison is not scientific thought). (wikipedia.org)
  • Especially for lowlanders who traverse past 6000 meters in altitude, the limit of prolonged human exposure to hypoxia, HVR may result in hyperventilation and ultimately the deterioration of the body. (wikipedia.org)
  • MTA3 is overexpressed in non-small cell lung cancer and human placenta and chorionic carcinoma cells. (wikipedia.org)
  • Thus, all the progeny of the infected human ancestor would have this viral genome integrated into every cell in their bodies. (wikipedia.org)
  • Performing multiple-tissue Northern Blots on a variety of human tissues lead to the discovery of 8-, 3.1- and 1.3-kb transcripts in placental tissue not expressed in heart, brain, lung, liver, skeletal muscle, kidney or pancreas cells. (wikipedia.org)
  • A third ras gene was subsequently discovered by researchers in the group of Robin Weiss at the Institute of Cancer Research, and Michael Wigler at Cold Spring Harbor Laboratory, named NRAS, for its initial identification in human neuroblastoma cells. (wikipedia.org)
  • 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)
  • Unless corrected or reversed, intracellular function ceases, eventually leading to cell death. (wisegeek.com)
  • Ion leakage across cell membranes occurs as a result of both intracellular and extracellular ions drifting towards their thermodynamic equilibrium. (biologists.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)
  • 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)
  • On the other hand, hypoxia may modulate NO production by regulating intracellular calcium which is important for Ca 2+ /calmodulin-dependent eNOS and nNOS activity, and NO increase in turn may inhibit mitochondrial complex IV [ 8 ]. (hindawi.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)
  • The data presented here provide an additional mechanism of action for haNK cells that are currently being evaluated in clinical trials for several tumor types. (nih.gov)
  • 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)
  • This mechanism is relevant when used as a means to decrease hypertension or increase bone mineral density An understanding of proper dosage is needed in order to design an effective intermittent hypoxia protocol, particularly due to the comorbidities associated with hypoxia. (wikipedia.org)
  • Autophagy (or autophagocytosis) (from the Ancient Greek αὐτόφαγος autóphagos, meaning "self-devouring" and κύτος kýtos, meaning "hollow") is the natural, regulated, destructive mechanism of the cell that disassembles unnecessary or dysfunctional components. (wikipedia.org)
  • A mechanism has been proposed for the cell's KATP reaction to hypoxia and ischemia. (wikipedia.org)
  • Hypoxia and hypoxia inducible factors in cancer stem cell maintenance. (nih.gov)
  • Cancer stem cells are believed to be the key drivers in tumor growth and therapy resistance. (nih.gov)
  • Hypoxia has been shown to help maintain multiple normal stem cell population but its roles in cancer stem cells were largely unknown. (nih.gov)
  • Targeting hypoxia niches may therefore improve therapy efficacy by eliminating cancer stem cell population. (nih.gov)
  • Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, 90095, USA. (nih.gov)
  • Pluripotency factors, such as NANOG, play a critical role in the maintenance and specification of cancer stem cells, which are required for primary tumor formation and metastasis. (pnas.org)
  • Is the Subject Area "Cancer stem cells" applicable to this article? (plos.org)
  • Neural stem/progenitor cells (NSPCs) are multipotent cells with self-renewing capabilities. (wiley.com)
  • 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)
  • 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)
  • IntroductionA feature which makes stem cells promising candidates for cell therapy is their ability to effectively migrate into damaged or diseased tissues. (7thspace.com)
  • They are grown on a feeder layer of cells, which is believed to be supportive in maintaining the pluripotent characteristics of embryonic stem cells. (wikipedia.org)
  • Adult stem cells remain in an undifferentiated state throughout adult life. (wikipedia.org)
  • It is believed that correct culturing conditions of adult stem cells needs to be improved so that adult stem cells can maintain their stemness over time. (wikipedia.org)
  • citation needed] A Nature Insight review defines niche as follows: "Stem-cell populations are established in 'niches' - specific anatomic locations that regulate how they participate in tissue generation, maintenance and repair. (wikipedia.org)
  • The simple location of stem cells is not sufficient to define a niche. (wikipedia.org)
  • In particular in intestinal crypt, two distinct groups of SCs have been identified: the "border stem cells" located in the upper part of the niche at the interface with transit amplifying cells (TAs), and "central stem cells" located at the crypt base. (wikipedia.org)
  • This bi-compartmental structure of stem cell niche has been mathematically modeled to obtain the optimal architecture that leads to the maximum delay in double-hit mutant production. (wikipedia.org)
  • GATA2 is expressed in hematopoietic progenitors, including early erythroid cells, mast cells, and megakaryocytes, and also in nonhematopoietic embryonic stem cells. (wikipedia.org)
  • Injection of cardiomyogenic and/or angiogenic stem cells have been proposed as alternatives to existing treatments. (wikipedia.org)
  • Recent studies[citation needed] have suggested that mammal hearts also host naturally occurring cardiac stem cells which are capable of differentiating themselves into cardiomyocytes, endothelial cells and cardiac fibroblasts. (wikipedia.org)
  • To resume, stem cells and delivery routes aforementioned are suitable for cardiomyoplasty as demonstrated safe with some degree of benefit for the patient. (wikipedia.org)
  • Induced stem cells (iSC) are stem cells derived from somatic, reproductive, pluripotent or other cell types by deliberate epigenetic reprogramming. (wikipedia.org)
  • Some types of mature, specialized adult cells can naturally revert to stem cells. (wikipedia.org)
  • For example, "chief" cells express the stem cell marker Troy. (wikipedia.org)
  • While they normally produce digestive fluids for the stomach, they can revert into stem cells to make temporary repairs to stomach injuries, such as a cut or damage from infection. (wikipedia.org)
  • Moreover, they can make this transition even in the absence of noticeable injuries and are capable of replenishing entire gastric units, in essence serving as quiescent "reserve" stem cells. (wikipedia.org)
  • This capacity to regenerate does not decline with age and may be linked to their ability to make new stem cells from muscle cells on demand. (wikipedia.org)
  • A variety of nontumorigenic stem cells display the ability to generate multiple cell types. (wikipedia.org)
  • Stem cells can also be identified by functional assays. (wikipedia.org)
  • Stem Cell Information. (wikipedia.org)
  • Normally, only stem cells and progenitor cells express MET, which allows these cells to grow invasively in order to generate new tissues in an embryo or regenerate damaged tissues in an adult. (wikipedia.org)
  • However, cancer stem cells are thought to hijack the ability of normal stem cells to express MET, and thus become the cause of cancer persistence and spread to other sites in the body. (wikipedia.org)
  • There are 2 types of hematopoiesis that occur in humans: Primitive hematopoiesis - blood stem cells differentiate into only a few specialized blood lineages (typically isolated to early fetal development). (wikipedia.org)
  • The pioneering work of Till and McCulloch in 1961 experimentally confirmed the development of blood cells from a single precursor hematopoietic stem cell (HSC), creating the framework for the field of hematopoiesis to be studied over the following decades. (wikipedia.org)
  • In 1978, after observing that the prototypical colony-forming stem cells were less capable at replacing differentiated cells than bone marrow cells injected into irradiated animals, Schofield proposed that a specialized environment in the bone marrow allows these precursor cells to maintain their cellular reconstitution potential. (wikipedia.org)
  • During this time, the field exploded with studies aimed at determining the components of the "hematopoietic stem cell niche" that made this possible. (wikipedia.org)
  • A muse cell (multi-lineage differentiating stress enduring cell) is a endogenous non-tumorigenic pluripotent stem cell. (wikipedia.org)
  • Pluripotent stem cells, which can generate various kinds of the cells representative of all three germ layers have the ability to self-renew. (wikipedia.org)
  • This indicates that Muse cells do not belong to previously investigated stem cell types. (wikipedia.org)
  • Unlike ES and iPS cells, transplanted Muse cells in testes of immunodeficient mice -a commonly used experiment to test the tumorigenicity of stem cells- have not been reported to form teratomas, even after six months. (wikipedia.org)
  • Because of its real-time nature, micro-ultrasound can also guide micro-injections of drugs, stem cells, etc. into small animals without the need for surgical intervention. (wikipedia.org)
  • Moreover, activated T cells accumulate and function in an area of inflammation or tumor growth, both of which are known to be hypoxic ( 10 ). (jimmunol.org)
  • The process of EMT is also noted as an important and noteworthy process in tumor growth, through the invasion and metastasis of tumor cells due to repression of E-cadherin adhesion molecules. (wikipedia.org)
  • Possibly, cell type-dependent and stimulus-dependent factors may control ROS dependency or redox sensitivity of HIF1-α and thus HIF1-α activation either directly or by induction of specific signaling cascades. (aacrjournals.org)
  • Conclusions: The results of this study indicate that high directional migration of hMSCs permanently grown in hypoxia is associated with the enhanced activation of RhoA. (7thspace.com)
  • Hypoxia-regulated delta-like 1 homologue enhances cancer cell stemness and tumorigenicity. (nih.gov)
  • 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)
  • Here, treatment with doxorubicin, under hypoxia or normoxia in different liver cancer cell lines, was evaluated. (diva-portal.org)
  • Liver cancer cells HepG2, Huh7, and SNU449 were exposed to doxorubicin, hypoxia, or doxorubicin + hypoxia with different duration. (diva-portal.org)
  • The evaluation of the clinical relevance of disseminated tumor cells (DTCs) in bone marrow (BM) of patients with gastric cancer (GC) and their association with primary tumor hypoxia. (hindawi.com)
  • Disseminated Tumor Cells in Bone Marrow of Gastric Cancer Patients: Correlation with Tumor Hypoxia and Clinical Relevance," Journal of Oncology , vol. 2014, Article ID 582140, 7 pages, 2014. (hindawi.com)
  • Linc-RoR was highly expressed in extracellular RNA released by hepatocellular cancer (HCC) cells during hypoxia. (biologists.org)
  • Through understanding the behavior of such hypoxic tumor cells, strategies which better target this potentially dangerous cancer cell population may be devised. (asm.org)
  • Prostate cancer (LNCaP) cells were transfected with recombinant plasmid pcDNA3.1(-)/HIF-1alpha and pcDNA3.1(-) control vector using a commercial system, designated as LNCaP/HIF-1alpha and LNCaP/pcDNA3.1, respectively. (nih.gov)
  • Intratumoral hypoxia has been correlated with poor clinical outcome in prostate cancer. (nih.gov)
  • Prostate cancer cells can be genetically unstable and have altered DNA repair. (nih.gov)
  • These results suggest a potential role for targeting IGF1R in the prevention of hypoxia-induced cancer progression and metastasis mediated by EMT. (sigmaaldrich.com)
  • Hypoxia is associated with various pathophysiological events, including cancer, lung and cardiovascular diseases. (spandidos-publications.com)
  • These O XPHOS cells represent a prototype of cancer cell bioenergetics with mixed aerobic glycolysis and OXPHOS. (frontiersin.org)
  • We aimed to determine fractions of (i) glutaminolytic pathway involving aminotransferase reaction supplying 2-oxoglutarate (2OG) to the Krebs cycle vs. (ii) active segment of the Krebs cycle with aconitase and isocitrate dehydrogenase-3 (ACO-IDH3), which is typically inactive in cancer cells due to the citrate export from mitochondria. (frontiersin.org)
  • Consequently, a wide acceptance of the irreversible and exclusive Warburg phenotype in cancer cells is incorrect. (frontiersin.org)
  • however, typical cancer cell culture rarely uses hypoxia and pressure nor utilizes substrates similar to the native extracellular matrix (ECM). (aacrjournals.org)
  • According to the American Cancer Society, more than 90% of cancer patients die from different degrees of tumor cell resistance. (frontiersin.org)
  • It has been theorized that constitutively activating HIF in any cell could lead to cancer, but that there are redundant regulators of HIF in organs not affected by VHL syndrome. (wikipedia.org)
  • High amount of aerobic glycolysis (also known as the Warburg effect) distinguishes cancer cells from normal cells. (wikipedia.org)
  • In this regard, cancer cells and stromal cells can symbiotically recycle and maximize the use of nutrients. (wikipedia.org)
  • These cells can be the source of several types of lung cancer- most notably, small cell carcinoma of the lung, and bronchial carcinoid tumor. (wikipedia.org)
  • Because of the genetic defect in DNA repair, cells from people with FA are sensitive to drugs that treat cancer by DNA crosslinking, such as mitomycin C. The typical age of death was 30 years in 2000. (wikipedia.org)
  • Several studies have shown that PUMA function is affected or absent in cancer cells. (wikipedia.org)
  • Even though PUMA function is compromised in most cancer cells, it does not appear that genetic inactivation of PUMA is a direct target of cancer. (wikipedia.org)
  • Cancer Cell. (wikipedia.org)
  • Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is therapy using ionizing radiation, generally as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. (wikipedia.org)
  • Highly radiosensitive cancer cells are rapidly killed by modest doses of radiation. (wikipedia.org)
  • Renal cell cancer and melanoma are generally considered to be radioresistant but radiation therapy is still a palliative option for many patients with metastatic melanoma. (wikipedia.org)
  • In breast cancer, loss of MTA3 promotes EMT and invasiveness of breast cancer cells via upregulating Snail, which in turn represses E-cadherin adhesion molecule. (wikipedia.org)
  • Because these signals result in cell growth and division, overactive Ras signaling can ultimately lead to cancer. (wikipedia.org)
  • Through knockout models, one study has shown the importance of SNAI1 in the growth of breast cancer cells. (wikipedia.org)
  • Though expressed highly in eye lens and muscle tissues, αBC can also be found in several types of cancer, among which head and neck squamous cell carcinoma (HNSCC) and breast carcinomas, as well as in patients with tuberous sclerosis. (wikipedia.org)
  • Gopal Chandra Kundu (born 1959) is an renowned Indian cell and cancer biologist and a Senior Scientist (Scientist-G) at National Centre for Cell Science. (wikipedia.org)