• Hypoxia is a common phenomenon in solid tumours because impaired vascular function results in an inadequate blood supply. (bmj.com)
  • Under hypoxic conditions, hypoxia inducible factor-1 alpha (HIF-1a) is stabilized and the transcription factor HIF-1 transactivates the CA9 gene, resulting in expression of the CAIX protein in the hypoxic cells. (prnewswire.com)
  • Promoter analyses revealed increased hypoxia-inducible factor-2 binding to the CXCL12 promoter under hypoxic conditions. (haematologica.org)
  • CoCl2 was used in rat liver tumor cell line McA RH-7777 to stimulate hypoxia to mimic the hypoxic conditions induced by transcatheter arterial chemoembolization (TACE). (elis.sk)
  • Real-time qRT-PCR, western blot and ELISA assays were used to measure the expression of HIF-1α and VEGF in McA RH-7777 cells under hypoxic conditions, respectively. (elis.sk)
  • The mRNA and protein expression level of HIF-1α and VEGF were remarkably up-regulated in McA RH-7777 cells under hypoxic conditions, respectively. (elis.sk)
  • Our findings showed that HIF-1α play an important role in the stimulation of the secreted VEGF expression under hypoxic conditions, suggesting that targeting both HIF-1α and VEGF could represent a potential therapeutic strategy in combination with TACE in the treatment of liver tumors. (elis.sk)
  • Pretreatment of murine myoblast (C2C12) cells with octyl-D-carnosine or carnosine enhanced HIF-1α protein expression, VEGF mRNA levels and VEGF release under hypoxic conditions. (frontiersin.org)
  • HIF-1α is known to be mainly post-transcriptionally regulated by protein ubiquitination and interaction with the Von Hippel-Lindau tumour suppressor protein, and then degraded by the proteasome. (biomedcentral.com)
  • For example, studies suggest that ccRCC is closely associated with tumor suppressor von-Hippel Lindau ( VHL ) gene mutations that lead to stabilization of hypoxia inducible factors (HIF-1 α and HIF-2 α , also known as HIF1A and EPAS1) in both sporadic and familial forms [ 5 , 6 ]. (hindawi.com)
  • Inactivating mutations of the von Hippel-Lindau (VHL ) tumor suppressor gene are associated with inherited VHL syndrome, which is characterized by susceptibility to a variety of neoplasms, including central nervous system hemangioblastoma and clear cell renal cell carcinoma (CCRCC). (aspetjournals.org)
  • William Kaelin, Jr. was in 1995 engaged in the study of the von Hippel-Lindau tumor suppressor gene, and after isolation of the first full-length clone of the gene showed that it could suppress tumor growth in VHL mutant tumorigenic cell lines. (nobelprize.org)
  • The key regulator of this process, hypoxia inducible factor 1 (HIF-1), can initiate apoptosis by inducing high concentrations of proapoptotic proteins, such as BNIP3, and can cause stabilisation of p53. (bmj.com)
  • In addition, a PPI network can be modeled as an undirected graph, where vertices represent proteins and edges represent interactions between proteins, to prioritize disease associated genes or pathways and to understand the modus operandi of disease mechanisms [ 9 , 10 ]. (hindawi.com)
  • HIF-1 regulates production of multiple proteins, including vascular-endothelial growth factor (VEGF) and other cell regulatory proteins that are normally kept in check but which are significantly elevated in times of hypoxia, starvation, and stress. (renalandurologynews.com)
  • The potential proteins of DGP were acquired from TCMSP database, while the potential genes of ONFH were obtained from Gene Cards and Pubmed Gene databases. (researchsquare.com)
  • The HIF-1 protein is composed of two HIF-1α and HIF-1β/aryl hydrocarbon receptor nuclear translocator (ARNT) subunits. (biomedcentral.com)
  • Vascular endothelial growth factor (VEGF) is the critical stimulus for tumor angiogenesis, and we have demonstrated the novel upregulation of VEGF by the Wnt pathway. (harvard.edu)
  • 77 IL-8 acts through chemokine receptors 1 and 2 (CXCR1 and 2) and is involved in promoting angiogenesis through overexpression of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). (oncologynurseadvisor.com)
  • Hypoxia-inducible factor-1α (HIF-1α) is a key transcription factor to initiate the expressions of distinct pro-angiogenic growth genes, particularly the expression of vascular endothelial growth factor (VEGF). (elis.sk)
  • A conditional knockout of the Hif1a gene was reported to affect the development of sympathetic ganglia and sympathetic innervation of the heart. (labgenexp.eu)
  • The HIF1A rs2057482 polymorphism is associated with risk of developing premature coronary artery disease and with some metabolic and cardiovascular risk factors. (cdc.gov)
  • Single nucleotide polymorphisms of the HIF1A gene are associated with susceptibility to pulmonary arterial hypertension in systemic sclerosis and contribute to SSc-PAH disease severity. (cdc.gov)
  • The alleles of AGT and HIF1A gene affect the risk of hypertension in plateau residents. (cdc.gov)
  • Research has demonstrated increased expression of hypoxia-inducible target genes in lesional tissue, suggesting hypoxic injury may be involved in the pathogenesis. (medscape.com)
  • GB004 induction of HIF-1a target genes improves barrier integrity and reduces barrier permeability in rodent models of colitis. (ecco-ibd.eu)
  • Barrier integrity was assessed by Transepithelial Endothelial Electric Resistance (TEER), HIF-1a target genes were assessed in cell lysates, and tight junction formation and epithelial monolayer viability were investigated by immunofluorescence staining. (ecco-ibd.eu)
  • Luciferase assays showed that T471C and C862T could significantly increase the expression efficiency of downstream target genes. (jcancer.org)
  • The goals of the laboratory are: (1) to define the molecular pathogenesis of endocrine tumors of the GI tract. (harvard.edu)
  • Hypoxia in tumors is closely associated with tumor aggressiveness and resistance to radio- and chemotherapeutic treatment. (prnewswire.com)
  • 71 Clusterin is a small heat shock glycoprotein overexpressed in most of the solid tumors, which promotes apoptosis by binding to various molecules such as BAX (BCL2-associated X protein) 72 and signal transducer and activator of transcription (STAT)−1. (oncologynurseadvisor.com)
  • Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and accounts for approximately 60% to 70% of all renal tumors [ 1 ]. (hindawi.com)
  • Hypoxia is the most common characteristic in the microenvironment of solid tumors because tumor progression and metastasis depend on the ability of cancer cells to initiate angiogenesis and ensure the delivery of oxygen and nutrients ( 11 , 12 ). (jcancer.org)
  • Total RNA from tumors the expression of thousands of genes (3) to address complex questions was isolated using two successive rounds of Trizol. (lu.se)
  • Apoptosis can be induced in response to hypoxia. (bmj.com)
  • Cells adapt to this environmental stress, so that after repeated periods of hypoxia, selection for resistance to hypoxia induced apoptosis occurs. (bmj.com)
  • During hypoxia, an intricate balance exists between factors that induce or counteract apoptosis, or even stimulate proliferation. (bmj.com)
  • Understanding the regulation of apoptosis during hypoxia and the mechanisms of resistance to apoptosis might lead to more specific treatments for solid tumours. (bmj.com)
  • 7 Severe hypoxia in the presence of energy stimulates cells to undergo apoptosis, whereas oxygen levels above 0.5% prevent cell death. (bmj.com)
  • The pathophysiological nature of MIRI is the short-term disturbance of myocardial energy and metabolism caused by reflow after ischemia and hypoxia in the coronary artery and the dynamic changes in apoptosis and the prosurvival signaling pathways in response to related injury factors. (hindawi.com)
  • During treatment with taxanes, BCL2 is phosphorylated, which prevents heterodimerization with other BCL family genes, thereby promoting apoptosis. (oncologynurseadvisor.com)
  • 70 Mcl1 (myeloid cell leukemia differentiation protein 1) and other members of the BCL family, such as BCL-xl (B-cell lymphoma-extra-large), are also involved in resistance to Interleukin (IL)-6, stromal cell derived factor-1, and cytokine-induced apoptosis. (oncologynurseadvisor.com)
  • 75,76 Tumor necrosis factor (TNF)-α inhibits apoptosis by activating NF-κB and its downstream pathway, including IL6 and IL8, in androgen-independent prostate cancer cells, whereas it promotes apoptosis in androgen-dependent cancer cells. (oncologynurseadvisor.com)
  • The protective role of GB004 on barrier integrity was further supported by immunostaining experiments demonstrating that GB004 treatment protected epithelial cells from TNFa-induced cell apoptosis, improving both epithelial cell number and tight junction protein ZO-1 staining. (ecco-ibd.eu)
  • Although HIF-1α protein regulation has been well studied, HIF-1α messenger regulation has only recently begun to be documented [ 15 ]. (biomedcentral.com)
  • However, it is still largely unknown how cancer cells orchestrate gene regulation to balance their glycolysis and OXPHOS activities. (nih.gov)
  • Previously, by modeling the gene regulation of cancer metabolism we have reported that cancer cells can acquire a stable hybrid metabolic state in which both glycolysis and OXPHOS can be used. (nih.gov)
  • Here, to comprehensively characterize cancer metabolic activity, we establish a theoretical framework by coupling gene regulation with metabolic pathways. (nih.gov)
  • The role of hypoxia-inducible factors-1 and -2 in the regulation of CXCL12 expression was examined using over-expression and short hairpin RNA knockdown constructs, electrophoretic mobility shift assays and chromatin immunoprecipitation. (haematologica.org)
  • Kaelin and Ratcliffe then uncovered the cellular mechanisms behind the regulation of HIF-1. (the-scientist.com)
  • Regulation of gene expression by HIF-1. (uchicago.edu)
  • The recent discovery of transcription factor hypoxia inducible factor-1 (HIF-1) has unfolded a molecular link between hypoxia and regulation of a variety of genes involved in cellular adaptation to hypoxia. (rotrf.org)
  • For example proteoglycans sequester biomolecules such as growth factors (TGF-β, VEGF, FGF etc.) and MMPs (Matrix Metalloproteinases). (springer.com)
  • Lentivirus-mediated HIF-1α and/or VEGF-specific shRNA was used to establish single or HIF-1α and VEGF double knocking-down McA RH-7777 cells. (elis.sk)
  • Transwell assays were performed to examine the effect of HIF-1α and VEGF knocking-down on McA RH-7777 cells migration and invasion. (elis.sk)
  • The knockdown of HIF-1α or VEGF significantly reduced the expression of the secreted VEGF. (elis.sk)
  • More importantly, knockdown of both HIF-1α and VEGF resulted in the best effective inhibitory effect in VEGF expression, and in turn remarkably reduced the cell migration and invasion activity. (elis.sk)
  • Consistent with our hypothesis, carnosine supplementation augmented HIF-1α and VEGF expression in the ischemic limb and the mobilization of proangiogenic Flk-1 + /Sca-1 + cells into circulation. (frontiersin.org)
  • In contrast, pretreatment of hypoxic C2C12 cells with methylcarcinine, a carnosine analog, lacking Fe 2+ chelating capacity, had no effect on HIF-1α levels and VEGF release. (frontiersin.org)
  • Collectively, these data suggest that carnosine promotes post ischemic revascularization via augmentation of pro-angiogenic HIF-1α/VEGF signaling, possibly by Fe 2+ chelation. (frontiersin.org)
  • Semaphorin 4D (Sema4D) has been proven to be one of the hypoxia effectors regulated by hypoxia inducible factor (HIF-1) in multiple cells, and play a role in angiogenesis like VEGF. (jcancer.org)
  • Hypoxia stabilises HIF-1α protein by relaxing its ubiquitin-proteasome degradation [ 12 ] and affects subcellular localisation, DNA binding capacity and transcriptional activation function of the HIF-1 complex. (biomedcentral.com)
  • In the middle section of HIF-1α lies a Pro-Ser-Thr oxygen-dependent degradation domain (ODDD, amino acids 401 to 603), which is responsible for the stability of the HIF-1α protein [ 12 ]. (biomedcentral.com)
  • The VHL protein sequenced by this gene was found to complex with the hypoxia-inducible factor (HIF-1) to promote the degradation of HIF-1. (renalandurologynews.com)
  • In the first one, local adipose tissue hypoxia could induce fibrosis accumulation which in turn through adipocyte dysfunctions might provoke adipose tissue inflammation. (springer.com)
  • Secondary Erythrocytosis Secondary erythrocytosis is erythrocytosis that develops secondary to disorders that cause tissue hypoxia, inappropriately increased erythropoietin production, or increased sensitivity to erythropoietin. (msdmanuals.com)
  • Decreased ambient oxygen concentration, as occurs in people living at high altitudes, can result in compensatory erythrocytosis as a physiologic response to tissue hypoxia. (medscape.com)
  • In summary, our work serves as a platform to symmetrically study how tuning gene activity modulates metabolic pathway activity, and vice versa. (nih.gov)
  • ECM also modulates the bioavailability of many growth factors. (springer.com)
  • Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. (biomedcentral.com)
  • Transcriptional repression of human cad gene by hypoxia inducible factor-1. (tbi.org.tw)
  • In other animals, heat shock response is a transcriptional response driven by the heat shock transcription factor 1 ( HSF1 ) and thermal stress can trigger HSP70 expression to protect the organism via HSF1 . (biomedcentral.com)
  • Inactivation of VHL ubiquitin ligase is associated with normoxic stabilization of hypoxia-inducible factor-1α and 2-α (HIF-1α and HIF-2α), transcriptional regulators of tumor angiogenesis, invasion, survival, and glucose utilization. (aspetjournals.org)
  • Hypoxia inducible factor-1 (HIF-1) is a transcriptional complex which regulates systemic, local and intracellular homeostatic responses elicited by hypoxia. (enzolifesciences.com)
  • Runt-related transcription factor 3 ( RUNX3 ) is a potential tumor suppressor that is frequently hypermethylated in hepatocellular carcinoma (HCC). (geneticsmr.com)
  • 1 Severe hypoxia causes a high mutation rate, resulting in point mutations, which may be explained by reduced DNA mismatch repair activity resulting from decreased MLH1 and PMS2 concentrations, which are caused by hypoxia. (bmj.com)
  • 3- 5 Therefore, during severe hypoxia or anoxia, the cell initiates a cascade of events that leads to apoptotic cell death, thereby preventing the accumulation of cells with hypoxia induced mutations. (bmj.com)
  • Genetic testing for mutations in the VHL gene is performed at many laboratories throughout the United States and the world. (medscape.com)
  • De novo mutations occur in about 1:4.4 million live births and account for 20% of cases. (medscape.com)
  • Mutations in the VHL gene are also found in the majority of sporadic clear cell renal carcinoma, the most common malignant neoplasm of the human kidney. (aspetjournals.org)
  • Furthermore, secondary structure prediction showed that mutations at T471C and C862T apparently lead to change of the gene structure. (jcancer.org)
  • A full-length cDNA (Ov-phy-1) encoding a catalytically active alpha-subunit of Onchocerca volvulus prolyl 4-hydroxylase was isolated and characterized. (embl.de)
  • Our modeling results demonstrate a direct association between the activities of AMPK and HIF-1, master regulators of OXPHOS and glycolysis, respectively, with the activities of three major metabolic pathways: glucose oxidation, glycolysis, and fatty acid oxidation. (nih.gov)
  • The objective of this work is to identify dysregulated genes and pathways of ccRCC temporally according to systematic tracking of the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks. (hindawi.com)
  • Finally, gene compositions of altered modules were analyzed, and pathways enrichment analyses of genes in altered modules were carried out based on Expression Analysis Systematic Explored (EASE) test. (hindawi.com)
  • We successfully identified dysregulated genes and pathways of ccRCC in different stages, and these might be potential biological markers and processes for treatment and etiology mechanism in ccRCC. (hindawi.com)
  • Delineating the pathogenesis of ccRCC by investigating the gene and epigenetic changes and their effects on key molecules and their respective biologic pathways is of crucial importance for the improvement of current diagnostics, prognostics, and drug development [ 4 ]. (hindawi.com)
  • The investigation of this and other pathways in the HIF-1 cascade has led to a better understanding of the pathophysiology of RCC and the development of inhibitors of these pathways that have shown promise in the treatment of clear cell RCC. (renalandurologynews.com)
  • The function of Gene and potential pathways were researched by GO and KEGG pathway enrichment analysis. (researchsquare.com)
  • As a proangiogenic response effecter, the interaction of Sema4D with plexin-B1 is dependent on the COOH-terminal PDZ-binding motif of plexin-B1, which binds two guanine nucleotide exchange factors (GEFs) for Rho and is mediated by the activation of Rho-initiated (Ras homolog gene family) pathways ( 4 - 8 ). (jcancer.org)
  • The impact of HIF-1α alternative splice variant expression on breast cancer prognosis in terms of metastasis risk is not well known. (biomedcentral.com)
  • Our results show for the first time that mRNA expression of a HIF-1α TAG splice variant reflects a stage of breast cancer progression and is associated with a worse prognosis. (biomedcentral.com)
  • Cells will adapt by activating the expression of genes involved in metabolic adaptation, such as those involved in glycolysis. (bmj.com)
  • Hypoxia and hypoxia-inducible factor 1 repress SEMA4B expression to promote non-small cell lung cancer invasion. (nih.gov)
  • There are several proposed mechanisms for resistance, including increased androgen receptor (AR) signaling caused by increased AR expression, gene amplification, gene transcription, and tumor growth. (oncologynurseadvisor.com)
  • for example, Chu and Chen [ 13 ] combined PPI and gene expression data to construct a cancer perturbed PPI network in cervical carcinoma to study gain- and loss-of-function genes as potential drug targets. (hindawi.com)
  • 14 ] combined PPI and gene expression data to construct tissue-specific PPI networks for 60 tissues and used them to prioritize disease genes. (hindawi.com)
  • While the mechanisms responsible for aberrant plasma cell expression of CXCL12 remain to be determined, studies in other systems suggest a role for hypoxia and hypoxia-inducible transcription factors. (haematologica.org)
  • Design and Methods The expression of hypoxia-inducible factor protein was examined in patients' bone marrow biopsy specimens using immunohistochemistry. (haematologica.org)
  • Results Strong hypoxia-inducible factor-2 protein expression was detected in CD138 + multiple myeloma plasma cells in patients' biopsy specimens. (haematologica.org)
  • Prolonged exposure to hypoxia strongly up-regulated CXCL12 expression in multiple myeloma plasma cells and hypoxia-inducible factor-2 was found to play a key role in this response. (haematologica.org)
  • Over-expression of hypoxia-inducible factor in multiple myeloma plasma cells strongly induced in vivo angiogenesis, and administration of a CXCL12 antagonist decreased hypoxia-inducible factor-induced angiogenesis. (haematologica.org)
  • Conclusions Hypoxia-inducible factor-2 is a newly identified regulator of CXCL12 expression in multiple myeloma plasma cells and a major contributor to multiple myeloma plasma cell-induced angiogenesis. (haematologica.org)
  • 12 It is well established that hypoxia is an important selective force in the evolution of tumor cells, 13 and elevated expression of the hypoxia-inducible transcription factors HIF-1 and HIF-2 has been documented in several human cancers. (haematologica.org)
  • Co-expression of Ov-phy-1 with the O. volvulus homologue of protein disulfide isomerase in a baculovirus system resulted in the production of enzymatically active O. volvulus prolyl 4-hydroxylase. (embl.de)
  • Various growth factors, cytokines, and prostaglandins upregulate HGF gene expression, including basic fibroblast growth factor, oncostatin M, hypoxia-inducible factor 1α and nuclear factor-κB (NF-κB) ( 9 ). (spandidos-publications.com)
  • By contrast, transforming growth factor (TGF)-β1 was demonstrated to markedly downregulate HGF gene expression ( 10 , 11 ). (spandidos-publications.com)
  • Here we investigated gene expression and secretion of soluble factors elicited by GB004 treatment on immune cells and epithelial cells, human monolayer assays and immune co-culture studies to further explore its protective mechanism. (ecco-ibd.eu)
  • Thus, it has evolved a protection mechanism against heat stress by increasing the expression of the gene coding for heat shock protein (HSP) 70 under elevated temperatures. (biomedcentral.com)
  • We identified 150 genes responsive to heat shock including seven HSP genes, six of which belonging to the group of 17 HSP genes enriched in response to heat shock, according to weighted gene co-expression network analysis (WGCNA). (biomedcentral.com)
  • The results suggested that gene expression was correlated with HSF1 expression. (biomedcentral.com)
  • Our results revealed that the expression of HSP70 and HSP20 was initially triggered after 2 h of heat shock, and one of the HSP70 genes was potentially regulated by HSF1 . (biomedcentral.com)
  • HIF-1beta is constitutively expressed and serves as a dimerization partner for several other transcription factors, while HIF-1alpha and the closely related HIF-2 are unique to HIF-1 and their expression is tightly regulated by cellular oxygen concentration. (enzolifesciences.com)
  • Animal cells undergo fundamental shifts in gene expression when there are changes in the oxygen levels around them. (nobelprize.org)
  • These changes in gene expression alter cell metabolism, tissue re-modeling, and even organismal responses such as increases in heart rate and ventilation. (nobelprize.org)
  • Through the combined work of these three laureates it was thus demonstrated that the response by gene expression to changes in oxygen is directly coupled to oxygen levels in the animal cell, allowing immediate cellular responses to occur to oxygenation through the action of the HIF transcription factor. (nobelprize.org)
  • However, for most of the 20th century, it was not clear how adaptations to oxygen flux were regulated at the fundamental level of gene expression. (nobelprize.org)
  • BT-474 cells, obtained expression of the receptor has important implications for their biology from American Type Culture Collection, were maintained in RPMI 1640 and therapy (1). (lu.se)
  • Explore the normal functions of human genes and the health implications of genetic changes. (medlineplus.gov)
  • 2 In addition, hypoxia induces genetic instability by the induction of fragile sites causing gene amplification. (bmj.com)
  • Genetic studies of the families at high risk for developing renal cancer led to the cloning of genes whose alteration results in tumor formation. (medscape.com)
  • 14 , 15 HIF-1 and HIF-2 mediate adaptive responses to hypoxia by inducing the transcription of genes associated with erythropoiesis, glycolytic metabolism, cell survival and angiogenesis. (haematologica.org)
  • In 1995, Semenza's lab was the first to identify the genes that encode hypoxia-inducible factor-1 (HIF-1), a transcription factor that alters cellular responses to low oxygen. (the-scientist.com)
  • Kaelin's 1999 study of the tumor-suppressor gene VHL, which helps control HIF, has been crucial for understanding cellular responses to changes in oxygen levels, according to a Harvard Medical School press release . (the-scientist.com)
  • GB004 is a small molecule that stabilizes hypoxia inducible factor (HIF-1α), a key transcription factor involved in the cellular responses at the intersection of hypoxia and inflammation. (ecco-ibd.eu)
  • In studies during the early 1990's, Gregg Semenza identified, and then in 1995 purified and cloned, a transcription factor that regulates these oxygen-dependent responses. (nobelprize.org)
  • In breast cancers HIF-1α splice variant levels were compared to clinicopathological parameters including tumour microvessel density and metastasis-free survival. (biomedcentral.com)
  • Significant statistical association was found between tumour grade and HIF-1α TAG ( P = 0.048), and total HIF-1α ( P = 0.048) mRNA levels. (biomedcentral.com)
  • Assessment of Tumour Hypoxia for Prediction of Response to Therapy and Cancer Prognosis. (prnewswire.com)
  • Malignant pleural effusion (MPE) is defined as accumulation of significant exudates with the presence of malignant cells or tumour tissue in the pleural cavity ( 1 ). (biochemia-medica.com)
  • Due to the abnormal structure of tumour vessels and blood flow, the vessels become leaky, permitting the fluid accumulation in the intercellular space, thus increasing the level of hypoxia ( 11 ). (biochemia-medica.com)
  • Gene composition analyses of altered modules revealed that there were 56 common genes (such as MAPK1 , CCNA2 , and GSTM3 ) existing in the four stages. (hindawi.com)
  • Furthermore, based on differentially expressed genes and WGCNA analyses, we found that the hypoxia signaling pathway was enriched under heat shock conditions. (biomedcentral.com)
  • analyses, as well as others (8-11), support the hypothesis that adipose tissue-secreted factors may indeed be potent modulators of inflammation-related disorders such as obe- sity, type 2 diabetes, metabolic syndrome, atherosclerosis, inflammatory bowel disease, thyroid-associated (Graves') ophthalmopathy, breast cancer, and nonalcoholic fatty liver disease. (123dok.org)
  • Hypoxia-inducible factor 1 (HIF-1) plays a central role in cellular adaptation to changes in oxygen availability. (nih.gov)
  • His group found that HIF-1 responds to low oxygen levels by controlling which genes are used in a cell. (the-scientist.com)
  • That was a major accomplishment, but for years after that, nobody knew why it was that this transcription factor was turned on during low oxygen conditions and then turned off during high oxygen conditions," Paul Schumacker , a hypoxia researcher at Northwestern University Feinberg School of Medicine, tells The Scientist . (the-scientist.com)
  • Semenza, the C. Michael Armstrong Professor of Pediatrics at the School of Medicine, is best known for his groundbreaking discovery of hypoxia-inducible factor 1, or HIF-1, which helps cells cope with low oxygen levels. (jhu.edu)
  • The hypoxia-inducible factor 1 protein that he identified controls genes in response to changes in oxygen availability. (jhu.edu)
  • When oxygen levels are low, HIF-1 turns on genes to make new blood cells and blood vessels. (jhu.edu)
  • If the oxygen level is normal, there isn't much H1F-1alpha, but in stress conditions such as a lack of oxygen, there is more of this gene to protect the cell and organism from this stress. (neurosciencenews.com)
  • This knowledge gave us the opportunity to use a noninvasive tool to increase the levels of this factor by simply decreasing the levels of oxygen. (neurosciencenews.com)
  • Hepatocyte growth factor (HGF) is produced by stromal and mesenchymal cells, and it stimulates epithelial cell proliferation, motility, morphogenesis and angiogenesis in various organs via tyrosine phosphorylation of its cognate receptor, Met. (spandidos-publications.com)
  • HGF was cloned as a growth factor for hepatocytes ( 1 , 2 ), is identical to scatter factor (SF) and was originally discovered as a fibroblast-derived cell motility factor for epithelial cells ( 3 ). (spandidos-publications.com)
  • Impaired perfusion of the kidneys, which may lead to stimulation of erythropoietin [EPO] production, is usually due to local renal hypoxia in the absence of systemic hypoxia. (medscape.com)
  • Aneurysms affecting the aorta and renal vessels can lead to kidney infarction and hypoxia. (medscape.com)
  • Additionally, asparaginyl hydroxylation of HIF1α by FIH-1 (HIF1AN) at N803 impairs its interaction with CBP/P300. (wikipedia.org)
  • These subunits are members of the basic helix-loop-helix (bHLH) transcription factor superfamily containing a PAS [PER (Period Clock) -ARNT-SIM (Single-minded)] domain [ 2 ]. (biomedcentral.com)
  • [ 1 ] It accounts for approximately 3% of adult malignancies and 90-95% of neoplasms arising from the kidney. (medscape.com)
  • However, because the thrombopoietin receptor is the only growth factor receptor in hematopoietic stem cells, thrombocytosis can occur before erythrocytosis. (msdmanuals.com)
  • Prominin-1 (CD133), the first member of the prominin family, was first identified in 1997 by two independent study groups examining mouse neuroepithelial and human haematopoietic stem cells, and it was stated that prominin-1 was a common cell surface marker of both stem cells and cancer stem cells ( 6 , 7 ). (biochemia-medica.com)
  • CAIX is considered to be one of the best cellular biomarkers of hypoxia. (prnewswire.com)
  • Hypoxia-inducible factor 1-alpha inhibitor is a protein that in humans is encoded by the HIF1AN gene. (wikipedia.org)
  • Urine appears to be the major route of excretion, with a urine:fecal ratio of approximately 3:1 in humans. (cdc.gov)
  • The study objective was to determine whether hypoxia-inducible factor-1α (HIF-1α) and prominin-1 (CD133) in pleural fluid (P) and serum (S) could be used as biomarkers for diagnosis of lymph node involvement in patients with MPE. (biochemia-medica.com)
  • Concentrations of HIF-1α (P) and CD133/HIF-1α (S) ratio can be used as biomarkers in diagnosing lymph node involvement in MPE patients, according to this experiment. (biochemia-medica.com)
  • Combined the network analysis, molecular docking and in-vitro experiments, the results firstly demonstrated that the treatment effect of DGP on ONFH may be closely related to HIF-1α, VEGFA and HIF-1 signaling pathway. (researchsquare.com)
  • Notably, HSP genes, which function as molecular chaperones, play an important role in heat shock response. (biomedcentral.com)
  • Expressed sequence tag (EST) analysis and developmental polymerase chain reaction (PCR) studies demonstrated that Ov-phy-1 was expressed in L3 and adult parasites. (embl.de)
  • Development of asthma is multifactorial and depends on the interactions among multiple susceptibility genes and environmental factors. (msdmanuals.com)
  • The derived amino acid sequence of Ov-phy-1 encoded a peptide that was most similar to the two Caenorhabditis elegans prolyl 4-hydroxylase homologues and to the isoform II enzymes of vertebrates. (embl.de)
  • CCK8 assays were performed to examine the effect of hypoxia on cell viability. (elis.sk)
  • The association of functional polymorphisms in genes expressed in endothelial cells and smooth muscle cells with the myocardial infarction. (cdc.gov)
  • The prognostic relevance of HIF-1α protein overexpression has been shown in breast cancer. (biomedcentral.com)
  • IRVINE, Calif. , April 10, 2012 /PRNewswire/ -- GeneTex, a leading manufacturer of antibodies , is pleased to announce that they will be launching a new antibody against CAIX, a marker of hypoxia that shows great promise for cancer research. (prnewswire.com)
  • More recently, his group invented tools for cleavage-free large gene insertion via mining microbial recombination protein, and developed single-cell tracking approach for studying cancer biology and cancer immunology. (stanford.edu)
  • The team has shown that drugs that lower HIF-1 levels have anti-cancer properties and may be used as cancer therapies. (jhu.edu)
  • Malignant pleural effusion (MPE) and lymph node metastasis (LNM) presence are poor prognostic factors that have importance for cancer patients. (biochemia-medica.com)
  • A previous study showed that Sema4D could be a pro-vascular element in cancer ( 1 - 3 ). (jcancer.org)
  • Sema4D is regulated by HIF-1 and plays a role in tumor-associated macrophage-induced metastatic behavior and is clinically significant in colon cancer ( 9 ). (jcancer.org)
  • The association between the microsomal epoxide hydrolase 1 gene ( EPHX1 ) Tyr113His polymorphism and lung cancer and breast cancer risk has been reported in many recent studies, but there is no consensus among the results. (geneticsmr.com)
  • Recent evidence suggests that common functional polymorphisms in the hypoxia inducible factor-1α ( HIF-1 α ) gene may play an important role in the development and progression of digestive cancer, but individually published results are inconclusive. (geneticsmr.com)
  • Translocation of NF-κB leads to activation of the genes for IL-6, stress response elements, and many antiapoptotic elements such as IAPs. (oncologynurseadvisor.com)
  • The results indicated that DGP may exert the effect on ONFH targeting on HIF-1α and VEGFA via HIF-1 signaling pathway. (researchsquare.com)
  • The contribution of CXCL12 to hypoxia-induced angiogenesis was examined in vivo using a subcutaneous murine model of neovascularization. (haematologica.org)
  • Targeting the hypoxic niche, and more specifically hypoxia-inducible factor-2, may represent a viable strategy to inhibit angiogenesis in multiple myeloma and progression of this disease. (haematologica.org)
  • Even though the exact mechanisms underlying ischemic injury in the muscle are not completely understood, hypoxia-inducible factor-1 alpha (HIF-1α) has emerged as an attractive target to enhance post ischemic angiogenesis. (frontiersin.org)
  • the effects of hypoxia and fibrosis may also play a role in obesity complications via notably ectopic-lipid accumulation in non-adipocyte cells. (springer.com)
  • 74 Nuclear factor (NF)-κB plays a pivotal role in mounting an inflammatory response. (oncologynurseadvisor.com)
  • In addition, we found 48 and 47 genes that were upregulated and downregulated by HSF1 in response to heat shock, respectively. (biomedcentral.com)
  • In the upregulated genes, we identified one HSP70 potentially regulated by HSF1 in response to heat shock. (biomedcentral.com)
  • From these results, it is evident that not all heat-inducible genes were triggered simultaneously in response to heat shock stress. (biomedcentral.com)
  • The possible hypoxia response element (HRE) sequences in 5' non-coding Region before ATG start codon of Sema4D were screened, followed by point mutagenesis and luciferase assay analysis. (jcancer.org)
  • In this study, we tested the hypothesis that carnosine protects against post ischemia by augmenting HIF-1α angiogenic signaling by Fe 2+ chelation. (frontiersin.org)
  • Osteonecrosis of the femoral head (ONFH) is also defined as avascular necrosis or aseptic necrosis, which is characterized by impaired blood flow to the bone due to trauma or non-traumatic blood flow, resulting in bone cell death[1, 2]. (researchsquare.com)
  • It has been reported that about 80% of patients will suffer from femoral head collapse in 1 to 4 years and finally leading to necrosis even disability without effective treatment [3]. (researchsquare.com)
  • These results suggest that paraspeckles play a role in trapping nuclear PXR in the absence of the ligand to negatively regulate transactivation of its downstream gene. (aspetjournals.org)
  • It encodes the inactive pre-pro-HGF, a single chain of 728 amino acids (83 kDa), which includes a signal sequence ( 1 - 31 ), a heavy α chain (69 kDa), and a light β chain (34 kDa). (spandidos-publications.com)
  • In this review, we aim to describe the relationships and discussed sequence of events associated with hypoxia, ECM remodeling and inflammation in the development of obesity and associated complications. (springer.com)
  • His work has led to one of the first CRISPR/Cas9 gene-editing tools for in vivo gene therapy. (stanford.edu)
  • Two compounds, Compound 1 (1,4-dihydrophenanthrolin-4-one-3-carboxylic acid) and Compound 5 [8-(N-butyl-N-ethylcarbamoyl)-1,4-dihydrophenathrolin-4-one-3-carboxylic acid], with comparable potencies in vivo, were chosen to investigate the effect of the inhibition of the hydroxylation of newly synthesized uterine collagen on the turnover of this protein in vivo. (embl.de)
  • Therefore, reliable markers for hypoxia represent both valuable diagnostic markers and potential targets for therapeutic intervention. (prnewswire.com)
  • The gene encoding the Ov-phy-1 open reading frame contained 11 introns, similar in structure to the gene encoding human prolyl 4-hydroxylase isoform I. Genomic Southern blot, EST and genomic PCR studies demonstrated that the O. volvulus genome contained between three and eight genes closely related to Ov-phy-1. (embl.de)
  • Human genomics 2019 Jan 13 (1): 5. (cdc.gov)
  • These genes are either tumor suppressors ( VHL , TSC ) or oncogenes ( MET ). (medscape.com)