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https://www.readbyqxmd.com/read/28521842/clinical-and-prognostic-significance-of-hif-1%C3%AE-overexpression-in-oral-squamous-cell-carcinoma-a-meta-analysis
#1
Jianhua Zhou, Shengyun Huang, Lili Wang, Xiao Yuan, Quanjiang Dong, Dongsheng Zhang, Xuxia Wang
BACKGROUND: Recent studies have indicated an association between hypoxia inducible factor-1 alpha (HIF-1α) expression and poor prognosis in patients with oral squamous cell carcinoma (OSCC); however, definitive evidence of this association is yet to be obtained. We performed a meta-analysis to evaluate the association of HIF-1α expression with clinicopathological characteristics and overall survival (OS) of patients with OSCC. METHODS: A literature search for relevant studies published in English language as of February 05, 2016, was performed on PubMed, Web of Science, and EMBASE databases...
May 18, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28520516/mesenchymal-stem-cell-migration-and-proliferation-are-mediated-by-hypoxia-inducible-factor-1%C3%AE-upstream-of-notch-and-sumo-pathways
#2
María Ciria, Nahuel A García, Imelda Ontoria-Oviedo, Hernán González-King, Rubén Carrero, José Luis De La Pompa, José Anastasio Montero, Pilar Sepúlveda
Mesenchymal stem cells (MSCs) are effective in treating several pathologies. We and others have demonstrated that hypoxia or hypoxia-inducible factor 1 alpha (HIF-1α) stabilization improves several MSC functions, including cell adhesion, migration, and proliferation, thereby increasing their therapeutic potential. To further explore the mechanisms induced by HIF-1α in MSCs, we studied its relationship with Notch signaling and observed that overexpression of HIF-1α in MSCs increased protein levels of the Notch ligands Jagged 1-2 and Delta-like (Dll)1, Dll3, and Dll4 and potentiated Notch signaling only when this pathway was activated...
May 18, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28486965/site-specific-gene-expression-patterns-in-oral-cancer
#3
Gesche Frohwitter, Horst Buerger, Eberhard Korsching, Paul J van Diest, Johannes Kleinheinz, Thomas Fillies
BACKGROUND: Squamous cell carcinomas (SCCs) are the most prevalent malignant tumours within the head and neck. Evidence exists that distinct genes are differentially regulated in SCCs of the oral cavity compared to other head and neck regions. Given this background, the aim of this study was to investigate whether such tumour site-specific gene expression can also be observed in different localizations within the oral cavity. METHODS: Using tissue microarrays (TMAs), we investigated 76 SCCs of the floor of the mouth, 49 SCCs of the tongue and 68 SCCs of other anatomic regions within the oral cavity...
May 10, 2017: Head & Face Medicine
https://www.readbyqxmd.com/read/28486571/ras-oncogene-and-hypoxia-inducible-factor-1-alpha-hif-1%C3%AE-expression-in-the-amazon-fish-colossoma-macropomum-cuvier-1818-exposed-to-benzo-a-pyrene
#4
Grazyelle Sebrenski da Silva, Luciana Mara Lopes Fé, Maria de Nazaré Paula da Silva, Vera Maria Fonseca de Almeida E Val
Benzo[a]pyrene (B[a]P) is a petroleum derivative capable of inducing cancer in human and animals. In this work, under laboratory conditions, we analyzed the responses of Colossoma macropomum to B[a]P acute exposure through intraperitoneal injection of four different B[a]P concentrations (4, 8, 16 and 32 μmol/kg) or corn oil (control group). We analyzed expression of the ras oncogene and the Hypoxia-inducible factor-1 alpha (hif-1α) gene using quantitative real-time PCR. Additionally, liver histopathological changes and genotoxic effects were evaluated through the comet assay...
May 8, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28479297/nkx3-2-induces-oxygen-concentration-independent-and-lysosome-dependent-degradation-of-hif-1%C3%AE-to-modulate-hypoxic-responses-in-chondrocytes
#5
Suhjean Im, Dae-Won Kim
Hypoxia-inducible factor 1-alpha (HIF-1α) is a DNA-binding transcription factor regulating hypoxic responses. It plays a key role in vascularization and angiogenesis as well as various metabolic pathways. Interestingly, during early phase endochondral ossification when HIF expression in chondrocytes is evident, developing cartilage primordia remains avascular until hypertrophic calcification commences. In this work, we uncovered a novel pathway causing oxygen concentration-independent and proteasome-independent degradation of HIF-1α protein...
May 4, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28463588/the-lactate-dehydrogenase-inhibitor-gossypol-inhibits-radiation-induced-pulmonary-fibrosis
#6
Jennifer L Judge, Shannon H Lacy, Wei-Yao Ku, Kristina M Owens, Eric Hernady, Thomas H Thatcher, Jacqueline P Williams, Richard P Phipps, Patricia J Sime, R Matthew Kottmann
Exposure of the lung to ionizing radiation that occurs in radiotherapy, as well as after accidental or intentional mass casualty incident can result in pulmonary fibrosis, which has few treatment options. Pulmonary fibrosis is characterized by an accumulation of extracellular matrix proteins that create scar tissue. Although the mechanisms leading to radiation-induced pulmonary fibrosis remain poorly understood, one frequent observation is the activation of the profibrotic cytokine transforming growth factor-beta (TGF-β)...
May 2, 2017: Radiation Research
https://www.readbyqxmd.com/read/28456938/glioprotective-effect-of-resveratrol-an-emerging-therapeutic-role-for-oligodendroglial-cells
#7
Priscila Machado Rosa, Leo Anderson Meira Martins, Diogo Onofre Souza, André Quincozes-Santos
Resveratrol is a natural polyphenol compound highly found in red wine that displays several beneficial effects on the central nervous system (CNS), preventing or slowing the progression of a wide variety of neurological diseases. Its neuroprotective role is particularly associated to modulation of antioxidant and anti-inflammatory responses in glial cells in a mechanism dependent of heme oxygenase 1 (HO-1) signaling pathway. Oligodendrocyte progenitor cells (OPC), primarily known for giving rise to mature oligodendrocytes, have emerged as dynamic cells that are also important to maintain the CNS homeostasis...
April 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28425047/can-anti-vascular-endothelial-growth-factor-antibody-reverse-radiation-necrosis-a-preclinical-investigation
#8
Chong Duan, Carlos J Perez-Torres, Liya Yuan, John A Engelbach, Scott C Beeman, Christina I Tsien, Keith M Rich, Robert E Schmidt, Joseph J H Ackerman, Joel R Garbow
Anti-vascular endothelial growth factor (anti-VEGF) antibodies are a promising new treatment for late time-to-onset radiation-induced necrosis (RN). We sought to evaluate and validate the response to anti-VEGF antibody in a mouse model of RN. Mice were irradiated with the Leksell Gamma Knife Perfexion™ and then treated with anti-VEGF antibody, beginning at post-irradiation (PIR) week 8. RN progression was monitored via anatomic and diffusion MRI from weeks 4-12 PIR. Standard histology, using haematoxylin and eosin (H&E), and immunohistochemistry staining were used to validate the response to treatment...
April 19, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28423052/inflammation-induced-fetal-growth-restriction-in-rats-is-associated-with-increased-placental-hif-1%C3%AE-accumulation
#9
Kevin P Robb, Tiziana Cotechini, Camille Allaire, Arissa Sperou, Charles H Graham
INTRODUCTION: Hypoxia-inducible factor 1-alpha (HIF-1α) is the oxygen-sensitive subunit of the transcription factor HIF-1, and its expression is increased in placentas from pregnancies complicated by pre-eclampsia (PE). Fetal growth restriction (FGR) and PE often share a common pathophysiology; however, it is unknown whether increased placental HIF-1α occurs in FGR. We previously demonstrated that aberrant maternal inflammation in rats resulted in altered utero-placental perfusion and FGR, both of which were prevented by administration of the nitric oxide mimetic glyceryl trinitrate (GTN)...
2017: PloS One
https://www.readbyqxmd.com/read/28421447/inhibition-of-p-glycoprotein-stimulates-cell-death-under-hypoxia-mimicking-conditions
#10
A S Vdovin, P V Maximchik, A V Kulikov, B D Zhivotovsky, V G Gogvadze
The most common drug resistance mechanism in tumor cells is expression on their surface of the energy-dependent pump like P-glycoprotein (P-gp) that expels chemotherapeutic agents from the interior. An imitation of the hypoxic condition by the iron chelator deferoxamine caused Hypoxia-inducible factor 1-alpha (HIF-1α) stabilization and inhibition of doxorubicin-induced apoptosis in colon cancer НСТ116 cells. P-gp blocker verapamil suppressed doxorubicin accumulation leading to cell death induction. Considering these results, P-gp may be used as a potential target to stimulate chemotherapeutic drugs activity that will contribute to more efficient tumor cells elimination...
January 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28420787/activation-of-nlrp3-inflammasome-complex-potentiates-venous-thrombosis-in-response-to-hypoxia
#11
Neha Gupta, Anita Sahu, Amit Prabhakar, Tathagata Chatterjee, Tarun Tyagi, Babita Kumari, Nilofar Khan, Velu Nair, Nitin Bajaj, Manish Sharma, Mohammad Zahid Ashraf
Venous thromboembolism (VTE), caused by altered hemostasis, remains the third most common cause of mortality among all cardiovascular conditions. In addition to established genetic and acquired risk factors, low-oxygen environments also predispose otherwise healthy individuals to VTE. Although disease etiology appears to entail perturbation of hemostasis pathways, the key molecular determinants during immediate early response remain elusive. Using an established model of venous thrombosis, we here show that systemic hypoxia accelerates thromboembolic events, functionally stimulated by the activation of nucleotide binding domain, leucine-rich-containing family, pyrin domain containing 3 (NLRP3) inflammasome complex and increased IL-1β secretion...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28418093/hypoxia-inducible-factor-1-alpha-does-not-regulate-osteoclastogenesis-but-enhances-bone-resorption-activity-via-prolyl-4-hydroxylase-2
#12
Philippa A Hulley, Tammie Bishop, Aude Vernet, Jurgen E Schneider, James R Edwards, Nick A Athanasou, Helen J Knowles
Osteogenic-angiogenic coupling is promoted by the Hypoxia-Inducible Factor 1-alpha (HIF-1α) transcription factor, provoking interest in HIF activation as a therapeutic strategy to improve osteoblast mineralisation and treat pathological osteolysis. However, HIF also enhances the bone resorbing activity of mature osteoclasts. It is therefore essential to determine the full effect(s) of HIF on both the formation and bone-resorbing function of osteoclasts in order to understand how they might respond to such a strategy...
April 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28410378/metabolic-changes-and-inflammation-in-cultured-astrocytes-from-the-5xfad-mouse-model-of-alzheimer-s-disease-alleviation-by-pantethine
#13
Manuel van Gijsel-Bonnello, Kévin Baranger, Philippe Benech, Santiago Rivera, Michel Khrestchatisky, Max de Reggi, Bouchra Gharib
Astrocytes play critical roles in central nervous system homeostasis and support of neuronal function. A better knowledge of their response may both help understand the pathophysiology of Alzheimer's disease (AD) and implement new therapeutic strategies. We used the 5xFAD transgenic mouse model of AD (Tg thereafter) to generate astrocyte cultures and investigate the impact of the genotype on metabolic changes and astrocytes activation. Metabolomic analysis showed that Tg astrocytes exhibited changes in the glycolytic pathway and tricarboxylic acid (TCA) cycle, compared to wild type (WT) cells...
2017: PloS One
https://www.readbyqxmd.com/read/28410215/cardiac-glycosides-suppress-the-maintenance-of-stemness-and-malignancy-via-inhibiting-hif-1%C3%AE-in-human-glioma-stem-cells
#14
Dae-Hee Lee, Sang Cheul Oh, Amber J Giles, Jinkyu Jung, Mark R Gilbert, Deric M Park
Tissue hypoxia contributes to solid tumor pathogenesis by activating a series of adaptive programs. We previously showed that hypoxia promotes the preferential expansion and maintenance of CD133 positive human glioma stem cells (GSC) in a hypoxia inducible factor 1 alpha (HIF-1α)-dependent mechanism. Here, we examined the activity of digitoxin (DT), a cardiac glycoside and a putative inhibitor of HIF-1α, on human GSC in vitro and in vivo. During hypoxic conditions (1% O2), we observed the effect of DT on the intracellular level of HIF-1α and the extracellular level of vascular endothelial growth factor (VEGF) in human GSC...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28376567/hypoxia-inducible-factor-1%C3%AE-potentiates-jagged-1-mediated-angiogenesis-by-mesenchymal-stem-cell-derived-exosomes
#15
Hernán Gonzalez-King, Nahuel A García, Imelda Ontoria-Oviedo, María Ciria, José Anastasio Montero, Pilar Sepúlveda
Insufficient vessel growth associated with ischemia remains an unresolved issue in vascular medicine. Mesenchymal stem cells (MSCs) have been shown to promote angiogenesis via a mechanism that is potentiated by hypoxia. Overexpression of hypoxia inducible factor (HIF)-1α in MSCs improves their therapeutic potential by inducing angiogenesis in transplanted tissues. Here, we studied the contribution of exosomes released by HIF-1α-overexpressing donor MSCs (HIF-MSC) to angiogenesis by endothelial cells. Exosome secretion was enhanced in HIF-MSC...
April 4, 2017: Stem Cells
https://www.readbyqxmd.com/read/28320353/genome-independent-hypoxic-repression-of-estrogen-receptor-alpha-in-breast-cancer-cells
#16
Mercè Padró, Raymond J Louie, Brian V Lananna, Adam J Krieg, Luika A Timmerman, Denise A Chan
BACKGROUND: About 75-80% of breast tumors express the estrogen receptor alpha (ER-α) and are treated with endocrine-target therapeutics, making this the premier therapeutic modality in the breast cancer clinic. However, acquired resistance is common and about 20% of resistant tumors loose ER-α expression via unknown mechanisms. Inhibition of ER-α loss could improve endocrine therapeutic efficacy, benefiting a significant number of patients. Here we test whether tumor hypoxia might commonly produce ER-α loss...
March 20, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28295343/epithelial-membrane-protein-2-emp2-deficiency-alters-placental-angiogenesis-mimicking-features-of-human-placental-insufficiency
#17
Carmen J Williams, Alison Chu, Wendy N Jefferson, David Casero, Deepthi Sudhakar, Nevil Khurana, Claire P Hogue, Chinmayi Aryasomayajula, Priya Patel, Peggy Sullivan, Elizabeth Padilla-Banks, Shabnam Mohandessi, Carla Janzen, Madhuri Wadehra
Epithelial membrane protein-2 (EMP2) is a tetraspan protein predicted to regulate placental development. Highly expressed in secretory endometrium and trophectoderm cells, previous studies suggest that it may regulate implantation by orchestrating the surface expression of integrins and other membrane proteins. In order to test the role of EMP2 in pregnancy, mice lacking EMP2 (Emp2(-/-) ) were generated. Emp2(-/-) females are fertile but have reduced litter sizes when carrying Emp2(-/-) but not Emp2(+/-) fetuses...
June 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28278175/pneumococcal-infection-of-respiratory-cells-exposed-to-welding-fumes-role-of-oxidative-stress-and-hif-1-alpha
#18
Jonathan Grigg, Lisa Miyashita, Reetika Suri
Welders are more susceptible to pneumococcal pneumonia. The mechanisms are yet unclear. Pneumococci co-opt the platelet activating factor receptor (PAFR) to infect respiratory epithelial cells. We previously reported that exposure of respiratory cells to welding fumes (WF), upregulates PAFR-dependent pneumococcal infection. The signaling pathway for this response is unknown, however, in intestinal cells, hypoxia-inducible factor-1 α (HIF 1α) is reported to mediate PAFR-dependent infection. We sought to assess whether oxidative stress plays a role in susceptibility to pneumococcal infection via the platelet activating factor receptor...
2017: PloS One
https://www.readbyqxmd.com/read/28263965/l-2-hydroxyglutarate-production-arises-from-noncanonical-enzyme-function-at-acidic-ph
#19
Andrew M Intlekofer, Bo Wang, Hui Liu, Hardik Shah, Carlos Carmona-Fontaine, Ariën S Rustenburg, Salah Salah, M R Gunner, John D Chodera, Justin R Cross, Craig B Thompson
The metabolite 2-hydroxyglutarate (2HG) can be produced as either a D-R- or L-S- enantiomer, each of which inhibits α-ketoglutarate (αKG)-dependent enzymes involved in diverse biologic processes. Oncogenic mutations in isocitrate dehydrogenase (IDH) produce D-2HG, which causes a pathologic blockade in cell differentiation. On the other hand, oxygen limitation leads to accumulation of L-2HG, which can facilitate physiologic adaptation to hypoxic stress in both normal and malignant cells. Here we demonstrate that purified lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) catalyze stereospecific production of L-2HG via 'promiscuous' reduction of the alternative substrate αKG...
May 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28251972/-zinc-induces-normoxic-accumulation-of-transcriptionally-active-hypoxia-inducible-factor-1-alpha-in-mammary-epithelial-cells
#20
S-Y Lee, S Mustafa, Y-W Ching, N Shafee
Both zinc and the α-subunit of hypoxia-inducible factor (HIF-1α) play important roles in the remodelling of mammary gland tissues. In the present study, we examined the level and the transcriptional activity of HIF-1α in mammary cells upon zinc treatment. In MCF-7 mammary adenocarcinoma and MCF-10A mammary epithelial cell lines, the toxicity levels of zinc differ. Interestingly, both cell lines overexpress HIF-1α following zinc treatment. As it was evident from an up-regulation of its specific target gene CA9 that encodes carbonic anhydrase IX, the stabilized HIF-1α translocated to the nucleus and was transcriptionally active...
January 2017: Molekuliarnaia Biologiia
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