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https://www.readbyqxmd.com/read/29167950/hypoxia-increases-thyroid-cancer-stem-cell-enriched-side-population
#1
K Mahkamova, N Latar, S Aspinall, A Meeson
INTRODUCTION: Hypoxic stress is a feature of rapidly growing thyroid tumours. Cancer progression is thought to be driven by a small population of tumour cells possessing stem cell properties. Hypoxia-inducible factors (HIFs) are important mediators of hypoxia. Both HIF-1alpha and HIF-2alpha have been reported to be expressed in thyroid cancers. There is growing evidence that the HIF pathway plays a significant role in the maintenance of thyroid cancer stem cells (CSC). METHODOLOGY: We have isolated thyroid CSC from a papillary thyroid cancer-derived cell line (BCPAP) and an anaplastic thyroid cancer-derived cell line (SW1736) as side population (SP) cells (a putative stem cell population) and treated them with cobalt chloride (II) to induce hypoxia...
November 22, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/29137374/hypoxia-favors-myosin-heavy-chain-beta-gene-expression-in-an-hif-1alpha-dependent-manner
#2
Lucia Binó, Jiřina Procházková, Katarzyna Anna Radaszkiewicz, Jan Kučera, Jana Kudová, Jiří Pacherník, Lukáš Kubala
The potentiation of the naturally limited regenerative capacity of the heart is dependent on an understanding of the mechanisms that are activated in response to pathological conditions such as hypoxia. Under these conditions, the expression of genes suggested to support cardiomyocyte survival and heart adaptation is triggered. Particularly important are changes in the expression of myosin heavy chain (MHC) isoforms. We propose here that alterations in the expression profiles of MHC genes are induced in response to hypoxia and are primarily mediated by hypoxia inducible factor (HIF)...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29046352/the-lignan-manassantin-is-a-potent-and-specific-inhibitor-of-mitochondrial-complex-i-and-bioenergetic-activity-in-mammals
#3
Yibao Ma, Hae-Ki Min, Unsong Oh, Adam M Hawkridge, Wei Wang, Ahmed A Mohsin, Qun Chen, Arun Sanyal, Edward J Lesnefsky, Xianjun Fang
Dineolignans manassantin A and B from the plant Saururus cernuus are used in traditional medicine to manage a wide range of ailments such as edema, jaundice, and gonorrhea. Cell-based studies have identified several molecular target candidates of manassantin including NF-kappaB, MAPK, STAT3 and hypoxia-inducible factor 1 alpha (HIF-1alpha). It is unclear whether or how these structurally diverse proteins or pathways mediate any of the medical benefits of manassantin in vivo. Moreover, it has been recently reported that manassantin causes developmental arrest in zebrafish by inhibiting the mitochondrial complex I, but it is unknown whether manassantin inhibits mitochondrial respiration in intact mammalian cells and live animals...
October 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28946548/elevated-serum-level-of-lncrna-hif1a-as1-as-a-novel-diagnostic-predictor-for-worse-prognosis-in-colorectal-carcinoma
#4
Wanjun Gong, Ming Tian, Honggen Qiu, Zhenhua Yang
To evaluate the diagnostic efficacy and prognostic value of serum long non-coding RNA (lncRNA) HIF 1alpha-antisense RNA 1 (HIF1A-AS1) in patients with colorectal carcinoma (CRC). We obtained serum samples from 151 CRC patients and 160 health controls. Serum level of HIF1A-AS1 was detected via real-time PCR (RT-PCR). Receiver operating characteristics (ROC) curve analysis was conducted to determine the diagnostic value of HIF1A-AS1. Then HIF1A-AS1 in CRC was divided into high- and low-expression groups, and the associations of the HIF1A-AS1 serum level with clinicopathological features and prognosis were analyzed...
September 1, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28898700/muc1-and-hif-1alpha-signaling-crosstalk-induces-anabolic-glucose-metabolism-to-impart-gemcitabine-resistance-to-pancreatic-cancer
#5
Surendra K Shukla, Vinee Purohit, Kamiya Mehla, Venugopal Gunda, Nina V Chaika, Enza Vernucci, Ryan J King, Jaime Abrego, Gennifer D Goode, Aneesha Dasgupta, Alysha L Illies, Teklab Gebregiworgis, Bingbing Dai, Jithesh J Augustine, Divya Murthy, Kuldeep S Attri, Oksana Mashadova, Paul M Grandgenett, Robert Powers, Quan P Ly, Audrey J Lazenby, Jean L Grem, Fang Yu, José M Matés, John M Asara, Jung-Whan Kim, Jordan H Hankins, Colin Weekes, Michael A Hollingsworth, Natalie J Serkova, Aaron R Sasson, Jason B Fleming, Jennifer M Oliveto, Costas A Lyssiotis, Lewis C Cantley, Lyudmyla Berim, Pankaj K Singh
No abstract text is available yet for this article.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28708594/hypoxia-favors-myosin-heavy-chain-beta-gene-expression-in-an-hif-1alpha-dependent-manner
#6
Lucia Binó, Jiřina Procházková, Katarzyna Anna Radaszkiewicz, Jan Kučera, Jana Kudová, Jiří Pacherník, Lukáš Kubala
The potentiation of the naturally limited regenerative capacity of the heart is dependent on an understanding of the mechanisms that are activated in response to pathological conditions such as hypoxia. Under these conditions, the expression of genes suggested to support cardiomyocyte survival and heart adaptation is triggered. Particularly important are changes in the expression of myosin heavy chain (MHC) isoforms. We propose here that alterations in the expression profiles of MHC genes are induced in response to hypoxia and are primarily mediated by hypoxia inducible factor (HIF)...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28697344/muc1-and-hif-1alpha-signaling-crosstalk-induces-anabolic-glucose-metabolism-to-impart-gemcitabine-resistance-to-pancreatic-cancer
#7
Surendra K Shukla, Vinee Purohit, Kamiya Mehla, Venugopal Gunda, Nina V Chaika, Enza Vernucci, Ryan J King, Jaime Abrego, Gennifer D Goode, Aneesha Dasgupta, Alysha L Illies, Teklab Gebregiworgis, Bingbing Dai, Jithesh J Augustine, Divya Murthy, Kuldeep S Attri, Oksana Mashadova, Paul M Grandgenett, Robert Powers, Quan P Ly, Audrey J Lazenby, Jean L Grem, Fang Yu, José M Matés, John M Asara, Jung-Whan Kim, Jordan H Hankins, Colin Weekes, Michael A Hollingsworth, Natalie J Serkova, Aaron R Sasson, Jason B Fleming, Jennifer M Oliveto, Costas A Lyssiotis, Lewis C Cantley, Lyudmyla Berim, Pankaj K Singh
Poor response to cancer therapy due to resistance remains a clinical challenge. The present study establishes a widely prevalent mechanism of resistance to gemcitabine in pancreatic cancer, whereby increased glycolytic flux leads to glucose addiction in cancer cells and a corresponding increase in pyrimidine biosynthesis to enhance the intrinsic levels of deoxycytidine triphosphate (dCTP). Increased levels of dCTP diminish the effective levels of gemcitabine through molecular competition. We also demonstrate that MUC1-regulated stabilization of hypoxia inducible factor-1α (HIF-1α) mediates such metabolic reprogramming...
July 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28689265/aerobic-glycolysis-hypothesis-through-wnt-beta-catenin-pathway-in-exudative-age-related-macular-degeneration
#8
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Exudative age-related macular degeneration (AMD) is characterized by molecular mechanisms responsible for the initiation of choroidal neovascularization (CNV). Inflammatory processes are associated with upregulation of the canonical WNT/beta-catenin pathway in exudative AMD. We focus this review on the link between WNT/beta-catenin pathway activation and neovascular progression in exudative AMD through activation of aerobic glycolysis for production of angiogenic factors. Increased WNT/beta-catenin pathway involves hexokinase 2 (HK2) and pyruvate kinase M2 (PKM2)...
August 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28686658/a-hypoxia-response-element-in-the-vegfa-promoter-is-required-for-basal-vegfa-expression-in-skin-and-for-optimal-granulation-tissue-formation-during-wound-healing-in-mice
#9
Domenic Ciarlillo, Christophe Celeste, Peter Carmeliet, Derek Boerboom, Christine Theoret
Hypoxia in skin wounds is thought to contribute to healing through the induction of hypoxia inducible factor-1 (HIF-1). Although HIF-1 can regulate the expression of vascular endothelial growth factor A (Vegfa), whether hypoxia and HIF-1 are required to induce Vegfa expression in the context of wound healing is unknown. To test this hypothesis, we evaluated Vegfa expression and wound healing in mutant mice that lack a functional HIF-1 binding site in the Vegfa promoter. Full-thickness excisional wounds were made using a biopsy punch, left to heal by second intention, and granulation tissue isolated on a time course during healing...
2017: PloS One
https://www.readbyqxmd.com/read/28624453/folic-acid-attenuates-cobalt-chloride-induced-pge2-production-in-huvecs-via-the-no-hif-1alpha-cox-2-pathway
#10
Yuming Liang, Xiaozhou Zhen, Kaiwen Wang, Jing Ma
Prostaglandin E2 (PGE2), an important lipid inflammatory mediator involved in the progression of vascular diseases, can be induced by hypoxia in many cell types. While folic acid has been shown to protect against inflammation in THP-1 cells during hypoxia and hypoxia-induced endothelial cell injury, whether it might do so by attenuating PGE2 production remains unclear. To investigate this we constructed a hypoxia-induced injury model by treating human umbilical vein endothelial cells (HUVECs) with cobalt chloride (CoCl2), which mimics the effects of hypoxia...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28619363/acute-hypoxic-stress-effect-on-blood-parameters-antioxidant-enzymes-and-expression-of-hif-1alpha-and-glut-1-genes-in-largemouth-bass-micropterus-salmoides
#11
S Yang, T Yan, H Wu, Q Xiao, H M Fu, J Luo, J Zhou, L L Zhao, Y Wang, S Y Yang, J L Sun, X Ye, S J Li
Dissolved oxygen (DO) plays a crucial role in survival, growth, and normal physiological functions of aquatic organisms. Nevertheless, the mechanisms involved in hypoxic stress and adaptation have not been fully elucidated in Largemouth bass (Micropterus salmoides). To reveal the effect of acute hypoxia on Largemouth bass, we simulated acute hypoxia (DO: 1.2 ± 0.2 mg/L) in the laboratory and analyzed physiological parameters (RBCs, Hb, SOD, CAT, NA(+)/K(+)-ATPase, GPx, and MDA) and gene expression (HIF-1alpha and GLUT-1) in Largemouth bass exposed to various durations of acute hypoxia (0, 1, 2, 4, 8, 12, and 24 h)...
August 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28585205/adipose-tissue-hypoxia-in-obesity-and-its-impact-on-preadipocytes-and-macrophages-hypoxia-hypothesis
#12
REVIEW
Atilla Engin
Obese subjects exhibit lower adipose tissue oxygen consumption in accordance with the lower adipose tissue blood flow. Thus, compared with lean subjects, obese subjects have 44% lower capillary density and 58% lower vascular endothelial growth factor (VEGF). The VEGF expression together with hypoxia-inducible transcription factor-1 (HIF-1) activity also requires phosphatidylinositol 3-kinase (PI3K)- and target of rapamycin (TOR)-mediated signaling. HIF-1alpha is an important signaling molecule for hypoxia to induce the inflammatory responses...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28566998/relative-contribution-of-prolyl-hydroxylase-dependent-and-independent-degradation-of-hif-1alpha-by-proteasomal-pathways-in-cerebral-ischemia
#13
Yomna Badawi, Honglian Shi
Hypoxia inducible factor-1 (HIF-1) is a key regulator in hypoxia and can determine the fate of brain cells during ischemia. However, the mechanism of HIF-1 regulation is still not fully understood in ischemic brains. We tested a hypothesis that both the 26S and the 20S proteasomal pathways were involved in HIF-1α degradation under ischemic conditions. Using in vitro ischemic model (oxygen and glucose deprivation) and a mouse model of middle cerebral artery occlusion, we tested effects of inhibitors of proteasomes and prolyl hydroxylase (PHD) on HIF-1α stability and brain injury in cerebral ischemia...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28386604/hypoxia-determines-survival-outcomes-of-bacterial-infection-through-hif-1alpha-dependent-re-programming-of-leukocyte-metabolism
#14
A A R Thompson, R S Dickinson, F Murphy, J P Thomson, H M Marriott, A Tavares, J Willson, L Williams, A Lewis, A Mirchandani, P Dos Santos Coelho, C Doherty, E Ryan, E Watts, N M Morton, S Forbes, R H Stimson, A G Hameed, N Arnold, J A Preston, A Lawrie, V Finisguerra, M Mazzone, P Sadiku, J Goveia, F Taverna, P Carmeliet, S J Foster, E R Chilvers, A S Cowburn, D H Dockrell, R S Johnson, R R Meehan, M K B Whyte, S R Walmsley
Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer exposures to hypoxia, prior to infection, prevented these pathophysiological responses and profoundly dampened the transcriptome of circulating leukocytes...
February 10, 2017: Science Immunology
https://www.readbyqxmd.com/read/28330872/nadph-oxidase-1-supports-proliferation-of-colon-cancer-cells-by-modulating-reactive-oxygen-species-dependent-signal-transduction
#15
Agnes Juhasz, Susan Markel, Shikha Gaur, Han Liu, Jiamo Lu, Guojian Jiang, Xiwei Wu, Smitha Antony, Yongzhong Wu, Giovanni Melillo, Jennifer L Meitzler, Diana C Haines, Donna Butcher, Krishnendu Roy, James H Doroshow
Reactive oxygen species (ROS) play a critical role in cell signaling and proliferation. NADPH oxidase 1 (NOX1), a membrane-bound flavin dehydrogenase that generates O2(̇̄), is highly expressed in colon cancer. To investigate the role that NOX1 plays in colon cancer growth, we used shRNA to decrease NOX1 expression stably in HT-29 human colon cancer cells. The 80-90% decrease in NOX1 expression achieved by RNAi produced a significant decline in ROS production and a G1/S block that translated into a 2-3-fold increase in tumor cell doubling time without increased apoptosis...
May 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28213554/hypoxia-selectively-enhances-integrin-%C3%AE-5%C3%AE-1-receptor-expression-in-breast-cancer-to-promote-metastasis
#16
Julia A Ju, Inês Godet, I Chae Ye, Jungmin Byun, Hasini Jayatilaka, Sun Joo Lee, Lisha Xiang, Debangshu Samanta, Meng Horng Lee, Pei-Hsun Wu, Denis Wirtz, Gregg L Semenza, Daniele M Gilkes
Metastasis is the leading cause of breast cancer mortality. Previous studies have implicated hypoxia-induced changes in the composition and stiffness of the extracellular matrix (ECM) in the metastatic process. Therefore, the contribution of potential ECM-binding receptors in this process was explored. Using a bioinformatics approach, the expression of all integrin receptor subunits, in two independent breast cancer patient datasets, were analyzed to determine whether integrin status correlates with a validated hypoxia-inducible gene signature...
June 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28071583/anticancer-activities-of-new-n-hetaryl-2-cyanoacetamide-derivatives-incorporating-4-5-6-7-tetrahydrobenzo-b-thiophene-moiety
#17
Magda F Mohamed, Yasmin M Attia, Samia A Shouman, Ismail A Abdelhamid
AIMS: Novel series of N-(4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl) cyanoacetamide derivatives are synthesized. METHOD: The structure of these compounds was elucidated using different spectral tools. Compounds were evaluated for their cytotoxic activities against different types of human cancer cell lines including, breast (MCF-7, T47D, MDA MB231); liver (HEPG-2); colon (HCT116); prostate (PC3); and cervix (HELA) cells. In this study, we used compounds 11 and 12 that showed the highest cytotoxicity on PC3 and HEPG2 cells, to explore their effects on apoptosis, metastasis and angiogenesis of cancer cells...
2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27982675/differential-responsiveness-in-vegf-receptor-subtypes-to-hypoxic-stress-in-various-tissues-of-plateau-animals
#18
Hui-Chun Xie, Jin-Gang Li, Jian-Ping He
With hypoxic stress, hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) are elevated and their responses are altered in skeletal muscles of plateau animals [China Qinghai-Tibetan plateau pikas (Ochotona curzoniae)] as compared with control animals [normal lowland Sprague-Dawley (SD) rats]. The results indicate that HIF-1alpha and VEGF are engaged in physiological functions under hypoxic environment. The purpose of the current study was to examine the protein levels of VEGF receptor subtypes (VEGFRs: VEGFR-1, VEGFR-2 and VEGFR-3) in the end organs, namely skeletal muscle, heart and lung in response to hypoxic stress...
May 4, 2017: Physiological Research
https://www.readbyqxmd.com/read/27845876/hypoxia-induced-microrna-146a-represses-bcl-2-through-traf6-irak1-but-not-smad4-to-promote-chondrocyte-autophagy
#19
Guanghui Chen, Xin Gao, Jing Wang, Cheng Yang, Yang Wang, Yonggang Liu, Weiwei Zou, Tielong Liu
It has been shown that hypoxia stimulation promotes chondrocytes autophagy partly through HIF-1α, miR-146a and Bcl-2 progressively, and this mechanism represented the connection among hypoxia, miR-146a and autophagy, and provides a possible therapeutic strategy for osteoarthritis. However, the interaction between miR-146a and Bcl-2 is still unclear. Here in a hypoxic environment, we quantified the three reported miR-146a targets: two inflammation related targets Traf6, IRAK1; and the only reported target in chondrocytes Smad4...
April 1, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/27836247/implication-of-vhl-erk5-and-hif-1alpha-in-clear-cell-renal-cell-carcinoma-molecular-basis
#20
Leticia Serrano-Oviedo, José M Giménez-Bachs, Syongh Y Nam-Cha, Francisco J Cimas, Jesús García-Cano, Ricardo Sánchez-Prieto, Antonio S Salinas-Sánchez
OBJECTIVES: To determine the expression status of several proteins related to VHL gene function and its relationship with common clinicopathological parameters. MATERIAL AND METHODS: Observational, analytical, cross-sectional study with 50 patients diagnosed with clear cell renal cell carcinoma. The study analyzed VHL mutations and hypermethylation as well as protein expression of VHL, CA-IX, HIF-1alpha, VEGF, ERK1/2, and ERK5, relating them to clinical variables...
March 2017: Urologic Oncology
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