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hypoxic transcription factor

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https://www.readbyqxmd.com/read/28542038/hypoxia-as-a-target-for-drug-combination-therapy-of-liver-cancer
#1
Cressida Bowyer, Andrew L Lewis, Andrew W Lloyd, Gary J Phillips, Wendy M Macfarlane
Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer deaths worldwide. The standard of care for intermediate HCC is transarterial chemoembolization, which combines tumour embolization with locoregional delivery of the chemotherapeutic doxorubicin. Embolization therapies induce hypoxia, leading to the escape and proliferation of hypoxia-adapted cancer cells. The transcription factor that orchestrates responses to hypoxia is hypoxia-inducible factor 1 (HIF-1). The aim of this work is to show that targeting HIF-1 with combined drug therapy presents an opportunity for improving outcomes for HCC treatment...
May 24, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28535509/erythropoietin-inhibits-hypoxia-induced-epithelial-to-mesenchymal-transition-via-upregulation-of-mir-200b-in-hk-2-cells
#2
Jiuxu Bai, Xiao Xiao, Xiaoling Zhang, Hanmin Cui, Junfeng Hao, Jingming Han, Ning Cao
BACKGROUND/AIMS: Renal tubular epithelial-mesenchymal transition (EMT) is regarded as an important factor leading to renal interstitial fibrosis. Erythropoietin (EPO) has been reported to attenuate renal fibrosis. The mechanism underlying this protective effect of EPO remains unclear. In this study, we aim to identify possible mechanisms of the EPO renoprotective effect. METHODS: Hypoxia was induced in vitro by incubating human proximal tubular epithelial cell line HK-2 cells in 1% O2 and 5% CO2...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28534977/runx3-modulates-hypoxia-induced-endothelial-to-mesenchymal-transition-of-human-cardiac-microvascular-endothelial-cells
#3
Yanhua Liu, Jin Zou, Bingong Li, Yuqin Wang, Delong Wang, Yanqin Hao, Xuan Ke, Xingxing Li
Endothelial-mesenchymal transition (EndMT) is an essential mechanism in the cardiovascular system, for both cardiovascular development and cardiovascular diseases (CVDs). Recent studies indicate that runt-related transcription factor 3 (RUNX3) contributes to EndMT and endothelial cell dysfunction. However, the underlying molecular mechanism remains unknown. The present study was designed to investigate the role of RUNX3 in EndMT and endothelial cell function, and to elucidate the underlying molecular mechanism...
May 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28534514/integration-of-hypoxic-hif-%C3%AE-signaling-in-blood-cancers
#4
REVIEW
L Schito, S Rey, M Konopleva
Hypoxia (low O2) is a fundamental microenvironmental determinant of bone marrow (BM) pathophysiology. Recent data from molecular and clinical studies indicate that hematopoiesis and leukemogenesis are dependent upon hypoxia-inducible factors (HIFs), a family of essential transcriptional activators mediating the metazoan hypoxic response. In blood cancers, the synergism between HIF overexpression and stabilization within the hypoxic BM microenvironment promotes disease progression, therapy resistance and relapse...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28526370/synthesis-and-biological-evaluation-of-kresoxim-methyl-analogues-as-novel-inhibitors-of-hypoxia-inducible-factor-hif-1-accumulation-in-cancer-cells
#5
Sanghyuck Lee, Oh Seok Kwon, Chang-Soo Lee, Misun Won, Hyun Seung Ban, Choon Sup Ra
We designed and synthesized strobilurin analogues as hypoxia-inducible factor (HIF) inhibitors based on the molecular structure of kresoxim-methyl. Biological evaluation in human colorectal cancer HCT116 cells showed that most of the synthesized kresoxim-methyl analogues possessed moderate to potent inhibitory activity against hypoxia-induced HIF-1 transcriptional activation. Three candidates, compounds 11b, 11c, and 11d were identified as potent inhibitors against HIF-1 activation with IC50 values of 0.60-0...
May 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28526262/hypoxic-pathobiology-of-breast-cancer-metastasis
#6
REVIEW
Luana Schito, Sergio Rey
Dissemination of breast cancer cells (BCCs) to distant sites (metastasis) is the ultimate cause of mortality in patients with breast cancer. Hypoxia (low O2) is a microenvironmental hallmark of most solid cancers arising as a mismatch between cellular O2 consumption and supply. Hypoxic selection of BCCs triggers molecular and cellular adaptations dependent upon hypoxia-inducible factors (HIFs), a family of evolutionarily conserved transcriptional activators that coordinate the expression of numerous genes controlling each step of the metastatic process...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28525375/ros-enhance-angiogenic-properties-via-regulation-of-nrf2-in-tumor-endothelial-cells
#7
Takayuki Hojo, Nako Maishi, Alam Mohammad Towfik, Kosuke Akiyama, Noritaka Ohga, Masanobu Shindoh, Yasuhiro Hida, Kazuyuki Minowa, Toshiaki Fujisawa, Kyoko Hida
Reactive oxygen species (ROS) are unstable molecules that activate oxidative stress. Because of the insufficient blood flow in tumors, the tumor microenvironment is often exposed to hypoxic condition and nutrient deprivation, which induces ROS accumulation. We isolated tumor endothelial cells (TECs) and found that they have various abnormalities, although the underlying mechanisms are not fully understood. Here we showed that ROS were accumulated in tumor blood vessels and ROS enhanced TEC migration with upregulation of several angiogenesis related gene expressions...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521491/hif-1%C3%AE-acts-as-a-molecular-target-for-simvastatin-cytotoxicity-in-b16-f10-melanoma-cells-cultured-under-chemically-induced-hypoxia
#8
Emilia Licarete, Alina Sesarman, Valentin Florian Rauca, Lavinia Luput, Laura Patras, Manuela Banciu
Our previous studies reported that one of the main mechanisms of the antitumor activity of simvastatin (SIM) in B16.F10 murine melanoma cells was associated with strong suppression of the constitutive cell production of the α subunit of the heterodimeric transcription factor hypoxia-inducible factor (HIF)-1. Thus, the present study aimed to broaden this finding under hypoxic conditions induced by incubation of B16.F10 cells with cobalt chloride, when the constitutive production of HIF-1α in these melanoma cells is amplified by inducible expression of this factor...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28509582/tariquidar-sensitizes-multiple-myeloma-cells-to-proteasome-inhibitors-via-reduction-of-hypoxia-induced-p-gp-mediated-drug-resistance
#9
Barbara Muz, Hubert D Kusdono, Feda Azab, Pilar de la Puente, Cinzia Federico, Mark Fiala, Ravi Vij, Noha N Salama, Abdel Kareem Azab
Multiple myeloma (MM) presents a poor prognosis and high lethality of patients due to development of drug resistance. P-glycoprotein (P-gp), a drug-efflux transporter, is upregulated in MM patients post-chemotherapy and is involved in the development of drug resistance since many anti-myeloma drugs (including proteasome inhibitors) are P-gp substrates. Hypoxia develops in the bone marrow niche during MM progression and has long been linked to chemoresistance. Additionally, hypoxia-inducible transcription factor (HIF-1α) was demonstrated to directly regulate P-gp expression...
May 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28504714/cytoplasmic-translocation-of-mta1-coregulator-promotes-de-repression-of-sgk1-transcription-in-hypoxic-cancer-cells
#10
H Marzook, S Deivendran, B George, G Reshmi, T R Santhoshkumar, R Kumar, M R Pillai
Chromatin remodeling factor metastatic tumor protein 1 (MTA1), one of the most upregulated oncogene in human cancer, has an important role in gene expression, cell survival and promoting hypoxic response. Successful cancer progression is dependent on the ability of cells to utilize its survival pathways for adapting to hypoxic microenvironment. Although MTA1 is a stress-responsive gene, but whether hypoxia modulates its function and its role in engaging other core stress-responsive survival pathway(s) remains unknown...
May 15, 2017: Oncogene
https://www.readbyqxmd.com/read/28498432/time-%C3%A2-and-oxygen-dependent-expression-and-regulation-of-ndrg1-in-human-brain-cancer-cells
#11
Harun Muayad Said, Roghaiyeh Safari, Ghada Al-Kafaji, Ralf-Ingo Ernestus, Mario Löhr, Astrid Katzer, Michael Flentje, Carsten Hagemann
N-myc downstream-regulated gene 1 (NDRG1) is a tumor suppressor with the potential to suppress metastasis, invasion and migration of cancer cells. It is regulated under stress conditions such as starvation or hypoxia. NDRG1 regulation is both induced and controlled by HIF-1α-dependent and -independent pathways under hypoxic conditions. However, there are profound differences in the way NDRG1 expression is regulated by HIF-1α and other transcription factors. Therefore, we aimed to define the time-dependent pattern of NDRG1 mRNA and protein expression in human glioblastoma cell lines in extreme hypoxia and after re-oxygenation as well as under normoxic conditions...
May 3, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28497026/chchd4-regulates-intracellular-oxygenation-and-perinuclear-distribution-of-mitochondria
#12
Luke W Thomas, Oliver Staples, Mark Turmaine, Margaret Ashcroft
Hypoxia is a characteristic of the tumor microenvironment and is known to contribute to tumor progression and treatment resistance. Hypoxia-inducible factor (HIF) dimeric transcription factors control the cellular response to reduced oxygenation by regulating the expression of genes involved in metabolic adaptation, cell motility, and survival. Alterations in mitochondrial metabolism are not only a downstream consequence of HIF-signaling but mitochondria reciprocally regulate HIF signaling through multiple means, including oxygen consumption, metabolic intermediates, and reactive oxygen species generation...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28495754/phd3-is-a-transcriptional-coactivator-of-hif-1%C3%AE-in-nucleus-pulposus-cells-independent-of-the-pkm2-jmjd5-axis
#13
Zachary R Schoepflin, Elizabeth S Silagi, Irving M Shapiro, Makarand V Risbud
The role of prolyl hydroxylase (PHD)-3 as a hypoxia inducible factor (HIF)-1α cofactor is controversial and remains unknown in skeletal tissues. We investigated whether PHD3 controls HIF-1 transcriptional activity in nucleus pulposus (NP) cells through the pyruvate kinase muscle (PKM)-2-Jumonji domain--containing protein (JMJD5) axis. PHD3(-/-) mice (12.5 mo old) showed increased incidence of intervertebral disc degeneration with a concomitant decrease in expression of the HIF-1α targets VEGF-A, glucose transporter-1, and lactate dehydrogenase A...
May 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28487943/mir-26b-5p-regulates-hypoxia-induced-phenotypic-switching-of-vascular-smooth-muscle-cells-via-the-tgf-%C3%AE-smad4-signaling-pathway
#14
Changwu Ruan, Jide Lu, Hairong Wang, Zhiru Ge, Chenjun Zhang, Maochun Xu
Hypoxia contributes to the phenotypic switch of vascular smooth muscle cells (VSMCs). Various microRNAs (miRNAs) participate in this process as post‑transcriptional regulators, however the mechanism remains unclear. In the present study, mouse VSMCs (mVSMCs) harvested from aortas were cultured in normoxic and hypoxic conditions, and the mRNA levels of miR-26b-5p, desmin, H‑caldesmon and smoothelin were quantified using reverse transcription‑quantitative polymerase chain reaction. Following treatment with a miR‑26b‑5p antagonist (agomir) or non‑targeting control (scramble), the cell areas of normoxic and hypoxic mVSMCs were analyzed by immunofluorescence staining...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28487707/functional-balancing-of-the-hypoxia-regulators-rap2-12-and-hra1-takes-place-in-vivo-in-arabidopsis-thaliana-plants
#15
Beatrice Giuntoli, Francesco Licausi, Hans van Veen, Pierdomenico Perata
Plants are known to respond to variations in cellular oxygen availability and distribution by quickly adapting the transcription rate of a number of genes, generally associated to improved energy usage pathways, oxygen homeostasis and protection from harmful products of anaerobic metabolism. In terrestrial plants, such coordinated gene expression program is promoted by a conserved subfamily of ethylene responsive transcription factors called ERF-VII, which act as master activators of hypoxic gene transcription...
2017: Frontiers in Plant Science
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
#16
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/28476028/hif-2%C3%AE-dictates-the-susceptibility-of-pancreatic-cancer-cells-to-trail-by-regulating-survivin-expression
#17
Nanae Harashima, Keizo Takenaga, Miho Akimoto, Mamoru Harada
Cancer cells develop resistance to therapy by adapting to hypoxic microenvironments, and hypoxia-inducible factors (HIFs) play crucial roles in this process. We investigated the roles of HIF-1α and HIF-2α in cancer cell death induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) using human pancreatic cancer cell lines. siRNA-mediated knockdown of HIF-2α, but not HIF-1α, increased susceptibility of two pancreatic cancer cell lines, Panc-1 and AsPC-1, to TRAIL in vitro under normoxic and hypoxic conditions...
April 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28475716/the-role-of-hypoxia-in-angiogenesis-and-extracellular-matrix-regulation-of-intervertebral-disc-cells-during-inflammatory-reactions
#18
Woo-Keun Kwon, Hong Joo Moon, Taek-Hyun Kwon, Youn-Kwan Park, Joo Han Kim
BACKGROUND: The intervertebral disc (IVD) is an avascular structure, and is therefore stable under hypoxic conditions. Previous studies have demonstrated that hypoxia might be related to symptomatic degenerative disc diseases (DDDs); however, the pathomechanism is still poorly understood. OBJECTIVE: To identify the effect of hypoxia on the production of inflammatory mediators, angiogenic factors, and extracellular matrix-regulating enzymes of IVD cells during inflammatory reactions...
May 5, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28468914/rig-i-resists-hypoxia-induced-immunosuppression-and-dedifferentiation
#19
Christina Engel, Grethe Brügmann, Silke Lambing, Larissa H Mühlenbeck, Samira Marx, Christian Hagen, Dorottya Horváth, Marion Goldeck, Janos Ludwig, Anna-Maria Herzner, Jan W Drijfhout, Daniela Wenzel, Christoph Coch, Thomas Tüting, Martin Schlee, Veit Hornung, Gunther Hartmann, Jasper G Van den Boorn
A hypoxic tumor microenvironment is linked to poor prognosis. It promotes tumor cell dedifferentiation and metastasis and desensitizes tumor cells to type-I interferon (IFN), chemotherapy, and irradiation. The cytoplasmic immunoreceptor retinoic acid-inducible gene-I (RIG-I) is ubiquitously expressed in tumor cells and upon activation by 5'-triphosphate RNA (3pRNA) drives the induction of type I IFN and immunogenic cell death. Here, we analyzed the impact of hypoxia on the expression of RIG-I in various human and murine tumor and nonmalignant cell types and further investigated its function in hypoxic murine melanoma...
May 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28468297/hypoxia-hif-and-associated-signaling-networks-in-chronic-kidney-disease
#20
REVIEW
Jing Liu, Qingqing Wei, Chunyuan Guo, Guie Dong, Yu Liu, Chengyuan Tang, Zheng Dong
The pathogenesis of chronic kidney disease (CKD) is complex and apparently multifactorial. Hypoxia or decrease in oxygen supply in kidney tissues has been implicated in CKD. Hypoxia inducible factors (HIF) are a small family of transcription factors that are mainly responsive to hypoxia and mediate hypoxic response. HIF plays a critical role in renal fibrosis during CKD through the modulation of gene transcription, crosstalk with multiple signaling pathways, epithelial-mesenchymal transition, and epigenetic regulation...
April 30, 2017: International Journal of Molecular Sciences
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