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https://www.readbyqxmd.com/read/28446589/antifibrotic-effects-of-cyclosporine-a-on-tgf-%C3%AE-1-treated-lung-fibroblasts-and-lungs-from-bleomycin-treated-mice-role-of-hypoxia-inducible-factor-1%C3%AE
#1
Risa Yamazaki, Yoshitoshi Kasuya, Tetsuo Fujita, Hiroki Umezawa, Madoka Yanagihara, Hiroyuki Nakamura, Ichiro Yoshino, Koichiro Tatsumi, Toshihiko Murayama
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder that is characterized by aberrant tissue remodeling and the formation of fibroblastic foci that are composed of fibrogenic myofibroblasts. TGF-β1 is one of the factors that are responsible for fibrosis as it promotes fibroblast to myofibroblast differentiation (FMD) and is associated with up-regulation of α-smooth muscle actin. Therefore, inhibition of FMD may represent an effective strategy for the treatment of IPF. Here, we describe the treatment of human lung fibroblasts (WI-38 and HFL-1 cells) with cyclosporine A (CsA), which reduces TGF-β1-induced FMD via degradation of hypoxia-inducible factor-1α (HIF-1α)...
April 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28445928/regulation-of-angiogenic-behaviors-by-oxytocin-receptor-through-gli1-indcued-transcription-of-hif-1%C3%AE-in-human-umbilical-vein-endothelial-cells
#2
Ji Zhu, Huiyan Wang, Xiaoyan Zhang, Yin Xie
Angiogenesis is a dynamic hypoxia-stimulated process playing a key role in tissue growth and repair under various pathophysiological circumstances. Abnormal angiogenesis contributes to the pathogenesis of many human diseases. Oxytocin receptor is a classical G-protein-coupled receptor expressed on endothelial cells. The present study was aimed to investigate how oxytocin receptor regulated the angiogenic behaviors of human umbilical vein endothelial cells (HUVECs). We found that oxytocin at 0.1μM significantly increased cell proliferation, upregulated the mRNA and protein expression of CD31 and vWF (two important endothelial markers), and enhanced the tuber formation capacity in HUVECs...
April 22, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28444885/hypoxia-induced-apoptosis-of-mouse-spermatocytes-is-mediated-by-hif-1%C3%AE-through-a-death-receptor-pathway-and-a-mitochondrial-pathway
#3
Jun Yin, Bing Ni, Wei-Gong Liao, Yu-Qi Gao
Hypoxia in vivo induces oligozoospermia, azoospermia and degeneration of the germinal epithelium, but the underlying molecular mechanism of this induction is not fully clarified. The aim of this study was to investigate the role of the death receptor pathway and the mitochondrial pathway in hypoxia-induced apoptosis of mouse GC-2spd (GC-2) cells and the relationship between HIF-1α and apoptosis of GC-2 cells induced by hypoxia. GC-2 cells were subjected to 1% oxygen for 48 h. Apoptosis was detected by flow cytometry, TUNEL staining, LDH, caspase-3/8/9 in the absence and presence of HIF-1α siRNA...
April 26, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28443025/honokiol-induces-apoptosis-g1-arrest-and-autophagy-in-kras-mutant-lung-cancer-cells
#4
Lian-Xiang Luo, Ying Li, Zhong-Qiu Liu, Xing-Xing Fan, Fu-Gang Duan, Run-Ze Li, Xiao-Jun Yao, Elaine Lai-Han Leung, Liang Liu
Aberrant signaling transduction induced by mutant KRAS proteins occurs in 20∼30% of non-small cell lung cancer (NSCLC), however, a direct and effective pharmacological inhibitor targeting KRAS has not yet reached the clinic to date. Honokiol, a small molecular polyphenol natural biophenolic compound derived from the bark of magnolia trees, exerts anticancer activity, however, its mechanism remains unknown. In this study, we sought to investigate the in vitro effects of honokiol on NSCLC cell lines harboring KRAS mutations...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28436951/hypoxic-lung-cancer-secreted-exosomal-mir-23a-increased-angiogenesis-and-vascular-permeability-by-targeting-prolyl-hydroxylase-and-tight-junction-protein-zo-1
#5
Y-L Hsu, J-Y Hung, W-A Chang, Y-S Lin, Y-C Pan, P-H Tsai, C-Y Wu, P-L Kuo
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28435452/the-yap1-six2-axis-is-required-for-ddx3-mediated-tumor-aggressiveness-and-cetuximab-resistance-in-kras-wild-type-colorectal-cancer
#6
De-Wei Wu, Po-Lin Lin, Lee Wang, Chi-Chou Huang, Huei Lee
The mechanism underlying tumor aggressiveness and cetuximab (CTX) resistance in KRAS-wild-type (KRAS -WT) colorectal cancer remains obscure. We here provide evidence that DDX3 promoted soft agar growth and invasiveness of KRAS-WT cells, as already confirmed in KRAS-mutated cells. Mechanistically, increased KRAS expression induced ROS production, which elevated HIF-1α and YAP1 expression. Increased HIF-1α persistently promoted DDX3 expression via a KRAS/ROS/HIF-1α feedback loop. DDX3-mediated aggressiveness and CTX resistance were regulated by the YAP1/SIX2 axis in KRAS-WT cells and further confirmed in animal models...
2017: Theranostics
https://www.readbyqxmd.com/read/28433571/antitumor-and-chemosensitizing-action-of-3-bromopyruvate-implication-of-deregulated-metabolism
#7
Saveg Yadav, Shrish Kumar Pandey, Ajay Kumar, Praveen Kumar Kujur, Rana Pratap Singh, Sukh Mahendra Singh
3-Bromopyruvate (3-BP), brominated derivative of pyruvate, possesses strong antitumor potential, owing to its ability to inhibit multiple target molecules crucial for survival of neoplastic cells. Although, 3-BP displays cytotoxicity against a wide variety of tumors, there is no report with respect to malignancies of thymic origin. Therefore, we investigated its antineoplastic action in vitro against tumor cells of a murine transplantable lymphoma of thymoma origin, designated as Dalton's lymphoma (DL). 3-BP treatment of tumor cells inhibited metabolism and survival with augmented induction of apoptosis and necrosis...
April 19, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28425505/novel-interactions-of-the-von-hippel-lindau-pvhl-tumor-suppressor-with-the-cdkn1-family-of-cell-cycle-inhibitors
#8
Giovanni Minervini, Raffaele Lopreiato, Raissa Bortolotto, Antonella Falconieri, Geppo Sartori, Silvio C E Tosatto
Germline inactivation of the von Hippel-Lindau (VHL) tumor suppressor predisposes patients to develop different highly vascularized cancers. pVHL targets the hypoxia-inducible transcription factor (HIF-1α) for degradation, modulating the activation of various genes involved in hypoxia response. Hypoxia plays a relevant role in regulating cell cycle progression, inducing growth arrest in cells exposed to prolonged oxygen deprivation. However, the exact molecular details driving this transition are far from understood...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424584/hif-1%C3%AE-overexpression-improves-transplanted-bone-mesenchymal-stem-cells-survival-in-rat-mcao-stroke-model
#9
Bingke Lv, Feng Li, Jianbang Han, Jie Fang, Limin Xu, Chengmei Sun, Tian Hua, Zhongfei Zhang, Zhiming Feng, Xiaodan Jiang
Bone mesenchymal stem cells (BMSCs) death after transplantation is a serious obstacle impacting on the outcome of cell therapy for cerebral infarction. This study was aimed to investigate whether modification of BMSCs with hypoxia-inducible factor 1α (Hif-1α) could enhance the survival of the implanted BMSCs. BMSCs were isolated from Wistar rats, and were infected with Hif-1α-GFP lentiviral vector or Hif-1α siRNA. The modified BMSCs were exposed to oxygen-glucose deprivation (OGD) condition, cellular viability and apoptosis were then assessed...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28423580/procollagen-lysine-2-oxoglutarate-5-dioxygenase-2-promotes-hypoxia-induced-glioma-migration-and-invasion
#10
Yangyang Xu, Lin Zhang, Yuzhen Wei, Xin Zhang, Ran Xu, Mingzhi Han, Bing Huang, Anjing Chen, Wenjie Li, Qing Zhang, Gang Li, Jian Wang, Peng Zhao, Xingang Li
Poor prognosis of glioblastoma multiforme is strongly associated with the ability of tumor cells to invade the brain parenchyma, which is believed to be the major factor responsible for glioblastoma recurrence. Therefore, identifying the molecular mechanisms driving invasion may lead to the development of improved therapies for glioblastoma patients. Here, we investigated the role of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2), an enzyme catalyzing collagen cross-linking, in the biology of glioblastoma invasion...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420165/impact-of-acetazolamide-a-carbonic-anhydrase-inhibitor-on-the-development-of-intestinal-polyps-in-min-mice
#11
Nobuharu Noma, Gen Fujii, Shingo Miyamoto, Masami Komiya, Ruri Nakanishi, Misato Shimura, Sei-Ichi Tanuma, Michihiro Mutoh
Colorectal cancer is a common cancer worldwide. Carbonic anhydrase (CA) catalyzes the reversible conversion of carbon dioxide to bicarbonate ion and a proton, and its inhibitor is reported to reduce cancer cell proliferation and induce apoptosis. Therefore, we asked whether acetazolamide, a CA inhibitor, could inhibit intestinal carcinogenesis. Five-week-old male Apc-mutant mice, Min mice, were fed a AIN-76A diet containing 200 or 400 ppm acetazolamide. As a result, acetazolamide treatment reduced the total number of intestinal polyps by up to 50% compared to the control group...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28418174/hypoxia-upregulates-integrin-gene-expression-in-microvascular-endothelial-cells-and-promotes-their-migration-and-capillary-like-tube-formation
#12
Christina Befani, Panagiotis Liakos
Tissue hypoxia affects gene expression through the hypoxia-inducible transcription factors, HIF-1 and HIF-2, in both physiological and pathological angiogenesis. Angiogenesis is a complex response of endothelial cells integrating cell proliferation, migration, tube formation and their interaction with the extracellular matrix through integrin receptors. In this report, we studied the effect of hypoxia on the angiogenic functions of human microvascular endothelial cells (HMEC-1) as well as on expression of the angiogenic integrins αν β3 , αν β5 and α5 β1 ...
April 18, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28415624/hypoxia-inducible-factor-1a-induces-phenotype-switch-of-human-aortic-vascular-smooth-muscle-cell-through-pi3k-akt-aeg-1-signaling
#13
Kai Liu, Changcun Fang, Yuwen Shen, Zhengqin Liu, Min Zhang, Bingbing Ma, Xinyan Pang
To date, hypoxia-inducible factor 1a (HIF-1a) and astrocyte elevated gene-1 (AEG-1) have been involved in the proliferation, migration and morphological changes of vascular smooth muscle cells. However, the potential relationship of HIF-1a-AEG-1 pathway in human aortic smooth muscle cell (HASMC) has not been reported. In the present study, in-vitro assays were utilized to explore the potential impact of HIF-1a-AEG-1 signaling on HASMC phenotype. Here, we found that HIF-1a expression was up-regulated in the media of thoracic aortic dissection tissues as compared with normal aortic tissues, and was associated with increased apoptotic SMCs and decreased AEG-1 expression...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415047/plod2-in-cancer-research
#14
REVIEW
Hongzhi Du, Mao Pang, Xiaoying Hou, Shengtao Yuan, Li Sun
Collagen is not only the most abundant protein providing the scaffold for assembly of the extracellular matrix (ECM), but also considered to be the "highway" for cancer cell migration and invasion depending on the different collagen organizations. The accumulation of stabilized collagen is enhanced by different covalent collagen cross-links, lysyl hydroxylases 2 (encoded by the PLOD2 gene) is the key enzyme mediating the formation of the stabilized collagen cross-link. Interestingly, PLOD2 is overexpressed in different cancers and closely related to a poor prognosis...
April 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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
#15
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/28409544/hypoxia-and-the-hypoxia-regulated-transcription-factor-hif-1%C3%AE-suppress-the-host-defence-of-airway-epithelial-cells
#16
Markus Polke, Frederik Seiler, Philipp M Lepper, Andreas Kamyschnikow, Frank Langer, Dominik Monz, Christian Herr, Robert Bals, Christoph Beisswenger
Chronic diseases of the respiratory tract, such as cystic fibrosis, are associated with mucosal and systemic hypoxia. Innate immune functions of airway epithelial cells are required to prevent and control infections of the lung parenchyma. The transcription factor hypoxia-inducible factor 1α (HIF-1α) regulates cellular adaptation to low oxygen conditions. Here, we show that hypoxia and HIF-1α regulate innate immune mechanisms of cultured human bronchial epithelial cells (HBECs). Exposure of primary HBECs to hypoxia or the prolyl hydroxylase inhibitor dimethyloxaloylglycine (DMOG) resulted in a significantly decreased expression of inflammatory mediators (IL-6, IFN-γ-induced protein 10) in response to ligands for TLRs (flagellin, polyI:C) and Pseudomonas aeruginosa, whereas the expression of inflammatory mediators was not affected by hypoxia or DMOG in the absence of microbial factors...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28406476/wisp-1-positively-regulates-angiogenesis-by-controlling-vegf-a-expression-in-human-osteosarcoma
#17
Hsiao-Chi Tsai, Huey-En Tzeng, Chun-Yin Huang, Yuan-Li Huang, Chun-Hao Tsai, Shih-Wei Wang, Po-Chuan Wang, An-Chen Chang, Yi-Chin Fong, Chih-Hsin Tang
In recent years, much research has focused on the role of angiogenesis in osteosarcoma, which occurs predominantly in adolescents and young adults. The vascular endothelial growth factor-A (VEGF-A) pathway is the key regulator of angiogenesis and in osteosarcoma. VEGF-A expression has been recognized as a prognostic marker in angiogenesis. Aberrant WNT1-inducible signaling pathway protein-1 (WISP-1) expression is associated with various cancers. However, the function of WISP-1 in osteosarcoma angiogenesis is poorly understood...
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28404924/antitumor-effects-of-cyclin-dependent-kinase-9-inhibition-in-esophageal-adenocarcinoma
#18
Zhimin Tong, Devkumar Chatterjee, Defeng Deng, Omkara Veeranki, Alicia Mejia, Jaffer A Ajani, Wayne Hofstetter, Steven Lin, Sushovan Guha, Scott Kopetz, Sunil Krishnan, Dipen Maru
Role of cyclin dependent kinase 9(CDK9) as a potential target in esophageal adenocarcinoma (EAC) is unknown. We investigated CDK9 protein expression in EAC and Barrett's esophagus and role of CDK9 in oncogenic processes of EAC in vitro and in murine xenografts. The CDK9 expression was significantly higher in EAC as compared to Barrett's esophagus in patient samples. Stable shCDK9 in SKGT4 reduced proliferation by 37% at day 4, increased apoptosis at 48 hours and induced G1 cell cycle arrest at 48 hours (58...
February 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404914/the-preclinical-assessment-of-xl388-a-mtor-kinase-inhibitor-as-a-promising-anti-renal-cell-carcinoma-agent
#19
Zuquan Xiong, Yiwen Zang, Shan Zhong, Lujia Zou, Yishuo Wu, Shenghua Liu, Zujun Fang, Zhoujun Shen, Qiang Ding, Shanwen Chen
XL388 is a mammalian target of rapamycin (mTOR) kinase inhibitor. We demonstrated that XL388 inhibited survival and proliferation of renal cell carcinoma (RCC) cell lines (786-0 and A549) and primary human RCC cells. XL388 activated caspase-dependent apoptosis in the RCC cells. XL388 blocked mTOR complex 1 (mTORC1) and mTORC2 activation, and depleted hypoxia-inducible factor 1α (HIF1α) and HIF-2α expression in RCC cells. Yet, XL388 was ineffective in RCC cells with mTOR shRNA knockdown or kinase-dead mutation...
February 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28400504/cardiopulmonary-phenotype-associated-with-human-phd2-mutation
#20
Nick P Talbot, Thomas G Smith, George M Balanos, Keith L Dorrington, Patrick H Maxwell, Peter A Robbins
Oxygen-dependent regulation of the erythropoietin gene is mediated by the hypoxia-inducible factor (HIF) family of transcription factors. When oxygen is plentiful, HIF undergoes hydroxylation by a family of oxygen-dependent prolyl hydroxylase domain (PHD) proteins, promoting its association with the von Hippel-Lindau (VHL) ubiquitin E3 ligase and subsequent proteosomal degradation. When oxygen is scarce, the PHD enzymes are inactivated, leading to HIF accumulation and upregulation not only of erythropoietin expression, but also the expression of hundreds of other genes, including those coordinating cardiovascular and ventilatory adaptation to hypoxia...
April 2017: Physiological Reports
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