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https://www.readbyqxmd.com/read/28718406/targeting-hypoxia-inducible-factors-for-antiangiogenic-cancer-therapy
#1
REVIEW
Sergio Rey, Luana Schito, Bradly G Wouters, Scott Eliasof, Robert S Kerbel
Hypoxia (low O2) is a pathobiological hallmark of solid cancers, resulting from the imbalance between cellular O2 consumption and availability. Hypoxic cancer cells (CCs) stimulate blood vessel sprouting (angiogenesis), aimed at restoring O2 delivery to the expanding tumor masses through the activation of a transcriptional program mediated by hypoxia-inducible factors (HIFs). Here, we review recent data suggesting that the efficacy of antiangiogenic (AA) therapies is limited in some circumstances by HIF-dependent compensatory responses to increased intratumoral hypoxia...
July 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28716863/opposing-regulation-and-roles-for-phd3-in-lung-dendritic-cells-and-alveolar-macrophages
#2
Simon J Tavernier, Nele Vanlangenakker, Jessica Vetters, Peter Carmeliet, Sophie Janssens, Bart N Lambrecht
The prolyl hydroxylase domain-containing enzymes (PHDs) are important metabolic sensors of the cell and its environment, which might be employed to alert cells of the immune system. These enzymes regulate the expression of the hypoxia inducible factor (HIF) isoforms and NF-κB, crucial transcription factors controlling cellular metabolism and inflammation. PHD/HIF signaling is activated in the allergic lung and is proposed as a potential druggable pathway. Here, we investigated the regulation and role of the PHD isoforms in CD11c-expressing dendritic cells (DCs) and macrophages (Mϕ), sensors of the environment and crucial antigen-presenting cells in the pathogenesis of asthma...
July 17, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28716107/biomarkers-of-resistance-to-radiation-therapy-a-prospective-study-in-cervical-carcinoma
#3
P Moreno-Acosta, A Vallard, S Carrillo, O Gamboa, A Romero-Rojas, M Molano, J Acosta, D Mayorga, C Rancoule, M A Garcia, M Cotes Mestre, N Magné
BACKGROUND: Clinical parameters and proteins have recently been suggested as possible causes of radiotherapy (RT) resistance in cervical carcinoma (CC). The objective of the present study was to validate prognostic biomarkers of radiation resistance. METHODS: The present prospective study included patients undergoing RT with curative intent for histologically proven locally advanced squamous cell CC. Tissues and blood samples were systematically collected before RT initiation...
July 17, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28715868/microrna-150-attenuates-hypoxia-induced-excessive-proliferation-and-migration-of-pulmonary-arterial-smooth-muscle-cells-through-reducing-hif-1%C3%AE-expression
#4
Mantian Chen, Chengxing Shen, Yi Zhang, Hong Shu
Pulmonary arterial hypertension (PAH) is a progressive, fatal disease for which currently there is no curative therapy available. Pathologic changes in this disease involve excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). However, the underlying role of miR-150 in PASMCs remains elusive. Here in this study, miR-150 down-regulation was observed in hypoxia-treated PASMCs. Restoration of miR-150 attenuates hypoxia-treated PASMC proliferation and migration. Luciferase reporter assay showed that miR-150 directly regulated expression of HIF-1α...
July 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28715484/multiple-renal-cancer-susceptibility-polymorphisms-modulate-the-hif-pathway
#5
Steffen Grampp, Virginia Schmid, Rafik Salama, Victoria Lauer, Franziska Kranz, James L Platt, James Smythies, Hani Choudhry, Margarete Goppelt-Struebe, Peter J Ratcliffe, David R Mole, Johannes Schödel
Un-physiological activation of hypoxia inducible factor (HIF) is an early event in most renal cell cancers (RCC) following inactivation of the von Hippel-Lindau tumor suppressor. Despite intense study, how this impinges on cancer development is incompletely understood. To test for the impact of genetic signals on this pathway, we aligned human RCC-susceptibility polymorphisms with genome-wide assays of HIF-binding and observed highly significant overlap. Allele-specific assays of HIF binding, chromatin conformation and gene expression together with eQTL analyses in human tumors were applied to mechanistic analysis of one such overlapping site at chromosome 12p12...
July 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28713928/upregulation-of-wnt-signaling-under-hypoxia-promotes-lung-cancer-progression
#6
Chun-Fu Hong, Wei-You Chen, Cheng-Wen Wu
The hypoxic tumor microenvironment induces epithelial-mesenchymal transition (EMT) in tumor cells and increases tumor cell malignancy. Previous studies indicated that malfunction of Wnt signaling is observed in some lung cancer patients. Athough crosstalk between hypoxia and Wnt signaling in tumor cells has recently been revealed, the detailed underlying mechanisms have not been well defined. In the present study, we demonstrated that hypoxia in lung adenocarcinoma cells can enhance Wnt signaling activity by stabilizing β-catenin and altering its localization into the nucleus...
July 12, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28712399/-expressions-of-stem-cell-factor-and-hypoxia-inducible-factor-1-alpha-in-pancreatic-cancer-cells-and-related-mechanism
#7
Min Zhang, Yunjian Wang, Qiong Li, Qingjun Li, Nanmu Yang, Guohua You, Li Wang
Objective To study the correlation between the expressions of stem cell factor (SCF) and hypoxia inducible factor 1 alpha (HIF-1α) in pancreatic cancer, and investigate the mechanism by which SCF regulates the expression of HIF-1α. Methods Immunohistochemistry was used to detect the expressions of SCF and HIF-1α in pancreatic cancer specimens and to analyze the correlation between SCF and HIF-1α expressions. Pancreatic cancer PANC-1 cells were treated with different doses of SCF (0, 1, 10, 100 ng/mL) alone or combined with c-KIT inhibitor Gleevec (5 μmol/L)...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28712397/-stem-cell-factor-enhances-invasive-ability-of-bxpc-3-cells-via-hypoxia-inducible-factor-1%C3%AE-hif-1%C3%AE
#8
Min Zhang, Kang Guo, Qiong Li, Yunjian Wang, Ling Zhang, Tao He, Baishun Wan, Xiaoqian Wang
Objective To investigate the effect of stem cell factor (SCF)/c-KIT system on the invasion of BxPC-3 pancreatic cancer cells and the role of hypoxia-inducible factor 1 alpha (HIF-1α) in this effect. Methods BxPC-3 cells were cultured in normoxia and hypoxia. The cells cultured in normoxia were treated with SCF. Real-time quantitative PCR and Western blotting were used to investigate the expressions of HIF-1α mRNA and protein, respectively. Small interference RNA of HIF-1α (siHIF-1α) was designed and synthesized, and then transfected into BxPC-3 cells...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28711911/human-steroid-sulfatase-induces-wnt-%C3%AE-catenin-signaling-and-epithelial-mesenchymal-transition-by-upregulating-twist1-and-hif-1%C3%AE-in-human-prostate-and-cervical-cancer-cells
#9
Sangyun Shin, Hee-Jung Im, Yeo-Jung Kwon, Dong-Jin Ye, Hyoung-Seok Baek, Donghak Kim, Hyung-Kyoon Choi, Young-Jin Chun
Steroid sulfatase (STS) catalyzes the hydrolysis of estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) to their unconjugated biologically active forms. Although STS is considered a therapeutic target for estrogen-dependent diseases, the cellular functions of STS remain unclear. We found that STS induces Wnt/β-catenin s Delete ignaling in PC-3 and HeLa cells. STS increases levels of β-catenin, phospho-β-catenin, and phospho-GSK3β. Enhanced translocation of β-catenin to the nucleus by STS might activate transcription of target genes such as cyclin D1, c-myc, and MMP-7...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28710377/antiangiogenic-activity-of-phthalides-enriched-angelica-sinensis-extract-by-suppressing-wsb-1-pvhl-hif-1%C3%AE-vegf-signaling-in-bladder-cancer
#10
Meng-Chuan Chen, Wen-Lin Hsu, Wen-Liang Chang, Tz-Chong Chou
The hypoxia-inducible factor-1α (HIF-1α) plays a critical role in tumor angiogenesis. It has been reported that the acetone extract of Angelica sinensis (AE-AS) rich in phthalides is able to inhibit cancer cell proliferation. However, whether AE-AS reduces cancer angiogenesis remains unknown. In this study, we demonstrated that AE-AS significantly inhibited the angiogenesis in vitro and in vivo evidenced by attenuation of the tube formation in hypoxic human umbilical vascular endothelial cells (HUVECs), and the vasculature generation in Matrigel plug, the chicken chorioallantoic membrane, and tumors...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709643/hypoxia-induced-suppression-of-c-myc-by-hif-2%C3%AE-in-human-pulmonary-endothelial-cells-attenuates-tfam-expression
#11
Ali J Zarrabi, Derrick Kao, Dustin T Nguyen, Joseph Loscalzo, Diane E Handy
The adaptive response to hypoxia is mediated in large part by stabilization of the hypoxia-inducible factors, HIF-1α and HIF-2α. A hallmark of this response is the metabolic shift to decreased oxidative phosphorylation and increased glycolysis. We hypothesized that hypoxic responses would include a suppression of mitochondrial gene expression. We determined the effects of hypoxia on TFAM, a key mitochondrial transcription factor, in normal pulmonary artery endothelial cells. Hypoxia decreased gene expression of TFAM and that of its upstream regulator, the transcriptional co-activator PGC1β...
July 11, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28709426/xue-fu-zhu-yu-decoction-protects-rats-against-retinal-ischemia-by-downregulation-of-hif-1%C3%AE-and-vegf-via-inhibition-of-rbp2-and-pkm2
#12
Shu-Qiu Tan, Xue Geng, Jorn-Hon Liu, Wynn Hwai-Tzong Pan, Li-Xiang Wang, Hui-Kang Liu, Lei Hu, Hsiao-Ming Chao
BACKGROUND: Retinal ischemia-related eye diseases result in visual dysfunction. This study investigates the protective effects and mechanisms of Xue-Fu-Zhu-Yu decoction (XFZYD) with respect to retinal ischemia. METHODS: Retinal ischemia (I) was induced in Wistar rats by a high intraocular pressure (HIOP) of 120 mmHg for 1 h, which was followed by reperfusion of the ischemic eye; the fellow untreated eye acted as a control. Electroretinogram (ERG), biochemistry and histopathology investigations were performed...
July 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28708941/regulation-of-the-insulin-akt-signaling-pathway-and-glycolysis-during-dehydration-stress-in-the-african-clawed-frog-xenopus-laevis
#13
Cheng-Wei Wu, Shannon N Tessier, Kenneth B Storey
Estivation is an adaptive stress response utilized by some amphibians during periods of drought in the summer season. In this study, we examine the regulation of the insulin signaling cascade and glycolysis pathway in the African clawed frog Xenopus laevis during dehydration stress induced state of estivation. We show that in the brain and heart of X. laevis, dehydration reduces the phosphorylation of the insulin growth factor-1 receptor (IGF-1R), and this is followed by similar reductions in the phosphorylation of the Akt and mechanistic target of rapamycin (mTOR) kinase...
July 14, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28708594/hypoxia-favors-myosin-heavy-chain-beta-gene-expression-in-an-hif-1alpha-dependent-manner
#14
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/28708593/microrna-33a-5p-increases-radiosensitivity-by-inhibiting-glycolysis-in-melanoma
#15
Ke Cao, Jingjing Li, Jia Chen, Li Qian, Aijun Wang, Xiang Chen, Wei Xiong, Jintian Tang, Shijie Tang, Yong Chen, Yao Chen, Yan Cheng, Jianda Zhou
Glycolysis was reported to have a positive correlation with radioresistance. Our previous study found that the miR-33a functioned as a tumor suppressor in malignant melanoma by targeting hypoxia-inducible factor1-alpha (HIF-1α), a gene known to promote glycolysis. However, the role of miR-33a-5p in radiosensitivity remains to be elucidated. We found that miR-33a-5p was downregulated in melanoma tissues and cells. Cell proliferation was downregulated after overexpression of miR-33a-5p in WM451 cells, accompanied by a decreased level of glycolysis...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28708281/cooperation-of-hif-and-ncam-mediated-mechanisms-in-cell-viability-of-hippocampal-cultures-after-oxygen-glucose-deprivation
#16
Lushnikova Iryna, Nikandrova Yelyzaveta, Skibo Galyna
Neurodegenerative diseases of different genesis are the result of cellular damages including those caused by oxygen and glucose deficit. Neuronal survival or death in brain pathologies depends on a variety of interrelated molecular mechanisms. A key role in modulation of neuron viability belongs to HIF (hypoxia-inducible factor) and NCAM (neural cell adhesion molecules) signaling pathways. In this work we used organotypic and dissociated hippocampal cultures to analyze cell viability and HIF-1α immunopositive (HIF-1α(+) ) signal after 30 minutes oxygen-glucose deprivation (OGD) followed by 24 h of reoxygenation in the presence of FGL (synthetic NCAM-derived mimetic peptide)...
July 14, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28707593/effects-of-some-indigenous-plants-of-north-karnataka-india-on-cardiovascular-and-glucose-regulatory-systems-in-diabetic-rats
#17
Kusal K Das, Kailash S Chadchan, R Chandramouli Reddy, M S Biradar, Pallavi S Kanthe, Bheemshetty S Pati, Jeevan G Ambekar, Ishwar B Bagoji, Swastika Das
BACKGROUND: The medicinal plants of north Karnataka, India are always researchers delight as many of these plants are rarely found in elsewhere other than this part of India. Kenaf leaves (Hibiscus cannabinus Linn, Pundi), Chick pea leaves (Cicer arietinum Linn, Chana) and Prickly lettuce leaves (Lactuca scariola Linn, Hattaraki.) are a few of these indigenous plants which are routinely consumed by the people as diet in this part of India. Various studies were done on these plants to find out some potential anti diabetic efficacies but reports are still not encouraging...
July 12, 2017: Cardiovascular & Hematological Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28707199/radiation-induced-inflammatory-cascade-and-its-reverberating-crosstalks-as-potential-cause-of-post-radiotherapy-second-malignancies
#18
REVIEW
Sonia Gandhi, Sudhir Chandna
The disease-free survival following radiotherapy is often limited by the development of second/secondary cancers. This significant impediment to effective cancer treatment implicated even in the modern-day radiotherapy needs to be countered effectively. Critical analysis reveals that besides achieving effective tumor control, radiotherapy elicits certain cellular and systemic inflammatory events in tumor infiltrate, which remain relatively stable and tend to facilitate "in-field" or "out of field" oncogenesis in due course of time...
July 13, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28707162/pulmonary-surfactant-associated-proteins-and-inflammatory-factors-in-obstructive-sleep-apnea
#19
Dongmei Lu, Ayiniger Abulimiti, Ting Wu, Ailigen Abudureyim, Nanfang Li
PURPOSE: Pulmonary surfactant (PS) plays roles in promoting the removal of the liquid, host defense, and immune regulation in the tracheal, bronchial, and alveoli epithelium. PS protein expression level can be regulated by oxygen levels and related free radicals. Obstructive sleep apnea (OSA) is featured with oxygen free radical production for damaging epithelial tissues and thus may affect PS production. The study was to explore the relationship between PS protein and OSA severity. METHODS: We collected serum and bronchoalveolar lavage fluid (BALF) samples from 35 OSA patients and 22 healthy subjects...
July 13, 2017: Sleep & Breathing, Schlaf & Atmung
https://www.readbyqxmd.com/read/28706950/effects-of-cobalt-chloride-a-hypoxia-mimetic-agent-on-autophagy-and-atrophy-in-skeletal-c2c12-myotubes
#20
Rui Chen, Ting Jiang, Yanling She, Jiehua Xu, Cheng Li, Shanyao Zhou, Huijuan Shen, Huacai Shi, Shuang Liu
BACKGROUND: Hypoxia-induced autophagy and muscle wasting occur in several environmental and pathological conditions. However, the molecular mechanisms underlying the effects of the hypoxia-mimetic agent CoCl2 on autophagy and muscle atrophy are still unclear. METHODS: C2C12 myotubes were exposed to increasing concentrations of CoCl2 for 24 hours. Quantitative RT-PCR, Western blotting, and transmission electron microscopy were performed to confirm autophagy occurs...
2017: BioMed Research International
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