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Tumor hypoxia

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https://www.readbyqxmd.com/read/29145444/inhibition-of-the-h3k9-methyltransferase-g9a-attenuates-oncogenicity-and-activates-the-hypoxia-signaling-pathway
#1
Jolene Caifeng Ho, Lissa Nurrul Abdullah, Qing You Pang, Sudhakar Jha, Edward Kai-Hua Chow, Henry Yang, Hiroyuki Kato, Lorenz Poellinger, Jun Ueda, Kian Leong Lee
Epigenetic mechanisms play important roles in the regulation of tumorigenesis, and hypoxia-induced epigenetic changes may be critical for the adaptation of cancer cells to the hypoxic microenvironment of solid tumors. Previously, we showed that loss-of-function of the hypoxia-regulated H3K9 methyltransferase G9A attenuates tumor growth. However, the mechanisms by which blockade of G9A leads to a tumor suppressive effect remain poorly understood. We show that G9A is highly expressed in breast cancer and is associated with poor patient prognosis, where it may function as a potent oncogenic driver...
2017: PloS One
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#2
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29144032/microrna-106b-overexpression-alleviates-inflammation-injury-of-cardiac-endothelial-cells-by-targeting-blnk-via-the-nf-%C3%AE%C2%BAb-signaling-pathway
#3
Zhe An, Guang Yang, Wei Nie, Jin Ren, Dan Wang
We aim to investigate whether microRNA-106b (miR-106b) affects the inflammation injury of cardiac endothelial cells (ECs) by targeting B-cell linker (BLNK) via the NF-κB signaling pathway. Human cardiac microvascular endothelial cells (HCMECs) were assigned into the control, hypoxia/reoxygenation (H/R), negative control (NC), pyrrolidine dithiocarbamate (PDTC), miR-106b mimic, miR-106b inhibitor, and si-BLNK and miR-106b inhibitor + si-BLNK groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were conducted for miR-106b expression and expressions of BLNK, interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, NF-κB, pIκBα, BTK, and PLC-γ2...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29142596/role-and-underlying-mechanisms-of-the-interstitial-protein-periostin-in-the-diagnosis-and-treatment-of-malignant-tumors
#4
Dong Ye, Zhi Sen Shen, Shi Jie Qiu, Qun Li, Guo Li Wang
Invasion and metastasis are the major characteristics of malignant tumors and are complex processes involving multiple genes. Gene regulation is a precise, large and complex biological control system, and its underlying mechanisms remain to be elucidated. Mesenchymal-specific genes are expressed primarily by mesenchymal cells, and the expression products of these genes are molecules with various structures and functions, including secreted proteins and extracellular matrix proteins. The periostin gene has been newly identified as a mesenchymal-specific gene and an extracellular-matrix secreted protein...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29142464/bmpr2-and-hif1-%C3%AE-overexpression-in-resected-osteosarcoma-correlates-with-distant-metastasis-and-patient-survival
#5
Shidong Wang, Tingting Ren, Yi Huang, Xing Bao, Kunkun Sun, Danhua Shen, Wei Guo
Objective: Bone morphogenetic protein receptor 2 (BMPR2) and hypoxia-inducible factor 1-α (HIF1-α) existed abnormal expression in several types of cancer. However, their expressions and related roles in osteosarcoma are largely unknown. Methods: To investigate the clinical significance of BMPR2 and HIF1-α in osteosarcoma, we analyzed their expression levels in 103 osteosarcoma specimens by immunochemistry. Meanwhile, we conducted a follow-up to examine the metastatic behavior and overall survival (OS) of osteosarcoma patients...
October 2017: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/29141220/phosphorylation-and-ubiquitination-regulate-protein-phosphatase-5-activity-and-its-prosurvival-role-in-kidney-cancer
#6
Natela Dushukyan, Diana M Dunn, Rebecca A Sager, Mark R Woodford, David R Loiselle, Michael Daneshvar, Alexander J Baker-Williams, John D Chisholm, Andrew W Truman, Cara K Vaughan, Timothy A Haystead, Gennady Bratslavsky, Dimitra Bourboulia, Mehdi Mollapour
The serine/threonine protein phosphatase 5 (PP5) regulates multiple cellular signaling networks. A number of cellular factors, including heat shock protein 90 (Hsp90), promote the activation of PP5. However, it is unclear whether post-translational modifications also influence PP5 phosphatase activity. Here, we show an "on/off switch" mechanism for PP5 regulation. The casein kinase 1δ (CK1δ) phosphorylates T362 in the catalytic domain of PP5, which activates and enhances phosphatase activity independent of Hsp90...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29138796/reactive-oxygen-species-induce-injury-of-the-intestinal-epithelium-during-hyperoxia
#7
Min Zhao, Shimiao Tang, Junchi Xin, Yingliang Wei, Dongyan Liu
Long-term therapeutic hyperoxia may exert serious toxic effects on intestinal epithelial cells in vitro and in vivo. The aim of the present study was to investigate the cause of this intestinal injury under conditions of hyperoxia. Caco-2 cells were treated with different concentrations of hydrogen peroxide (H2O2) and 85% hyperoxia for 24 h. higher rates of injury of Caco-2 cells were observed in the hyperoxia and H2O2 groups compared with the control group. The reactive oxygen species (ROS) level of the hyperoxia group was significantly higher compared with that of the 400 µM H2O2 group...
November 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29138370/-development-of-holistic-cancer-treatment-centering-cancer-patients-from-the-standpoint-of-hypoxia-and-hedgehog-signaling
#8
Hideya Onishi, Toshitatsu Ogino, Takashi Morisaki, Mitsuo Katano
Recently, hypoxia that is one of cancer microenvironments, takes much attention. Because circumstance that we usually perform experiment is 20% O2 condition, it is likely that different signaling pathways may be activated in vivo cancer. We focused Hedgehog(Hh)signaling as one of activated pathways under hypoxia. It has been shown that Hh signaling is activated under hypoxia, followed by inducing malignant phenotypes in pancreatic cancer. Therefore, Hh signaling inhibitor should elicit anti-tumor effect. However, if we consider "whole-person therapy" we should confirm how Hh signaling affects the function of immune cells...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29138369/-metabolic-competition-in-tumor-microenvironment
#9
Shingo Eikawa, Heiichiro Udono
Metabolic pathways tightly regulate T cell response in host defense against infection and cancer. Glycolysis plays a key role in effector T cell differentiation and its function. More recent studies have demonstrated that tumor microenvironment forms hypoxia and metabolic disadvantage of immune cells. These environmental attributions impair the effector T cell survival, proliferation and function. Therefore repurposing of metabolic drugs might develop a novel cancer immunotherapy based on the targeting of T cell immunometabolism...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29137886/diesel-exhaust-inhalation-exposure-induces-pulmonary-arterial-hypertension-in-mice
#10
Jing Liu, Xiaoqing Ye, Dapeng Ji, Xiaofei Zhou, Cong Qiu, Weiping Liu, Luyang Yu
Diesel exhaust (DE) is one of the main sources of urban air pollution. An increasing number of evidence showed the association of air pollution with cardiovascular diseases. Pulmonary arterial hypertension (PAH) is one of the most disastrous vascular diseases, which results in right ventricular failure and death. However, the relationship of DE inhalation exposure with PAH is still unknown. In this study, male adult mice were exposed by inhalation to filtered ambient air (negative control), 10% O2 hypoxia (PAH-phenotype positive control), 350 μg/m(3) particulate matter whole DE, or the combination of DE and hypoxic condition...
November 11, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29137421/gper-mediates-differential-effects-of-estrogen-on-colon-cancer-cell-proliferation-and-migration-under-normoxic-and-hypoxic-conditions
#11
Viviana Bustos, Áine M Nolan, Anke Nijhuis, Harry Harvey, Alexandra Parker, Richard Poulsom, Jean McBryan, Warren Thomas, Andrew Silver, Brian J Harvey
The estrogen receptor ERβ is the predominant ER subtype expressed in normal well-differentiated colonic epithelium. However, ERβ expression is lost under the hypoxic microenvironment as colorectal cancer (CRC) malignancy progresses. This raises questions about the role of signalling through other estrogen receptors such as ERα or G-protein coupled estrogen receptor (GPER, GPR30) by the estrogen 17β-estradiol (E2) under hypoxic conditions after ERβ is lost in CRC progression. We tested the hypothesis that E2 or hypoxia can act via GPER to contribute to the altered phenotype of CRC cells...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137372/microrna-33a-5p-increases-radiosensitivity-by-inhibiting-glycolysis-in-melanoma
#12
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...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137361/downregulation-of-mir-199a-5p-promotes-prostate-adeno-carcinoma-progression-through-loss-of-its-inhibition-of-hif-1%C3%AE
#13
Jinjing Zhong, Rui Huang, Zhengzheng Su, Mengni Zhang, Miao Xu, Jing Gong, Ni Chen, Hao Zeng, Xueqin Chen, Qiao Zhou
Hypoxia-inducible factor-1 alpha (HIF-1α) plays key roles in cell survival under both hypoxia and normoxia conditions. Regulation of HIF-1α is complex and involves numerous molecules and pathways, including post-transcriptional regulation by microRNAs (miRNAs). Although upregulation of HIF-1α has been shown to promote prostate adenocarcinoma (PCa) progression, the mechanism by which miRNAs modulate HIF-1α in prostate cancer has not been clarified. Here, we show that miR-199a-5p is underexpressed in prostate adenocarcinoma...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137326/overexpression-of-carbonic-anhydrase-ix-induces-cell-motility-by-activating-matrix-metalloproteinase-9-in-human-oral-squamous-cell-carcinoma-cells
#14
Jia-Sin Yang, Chiao-Wen Lin, Yi-Hsien Hsieh, Ming-Hsien Chien, Chun-Yi Chuang, Shun-Fa Yang
Oral cancer is a solid malignant tumor that is prone to occur following hypoxia. There are no clear studies showing a link between hypoxia and oral carcinogenesis. Carbonic anhydrase IX (CAIX), which is a hypoxia-induced transmembrane protein, is highly expressed in various types of human cancer. However, the effects of CAIX on the metastasis of human oral cancer cells and the underlying molecular mechanisms have not been clarified. In this study, we observed that CAIX overexpression increased the migratory and invasive abilities of SCC-9 and SAS cells...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137269/local-blockage-of-self-sustainable-erythropoietin-signaling-suppresses-tumor-progression-in-non-small-cell-lung-cancer
#15
Lei He, Shouzhen Wu, Qiang Hao, Elhadji M Dioum, Kuo Zhang, Cun Zhang, Weina Li, Wei Zhang, Yingqi Zhang, Jiming Zhou, Zhijun Pang, Lijuan Zhao, Xiaowen Ma, Meng Li, Qiuyang Zhang
Functional significance of co-expressed erythropoietin (EPO) and its receptor (EPOR) in non-small cell lung cancer (NSCLC) had been under debate. In this study, co-overexpression of EPO/EPOR was confirmed to be positively associated with poor survival in NSCLC. The serum EPO in 14 of 35 enrolled NSCLC patients were found elevated significantly and decreased to normal level after tumor resection. With primary tumor cell culture and patient-derived tumor xenograft (PDX) mouse model, the EPO secretion from the tumors of these 14 patients was verified...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136455/lbh589-inhibits-glioblastoma-growth-and-angiogenesis-through-suppression-of-hif-1%C3%AE-expression
#16
Zhi-Gang Yao, Wen-Huan Li, Fang Hua, Hong-Xia Cheng, Miao-Qing Zhao, Xi-Chao Sun, Ye-Jun Qin, Jia-Mei Li
Glioblastoma (GBM) is an angiogenic malignancy with a highly unfavorable prognosis. Angiogenesis in GBM represents an adaptation to a hypoxic microenvironment and is correlated with tumor growth, invasion, clinical recurrence, and lethality. LBH589 (also called panobinostat) is a histone deacetylase (HDAC) inhibitor with potent antitumor activity. In the current study, we investigated the mechanism and effects of LBH589 on GBM growth and hypoxia-induced angiogenesis in vitro and in vivo. To determine the antitumor and angiogenesis activity and mechanism of LBH589, we used cell proliferations in vitro and GBM xenografts in vivo...
December 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29134362/selecting-patients-for-hyperthermia-combined-with-preoperative-chemoradiotherapy-for-locally-advanced-rectal-cancer
#17
Sang-Won Kim, Ji Woon Yea, Jae Hwang Kim, Mi Jin Gu, Min Kyu Kang
BACKGROUND: This study investigated the role of hyperthermia combined with preoperative concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer (LARC) according to hypoxic marker expression. METHODS: One hundred and nine LARC patients with tissue blocks available for immunohistochemical assessment of carbonic anhydrase 9 (CA9) expression were reviewed. CA9 expression was considered positive when the staining percentage of tumor cells was >25% (n = 31)...
November 13, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29134130/recent-progress-in-the-research-of-cold-inducible-rna-binding-protein
#18
REVIEW
Peng Zhong, He Huang
Cold-inducible RNA-binding protein (CIRP) is a cold-shock protein which can be induced after exposure to a moderate cold-shock in different species ranging from amphibians to humans. Expression of CIRP can also be regulated by hypoxia, UV radiation, glucose deprivation, heat stress and H2O2, suggesting that CIRP is a general stress-response protein. In response to stress, CIRP can migrate from the nucleus to the cytoplasm and regulate mRNA stability through its binding site on the 3'-UTR of its targeted mRNAs...
November 2017: Future Science OA
https://www.readbyqxmd.com/read/29133922/essential-role-of-mitochondrial-stat3-in-p38-mapk-mediated-apoptosis-under-oxidative-stress
#19
Xinlai Cheng, Christiane Peuckert, Stefan Wölfl
Stat3 is an oncogene, frequently associated with malignant transformation. A body of evidence implicates that phospho-Stat3(Y705) contributes to its nucleic translocation, while phospho-Stat3(S727) leads to the accumulation in mitochondria. Both are of importance for tumor cell proliferation. In comparison to well-characterized signaling pathways interplaying with Stat3(Y705), little is known about Stat3(S727). In this work, we studied the influence of Stat3 deficiency on the viability of cells exposed to H2O2 or hypoxia using siRNA and CRISPR/Cas9 genome-editing...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133618/therapeutic-impact-of-nanoparticle-therapy-targeting-tumor-associate-macrophages
#20
Courtney Penn, Kun Yang, Hong Zong, Jae-Young Lim, Alex Cole, Dongli Yang, James Baker, Sascha N Goonewardena, Ronald J Buckanovich
Antiangiogenic therapies, despite initial encouragement, have demonstrated a limited benefit in ovarian cancer. Laboratory studies suggest anti-angiogenic therapy induced hypoxia can induce tumor "stemness' as resistance to antiangiogenic therapy develops and limits the therapeutic benefit. Resistance to antiangiogenic therapy and an induction of tumor stemness may be mediated by proangiogenic tumor associated macrophages (TAMs). As such TAMs have been proposed as a therapeutic target. We demonstrate here that ovarian TAMs express high levels of the folate receptor-2 (FOLR2) and can be selectively targeted using G5-dendrimer nanoparticles using methotrexate as both a ligand and a toxin...
November 13, 2017: Molecular Cancer Therapeutics
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