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https://www.readbyqxmd.com/read/28928383/human-stem-cells-alter-the-invasive-properties-of-somatic-cells-via-paracrine-activation-of-mtorc1
#1
Margit Rosner, Ha Thi Thanh Pham, Richard Moriggl, Markus Hengstschläger
Controlled invasion is essential during many physiological processes, whereas its deregulation is a hallmark of cancer. Here we demonstrate that embryonic, induced pluripotent and amniotic fluid stem cells share the property to induce the invasion of primary somatic cells of various origins through insulin-like growth factor I (IGF-I)- or II (IGF-II)-mediated paracrine activation of mechanistic target of rapamycin complex 1 (mTORC1). We propose a model in which downstream of mTORC1 this stem cell-induced invasion is mediated by hypoxia-inducible factor 1-alpha (HIF-1α)-regulated matrix metalloproteinases...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928287/hif-3%C3%AE-promotes-metastatic-phenotypes-in-pancreatic-cancer-by-transcriptional-regulation-of-the-rhoc-rock1-signaling-pathway
#2
Xianfei Zhou, Xingjun Guo, Meiyuan Chen, Chencheng Xie, Jianxin Jiang
Hypoxia contributes to pancreatic cancer progression and promotes its growth and invasion. Previous research principally focused on hypoxia-inducible factor-1 alpha and HIF-2α (HIF1A and EPAS1) as the major hypoxia-associated transcription factors in pancreatic cancer. However, the role of HIF-3α (HIF3A) has not been investigated. Therefore, HIF-1α, HIF-2α, and HIF-3α expression levels were measured under normoxic and hypoxic conditions. In addition, HIF-3α expression was measured in human pancreatic cancer tissue specimens and the impact of altered HIF-3α expression on cell invasion and migration was investigated in vitro and in vivo, as well as the underlying mechanisms...
September 19, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28923650/does-renal-tubular-injury-induced-local-tissue-hypoxia-involve-post-transplantation-erythrocytosis
#3
A Unal, S Ata, C Karakurkcu, M Z Ciraci, I Kocyigit, M H Sipahioglu, B Tokgoz, O Oymak
BACKGROUND: The pathogenesis of post-transplantation erythrocytosis (PTE) is not well understood and appears to be multifactorial. Our hypothesis in this study was that several factors, including toxicity of calcineurin inhibitor, immunologic factors, and chronic allograft nephropathy, can trigger local tissue hypoxia in peritubular interstitium, which is where production of erythropoietin (EPO) takes place. This local interstitial tissue hypoxia can cause an increase in renal EPO production, which induces the development of PTE...
October 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28922425/hypoxia-inducible-factor-1-alpha-as-a-therapeutic-target-for-primary-effusion-lymphoma
#4
Prabha Shrestha, David A Davis, Ravindra P Veeranna, Robert F Carey, Coralie Viollet, Robert Yarchoan
Primary effusion lymphoma (PEL) is an aggressive B-cell lymphoma with poor prognosis caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Previous studies have revealed that HIF-1α, which mediates much of the cellular response to hypoxia, plays an important role in life cycle of KSHV. KSHV infection promotes HIF-1α activity, and several KSHV genes are in turn activated by HIF-1α. In this study, we investigated the effects of knocking down HIF-1α in PELs. We observed that HIF-1α knockdown in each of two PEL lines leads to a reduction in both aerobic and anaerobic glycolysis as well as lipid biogenesis, indicating that HIF-1α is necessary for maintaining a metabolic state optimal for growth of PEL...
September 18, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28915577/vorinostat-suppresses-hypoxia-signaling-by-modulating-nuclear-translocation-of-hypoxia-inducible-factor-1-alpha
#5
Chao Zhang, Chunzhang Yang, Michael J Feldman, Herui Wang, Ying Pang, Dominic M Maggio, Dongwang Zhu, Cody L Nesvick, Pauline Dmitriev, Petra Bullova, Prashant Chittiboina, Roscoe O Brady, Karel Pacak, Zhengping Zhuang
Histone deacetylase inhibitors (HDACis) are a potent class of tumor-suppressive agents traditionally believed to exert their effects through loosening tightly-wound chromatin resulting in de-inhibition of various tumor suppressive genes. Recent literature however has shown altered intratumoral hypoxia signaling with HDACi administration not attributable to changes in chromatin structure. We sought to determine the precise mechanism of HDACi-mediated hypoxia signaling attenuation using vorinostat (SAHA), an FDA-approved class I/IIb/IV HDACi...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878214/hypoxia-inducible-factor-1-alpha-promotes-cancer-stem-cells-like-properties-in-human-ovarian-cancer-cells-by-upregulating-sirt1-expression
#6
Jie Qin, Yan Liu, Yongkui Lu, Meiling Liu, Manli Li, Juan Li, Lijuan Wu
Ovarian cancer have a poor overall survival rate in patients, and late disease presentation and chemoresistance are the main factors that lead to the mortality of ovarian cancer. Cancer stem cells (CSCs), a small subpopulation of cancer cells, have been associated with resistance to chemo- and radio-therapy in cancer treatment. Hypoxia is a common characteristic of many malignant tumors, and increased HIF-1α expression predicts the poor prognosis of ovarian cancer. In this study, we reported the relationship between hypoxia and cancer stem cells-like properties in human ovarian cancer cell lines SKOV3 and HO8910, we found that hypoxia induced cancer stem cells-like properties in ovarian cancer cells...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874716/cell-spheroids-with-enhanced-aggressiveness-to-mimic-human-liver-cancer-in-vitro-and-in-vivo
#7
Hong-Ryul Jung, Hyun Mi Kang, Jea-Woon Ryu, Dae-Soo Kim, Kyung Hee Noh, Eun-Su Kim, Ho-Joon Lee, Kyung-Sook Chung, Hyun-Soo Cho, Nam-Soon Kim, Dong-Soo Im, Jung Hwa Lim, Cho-Rok Jung
We fabricated a spheroid-forming unit (SFU) for efficient and economic production of cell spheroids. We optimized the protocol for generating large and homogenous liver cancer cell spheroids using Huh7 hepatocellular carcinoma (HCC) cells. The large Huh7 spheroids showed apoptotic and proliferative signals in the centre and at the surface, respectively. In particular, hypoxia-induced factor-1 alpha (HIF-1α) and ERK signal activation were detected in the cell spheroids. To diminish core necrosis and increase the oncogenic character, we co-cultured spheroids with 2% human umbilical vein endothelial cells (HUVECs)...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28865600/the-association-of-genetic-polymorphisms-of-hypoxia-inducible-factor-1-alpha-and-vascular-endothelial-growth-factor-with-increased-risk-of%C3%A2-chronic-obstructive-pulmonary-disease-a%C3%A2-case-control-study
#8
Zhen-Gang Yu, Bing-Zhe Wang, Zhao-Zhong Cheng
Accumulated data over the years have suggested that hypoxia inducible factor-1 alpha (HIF-1α) and its downstream vascular endothelial growth factor (VEGF) gene may be linked with chronic obstructive pulmonary disease (COPD). This study aims to investigate the association of HIF-1α and VEGF genetic polymorphisms and their correlated risks with COPD. COPD patients (case group) and healthy individuals (control group) were recruited. DNA was extracted to detect HIF-1α and VEGF genetic polymorphisms. Basal lung volume and forced expiratory capacity in 1st second (FEV1)/forced vital capacity (FVC) and FEV1/predicted value (pred)% were calculated...
September 2017: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/28857653/polo-like-kinase-3-hypoxic-responses-and-tumorigenesis
#9
Dazhong Xu, Wei Dai, Cen Li
The cellular hypoxic response contributes to cell transformation and tumor progression. Hypoxia-inducible factor 1 (HIF-1) is a key transcription factor that mediates transcription of genes whose products are essential for cellular adaptation to hypoxia. The activity of HIF-1 is largely regulated by the abundance of its alpha subunit (HIF-1α), which is primarily regulated by an oxygen-dependent and ubiquitin/proteasome-mediated degradation process. The HIF-1α protein level is also regulated by protein kinases through phosphorylation...
August 31, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28857035/two-common-variants-of-human-papillomavirus-type-16-e6-differentially-deregulate-sugar-metabolism-and-hypoxia-signalling-in-permissive-human-keratinocytes
#10
Sean Cuninghame, Robert Jackson, Simon J Lees, Ingeborg Zehbe
Human papillomavirus type 16 (HPV16) is responsible for most cancers attributable to HPV infection and naturally occurring variants of the HPV16 E6 oncoprotein predispose individuals to varying risk for developing cancer. Population studies by us and others have demonstrated that the common Asian-American E6 (AAE6) variant is a higher risk factor for cervical cancer than the E6 of another common variant, the European prototype (EPE6). However, a complete understanding of the molecular processes fundamental to these epidemiological findings is still lacking...
September 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28855859/%C3%AE-2-adrenergic-receptor-mediated-hif-1%C3%AE-upregulation-mediates-blood-brain-barrier-damage-in-acute-cerebral-ischemia
#11
Yanyun Sun, Xi Chen, Xinyu Zhang, Xianzhi Shen, Mengwei Wang, Xiaona Wang, Wen-Cao Liu, Chun-Feng Liu, Jie Liu, Wenlan Liu, Xinchun Jin
Disruption of the blood brain barrier (BBB) within the thrombolytic time window is an antecedent event to intracerebral hemorrhage in ischemic stroke. Our recent studies showed that 2-h cerebral ischemia induced BBB damage in non-infarcted area and secreted matrix metalloproteinase-2 (MMP-2) accounted for this disruption. However, the factors that affect MMP-2 secretion and regulate BBB damage remains unknown. Since hypoxia-inducible factor-1 alpha (HIF-1α) was discovered as a mater regulator in hypoxia, we sought to investigate the roles of HIF-1α in BBB damage as well as the factors regulating HIF-1α expression in the ischemic brain...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28843785/hif-1%C3%AE-coordinates-epigenetic-activation-of-siah1-in-hepatocytes-in-response-to-nutritional-stress
#12
Zhiwen Fan, Zilong Li, Yuyu Yang, Shuai Liu, Junli Guo, Yong Xu
Hypoxia inducible factor 1 alpha (HIF-1α) regulates a diverse range of pathophysiological processes. It has been demonstrated previously that HIF-1α plays a role in the pathogenesis of steatosis mediating the effects of excessive nutritional insults. In the present study we investigated the role of HIF-1α in trans‑activating the seven in absentia homolog 1 (SIAH1) gene and the underlying mechanism. We report that in response to nutritional stress, SIAH1 expression was up-regulated in the liver in mice and in cultured hepatocytes...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28819379/hypoxia-inducible-factor-1-alpha-correlates-with-tumor-associated-macrophages-infiltration-influences-survival-of-gastric-cancer-patients
#13
Wei-Jie Zhang, Cheng Chen, Zhi-Hua Zhou, Shan-Ting Gao, Teong Jin Tee, Liu-Qing Yang, Yuan-Yuan Xu, Tao-Hong Pang, Xin-Yun Xu, Qi Sun, Min Feng, Hao Wang, Chun-Lei Lu, Guo-Zhong Wu, Sheng Wu, Wen-Xian Guan, Gui-Fang Xu
Background: Hypoxia was a common feature for accelerating tumor metastasis by both inducting epithelial-mesenchymal transition (EMT) of tumor cells and polarization of tumor-associated macrophages (TAMs). The association and roles between hypoxia, EMT and TAMs in the biological behavior of gastric cancer (GC) for the time being recurrence is unclear. Material and methods: hypoixa by expression of hypoxia-inducible factor-1 alpha (HIF-1α), polarized functional status of infiltrated TAMs by immunohistochemical staining of CD68 and CD163, and the expression of E-cadherin as EMT property had been evaluated in 236 patients consecutive with histologically confirmed GC...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28817115/administration-of-follicle-stimulating-hormone-induces-autophagy-via-upregulation-of-hif-1%C3%AE-in-mouse-granulosa-cells
#14
Jilong Zhou, Wang Yao, Chengyu Li, Wangjun Wu, Qifa Li, Honglin Liu
Recent studies reported the important role of autophagy in follicular development. However, the underlying molecular mechanisms remain elusive. In this study, we investigated the effect of follicle-stimulating hormone (FSH) on mouse granulosa cells (MGCs). Results indicated that autophagy was induced by FSH, which is known to be the dominant hormone regulating follicular development and granulosa cell (GC) proliferation. The activation of mammalian target of rapamycin (mTOR), a master regulator of autophagy, was inhibited during the process of MGC autophagy...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28808223/metastasis-associated-protein-1-deficiency-results-in-compromised-pulmonary-alveolar-capillary-angiogenesis-in-mice
#15
Jun-Hui Qin, Zhen-Yu Ke, Qiang Zhou, Li Wang, Yuan Liang, Ying-Mei Wang, Tong Yang, Xing Gao, Jing Ye, Rekesh Kumar, Rui-An Wang
BACKGROUND The aim of this study was to investigate the effects of metastasis-associated protein 1 (MTA1) deficiency during angiogenesis of pulmonary alveolar capillaries in mice and to determine the molecular mechanisms involved. MATERIAL AND METHODS The expressions of MTA1, CD34, vascular endothelial growth factor (VEGF), alpha smooth muscle actin (α-SMA), and HIF-1α were analyzed in the lungs of MTA1-knockout (KO) and wild-type mice at embryonic day 18.5 and 2 months by quantitative PCR, immunoblotting, and immunohistochemistry...
August 15, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28790395/knockdown-of-hif-1%C3%AE-by-sirna-expressing-plasmid-delivered-by-attenuated-salmonella-enhances-the-antitumor-effects-of-cisplatin-on-prostate-cancer
#16
Junlian Gu, Yang Li, Jun Zeng, Bo Wang, Kun Ji, Yufeng Tang, Qing Sun
Resistance to cisplatin (DDP) and dose-related toxicity remain two important obstacles in the treatment of prostate cancer (PCa) patients with DDP-based chemotherapy. We have investigated whether the knockdown of hypoxia-inducible factor-1 alpha (HIF-1α) by siRNA could enhance the antitumor activity of DDP, and aimed to determine the underlying mechanisms. Intravenous injection of attenuated Salmonella carrying a HIF-1α siRNA-expressing plasmid was used to knockdown HIF-1α in a PC-3 xenograft model. The in vitro and in vivo effects of HIF-1α siRNA treatment and/or DPP on PCa cell proliferation, apoptosis, glycolysis, and production of reactive oxygen species (ROS) were assessed by examining molecular markers specific to each process...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28774305/renal-injury-is-accelerated-by-global-hypoxia-inducible-factor-1-alpha-deficiency-in-a-mouse-model-of-stz-induced-diabetes
#17
Romana Bohuslavova, Radka Cerychova, Katerina Nepomucka, Gabriela Pavlinkova
BACKGROUND: Hypoxia inducible factor 1 (HIF-1) activates protective pathways to counteract hypoxia and prevent tissue damage in conjunction with renal injury. The aim of this study was to evaluate a role of HIF-1 in diabetes-induced kidney damage. METHODS: We used a streptozotocin-induced diabetes mouse model and compared biochemical, histological and molecular parameters associated with kidney damage in Hif1α deficient (Hif1α (+/-) ) and wild-type mice. RESULTS: We showed that Hif1α deficiency accelerated pathological changes in the early stage of DN...
August 3, 2017: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/28764685/notch1-signaling-induces-epithelial-mesenchymal-transition-in-lens-epithelium-cells-during-hypoxia
#18
Lei Liu, Wei Xiao
BACKGROUND: Posterior Capsular Opacification (PCO) is one of the most common complications of cataract surgery which can result in severe visual damage. Epithelial-Mesenchymal Transition (EMT) of lens epithelium cells (LEC) is the pathological basis of PCO. Recent research showed that hypoxia acted as an inducer of EMT through a Notch1/Snail1/E-cadherin pathway. However, it remains unclear whether the Notch1/Snail1/E-cadherin pathway is involved in PCO under hypoxia. METHODS: The morphology of SRA01/04 cells treating with Cobalt Chloride (CoCl2) was observed and the markers of EMT and Notch1/Snail1/E-cadherin pathway were analyzed by Western blot and Immunocytochemistry assay...
August 1, 2017: BMC Ophthalmology
https://www.readbyqxmd.com/read/28754906/kras-activation-and-over-expression-of-sirt1-bcl6-contributes-to-the-pathogenesis-of-endometriosis-and-progesterone-resistance
#19
Jung-Yoon Yoo, Tae Hoon Kim, Asgerally T Fazleabas, Wilder A Palomino, Soo Hyun Ahn, Chandrakant Tayade, David P Schammel, Steven L Young, Jae-Wook Jeong, Bruce A Lessey
Endometriosis is an inflammatory condition that is associated with progesterone resistance and cell proliferation, resulting in pain, infertility and pregnancy loss. We previously demonstrated phosphorylation of STAT3 in eutopic endometrium of infertile women with this disorder leading to over-expression of the oncogene BCL6 and stabilization of hypoxia-induced factor 1 alpha (HIF-1α). Here we report coordinated activation of KRAS and over-expression of Sirtuin 1 (SIRT1), a histone deacetylase and gene silencer, in the eutopic endometrium from women with endometriosis throughout the menstrual cycle...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28753621/mechanical-versus-humoral-determinants-of-brain-death-induced-lung-injury
#20
Asmae Belhaj, Laurence Dewachter, Sandrine Rorive, Myriam Remmelink, Birgit Weynand, Christian Melot, Emeline Hupkens, Céline Dewachter, Jacques Creteur, Kathleen Mc Entee, Robert Naeije, Benoît Rondelet
BACKGROUND: The mechanisms of brain death (BD)-induced lung injury remain incompletely understood, as uncertainties persist about time-course and relative importance of mechanical and humoral perturbations. METHODS: Brain death was induced by slow intracranial blood infusion in anesthetized pigs after randomization to placebo (n = 11) or to methylprednisolone (n = 8) to inhibit the expression of pro-inflammatory mediators. Pulmonary artery pressure (PAP), wedged PAP (PAWP), pulmonary vascular resistance (PVR) and effective pulmonary capillary pressure (PCP) were measured 1 and 5 hours after Cushing reflex...
2017: PloS One
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