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https://www.readbyqxmd.com/read/29156796/downregulation-of-dna-repair-proteins-and-increased-dna-damage-in-hypoxic-colon-cancer-cells-is-a-therapeutically-exploitable-vulnerability
#1
Jennifer M J Jongen, Lizet M van der Waals, Kari Trumpi, Jamila Laoukili, Niek A Peters, Susanne J Schenning-van Schelven, Klaas M Govaert, Inne H M Borel Rinkes, Onno Kranenburg
Surgical removal of colorectal cancer (CRC) liver metastases generates areas of tissue hypoxia. Hypoxia imposes a stem-like phenotype on residual tumor cells and promotes tumor recurrence. Moreover, in primary CRC, gene expression signatures reflecting hypoxia and a stem-like phenotype are highly expressed in the aggressive Consensus Molecular Subtype 4 (CMS4). Therapeutic strategies eliminating hypoxic stem-like cells may limit recurrence following resection of primary tumors or metastases. Here we show that expression of DNA repair genes is strongly suppressed in CMS4 and inversely correlated with hypoxia-inducible factor-1 alpha (HIF1α) and HIF-2α co-expression signatures...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29146180/chlorogenic-acid-attenuates-diabetic-retinopathy-by-reducing-vegf-expression-and-inhibiting-vegf-mediated-retinal-neoangiogenesis
#2
Xiyu Mei, Lingyu Zhou, Tianyu Zhang, Bin Lu, Yuchen Sheng, Lili Ji
Diabetic retinopathy (DR) is one of the most common and serious complications of diabetes mellitus (DM). This study aims to investigate the amelioration of chlorogenic acid (CGA) on proliferative DR (PDR) via focusing on inhibiting retinal neoangiogenesis. CGA reduced the increased cell proliferation, migration and tube formation induced by vascular endothelial growth factor (VEGF) in human retinal endothelial cells (HREC) and choroid-retinal endothelial RF/6A cells. CGA abrogated VEGF-induced the phosphorylation of VEGFR2 and its downstream mitogen-activated extracellular regulated kinase (MEK1/2), extracellular regulated protein kinase (ERK1/2) and p38 kinase...
November 13, 2017: Vascular Pharmacology
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#3
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/29140729/gene-expression-and-gene-associations-during-the-development-of-heart-failure-with-preserved-ejection-fraction-in-the-dahl-salt-sensitive-model-of-hypertension
#4
Jeffrey Yim, Hyokeun Cho, Simon W Rabkin
Gene expression and associations were examined in a model of heart failure with preserved ejection fraction (HFpEF), a condition with minimal effective treatment. Genes with at least two studies showing significant changes in Dahl rat with heart failure were examined by meta-analysis. Significantly increased in expression were iNOS, p47phox, ADM, ANP, OPN, ACE, MCP-1, GP91PHOX, ICAM-1, TGF-β1, CTGF, ET-1, p22phox, ETB, BNP, ETA, MMP13, Col1a1, MMP2, TIMP1, Col3a1, Il-1β, β-MHC, ECE1, MMP14, AGT, and MMP9...
November 15, 2017: Clinical and Experimental Hypertension: CHE
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
#5
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/29132470/-effects-of-bone-marrow-mesenchymal-stem-cell-transplantation-on-retinal-neovascularization-in-neonatal-rats-with-oxygen-induced-retinopathy
#6
Qing-Jie Mu, Yue-Hua Zhao, Dan-Dan Cheng, Hai-Yu Wang, Lan-Fen Chen, Yan-Song Zhao, Xiao-Li Wang
OBJECTIVE: To explore the effects of rat bone mesenchymal stem cell (BMSC) transplantation on retinal neovascularization, and to observe the changes of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factors (VEGF) in rats with oxygen-induced retinopathy (OIR). METHODS: Seventy-two seven-day-old Sprague-Dawley rats were randomly divided into three groups: normal control (CON), model (OIR) and BMSC transplantation. In the BMSC transplantation group, BMSCs were transplanted 5 days after oxygen conditioning...
November 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29052350/platelet-lysate-activates-quiescent-cell-proliferation-and-reprogramming-in-human-articular-cartilage-involvement-of-hypoxia-inducible-factor-1
#7
Van Thi Nguyen, Ranieri Cancedda, Fiorella Descalzi
The idea of rescuing the body self-repair capability lost during evolution is progressively gaining ground in Regenerative Medicine. In particular, growth factors and bioactive molecules derived from activated platelets emerged as promising therapeutic agents acting as trigger for repair of tissue lesions and restoration of tissue functions. Aim of this study was to assess the potential of a Platelet Lysate (PL) for human articular cartilage repair considering its activity on progenitor cells and differentiated chondrocytes...
October 19, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29050261/alpha-linolenic-acid-stabilizes-hif-1-%C3%AE-and-downregulates-fasn-to-promote-mitochondrial-apoptosis-for-mammary-gland-chemoprevention
#8
Subhadeep Roy, Atul Kumar Rawat, Shreesh Raj Sammi, Uma Devi, Manjari Singh, Swetlana Gautam, Rajnish Kumar Yadav, Jitendra Kumar Rawat, Lakhveer Singh, Mohd Nazam Ansari, Abdulaziz S Saeedan, Rakesh Pandey, Dinesh Kumar, Gaurav Kaithwas
Alpha linolenic acid is an essential polyunsaturated fatty acid and is reported to have the anti-cancer potential with no defined hypothesis or mechanism/s. Henceforth present study was in-quested to validate the effect of alpha linolenic acid on mitochondrial apoptosis, hypoxic microenvironment and de novo fatty acid synthesis using in-vitro and in-vivo studies. The IC50 value of alpha linolenic acid was recorded to be 17.55μM against ER+MCF-7 cells. Treatment with alpha linolenic acid was evident for the presence of early and late apoptotic signals along with mitochondrial depolarization, when studied through acridine orange/ethidium bromide and JC-1 staining...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29047187/a-novel-hif1an-substrate-kank3-plays-a-tumor-suppressive-role-in-hepatocellular-carcinoma
#9
Iljin Kim, Jengmin Kang, Heon Yung, Jong-Wan Park
The KN motif and ankyrin repeat domain-containing protein (KANK) family is involved in actin cytoskeleton organization and cell motility. Compared with other KANK members, the biological function of KANK3 is not clear. Here, we identified KANK3 as a new substrate for the oxygen sensor hypoxia-inducible factor 1-alpha inhibitor (HIF1AN), which hydroxylates HIF-1/2α and other ankyrin repeat domain-containing proteins at asparagine residues. An in vitro hydroxylation assay clearly demonstrated asparaginyl hydroxylation of KANK3 by HIF1AN, and mass spectroscopic analysis revealed that KANK3 is hydroxylated at three asparagine residues within the ankyrin repeat domain...
October 19, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29046352/the-lignan-manassantin-is-a-potent-and-specific-inhibitor-of-mitochondrial-complex-i-and-bioenergetic-activity-in-mammals
#10
Yibao Ma, Hae-Ki Min, Unsong Oh, Adam M Hawkridge, Wei Wang, Ahmed A Mohsin, Qun Chen, Arun Sanyal, Edward J Lesnefsky, Xianjun Fang
Dineolignans manassantin A and B from the plant Saururus cernuus are used in traditional medicine to manage a wide range of ailments such as edema, jaundice, and gonorrhea. Cell-based studies have identified several molecular target candidates of manassantin including NF-kappaB, MAPK, STAT3 and hypoxia-inducible factor 1 alpha (HIF-1alpha). It is unclear whether or how these structurally diverse proteins or pathways mediate any of the medical benefits of manassantin in vivo. Moreover, it has been recently reported that manassantin causes developmental arrest in zebrafish by inhibiting the mitochondrial complex I, but it is unknown whether manassantin inhibits mitochondrial respiration in intact mammalian cells and live animals...
October 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29031854/angptl-4-induces-diabetic-retinal-inflammation-by-activating-profilin-1
#11
Qianyi Lu, Peirong Lu, Wei Chen, Li Lu, Zhi Zheng
Diabetic retinopathy (DR), the most common cause of irreversible blindness in working-age adults, results in central vision loss that is caused by microvascular damage to the inner lining of the back of the eye, the retina. The aim of this work was to assess the temporal relationships between angiopoietin-like protein-4 (ANGPTL-4), a novel adipocytokine factor, and diabetic retinal inflammation and microvascular dysfunction. The downstream pathway(s) and upstream mediator(s) of ANGPTL-4 were then determined under high glucose (HG) conditions...
October 13, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/29017924/lncrna-cps1-it1-suppresses-emt-and-metastasis-of-colorectal-cancer-by-inhibiting-hypoxia-induced-autophagy-through-inactivation-of-hif-1%C3%AE
#12
Wei Zhang, Weitang Yuan, Junmin Song, Shijun Wang, Xiaoming Gu
OBJECTIVE: Hypoxia is a common phenomenon in solid tumor microenvironment. Thereby, the aim of this study was to investigate the molecular mechanisms of tumor metastasis and epithelial-mesenchymal transition (EMT) regulated by lncRNA CPS1 intronic transcript 1 (CPS1-IT1) under hypoxia in CRC. METHODS: Expression of lncRNA CPS1-IT1, hypoxia-inducible factor-1 alpha (HIF-1α) and autophagy related protein (LC3) were initially assessed in human CRC tissues and in a series of CRC cell lines...
October 7, 2017: Biochimie
https://www.readbyqxmd.com/read/28978278/vascularization-of-the-arterio-venous-loop-in-a-rat-isolation-chamber-model-quantification-of-hypoxia-and-evaluation-of-its-effects
#13
Quan Yuan, Andreas Arkudas, Raymund E Horch, Matthias Hammon, Oliver Bleiziffer, Michael Uder, Hannes Seuss
Introduction The aim of this study was to analyze the three-dimensional distribution of hypoxia in the arterio-venous (AV) loop model in rats, by examining the distribution of hypoxia-inducible factor-1 alpha (HIF-1α). Materials and Methods AV loops were created from the femoral artery and vein of male Lewis rats and an interpositional graft from the contralateral femoral vein. This arteriovenous fistula was embedded in a fibrin-filled isolation chamber and subcutaneously implanted into the thigh. The specimens were harvested after 7 days (n=4), 10 days (n=5) and 14 days (n=4)...
October 5, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28965583/the-copper-dependent-lysyl-oxidases-contribute-to-the-pathogenesis-of-pulmonary-emphysema-in-chronic-obstructive-pulmonary-disease-patients
#14
Neziha Besiktepe, Ozgecan Kayalar, Ezel Ersen, Fusun Oztay
Abnormalities in the elastic fiber biology are seen in pulmonary emphysema (PE). The copper-dependent lysyl oxidases regulate the production and accumulation of elastic fibers in the connective tissue. This study focused on the relationship between lysyl oxidase (LOX), LOX-like protein 1 (LOXL1), and LOXL2 and PE pathogenesis. Lung samples with or without PE from patients with chronic obstructive lung disease (n=35) were used. Protein levels of elastin, LOX, LOXL1, LOXL2, hypoxia inducible factor 1-alpha (HIF-1α), copper metabolism domain containing-1 (COMMD1), and phosphatase and tensin homolog (PTEN) were assayed using microscopic and biochemical methods The emphysematous areas were characterized by enlargement of the alveoli, destruction of the alveolar structure, accumulation of macrophages in the alveolar lumens, and showed increased HIF-1α immunoreactivity...
December 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28964603/bisphenol-a-induces-proliferative-effects-on-both-breast-cancer-cells-and-vascular-endothelial-cells-through-a-shared-gper-dependent-pathway-in-hypoxia
#15
Fangyi Xu, Xiaoning Wang, Nannan Wu, Shuiqing He, Weijie Yi, Siyun Xiang, Piwei Zhang, Xiao Xie, Chenjiang Ying
Based on the breast cancer cells and the vascular endothelial cells are both estrogen-sensitive, we proposed a close reciprocity existed between them in the tumor microenvironment, via shared molecular mechanism affected by environmental endocrine disruptors (EDCs). In this study, bisphenol A (BPA), via triggering G-protein estrogen receptor (GPER), stimulated cell proliferation and migration of bovine vascular endothelial cells (BVECs) and breast cancer cells (SkBr-3 and MDA-MB-231) and enhanced tumor growth in vivo...
December 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28962641/overexpression-of-hypoxia-inducible-factor-1-alpha-improves-immunomodulation-by-dental-mesenchymal-stem-cells
#16
Victor G Martinez, Imelda Ontoria-Oviedo, Carolina P Ricardo, Sian E Harding, Rosa Sacedon, Alberto Varas, Agustin Zapata, Pilar Sepulveda, Angeles Vicente
BACKGROUND: Human dental mesenchymal stem cells (MSCs) are considered as highly accessible and attractive MSCs for use in regenerative medicine, yet some of their features are not as well characterized as other MSCs. Hypoxia-preconditioning and hypoxia-inducible factor 1 (HIF-1) alpha overexpression significantly improves MSC therapeutics, but the mechanisms involved are not fully understood. In the present study, we characterize immunomodulatory properties of dental MSCs and determine changes in their ability to modulate adaptive and innate immune populations after HIF-1 alpha overexpression...
September 29, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28928383/human-stem-cells-alter-the-invasive-properties-of-somatic-cells-via-paracrine-activation-of-mtorc1
#17
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
#18
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
#19
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
#20
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 2017: PLoS Pathogens
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