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hypoxia cancer

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https://www.readbyqxmd.com/read/28214471/che-1-sustains-hypoxic-response-of-colorectal-cancer-cells-by-affecting-hif-1%C3%AE-stabilization
#1
Tiziana Bruno, Mariacristina Valerio, Luca Casadei, Francesca De Nicola, Frauke Goeman, Matteo Pallocca, Valeria Catena, Simona Iezzi, Cristina Sorino, Agata Desantis, Cesare Manetti, Giovanni Blandino, Aristide Floridi, Maurizio Fanciulli
BACKGROUND: Solid tumours are less oxygenated than normal tissues. Consequently, cancer cells acquire to be adapted to a hypoxic environment. The poor oxygenation of solid tumours is also a major indicator of an adverse cancer prognosis and leads to resistance to conventional anticancer treatments. We previously showed the involvement of Che-1/AATF (Che-1) in cancer cell survival under stress conditions. Herein we hypothesized that Che-1 plays a role in the response of cancer cells to hypoxia...
February 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28213554/hypoxia-selectively-enhances-integrin-receptor-expression-to-promote-metastasis
#2
Julia A Ju, Ines Godet, I Chae Ye, Jungmin Byun, Hasini Jayatilaka, Sun Joo Lee, Lisha Xiang, Debangshu Samanta, Meng Horng Lee, Pei-Hsun Wu, Denis Wirtz, Gregg L Semenza, Daniele M Gilkes
: Metastasis is the leading cause of breast cancer (BCa)mortality. Previous studies have implicated hypoxia-induced changes in the composition and stiffness of the extracellular matrix (ECM) in the metastatic process. Therefore, the contribution of potential ECM binding receptors in this process was explored. Using a bioinformatics approach the expression of all integrin receptor subunits, in two independent BCa patient data sets, were analyzed to determine if integrin status correlates with a validated hypoxiainducible gene signature...
February 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28212558/ataxin-1-regulates-epithelial-mesenchymal-transition-of-cervical-cancer-cells
#3
A-Ram Kang, Hyoung-Tae An, Jesang Ko, Seongman Kang
The mutant form of the protein ataxin-1 (ATXN1) causes the neurodegenerative disease spinocerebellar ataxia type-1. Recently, ATXN1 was reported to enhance E-cadherin expression in the breast cancer cell line MCF-7, suggesting a potential association between ATXN1 and cancer development. In the present study, we discovered a novel mechanism through which ATXN1 regulates the epithelial-mesenchymal transition (EMT) of cancer cells. Hypoxia-induced upregulation of the Notch intracellular domain expression decreased ATXN1 expression via MDM2-associated ubiquitination and degradation...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28210996/quantitative-evaluation-of-oxygen-metabolism-in-the-intratumoral-hypoxia-18-f-fluoromisonidazole-and-15-o-labelled-gases-inhalation-pet
#4
Tadashi Watabe, Yasukazu Kanai, Hayato Ikeda, Genki Horitsugi, Keiko Matsunaga, Hiroki Kato, Kayako Isohashi, Kohji Abe, Eku Shimosegawa, Jun Hatazawa
BACKGROUND: Intratumoral hypoxia is one of the resistant factors in radiotherapy and chemotherapy for cancer. Although it is detected by (18)F-fluoromisonidazole (FMISO) PET, the relationship between intratumoral hypoxia and oxygen metabolism has not been studied. The purpose of this study was to evaluate the intratumoral perfusion and oxygen metabolism in hypoxic regions using the rat xenograft model. Ten male Fischer rats with C6 glioma (body weight = 220 ± 15 g) were investigated with (18)F-FMISO PET and steady-state inhalation method of (15)O-labelled gases PET...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28210075/pancreatic-stellate-cell-pandora-s-box-for-pancreatic-disease-biology
#5
REVIEW
Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28209906/first-evaluation-of-pet-based-human-biodistribution-and-dosimetry-of-18-f-faza-a-tracer-for-imaging-tumor-hypoxia
#6
Savi Annarita, Elena Incerti, Federico Fallanca, Valentino Bettinardi, Francesca Rossetti, Cristina Monterisi, Antonia Compierchio, Giampiero Negri, Piero Zannini, Luigi Gianolli, Maria Picchio
Fluorine-18 labelled fluoroazomycinarabinoside ((18)F-FAZA) is a positron emission tomography (PET) biomarker for non-invasive identification of regional tumor hypoxia. Aim of the present Phase I study was to firstly evaluate in non-small cell lung cancer patients the human biodistribution and dosimetry of (18)F-FAZA. Methods: Five patients awaiting surgical resection after histologically proven or radiologically suspected non-small cell lung cancer were prospectively enrolled for the study. The patients underwent a PET/computed tomography (CT) study after the injection of 371±32 MBq of (18)F-FAZA...
February 16, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28209257/synthesis-and-evaluation-of-n-benzofuran-5-yl-aromaticsulfonamide-derivatives-as-novel-hif-1-inhibitors-that-possess-anti-angiogenic-potential
#7
Jinlian Wei, Yingrui Yang, Yali Li, Xiaofei Mo, Xiaoke Guo, Xiaojin Zhang, Xiaoli Xu, Zhengyu Jiang, Qidong You
Hypoxia-inducible factor-1 (HIF-1) as a key mediator in tumor metastasis, angiogenesis, and poor patient prognosis has been recognized as an important cancer drug target. A novel series of N-(benzofuran-5-yl)aromaticsulfonamide derivatives were synthesized and evaluated as HIF-1 inhibitor. Among these compounds, 7q exhibited specific inhibitory effects on HIF-1 by downregulating the expression of HIF-1α under hypoxic conditions. It inhibited the HIF-1 transcriptional activity (IC50=12.5±0.7μM) and secretion of VEGF (IC50=18...
June 11, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28207045/remodelling-of-micrornas-in-colorectal-cancer-by-hypoxia-alters-metabolism-profiles-and-5-fluorouracil-resistance
#8
Anke Nijhuis, Hannah Thompson, Julie Adam, Alexandra Parker, Luke Gammon, Amy Lewis, Jacob G Bundy, Tomoyoshi Soga, Aisha Jalaly, David Propper, Rosemary Jeffery, Nirosha Suraweera, Sarah McDonald, Mohamed A Thaha, Roger Feakins, Robert Lowe, Cleo L Bishop, Andrew Silver
No abstract text is available yet for this article.
February 16, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28205588/hypoxia-induced-angiotensin-ii-by-the-lactate-chymase-dependent-mechanism-mediates-radioresistance-of-hypoxic-tumor-cells
#9
Guozhu Xie, Ying Liu, Qiwei Yao, Rong Zheng, Lanfang Zhang, Jie Lin, Zhaoze Guo, Shasha Du, Chen Ren, Quan Yuan, Yawei Yuan
The renin-angiotensin system (RAS) is a principal determinant of arterial blood pressure and fluid and electrolyte balance. RAS component dysregulation was recently found in some malignancies and correlated with poor patient outcomes. However, the exact mechanism of local RAS activation in tumors is still unclear. Here, we find that the local angiotensin II predominantly exists in the hypoxic regions of tumor formed by nasopharyngeal carcinoma CNE2 cells and breast cancer MDA-MB-231 cells, where these tumor cells autocrinely produce angiotensin II by a chymase-dependent rather than an angiotensin converting enzyme-dependent mechanism...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199842/the-mtor-and-pp2a-pathways-regulate-phd2-phosphorylation-to-fine-tune-hif1%C3%AE-levels-and-colorectal-cancer-cell-survival-under-hypoxia
#10
Giusy Di Conza, Sarah Trusso Cafarello, Stefan Loroch, Daniela Mennerich, Sofie Deschoemaeker, Mario Di Matteo, Manuel Ehling, Kris Gevaert, Hans Prenen, Rene Peiman Zahedi, Albert Sickmann, Thomas Kietzmann, Fabiola Moretti, Massimiliano Mazzone
Oxygen-dependent HIF1α hydroxylation and degradation are strictly controlled by PHD2. In hypoxia, HIF1α partly escapes degradation because of low oxygen availability. Here, we show that PHD2 is phosphorylated on serine 125 (S125) by the mechanistic target of rapamycin (mTOR) downstream kinase P70S6K and that this phosphorylation increases its ability to degrade HIF1α. mTOR blockade in hypoxia by REDD1 restrains P70S6K and unleashes PP2A phosphatase activity. Through its regulatory subunit B55α, PP2A directly dephosphorylates PHD2 on S125, resulting in a further reduction of PHD2 activity that ultimately boosts HIF1α accumulation...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28199314/whole-genome-landscape-of-pancreatic-neuroendocrine-tumours
#11
Aldo Scarpa, David K Chang, Katia Nones, Vincenzo Corbo, Ann-Marie Patch, Peter Bailey, Rita T Lawlor, Amber L Johns, David K Miller, Andrea Mafficini, Borislav Rusev, Maria Scardoni, Davide Antonello, Stefano Barbi, Katarzyna O Sikora, Sara Cingarlini, Caterina Vicentini, Skye McKay, Michael C J Quinn, Timothy J C Bruxner, Angelika N Christ, Ivon Harliwong, Senel Idrisoglu, Suzanne McLean, Craig Nourse, Ehsan Nourbakhsh, Peter J Wilson, Matthew J Anderson, J Lynn Fink, Felicity Newell, Nick Waddell, Oliver Holmes, Stephen H Kazakoff, Conrad Leonard, Scott Wood, Qinying Xu, Shivashankar Hiriyur Nagaraj, Eliana Amato, Irene Dalai, Samantha Bersani, Ivana Cataldo, Angelo P Dei Tos, Paola Capelli, Maria Vittoria Davì, Luca Landoni, Anna Malpaga, Marco Miotto, Vicki L J Whitehall, Barbara A Leggett, Janelle L Harris, Jonathan Harris, Marc D Jones, Jeremy Humphris, Lorraine A Chantrill, Venessa Chin, Adnan M Nagrial, Marina Pajic, Christopher J Scarlett, Andreia Pinho, Ilse Rooman, Christopher Toon, Jianmin Wu, Mark Pinese, Mark Cowley, Andrew Barbour, Amanda Mawson, Emily S Humphrey, Emily K Colvin, Angela Chou, Jessica A Lovell, Nigel B Jamieson, Fraser Duthie, Marie-Claude Gingras, William E Fisher, Rebecca A Dagg, Loretta M S Lau, Michael Lee, Hilda A Pickett, Roger R Reddel, Jaswinder S Samra, James G Kench, Neil D Merrett, Krishna Epari, Nam Q Nguyen, Nikolajs Zeps, Massimo Falconi, Michele Simbolo, Giovanni Butturini, George Van Buren, Stefano Partelli, Matteo Fassan, Kum Kum Khanna, Anthony J Gill, David A Wheeler, Richard A Gibbs, Elizabeth A Musgrove, Claudio Bassi, Giampaolo Tortora, Paolo Pederzoli, John V Pearson, Nicola Waddell, Andrew V Biankin, Sean M Grimmond
The diagnosis of pancreatic neuroendocrine tumours (PanNETs) is increasing owing to more sensitive detection methods, and this increase is creating challenges for clinical management. We performed whole-genome sequencing of 102 primary PanNETs and defined the genomic events that characterize their pathogenesis. Here we describe the mutational signatures they harbour, including a deficiency in G:C > T:A base excision repair due to inactivation of MUTYH, which encodes a DNA glycosylase. Clinically sporadic PanNETs contain a larger-than-expected proportion of germline mutations, including previously unreported mutations in the DNA repair genes MUTYH, CHEK2 and BRCA2...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28198519/correlation-of-hypoxia-inducible-transcription-factor-in-breast-cancer-and-suvmax-of-f-18-fdg-pet-ct
#12
Young-Ju Jeong, Jae-Won Jung, Yoon-Young Cho, Sung-Hwan Park, Hoon-Kyu Oh, Sungmin Kang
BACKGROUND: Tumor hypoxia induces the expression of several genes via the hypoxia-inducible transcription factor-1 alpha (HIF-1a). It is associated with the prognosis of several cancers. We studied the immunohistochemical expression of HIF-1a in patients with invasive ductal cancer (IDC) of the breast and the possible correlation with the maximum standardized uptake value of the primary tumor (pSUVmax) as well as other biological parameters. Prognostic significance of pSUVmax and expression of HIF-1a for the prediction of progression-free survival (PFS) was also assessed...
2017: Nuclear Medicine Review. Central & Eastern Europe
https://www.readbyqxmd.com/read/28198007/modulating-tumor-hypoxia-by-nanomedicine-for-effective-cancer-therapy
#13
REVIEW
Rana Jahanban-Esfahlan, Miguel de la Guardia, Delshad Ahmadi, Bahman Yousefi
Hypoxia, a characteristic feature of tumors, is indispensable to tumor angiogenesis, metastasis, and multi drug resistance. Hypoxic avascular regions, deeply embedded inside the tumors significantly hinder delivery of therapeutic agents. The low oxygen tension results in resistance to the current applied anti-cancer therapeutics including radiotherapy, chemotherapy and photodynamic therapy, the efficacy of which is firmly tied to the level of tumor oxygen supply. However, emerging data indicate that nanocarriers/nanodrugs can offer substantial benefits to improve the efficacy of current therapeutics, through modulation of tumor hypoxia...
February 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28197812/mcpip1-contributes-to-clear-cell-renal-cell-carcinomas-development
#14
Janusz Ligeza, Paulina Marona, Natalia Gach, Barbara Lipert, Katarzyna Miekus, Waclaw Wilk, Janusz Jaszczynski, Andrzej Stelmach, Agnieszka Loboda, Jozef Dulak, Wojciech Branicki, Janusz Rys, Jolanta Jura
Monocyte Chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, is encoded by the ZC3H12a gene, and it mediates inflammatory processes by regulating the stability of transcripts coding for proinflammatory cytokines and controlling activity of transcription factors, such as NF-κB and AP1. We found that MCPIP1 transcript and protein levels are strongly downregulated in clear cell renal cell carcinoma (ccRCC) samples, which were derived from patients surgically treated for renal cancer compared to surrounded normal tissues...
February 14, 2017: Angiogenesis
https://www.readbyqxmd.com/read/28197638/cobalt-chloride-treatment-induces-autophagic-apoptosis-in-human-glioma-cells-via-a-p53-dependent-pathway
#15
Bor-Chin Cheng, Jui-Tai Chen, Shun-Tai Yang, Chung-Ching Chio, Shing-Hwa Liu, Ruei-Ming Chen
Malignant glioma is the most aggressive brain tumor. Hypoxic condition has been explored for killing cancer stem cells or drug-resistant tumor cells. This study investigated the effects of hypoxia on autophagic death and the possible mechanisms. Exposure of human malignant glioma U87-MG cells to cobalt chloride (CoCl2) increased cellular hypoxia-inducible factor-1α levels and concurrently decreased cell viability concentration- and time-dependently. In parallel, treatment with CoCl2 suppressed proliferation of human U87-MG cells...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28197395/characterization-of-the-tumor-microenvironment-and-tumor-stroma-interaction-by-non-invasive-preclinical-imaging
#16
REVIEW
Nirilanto Ramamonjisoa, Ellen Ackerstaff
Tumors are often characterized by hypoxia, vascular abnormalities, low extracellular pH, increased interstitial fluid pressure, altered choline-phospholipid metabolism, and aerobic glycolysis (Warburg effect). The impact of these tumor characteristics has been investigated extensively in the context of tumor development, progression, and treatment response, resulting in a number of non-invasive imaging biomarkers. More recent evidence suggests that cancer cells undergo metabolic reprograming, beyond aerobic glycolysis, in the course of tumor development and progression...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28197369/the-transcriptome-of-lung-tumor-infiltrating-dendritic-cells-reveals-a-tumor-supporting-phenotype-and-a-microrna-signature-with-negative-impact-on-clinical-outcome
#17
Lotte Pyfferoen, Elisabeth Brabants, Celine Everaert, Nancy De Cabooter, Kelly Heyns, Kim Deswarte, Manon Vanheerswynghels, Sofie De Prijck, Glenn Waegemans, Melissa Dullaers, Hamida Hammad, Olivier De Wever, Pieter Mestdagh, Jo Vandesompele, Bart N Lambrecht, Karim Y Vermaelen
Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the biology of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogeneous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs are emerging as clinically relevant parameters in lung cancer. In this study, we used an orthotopic preclinical model of lung cancer to dissect how the lung tumor micro-environment affects tissue-resident DCs and extract novel biologically and clinically relevant information...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196140/hypoxia-inducible-factors-regulate-the-transcription-of-the-sprouty2-gene-and-expression-of-the-sprouty2-protein
#18
Xianlong Gao, Kristin C Hicks, Paul Neumann, Tarun B Patel
Receptor Tyrosine Kinase (RTK) signaling plays a major role in tumorigenesis and normal development. Sprouty2 (Spry2) attenuates RTK signaling and inhibits processes such as angiogenesis, cell proliferation, migration and survival, which are all upregulated in tumors. Indeed in cancers of the liver, lung, prostate and breast, Spry2 protein levels are markedly decreased correlating with poor patient prognosis and shorter survival. Thus, it is important to understand how expression of Spry2 is regulated. While prior studies have focused on the post-translation regulation of Spry2, very few studies have focused on the transcriptional regulation of SPRY2 gene...
2017: PloS One
https://www.readbyqxmd.com/read/28194632/characterization-of-an-orthotopic-colorectal-cancer-mouse-model-and-its-feasibility-for-accurate-quantification-in-positron-emission-tomography
#19
Sara Rapic, Christel Vangestel, Jeroen Verhaeghe, Tim Van den Wyngaert, Rukun Hinz, Marleen Verhoye, Patrick Pauwels, Steven Staelens, Sigrid Stroobants
PURPOSE: Quantification in positron emission tomography (PET) imaging of an orthotopic mouse model of colorectal cancer (CRC) is challenging due to difficult tumor delineation. We aimed to establish a reproducible delineation approach, evaluate its feasibility for reliable PET quantification and compare its added translational value with its subcutaneous counterpart. PROCEDURES: A subcutaneous Colo205-luc2 tumor fragment harvested from a donor mouse was transplanted onto the caecum of nude mice, with (n = 10) or without (n = 10) the addition of an X-ray detectable thread...
February 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28194552/a-novel-synthetic-small-molecule-yf-452-inhibits-tumor-growth-through-antiangiogenesis-by-suppressing-vegf-receptor-2-signaling
#20
Yongrui Liu, Yuan He, Feifei Yang, Xiaonan Cong, Jinhua Wang, Shihong Peng, Dan Gao, Weifang Wang, Liping Lan, Xuexiang Ying, Mingyao Liu, Yihua Chen, Zhengfang Yi
Tumor angiogenesis is characterized by abnormal vessel morphology, endowing tumor with highly hypoxia and unresponsive toward treatment. To date, mounting angiogenic factors have been discovered as therapeutic targets in antiangiogenic drug development. Among them, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors exerts potent antiangiogenic activity in tumor therapy. Therefore, it may provide a valid strategy for cancer treatment through targeting the tumor angiogenesis via VEGFR2 pathway...
February 13, 2017: Science China. Life Sciences
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