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Tumor hypoxia

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https://www.readbyqxmd.com/read/28813675/cd44-interacts-with-hif-2%C3%AE-to-modulate-the-hypoxic-phenotype-of-perinecrotic-and-perivascular-glioma-cells
#1
Elinn Johansson, Elisa S Grassi, Vasiliki Pantazopoulou, Bei Tong, David Lindgren, Tracy J Berg, Elin J Pietras, Håkan Axelson, Alexander Pietras
Hypoxia-inducible factors enhance glioma stemness, and glioma stem cells have an amplified hypoxic response despite residing within a perivascular niche. Still, little is known about differential HIF regulation in stem versus bulk glioma cells. We show that the intracellular domain of stem cell marker CD44 (CD44ICD) is released at hypoxia, binds HIF-2α (but not HIF-1α), enhances HIF target gene activation, and is required for hypoxia-induced stemness in glioma. In a glioma mouse model, CD44 was restricted to hypoxic and perivascular tumor regions, and in human glioma, a hypoxia signature correlated with CD44...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28812986/epigenome-aberrations-emerging-driving-factors-of-the-clear-cell-renal-cell-carcinoma
#2
REVIEW
Ali Mehdi, Yasser Riazalhosseini
Clear cell renal cell carcinoma (ccRCC), the most common form of Kidney cancer, is characterized by frequent mutations of the von Hippel-Lindau (VHL) tumor suppressor gene in ~85% of sporadic cases. Loss of pVHL function affects multiple cellular processes, among which the activation of hypoxia inducible factor (HIF) pathway is the best-known function. Constitutive activation of HIF signaling in turn activates hundreds of genes involved in numerous oncogenic pathways, which contribute to the development or progression of ccRCC...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28811968/il-32%C3%AE-induced-inflammation-constitutes-a-link-between-obesity-and-colon-cancer
#3
Victoria Catalán, Javier Gómez-Ambrosi, Amaia Rodríguez, Beatriz Ramírez, Victor A Ortega, José Luis Hernández-Lizoain, Jorge Baixauli, Sara Becerril, Fernando Rotellar, Víctor Valentí, Rafael Moncada, Camilo Silva, Javier Salvador, Gema Frühbeck
Growing evidence indicates that adipose tissue inflammation is an important mechanism whereby obesity promotes cancer risk and progression. Since IL-32 is an important inflammatory and remodeling factor in obesity and is also related to colon cancer (CC) development, the aim of this study was to explore whether IL-32 could function as an inflammatory factor in human obesity-associated CC promoting a microenvironment favorable for tumor growth. Samples obtained from 84 subjects [27 lean (LN) and 57 obese (OB)] were used in the study...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28810624/high-mobility-group-box-1-protein-attenuates-myocardial-ischemia-reperfusion-injury-via-inhibition-of-the-p38-mitogen-activated-protein-kinase-signaling-pathway
#4
Yan-Hong Zhou, Qian-Feng Han, Lan-Hua Wang, Tao Liu, Xiao-Yan Meng, Lei Wu, Tai Li, Yue-Ru Jiao, Heng-Chen Yao, De-Yong Zhang
The present study aimed to determine the effects of high mobility group box 1 protein (HMGB1) on myocardial ischemia reperfusion (I/R) injury in rats following acute myocardial ischemia and investigate the underlying molecular mechanisms of these effects. Male Wistar rats were randomly divided into the following groups (n=10/group): Sham operation; I/R; HMGB50 (50 ng/kg HMGB1 before I/R); HMGB100 (100 ng/kg HMGB1 before I/R); and HMGB200 (200 ng/kg HMGB1 before I/R). Serum cardiac troponin I (cTnI), interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels were subsequently measured...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810543/atorvastatin-has-a-protective-effect-in-a-mouse-model-of-bronchial-asthma-through-regulating-tissue-transglutaminase-and-triggering-receptor-expressed-on-myeloid-cells-1-expression
#5
Ming-Wei Liu, Rong Liu, Hai-Ying Wu, Mei Chen, Min-Na Dong, Yun-Qiao Huang, Chun-Hai Zhang, Yin-Zhong Wang, Jing Xia, Yang Shi, Feng-Mei Xie, Hua Luo, Xin-Yuan Zhao, Wei Wei, Mei-Xian Su
Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. Statin drugs have improved respiratory health and their therapeutic potential in asthma has been tested in clinical trials. However, the mechanism of action of statins in this context has remained elusive. The present study hypothesized that atorvastatin treatment of ovalbumin-exposed mice attenuates early features of airway remodeling via a mevalonate-dependent mechanism...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28809883/noninvasive-measurement-of-tissue-blood-oxygenation-with-cerenkov-imaging-during-therapeutic-radiation-delivery
#6
Xiaofeng Zhang, Sai Kit Lam, Gregory Palmer, Shiva Das, Mark Oldham, Mark Dewhirst
Tumor tissue oxygenation significantly affects the outcome of radiotherapy. Real-time monitoring of tumor hypoxia is highly desirable for effective radiotherapy, and is the basis for improved treatment because hypoxic tumor cells are more resistant to radiation damage than fully oxygenated cells. We propose to use Cerenkov imaging to monitor tumor hypoxia by means of tissue blood oxygenation without the need for any exogenous contrast agent. Using a rodent hypoxia model, we demonstrate that Cerenkov imaging can be used as a noninvasive and noncontact method to measure tissue blood oxygenation level during radiation delivery...
August 15, 2017: Optics Letters
https://www.readbyqxmd.com/read/28808589/anti-angiogenic-agents-for-the-treatment-of-solid-tumors-potential-pathways-therapy-and-current-strategies-a-review
#7
REVIEW
Ahmed M Al-Abd, Abdulmohsin J Alamoudi, Ashraf B Abdel-Naim, Thikryat A Neamatallah, Osama M Ashour
Recent strategies for the treatment of cancer, other than just tumor cell killing have been under intensive development, such as anti-angiogenic therapeutic approach. Angiogenesis inhibition is an important strategy for the treatment of solid tumors, which basically depends on cutting off the blood supply to tumor micro-regions, resulting in pan-hypoxia and pan-necrosis within solid tumor tissues. The differential activation of angiogenesis between normal and tumor tissues makes this process an attractive strategic target for anti-tumor drug discovery...
November 2017: Journal of Advanced Research
https://www.readbyqxmd.com/read/28806945/tumor-microenvironment-conditions-alter-akt-and-na-h-exchanger-nhe1-expression-in-endothelial-cells-more-than-hypoxia-alone-implications-for-endothelial-cell-function-in-cancer
#8
A K Pedersen, J Mendes Lopes de Melo, N Mørup, K Tritsaris, S F Pedersen
BACKGROUND: Chronic angiogenesis is a hallmark of most tumors and takes place in a hostile tumor microenvironment (TME) characterized by hypoxia, low nutrient and glucose levels, elevated lactate and low pH. Despite this, most studies addressing angiogenic signaling use hypoxia as a proxy for tumor conditions. Here, we compared the effects of hypoxia and TME conditions on regulation of the Na(+)/H(+) exchanger NHE1, Ser/Thr kinases Akt1-3, and downstream effectors in endothelial cells...
August 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28805936/characterizing-hypoxia-in-human-glioma-a-simultaneous-multimodal-mri-and-pet-study
#9
Christine Preibisch, Kuangyu Shi, Anne Kluge, Mathias Lukas, Benedikt Wiestler, Jens Göttler, Jens Gempt, Florian Ringel, Mohamed Al Jaberi, Jürgen Schlegel, Bernhard Meyer, Claus Zimmer, Thomas Pyka, Stefan Förster
Hypoxia plays an important role for the prognosis and therapy response of cancer. Thus, hypoxia imaging would be a valuable tool for pre-therapeutic assessment of tumor malignancy. However, there is no standard validated technique for clinical application available yet. Therefore, we performed a study in 12 patients with high-grade glioma, where we directly compared the two currently most promising techniques, namely the MR-based relative oxygen extraction fraction (MR-rOEF) and the PET hypoxia marker H-1-(3-[(18) F]-fluoro-2-hydroxypropyl)-2-nitroimidazole ([(18) F]-FMISO)...
August 14, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28805796/bifidobacterium-breve-as-a-delivery-vector-of-il-24-gene-therapy-for-head-and-neck-squamous-cell-carcinoma-in-vivo
#10
L Wang, I Vuletic, D Deng, W Crielaard, Z Xie, K Zhou, J Zhang, H Sun, Q Ren, C Guo
Beneficial bacteria are becoming ever more popular gene delivery method for hypoxia- tumor targeting in vivo. In this study we investigated the therapeutic effect of new recombinant Bifidobacterium breve strain expressing IL-24 gene (B.breve-IL24) on head and neck tumor xenograft in mice. Briefly, B.breve transformants were obtained through electro-transformation. Bacteria-tumor targeting ability were analyzed in vivo over different time points (1, 3 and 7 days post- bacteria injection). Furthermore, the therapeutic effect of bacteria on tumor cells in vivo were analyzed as follows: 30 Balb/c nude mice bearing subcutaneous tumor were randomly divided in three groups (Drug group, GFP group and Saline group)...
August 14, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28804704/hypoxia-in-cervical-cancer-from-biology-to-imaging
#11
REVIEW
Heidi Lyng, Eirik Malinen
PURPOSE: Hypoxia imaging may improve identification of cervical cancer patients at risk of treatment failure and be utilized in treatment planning and monitoring, but its clinical potential is far from fully realized. Here, we briefly describe the biology of hypoxia in cervix tumors of relevance for imaging, and evaluate positron emission tomography (PET) and magnetic resonance imaging (MRI) techniques that have shown promise for assessing hypoxia in a clinical setting. We further discuss emerging imaging approaches, and how imaging can play a role in future treatment strategies to target hypoxia...
2017: Clinical and Translational Imaging: Reviews in Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28803235/18f-fdg-uptake-in-well-differentiated-neuroendocrine-tumors-correlates-with-both-ki-67-and-vhl-pathway-inactivation
#12
Margot Bucau, Astrid Laurent-Bellue, Nicolas Poté, Olivia Hentic, Jérôme Cros, Nidaa Mikail, Vinciane Rebours, Philippe Ruszniewski, Rachida Lebtahi, Anne Couvelard
<br>Introduction: 18FDG PET-scanner positivity correlates with poor prognosis in neuroendocrine neoplasms (NEN). Glucose transporter 1 (GLUT1) and carbonic anhydrase 9 (CA9) are markers of agressivity in tumors. Together with pVHL, they are involved in tumor cell metabolism via the hypoxia-inducible factor (HIF) signaling pathway. The aim of this study was to compare, in a series of well-differentiated neuroendocrine tumors (NET), the 18-FDG uptake and expression of proliferation marker Ki-67, GLUT-1, CA9 and pVHL...
August 11, 2017: Neuroendocrinology
https://www.readbyqxmd.com/read/28801910/application-of-synthetic-tumor-specific-promoters-responsive-to-the-tumor-microenvironment
#13
Eduardo G Cafferata, Maria Veronica Lopez, Felipe J Nuñez, Maria A R Maenza, Osvaldo L Podhajcer
Activity of endogenous promoters can be altered by including additional responsive elements (REs). These elements can be responsive to features of the tumor environment or alternatively to signaling pathways specifically activated in cancer cells. These REs incorporated into tumor-specific promoters can improve cancer targeting, the replicative capacity, and lytic activity of conditionally replicative adenovirus. Here we outline an approach to incorporate hypoxia and inflammation REs into a specific fragment of the SPARC promoter and the steps to clone a nucleosome positioning sequence (NPS ) identified in the osteocalcin promoter that contains a Wnt RE upstream of a heterologous synthetic promoter...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28801636/inhibition-of-hypoxic-response-decreases-stemness-and-reduces-tumorigenic-signaling-due-to-impaired-assembly-of-hif1-transcription-complex-in-pancreatic-cancer
#14
Olivia McGinn, Vineet K Gupta, Patricia Dauer, Nivedita Arora, Nikita Sharma, Alice Nomura, Vikas Dudeja, Ashok Saluja, Sulagna Banerjee
Pancreatic tumors are renowned for their extremely hypoxic centers, resulting in upregulation of a number of hypoxia mediated signaling pathways including cell proliferation, metabolism and cell survival. Previous studies from our laboratory have shown that Minnelide, a water-soluble pro-drug of triptolide (anti-cancer compound), decreases viability of cancer cells in vitro as well as in vivo. However, its mechanism of action remain elusive. In the current study we evaluated the effect of Minnelide, on hypoxia mediated oncogenic signaling as well as stemness in pancreatic cancer...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801308/egfr-mutations-compromise-hypoxia-associated-radiation-resistance-through-impaired-replication-fork-associated-dna-damage-repair
#15
Mohammad Saki, Haruhiko Makino, Prashanthi Javvadi, Nozomi Tomimatsu, Lianghao Ding, Jennifer E Clark, Elaine Gavin, Kenichi Takeda, Joel Andrews, Debabrata Saha, Michael D Story, Sandeep Burma, Chaitanya Nirodi
Epidermal growth factor receptor (EGFR) signaling has been implicated in hypoxia-associated resistance to radiation or chemotherapy. Non-small cell lung carcinomas (NSCLC) with activating L858R or ΔE746-E750 EGFR mutations exhibit elevated EGFR activity and downstream signaling. Here, relative to wild type (WT) EGFR, mutant (MT) EGFR expression significantly increases radiosensitivity in hypoxic cells. Gene expression profiling in human bronchial epithelial cells (HBEC) revealed that MT-EGFR expression elevated transcripts related to cell cycle and replication in aerobic and hypoxic conditions and down-regulated RAD50, a critical component of non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways...
August 11, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28799237/anticancer-efficacy-of-the-hypoxia-activated-prodrug-evofosfamide-is-enhanced-in-combination-with-proapoptotic-receptor-agonists-against-osteosarcoma
#16
Vasilios Liapis, Aneta Zysk, Mark DeNichilo, Irene Zinonos, Shelley Hay, Vasilios Panagopoulos, Alexandra Shoubridge, Christopher Difelice, Vladimir Ponomarev, Wendy Ingman, Gerald J Atkins, David M Findlay, Andrew C W Zannettino, Andreas Evdokiou
Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions of tumors, the DNA cross-linking toxin, Br-IPM, is released leading to cell death...
August 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28798257/aquaporin-1-mediated-changes-in-pulmonary-arterial-smooth-muscle-cell-migration-and-proliferation-involve-%C3%AE-catenin
#17
Xin Yun, Haiyang Jiang, Ning Lai, Jian Wang, Larissa A Shimoda
Exposure to hypoxia induces migration and proliferation of pulmonary arterial smooth muscle cells (PASMCs), leading to vascular remodeling and contributing to the development of hypoxic pulmonary hypertension. The mechanisms controlling PASMC growth and motility are incompletely understood, although aquaporin 1 plays an important role. In tumor, kidney and stem cells, AQP1 has been shown to interact with β-catenin, a dual function protein that activates the transcription of crucial target genes (i.e., c-Myc and cyclin D1) related to cell migration and proliferation...
August 10, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28797581/surviving-stress-modulation-of-atf4-mediated-stress-responses-in-normal-and-malignant-cells
#18
REVIEW
Inge M N Wortel, Laurens T van der Meer, Michael S Kilberg, Frank N van Leeuwen
Activating transcription factor 4 (ATF4) is a stress-induced transcription factor that is frequently upregulated in cancer cells. ATF4 controls the expression of a wide range of adaptive genes that allow cells to endure periods of stress, such as hypoxia or amino acid limitation. However, under persistent stress conditions, ATF4 promotes the induction of apoptosis. Recent advances point to a role for post-translational modifications (PTMs) and epigenetic mechanisms in balancing these pro- and anti-survival effects of ATF4...
August 7, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28796315/senp1-hif-1%C3%AE-feedback-loop-modulates-hypoxia-induced-cell-proliferation-invasion-and-emt-in-human-osteosarcoma-cells
#19
Xiaowei Wang, Xiaoju Liang, Huan Liang, Bing Wang
Hypoxia is an element intrinsic to most solid-tumor microenvironments, including that of osteosarcoma (OS), and is associated with resistance to therapy, poor survival, and a malignant phenotype. The purpose of the present study was to investigate the role and underlying mechanism of SUMO-specific protease 1 (SENP1)/hypoxia-inducible factor-1α (HIF-1α) feedback loop in hypoxic microenvironment of OS. We observed that the expression of SENP1 was remarkably upregulated in OS cells. Additionally, there was a concomitant high expression of HIF-1α and SENP1 in MG-63 cells under a hypoxic microenvironment...
August 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28796245/dioscin-induces-prostate-cancer-cell-apoptosis-through-activation-of-estrogen-receptor-%C3%AE
#20
Xufeng Tao, Lina Xu, Lianhong Yin, Xu Han, Yan Qi, Youwei Xu, Shasha Song, Yanyan Zhao, Jinyong Peng
Recent researches have shown that estrogen receptor-β (ERβ) activator may be a potent anticancer agent for prostate cancer (PCa), and our previous study also indicated that dioscin can upregulate the expression of ERβ in MC3T3-E1 cell. In the present work, the activity and mechanism of dioscin, a natural product, against PCa were investigated. The results showed that dioscin markedly inhibited cell viability, colony formation, motility and induced apoptosis in PC3 cells. Moreover, dioscin disrupted the formation of PC3 cell-derived mammospheres and reduced aldehyde dehydrogenase (ALDH) level and the CD133(+)/CD44(+) cells, indicating that dioscin had a potent inhibitory activity on prostate cancer stem cells (PCSCs)...
August 10, 2017: Cell Death & Disease
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