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Tumor hypoxia

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https://www.readbyqxmd.com/read/28430808/quantification-of-hypoxia-related-gene-expression-as-a-potential-approach-for-clinical-outcome-prediction-in-breast-cancer
#1
Abderrahim El Guerrab, Anne Cayre, Fabrice Kwiatkowski, Maud Privat, Jean-Marc Rossignol, Fabrice Rossignol, Frédérique Penault-Llorca, Yves-Jean Bignon
Breast cancers are solid tumors frequently characterized by regions with low oxygen concentrations. Cellular adaptations to hypoxia are mainly determined by "hypoxia inducible factors" that mediate transcriptional modifications involved in drug resistance and tumor progression leading to metastasis and relapse occurrence. In this study, we investigated the prognostic value of hypoxia-related gene expression in breast cancer. A systematic review was conducted to select a set of 45 genes involved in hypoxia signaling pathways and breast tumor progression...
2017: PloS One
https://www.readbyqxmd.com/read/28430666/myc-induced-glutaminolysis-bypasses-hif-driven-glycolysis-in-hypoxic-small-cell-lung-carcinoma-cells
#2
Matilda Munksgaard Thorén, Marica Vaapil, Johan Staaf, Maria Planck, Martin E Johansson, Sofie Mohlin, Sven Påhlman
We previously demonstrated that small cell lung carcinoma (SCLC) cells lack HIF-2α protein expression, whereas HIF-1α in these cells is expressed at both acute and prolonged hypoxia. Here we show that low HIF2A expression correlates with high expression of MYC genes. Knockdown of HIF1A expression had no or limited effect on cell survival and growth in vitro. Unexpectedly, hypoxic ATP levels were not affected by HIF-1α knockdown and SCLC cell viability did not decrease upon glucose deprivation. In line with these in vitro data, xenograft tumor-take and growth were not significantly affected by repressed HIF1A expression...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28429085/the-role-of-rna-alternative-splicing-in-regulating-cancer-metabolism
#3
REVIEW
Itamar Kozlovski, Zahava Siegfried, Adi Amar-Schwartz, Rotem Karni
Tumor cells alter their metabolism by a wide array of mechanisms to promote growth and proliferation. Dysregulated expression and/or somatic mutations of key components of the glycolytic pathway/TCA cycle as well as other metabolic pathways allow tumor cells to improve their ability to survive harsh conditions such as hypoxia and the presence of reactive oxygen species, as well as the ability to obtain nutrients to increase lipids, protein, and nucleic acids biogenesis. Approximately 95% of the human protein encoding genes undergo alternative splicing (AS), a regulated process of gene expression that greatly diversifies the proteome by creating multiple proteins from a single gene...
April 20, 2017: Human Genetics
https://www.readbyqxmd.com/read/28428273/assessing-prostate-cancer-aggressiveness-with-hyperpolarized-dual-agent-3d-dynamic-imaging-of-metabolism-and-perfusion
#4
Hsin-Yu Chen, Peder E Z Larson, Robert A Bok, Cornelius von Morze, Renuka Sriram, Romelyn Delos Santos, Justin Delos Santos, Jeremy W Gordon, Naeim Bahrami, Marcus Ferrone, John Kurhanewicz, Daniel B Vigneron
New magnetic resonance (MR) molecular imaging techniques offer the potential for non-invasive, simultaneous quantification of metabolic and perfusion parameters in tumors. This study applied a 3D dynamic dual-agent hyperpolarized (13)C magnetic resonance spectroscopic imaging (MRSI) approach with (13)C-pyruvate and (13)C-urea to investigate differences in perfusion and metabolism between low and high grade tumors in the TRAMP transgenic mouse model of prostate cancer. Dynamic MR data were corrected for T1 relaxation and RF excitation and modeled to provide quantitative measures of pyruvate to lactate flux (kPL) and urea perfusion (urea AUC) that correlated with TRAMP tumor histologic grade...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28427209/hif1%C3%AE-regulates-single-differentiated-glioma-cell-dedifferentiation-to-stem-like-cell-phenotypes-with-high-tumorigenic-potential-under-hypoxia
#5
Pan Wang, Chuan Lan, Shuanglong Xiong, Xiuwen Zhao, You'an Shan, Rong Hu, Wenwu Wan, Shuangjiang Yu, Bin Liao, Guangzhi Li, Junwei Wang, Dewei Zou, Bing Chen, Hua Feng, Nan Wu
The standard treatment for Glioblastoma multiforme (GBM) is surgical resection and subsequent radiotherapy and chemotherapy. Surgical resection of GBM is typically restricted because of its invasive growth, which results in residual tumor cells including glioma stem cells (GSCs) and differentiated cells. Recurrence has been previously thought to occur as a result of these GSCs, and hypoxic microenvironment maintains the GSCs stemness also plays an important role. Summarizing traditional studies and we find many researchers ignored the influence of hypoxia on differentiated cells...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427198/hypoxia-activates-placental-growth-factor-expression-in-lymphatic-endothelial-cells
#6
Laura Tudisco, Augusto Orlandi, Valeria Tarallo, Sandro De Falco
Placental growth factor (PlGF), a proangiogenic member of vascular endothelial growth family, is active during pathological conditions like cancer, metastasis formation and hind limb ischemia and in wound healing. Endothelial cells express PlGF and hypoxia positively modulates in vitro its expression. To verify whether hypoxia modulates PlGF expression in different cellular contexts and in vivo, we first analyzed five human and five mouse cancer cell lines showing that in eight of them hypoxia positively modulates PlGF...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28426974/cell-borne-2d-nanomaterials-for-efficient-cancer-targeting-and-photothermal-therapy
#7
Zhibin Li, Jundong Shao, Qian Luo, Xue-Feng Yu, Hanhan Xie, Haidi Fu, Siying Tang, Huaiyu Wang, Guangli Han, Paul K Chu
Two of the challenges for clinical implementation of nano-therapeutic strategies are optimization of tumor targeting and clearance of the nanoagents in vivo. Herein, a cell-mediated therapy by transporting 2D Bi2Se3 nanosheets within macrophage vehicles is described. The Bi2Se3 nanosheets with excellent near-infrared photothermal performance exhibit high macrophage uptake and negligible cytotoxicity thus facilitating the fabrication of Bi2Se3-laden-macrophages. Compared with bare Bi2Se3, the Bi2Se3-laden-macrophages after intravenous injection show prolonged blood circulation and can overcome the hypoxia-associated drug delivery barrier to target the tumor efficiently and dramatically enhance the efficiency of photothermal cancer therapy...
April 17, 2017: Biomaterials
https://www.readbyqxmd.com/read/28426202/chemical-design-and-synthesis-of-functionalized-probes-for-imaging-and-treating-tumor-hypoxia
#8
Jia-Nan Liu, Wenbo Bu, Jianlin Shi
Hypoxia development in tumor is closely associated with its increased aggressiveness and strong resistance to therapy, leading to the poor prognosis in several cancer types. Clinically, invasive oxygen microelectrode and high dosage radiotherapy are often utilized to accurately detect and effectively fight hypoxia. Recently, however, there has been a surge of interdisciplinary research aiming at developing functional molecules and nanomaterials that can be used to noninvasively image and efficiently treat hypoxic tumors...
April 20, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28426124/propofol-suppresses-lps-induced-nuclear-accumulation-of-hif-1%C3%AE-and-tumor-aggressiveness-in-non-small-cell-lung-cancer
#9
Nengli Yang, Yafeng Liang, Pei Yang, Fuhai Ji
Tumor hypoxia has been recognized as a characteristic of the tumor microenvironment and promotes metastasis in a variety of types of cancer. However, in lung cancer, the role of hypoxia-inducible factor 1α (HIF-1α) in modulating the cellular response to the inflammation-related microenvironment remains unclear. In the present study, enhanced expression of HIF-1α accompanied by an increased ROS level was observed in lipopolysaccharide (LPS)-stimulated non-small cell lung cancer (NSCLC) cells. In addition, propofol, a general anesthetic, was found to significantly reduce the LPS-induced upregulation of HIF-1α and ROS in a dose-dependent manner...
March 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28425583/sleep-apnea-syndrome-inflammation-and-oxidative-stress-in-hemodialysis-patients
#10
Olga Nikitidou, Euphemia Daskalopoulou, Aikaterini Papagianni, Vassilios Liakopoulos, Aikaterini Michalaki, Foteini Christidou, Paraskevi Argyropoulou, Dimitrios Kirmizis, Georgios Efstratiadis, Pavlos Nikolaidis, Michail Daniilidis, Nicholas Dombros
INTRODUCTION: Sleep apnea syndrome (SAS) is an established cardiovascular risk factor in the general population related to inflammation and oxidative stress and is very common among hemodialysis patients. Cardiovascular disease and its complications is the main cause of death among hemodialysis patients. The aim of the present study was to investigate the role of SAS in the promotion of inflammation and oxidative stress and thus in the augmentation of cardiovascular risk in hemodialysis patients...
April 20, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28425505/novel-interactions-of-the-von-hippel-lindau-pvhl-tumor-suppressor-with-the-cdkn1-family-of-cell-cycle-inhibitors
#11
Giovanni Minervini, Raffaele Lopreiato, Raissa Bortolotto, Antonella Falconieri, Geppo Sartori, Silvio C E Tosatto
Germline inactivation of the von Hippel-Lindau (VHL) tumor suppressor predisposes patients to develop different highly vascularized cancers. pVHL targets the hypoxia-inducible transcription factor (HIF-1α) for degradation, modulating the activation of various genes involved in hypoxia response. Hypoxia plays a relevant role in regulating cell cycle progression, inducing growth arrest in cells exposed to prolonged oxygen deprivation. However, the exact molecular details driving this transition are far from understood...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424337/physical-and-chemical-gradients-in-the-tumor-microenvironment-regulate-tumor-cell-invasion-migration-and-metastasis
#12
Madeleine J Oudin, Valerie M Weaver
Cancer metastasis requires the invasion of tumor cells into the stroma and the directed migration of tumor cells through the stroma toward the vasculature and lymphatics where they can disseminate and colonize secondary organs. Physical and biochemical gradients that form within the primary tumor tissue promote tumor cell invasion and drive persistent migration toward blood vessels and the lymphatics to facilitate tumor cell dissemination. These microenvironment cues include hypoxia and pH gradients, gradients of soluble cues that induce chemotaxis, and ions that facilitate galvanotaxis, as well as modifications to the concentration, organization, and stiffness of the extracellular matrix that produce haptotactic, alignotactic, and durotactic gradients...
April 19, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28423707/tropomyosin-related-kinase-b-mediated-signaling-contributes-to-the-induction-of-malignant-phenotype-of-gallbladder-cancer
#13
Makoto Kawamoto, Hideya Onishi, Keigo Ozono, Akio Yamasaki, Akira Imaizumi, Sachiko Kamakura, Kenji Nakano, Yoshinao Oda, Hideki Sumimoto, Masafumi Nakamura
This study aims to demonstrate the clinical and biological significance of Brain derived neurotrophic factor (BDNF)/Tropomyosin-related kinase B (TrkB) signaling in gallbladder cancer (GBC) through a series of in vitro and in vivo experiments. TrkB expression was detected in 63 (91.3%) out of 69 surgically resected primary GBC specimens by immunohistochemistry. TrkB expression in the invasive front correlated with T factor (p=0.0391) and clinical staging (p=0.0391). Overall survival was lower in patients with high TrkB expression in the invasive front than in those with low TrkB expression (p=0...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423608/anthracyclines-suppress-pheochromocytoma-cell-characteristics-including-metastasis-through-inhibition-of-the-hypoxia-signaling-pathway
#14
Ying Pang, Chunzhang Yang, Jan Schovanek, Herui Wang, Petra Bullova, Veronika Caisova, Garima Gupta, Katherine I Wolf, Gregg L Semenza, Zhengping Zhuang, Karel Pacak
Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, neuroendocrine tumors derived from adrenal or extra-adrenal chromaffin cells, respectively. Metastases are discovered in 3-36% of patients at the time of diagnosis. Currently, only suboptimal treatment options exist. Therefore, new therapeutic compounds targeting metastatic PHEOs/PGLs are urgently needed. Here, we investigated if anthracyclines were able to suppress the progression of metastatic PHEO. We explored their effects on experimental mouse PHEO tumor cells using in vitro and in vivo models, and demonstrated that anthracyclines, particularly idarubicin (IDA), suppressed hypoxia signaling by preventing the binding of hypoxia-inducible factor 1 and 2 (HIF-1 and HIF-2) to the hypoxia response element (HRE) sites on DNA...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423594/the-hypoxia-activated-prodrug-evofosfamide-in-combination-with-multiple-regimens-of-radiotherapy
#15
Katarzyna J Nytko, Ivo Grgic, Sabine Bender, Janosch Ott, Matthias Guckenberger, Oliver Riesterer, Martin Pruschy
The promising treatment combination of ionizing radiation (IR) with a hypoxia-activated prodrug (HAP) is based on biological cooperation. Here we investigated the hypoxia-activated prodrug evofosfamide in combination with different treatment regimens of IR against lung A549- and head&neck UT-SCC-14-derived tumor xenografts. DNA damage-related endpoints and clonogenic cell survival of A549 and UT-SCC-14 carcinoma cells were probed under normoxia and hypoxia.Evofosfamide (TH-302) induced DNA-damage and a dose-dependent antiproliferative response in A549 cells on cellular pretreatment under hypoxia, and supra-additively reduced clonogenic survival in combination with IR...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423580/procollagen-lysine-2-oxoglutarate-5-dioxygenase-2-promotes-hypoxia-induced-glioma-migration-and-invasion
#16
Yangyang Xu, Lin Zhang, Yuzhen Wei, Xin Zhang, Ran Xu, Mingzhi Han, Bing Huang, Anjing Chen, Wenjie Li, Qing Zhang, Gang Li, Jian Wang, Peng Zhao, Xingang Li
Poor prognosis of glioblastoma multiforme is strongly associated with the ability of tumor cells to invade the brain parenchyma, which is believed to be the major factor responsible for glioblastoma recurrence. Therefore, identifying the molecular mechanisms driving invasion may lead to the development of improved therapies for glioblastoma patients. Here, we investigated the role of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2), an enzyme catalyzing collagen cross-linking, in the biology of glioblastoma invasion...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423496/mtor-inhibitors-activate-perk-signaling-and-favor-viability-of-gastrointestinal-neuroendocrine-cell-lines
#17
Patricia Freis, Julien Bollard, Justine Lebeau, Patrick Massoma, Joëlle Fauvre, Cécile Vercherat, Thomas Walter, Serge Manié, Colette Roche, Jean-Yves Scoazec, Carole Ferraro-Peyret
mTOR and Unfolded Protein Response (UPR) are two signaling pathways frequently activated in cancer cells. The mTOR pathway has been shown to be up-regulated in most gastroenteropancreatic neuroendocrine tumors. In contrast, little is known about the UPR status in neoplastic neuroendocrine cells. However, these hormone-producing cells are likely to present distinctive adaptations of this pathway, as other secretory cells. We therefore analyzed the status of the three axes of UPR and their relation to mTOR pathway in two gastrointestinal neuroendocrine tumors (GI-NET) cell lines STC-1 and GluTag...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421747/multifunctional-probe-based-on-cationic-conjugated-polymers-for-nitroreductase-related-analysis-sensing-hypoxia-diagnosis-and-imaging
#18
Xiaoqian Zhang, Qi Zhao, Yanru Li, Xinrui Duan, Yanli Tang
Nitroreductase (NTR) is overexpressed in hypoxic tumors. Moreover, hypoxia is usually considered as a most important feature of various diseases. Thus it is important to build a sensitive and selective method for NTR detection and hypoxia diagnosis. Herein, a new cationic conjugated polymer (PBFBT-NP) with p-nitrophenyl group in the side chain was designed and synthesized as a fluorescent probe for the detection of NTR. In the absence of NTR, the fluorescence of PBFBT-NP was quenched due to photo-induced electron transfer (PET)...
April 19, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28421447/inhibition-of-p-glycoprotein-stimulates-cell-death-under-hypoxia-mimicking-conditions
#19
A S Vdovin, P V Maximchik, A V Kulikov, B D Zhivotovsky, V G Gogvadze
The most common drug resistance mechanism in tumor cells is expression on their surface of the energy-dependent pump like P-glycoprotein (P-gp) that expels chemotherapeutic agents from the interior. An imitation of the hypoxic condition by the iron chelator deferoxamine caused Hypoxia-inducible factor 1-alpha (HIF-1α) stabilization and inhibition of doxorubicin-induced apoptosis in colon cancer НСТ116 cells. P-gp blocker verapamil suppressed doxorubicin accumulation leading to cell death induction. Considering these results, P-gp may be used as a potential target to stimulate chemotherapeutic drugs activity that will contribute to more efficient tumor cells elimination...
January 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28420430/chronic-stress-induces-cd99-suppresses-autophagy-and-affects-spontaneous-adipogenesis-in-human-bone-marrow-stromal-cells
#20
Zvenyslava Husak, Michael N Dworzak
BACKGROUND: Bone marrow-derived mesenchymal stromal cells (MSCs) are multipotent cells with a high constitutive level of autophagy and low expression of CD99. Under certain conditions, MSCs may develop tumorigenic properties. However, these transformation-induced conditions are largely unknown. Recently, we have identified an association between Hsp70, a main participant in cellular stress response and tumorigenesis, and CD99. Preliminary observations had revealed upregulation of both proteins in stressed long-term cultured MSCs...
April 18, 2017: Stem Cell Research & Therapy
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