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Tumor hypoxia

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https://www.readbyqxmd.com/read/28340463/hypoxia-and-hydrogen-sulfide-differentially-affect-normal-and-tumor-derived-vascular-endothelium
#1
Serena Bianco, Daniele Mancardi, Annalisa Merlino, Benedetta Bussolati, Luca Munaron
BACKGROUND: endothelial cells play a key role in vessels formation both under physiological and pathological conditions. Their behavior is influenced by blood components including gasotransmitters (H2S, NO and CO). Tumor cells are subjected to a cyclic shift between pro-oxidative and hypoxic state and, in this scenario, H2S can be both cytoprotective and detrimental depending on its concentration. H2S effects on tumors onset and development is scarcely studied, particularly concerning tumor angiogenesis...
March 18, 2017: Redox Biology
https://www.readbyqxmd.com/read/28339582/hypoxia-in-the-glioblastoma-microenvironment-shaping-the-phenotype-of-cancer-stem-like-cells
#2
Nicole Colwell, Mioara Larion, Amber J Giles, Ashlee N Seldomridge, Saman Sizdahkhani, Mark R Gilbert, Deric M Park
Glioblastoma is the most common and aggressive malignant primary brain tumor. Cellular heterogeneity is a characteristic feature of the disease and contributes to the difficulty in formulating effective therapies. Glioma stem-like cells (GSCs) have been identified as a subpopulation of tumor cells that are thought to be largely responsible for resistance to treatment. Intratumoral hypoxia contributes to maintenance of the GSCs by supporting the critical stem cell traits of multipotency, self-renewal, and tumorigenicity...
January 19, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339070/125i%C3%A2-seed-irradiation-induces-apoptosis-and-inhibits-angiogenesis-by-decreasing-hif-1%C3%AE-and-vegf-expression-in-lung-carcinoma-xenografts
#3
Gui-Ling Xiang, Xin-Hong Zhu, Cun-Zhi Lin, Li-Jun Wang, Yong Sun, Yi-Wei Cao, Fang-Fang Wang
The purpose of this study was to examine the effects of irradiation by 125I seeds in human lung cancer xenograft model and to determine the underlying mechanisms involved, with a focus on angiogenesis. A group of 40 mice bearing A549 lung adenocarcinoma xenografts was randomly separated into 4 groups: control group (n=10), sham seed (0 mCi) implant group (n=10), 125I seed (0.6 mCi) implant group (n=10) and 125I seed (0.8 mCi) implant group (n=10), respectively. The body weight and tumor volume, were recorded every four days until the end of the study...
March 23, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28337373/heparanase-promotes-radiation-resistance-of-cervical-cancer-by-upregulating-hypoxia-inducible-factor-1
#4
Jianping Li, Xin Meng, Jing Hu, Ying Zhang, Yunzhi Dang, Lichun Wei, Mei Shi
Heparanase (HPSE1) is elevated in various types of cancers including cervical cancer, and correlated with poor prognosis. Current study is to investigate the effects of HPSE1 on radiation response in cervical cancer. Colony formation assays after radiation were performed to compare the radiation response among control, HPSE1 knockdown and HPSE1 overexpression HeLa cells. The mRNA and protein levels of HIF1, bFGF and VEGF were measured as indicators for the activity of HIF1 pathway. Xenograft mouse model were used to study the HPSE1 radiation regulator effects in vivo...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28337358/gastric-cancer-and-angiogenesis-is-vegf-a-useful-biomarker-to-assess-progression-and-remission
#5
REVIEW
Filipa Macedo, Kátia Ladeira, Adhemar Longatto-Filho, Sandra F Martins
Gastric cancer (GC) has high mortality owing to its aggressive nature. Tumor angiogenesis plays an essential role in the growth, invasion, and metastatic spread of GC. The aim of this work was to review the angiogenic biomarkers related to the behavior of GC, documented in the literature. A search of the PubMed database was conducted with the MeSH terms: "Stomach neoplasms/blood [MeSH] or stomach neoplasms/blood supply [MeSH] and angiogenic proteins/blood [Major]". A total of 30 articles were initially collected, and 4 were subsequently excluded...
March 2017: Journal of Gastric Cancer
https://www.readbyqxmd.com/read/28337221/cancer-stem-cells-and-their-microenvironment-biology-and-therapeutic-implications
#6
REVIEW
Eunice Yuen-Ting Lau, Nicole Pui-Yu Ho, Terence Kin-Wah Lee
Tumor consists of heterogeneous cancer cells including cancer stem cells (CSCs) that can terminally differentiate into tumor bulk. Normal stem cells in normal organs regulate self-renewal within a stem cell niche. Likewise, accumulating evidence has also suggested that CSCs are maintained extrinsically within the tumor microenvironment, which includes both cellular and physical factors. Here, we review the significance of stromal cells, immune cells, extracellular matrix, tumor stiffness, and hypoxia in regulation of CSC plasticity and therapeutic resistance...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28336782/functional-imaging-signature-of-patients-presenting-with-polycythemia-paraganglioma-syndromes
#7
Ingo Janssen, Clara Chi Chen, Zhenping Zhuang, Corina M Millo, Katherine Wolf, Alexander Ling, Frank I Lin, Karen T Adams, Peter Herscovitch, Richard A Feelders, Antonio T Fojo, David Taieb, Electron Kebebew, Karel Pacak
Rationale: Pheochromocytoma/paraganglioma (PPGL) syndromes associated with polycythemia have previously been described in association with mutations in the von Hippel-Lindau (VHL) gene. Recently, mutations in the prolyl hydroxylase gene (PHD) 1 and 2 and in the hypoxia-inducible factor 2 alpha (HIF2A) were also found to be associated with multiple and recurrent PPGL. Such patients also presented with PPGL and polycythemia, and later on, some presented with duodenal somatostatinoma. In additional patients presenting with PPGL and polycythemia, no further mutations have been discovered...
March 23, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28333070/evaluation-of-mct1-mct4-and-cd147-genes-in-peripheral-blood-cells-of-breast-cancer-patients-and-their-potential-use-as-diagnostic-and-prognostic-markers
#8
Maria Cláudia de B Luz, Matheus M Perez, Ligia A Azzalis, Luiz Vinícius de A Sousa, Fernando Adami, Fernando L A Fonseca, Beatriz da C A Alves
BACKGROUND: Patients with breast cancer-the deadliest cancer among women-are at constant risk of developing metastasis. Oxidative stress and hypoxia are common feature of tumor cells that can proliferate even in a resultant metabolic acidosis. Despite the low extracellular pH, intracellular pH of tumor cells remains relatively normal, or even more alkaline due to the action of a membrane protein family known as monocarboxylate transporters (MCTs). The objective of this study was to verify the diagnostic and prognostic value of MCT1, MCT4 and CD147 in tumor and peripheral blood samples of patients with breast cancer undergoing chemotherapic treatment...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28332352/development-of-inhibitors-targeting-hypoxia-inducible-factor-1-and-2-for-cancer-therapy
#9
REVIEW
Tianchi Yu, Bo Tang, Xueying Sun
Hypoxia is frequently observed in solid tumors and also one of the major obstacles for effective cancer therapies. Cancer cells take advantage of their ability to adapt hypoxia to initiate a special transcriptional program that renders them more aggressive biological behaviors. Hypoxia-inducible factors (HIFs) are the key factors that control hypoxia-inducible pathways by regulating the expression of a vast array of genes involved in cancer progression and treatment resistance. HIFs, mainly HIF-1 and -2, have become potential targets for developing novel cancer therapeutics...
May 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28331872/induction-of-erythropoiesis-by-hypoxia-inducible-factor-prolyl-hydroxylase-inhibitors-without-promotion-of-tumor-initiation-progression-or-metastasis-in-a-vegf-sensitive-model-of-spontaneous-breast-cancer
#10
Todd W Seeley, Mark D Sternlicht, Stephen J Klaus, Thomas B Neff, David Y Liu
The effects of pharmacological hypoxia-inducible factor (HIF) stabilization were investigated in the MMTV-Neu(ndl)-YD5 (NeuYD) mouse model of breast cancer. This study first confirmed the sensitivity of this model to increased vascular endothelial growth factor (VEGF), using bigenic NeuYD;MMTV-VEGF-25 mice. Tumor initiation was dramatically accelerated in bigenic animals. Bigenic tumors were also more aggressive, with shortened doubling times and increased lung metastasis as compared to NeuYD controls. In separate studies, NeuYD mice were treated three times weekly from 7 weeks of age until study end with two different HIF prolyl hydroxylase inhibitors (HIF-PHIs), FG-4497 or roxadustat (FG-4592)...
2017: Hypoxia
https://www.readbyqxmd.com/read/28330951/hypoxia-induced-proliferation-of-hela-cells-depends-on-epidermal-growth-factor-receptor-mediated-arginase-ii-induction
#11
Bhuvana A Setty, Natasha Pillay Smiley, Caitlyn M Pool, Yi Jin, Yusen Liu, Leif D Nelin
Solid tumors can often be hypoxic in regions, and cancer cells can respond to hypoxia with an increase in proliferation and a decrease in apoptosis, leading to a net increase in viable cell numbers. We have recently found that in an osteosarcoma cell line, hypoxia-induced proliferation depends on arginase II induction. Epidermal growth factor receptor (EGFR) has been shown to mediate the hypoxia-induced cellular proliferation in some cancer cell lines. We hypothesized that hypoxia-induced proliferation of HeLa cells would depend on arginase II induction and that this induction of arginase II would occur through EGFR activation...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28330870/nuclear-factor-erythroid-2-related-factor-2-enhances-carcinogenesis-by-suppressing-apoptosis-and-promoting-autophagy-in-nickel-transformed-cells
#12
Young-Ok Son, Poyil Pratheeshkumar, Sasidharan Padmaja Divya, Zhuo Zhang, Xianglin Shi
Nickel-containing compounds are used widely in industry. Nickel is a known human carcinogen that primarily targets the lungs. Proposed mechanisms of nickel-induced carcinogenesis include disruption of cellular iron homeostasis, generation of reactive oxygen species (ROS), and induction of hypoxia signaling. The precise molecular mechanisms of nickel-induced malignant transformation and tumor development remain unclear. This study shows that the transcription factor Nrf2 is highly expressed in lung tumor tissue and in nickel-transformed human lung bronchial epithelial BEAS-2B cells (NiT cells)...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28327905/phase-ii-study-of-idelalisib-a-selective-inhibitor-of-pi3k%C3%AE-for-relapsed-refractory-classical-hodgkin-lymphoma
#13
A K Gopal, M A Fanale, C H Moskowitz, A R Shustov, S Mitra, W Ye, A Younes, A J Moskowitz
Background: The phosphatidylinositol-3-kinase delta (PI3Kδ) inhibitor idelalisib has been shown to block downstream intracellular signaling, reduce the production of prosurvival chemokines and induce apoptosis in classical Hodgkin lymphoma (HL) cell lines. It has also been shown to inhibit regulatory T cells and myeloid-derived suppressor cells in other tumor models. We hypothesized that inhibiting PI3Kδ would have both direct and indirect antitumor effects by directly targeting the malignant cells as well as modulating the inflammatory microenvironment...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327666/hypoxia-induces-h19-expression-through-direct-and-indirect-hif-1%C3%AE-activity-promoting-oncogenic-effects-in-glioblastoma
#14
Weining Wu, Qi Hu, Er Nie, Tianfu Yu, Youzhi Wu, Tongle Zhi, Kuan Jiang, Feng Shen, Yingyi Wang, Junxia Zhang, Yongping You
H19 expression is elevated in many human tumors including glioblastomas, suggesting an oncogenic role for the long noncoding RNA; yet the upregulation of H19 in glioblastomas remains unclear. Here we report that hypoxia significantly stimulated H19 expression in glioblastoma cell lines, which was related to hypoxia-inducible factors 1α (Hif-1α). Hif-1α promoted H19 expression in U87 and U251 cells. Meanwhile PTEN is an advantageous factor to affect H19 expression, through attenuating Hif-1α stability. Hif-1α also positively correlates with H19 in human glioblastoma samples depending on PTEN status...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28324046/characteristics-of-pediatric-vs-adult-pheochromocytomas-and-paragangliomas
#15
Christina Pamporaki, Barbora Hamplova, Mirko Peitzsch, Aleksander Prejbisz, Felix Beuschlein, Henri J L M Timmers, Martin Fassnacht, Barbara Klink, Maya Lodish, Constantine A Stratakis, Angela Huebner, Stephanie Fliedner, Mercedes Robledo, Richard O Sinnott, Andrzej Januszewicz, Karel Pacak, Graeme Eisenhofer
Context: Pheochromocytomas and paragangliomas (PPGLs) in children are often hereditary and may present with different characteristics compared to adults. Hereditary PPGLs can be separated into two groups: cluster 1 and cluster 2 tumors due to mutations impacting hypoxia and kinase receptor signaling pathways respectively. Objective: To identify differences in presentation of PPGLs between children and adults. Design: A retrospective cross-sectional clinical study...
January 31, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323448/effects-of-chronic-ghrelin-treatment-on-hypoxia-induced-brain-oxidative-stress-and-inflammation-in-a-rat-normobaric-chronic-hypoxia-model
#16
Hasan Omrani, Mohammad Reza Alipour, Fereshteh Farajdokht, Hadi Ebrahimi, Mehran Mesgari Abbasi, Gisou Mohaddes
AIM: This study aimed to evaluate the probable antioxidant effects of ghrelin in the brain and serum and its effect on tumor necrosis factor-alpha (TNF-α) levels in the brain in a model of chronic systemic hypoxia in rats. METHODS: Systemic hypoxia was induced by a normobaric hypoxic chamber (O2 11%) for ten days. Adult male Wistar rats were divided into control (C), chronic ghrelin (80 μg/kg/10 days) (Ghr), chronic hypoxia (CH), and CH and ghrelin (80 μg/kg/ip/10 days) (CH + Gh) groups...
March 21, 2017: High Altitude Medicine & Biology
https://www.readbyqxmd.com/read/28323298/pegylated-and-folic-acid-functionalized-carbon-nanotubes-as-ph-controlled-carriers-of-doxorubicin-molecular-dynamics-analysis-of-the-stability-and-drug-release-mechanism
#17
Pawel Wolski, Krzysztof Nieszporek, Tomasz Panczyk
This work deals with an analysis of the covalent functionalization of a carbon nanotube using polyethylene glycol chains terminated by folic acid fragments. The analysis is focused on theoretical predictions, using molecular dynamics simulations, of the properties of such constructs as pH controlled carriers of the anticancer drug doxorubicin. The analyzed systems are expected to hold the doxorubicin in the inner cavity of the carbon nanotube at neutral pH and unload the drug at slightly acidic pH. This property comes from incorporation into the nanotube of some dye molecules (p-phenylenediamine or neutral red) which undergo protonation at slightly acidic pH...
March 21, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28322833/treatment-of-novel-il17a-inhibitor-in-glioblastoma-implementing-3rd-generation-co-culture-cell-line-and-patient-derived-tumor-model
#18
Md Shamsuddin Sultan Khan, Muhammad Asif, Mohammed Khadeer Ahamed Basheer, Cheng Wei Kang, Fouad Saleh Al-Suede, Oon Chern Ein, Jing Tang, Aman Shah Abdul Majid, Amin Malik Shah Abdul Majid
Despite many treatment options, cancer remains a growing problem and has become the second leading cause of death globally. Here, we present fluorescence molecular tomography (FMT) data regarding the reversion of third generation co-cultured U87+DBTRG and patient-derived GBM tumor model after treatment with novel IL17A inhibitor named FLVM and FLVZ (organic derivatives of caffeic acid). FMT was used to determine tumor angiogenesis volume (assessment of number of blood vessel; the expression of angiogenic factors CD34 and other angiogenic cancer bio-markers) in U87+DBTRG and patient-derived gliomas...
March 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28322329/an-expanded-multi-scale-monte-carlo-simulation-method-for-personalized-radiobiological-effect-estimation-in-radiotherapy-a-feasibility-study
#19
Ying Zhang, Yuanming Feng, Wei Wang, Chengwen Yang, Ping Wang
A novel and versatile "bottom-up" approach is developed to estimate the radiobiological effect of clinic radiotherapy. The model consists of multi-scale Monte Carlo simulations from organ to cell levels. At cellular level, accumulated damages are computed using a spectrum-based accumulation algorithm and predefined cellular damage database. The damage repair mechanism is modeled by an expanded reaction-rate two-lesion kinetic model, which were calibrated through replicating a radiobiological experiment. Multi-scale modeling is then performed on a lung cancer patient under conventional fractionated irradiation...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28320353/genome-independent-hypoxic-repression-of-estrogen-receptor-alpha-in-breast-cancer-cells
#20
Mercè Padró, Raymond J Louie, Brian V Lananna, Adam J Krieg, Luika A Timmerman, Denise A Chan
BACKGROUND: About 75-80% of breast tumors express the estrogen receptor alpha (ER-α) and are treated with endocrine-target therapeutics, making this the premier therapeutic modality in the breast cancer clinic. However, acquired resistance is common and about 20% of resistant tumors loose ER-α expression via unknown mechanisms. Inhibition of ER-α loss could improve endocrine therapeutic efficacy, benefiting a significant number of patients. Here we test whether tumor hypoxia might commonly produce ER-α loss...
March 20, 2017: BMC Cancer
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