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https://www.readbyqxmd.com/read/28436951/hypoxic-lung-cancer-secreted-exosomal-mir-23a-increased-angiogenesis-and-vascular-permeability-by-targeting-prolyl-hydroxylase-and-tight-junction-protein-zo-1
#1
Y-L Hsu, J-Y Hung, W-A Chang, Y-S Lin, Y-C Pan, P-H Tsai, C-Y Wu, P-L Kuo
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28435293/expression-and-significance-of-grhl2-in-esophageal-cancer
#2
Chengcheng Shao, Chushu Ji, Xiaoqiu Wang, Bing Hu
Esophageal cancer (EC) is one of the most common causes of cancer-related mortality in the world. Although much effort has been made to improve the 5-year survival rate of patients with EC, it still remains low due to diagnosis at an advanced stage, aggressive local invasion, early metastasis, and resistance to chemotherapy. Although grainyhead-like 2 (GRHL2) has attracted interest since it has been recently identified as a novel suppressor of the epithelial-mesenchymal transition, clinical values of GRHL2 and its relationship with the metastasis-related factors, such as hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF), remain unclear...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28435259/methotrexate-coupled-nanoparticles-and-magnetic-nanochemothermia-for-the-relapse-free-treatment-of-t24-bladder-tumors
#3
Marcus Stapf, Ulf Teichgräber, Ingrid Hilger
Heat-based approaches have been considered as promising tools due to their ability to directly eradicate tumor cells and/or increase the sensitivity of tumors to radiation- or chemotherapy. In particular, the heating of magnetic nanoparticles (MNPs) via an alternating magnetic field can provide a handy alternative for a localized tumor treatment. To amplify the efficacy of magnetically induced thermal treatments, we elucidated the superior tumor-destructive effect of methotrexate-coupled MNPs (MTX/MNPs) in combination with magnetic heating (nanochemothermia) over the thermal treatment alone...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28434868/hif-1%C3%AE-dependent-wound-healing-angiogenesis-in%C3%A2-vivo-can-be-controlled-by-site-specific-lentiviral-magnetic-targeting-of-shp-2
#4
Yvonn Heun, Kristin Pogoda, Martina Anton, Joachim Pircher, Alexander Pfeifer, Markus Woernle, Andrea Ribeiro, Petra Kameritsch, Olga Mykhaylyk, Christian Plank, Florian Kroetz, Ulrich Pohl, Hanna Mannell
Hypoxia promotes vascularization by stabilization and activation of the hypoxia inducible factor 1α (HIF-1α), which constitutes a target for angiogenic gene therapy. However, gene therapy is hampered by low gene delivery efficiency and non-specific side effects. Here, we developed a gene transfer technique based on magnetic targeting of magnetic nanoparticle-lentivirus (MNP-LV) complexes allowing site-directed gene delivery to individual wounds in the dorsal skin of mice. Using this technique, we were able to control HIF-1α dependent wound healing angiogenesis in vivo via site-specific modulation of the tyrosine phosphatase activity of SHP-2...
April 20, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28433571/antitumor-and-chemosensitizing-action-of-3-bromopyruvate-implication-of-deregulated-metabolism
#5
Saveg Yadav, Shrish Kumar Pandey, Ajay Kumar, Praveen Kumar Kujur, Rana Pratap Singh, Sukh Mahendra Singh
3-Bromopyruvate (3-BP), brominated derivative of pyruvate, possesses strong antitumor potential, owing to its ability to inhibit multiple target molecules crucial for survival of neoplastic cells. Although, 3-BP displays cytotoxicity against a wide variety of tumors, there is no report with respect to malignancies of thymic origin. Therefore, we investigated its antineoplastic action in vitro against tumor cells of a murine transplantable lymphoma of thymoma origin, designated as Dalton's lymphoma (DL). 3-BP treatment of tumor cells inhibited metabolism and survival with augmented induction of apoptosis and necrosis...
April 19, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28424532/stemness-and-differentiation-potential-recovery-effects-of-sinapic-acid-against-ultraviolet-a-induced-damage-through-the-regulation-of-p38-mapk-and-nf-%C3%AE%C2%BAb
#6
Young Sun Hwang, See-Hyoung Park, Mingyeong Kang, Sae Woong Oh, Kwangseon Jung, Yong Seek Park, Jongsung Lee
Ultraviolet A (UVA) irradiation exerts negative effects on stemness and differentiation potential of stem cells. This study aimed to explore the effect of sinapic acid on UVA-irradiation-induced damages to stemness and differentiation potential of human-adipose-tissue-derived mesenchymal stem cells (hAMSCs) and its UVA-antagonist mechanisms. Sinapic acid attenuated UVA-induced reduction in the proliferative potential and stemness by upregulating OCT4, SOX2, and NANOG. In addition, sinapic acid significantly recovered UVA-induced reduction in expression level of hypoxia-inducible factor (HIF)-1α...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423608/anthracyclines-suppress-pheochromocytoma-cell-characteristics-including-metastasis-through-inhibition-of-the-hypoxia-signaling-pathway
#7
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/28423580/procollagen-lysine-2-oxoglutarate-5-dioxygenase-2-promotes-hypoxia-induced-glioma-migration-and-invasion
#8
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/28420760/novel-lnc-rna-regulated-by-hif-1-inhibits-apoptotic-cell-death-in-the-renal-tubular-epithelial-cells-under-hypoxia
#9
Imari Mimura, Yosuke Hirakawa, Yasuharu Kanki, Natsuki Kushida, Ryo Nakaki, Yutaka Suzuki, Tetsuhiro Tanaka, Hiroyuki Aburatani, Masaomi Nangaku
Chronic tubulointerstitial hypoxia plays an important role as the final common pathway to end-stage renal disease. HIF-1 (hypoxia-inducible factor-1) is a master transcriptional factor under hypoxia, regulating downstream target genes. Genome-wide analysis of HIF-1 binding sites using high-throughput sequencers has clarified various kinds of downstream targets and made it possible to demonstrate the novel roles of HIF-1. Our aim of this study is to identify novel HIF-1 downstream epigenetic targets which may play important roles in the kidney...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28420165/impact-of-acetazolamide-a-carbonic-anhydrase-inhibitor-on-the-development-of-intestinal-polyps-in-min-mice
#10
Nobuharu Noma, Gen Fujii, Shingo Miyamoto, Masami Komiya, Ruri Nakanishi, Misato Shimura, Sei-Ichi Tanuma, Michihiro Mutoh
Colorectal cancer is a common cancer worldwide. Carbonic anhydrase (CA) catalyzes the reversible conversion of carbon dioxide to bicarbonate ion and a proton, and its inhibitor is reported to reduce cancer cell proliferation and induce apoptosis. Therefore, we asked whether acetazolamide, a CA inhibitor, could inhibit intestinal carcinogenesis. Five-week-old male Apc-mutant mice, Min mice, were fed a AIN-76A diet containing 200 or 400 ppm acetazolamide. As a result, acetazolamide treatment reduced the total number of intestinal polyps by up to 50% compared to the control group...
April 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28419670/sglt2-and-sglt1-renal-expression-in-patients-with-type-2-diabetes
#11
Anna Solini, Chiara Rossi, Chiara Maria Mazzanti, Agnese Proietti, Hermann Koepsell, Ele Ferrannini
AIMS: The notion of an increased expression of SGLT2 in the kidney of patients with type 2 diabetes (T2DM) is based on a single ex vivo study of tubular cells harvested from the urine. DESIGN AND METHODS: We measured SGLT2 and SGLT1 expression in unaffected renal tissue from 19 T2DM patients and 20 age- and eGFR-matched nondiabetic subjects (CT) undergoing unilateral nephrectomy. Expression of SGLT2 and SGLT1 - and their cognate basolateral transporters GLUT2 and GLUT1 - was quantified by real-time and digital PCR; an affinity-purified antibody against human SGLT2 was used localize SGLT2 by immunohistochemistry...
April 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28418174/hypoxia-upregulates-integrin-gene-expression-in-microvascular-endothelial-cells-and-promotes-their-migration-and-capillary-like-tube-formation
#12
Christina Befani, Panagiotis Liakos
Tissue hypoxia affects gene expression through the hypoxia-inducible transcription factors, HIF-1 and HIF-2, in both physiological and pathological angiogenesis. Angiogenesis is a complex response of endothelial cells integrating cell proliferation, migration, tube formation and their interaction with the extracellular matrix through integrin receptors. In this report, we studied the effect of hypoxia on the angiogenic functions of human microvascular endothelial cells (HMEC-1) as well as on expression of the angiogenic integrins αν β3 , αν β5 and α5 β1 ...
April 18, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28418093/hypoxia-inducible-factor-1-alpha-does-not-regulate-osteoclastogenesis-but-enhances-bone-resorption-activity-via-prolyl-4-hydroxylase-2
#13
Philippa A Hulley, Tammie Bishop, Aude Vernet, Jurgen E Schneider, James R Edwards, Nick A Athanasou, Helen J Knowles
Osteogenic-angiogenic coupling is promoted by the Hypoxia-Inducible Factor 1-alpha (HIF-1α) transcription factor, provoking interest in HIF activation as a therapeutic strategy to improve osteoblast mineralisation and treat pathological osteolysis. However, HIF also enhances the bone resorbing activity of mature osteoclasts. It is therefore essential to determine the full effect(s) of HIF on both the formation and bone-resorbing function of osteoclasts in order to understand how they might respond to such a strategy...
April 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28416613/hypoxia-inducible-factor-1%C3%AE-activates-insig-2-transcription-for-degradation-of-hmg-coa-reductase-in-the-liver
#14
Seonghwan Hwang, Andrew D Nguyen, Youngah Jo, Luke J Engelking, James Brugarolas, Russell A DeBose-Boyd
Cholesterol synthesis is a highly oxygen-consuming process. As such, oxygen deprivation (hypoxia) limits cholesterol synthesis through incompletely understood mechanisms mediated by the oxygen-sensitive transcription factor hypoxia-inducible factor (HIF)-1α. We show here that HIF-1α links pathways for oxygen sensing and feedback control of cholesterol synthesis in human fibroblasts by directly activating transcription of the INSIG-2 gene. Insig-2 is one of two endoplasmic reticulum (ER) membrane proteins that inhibit cholesterol synthesis by mediating sterol-induced ubiquitination and subsequent ER-associated degradation of the rate-limiting enzyme in the pathway, HMG CoA reductase (HMGCR)...
April 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28415047/plod2-in-cancer-research
#15
REVIEW
Hongzhi Du, Mao Pang, Xiaoying Hou, Shengtao Yuan, Li Sun
Collagen is not only the most abundant protein providing the scaffold for assembly of the extracellular matrix (ECM), but also considered to be the "highway" for cancer cell migration and invasion depending on the different collagen organizations. The accumulation of stabilized collagen is enhanced by different covalent collagen cross-links, lysyl hydroxylases 2 (encoded by the PLOD2 gene) is the key enzyme mediating the formation of the stabilized collagen cross-link. Interestingly, PLOD2 is overexpressed in different cancers and closely related to a poor prognosis...
April 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28410229/in-vivo-evaluation-of-the-effects-of-simultaneous-inhibition-of-glut-1-and-hif-1%C3%AE-by-antisense-oligodeoxynucleotides-on-the-radiosensitivity-of-laryngeal-carcinoma-using-micro-18f-fdg-pet-ct
#16
Li-Fang Shen, Xin Zhao, Shui-Hong Zhou, Zhong-Jie Lu, Kui Zhao, Jun Fan, Min-Li Zhou
PURPOSE: Hypoxia-inducible factor 1α (HIF-1α) and glucose transporter-1 (GLUT-1) are two important hypoxic markers associated with the radioresistance of cancers including laryngeal carcinoma. We evaluated whether the simultaneous inhibition of GLUT-1 and HIF-1α expression improved the radiosensitivity of laryngeal carcinoma. We explored whether the expression of HIF-1α and GLUT-1 was correlated with 2'-deoxy-2'-[18F]fluoro-D-glucose (18F-FDG) uptake and whether 18F-FDG positron emission tomography-computed tomography (PET/CT) was appropriate for early evaluation of the response of laryngeal carcinoma to targeted treatment in vivo...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410215/cardiac-glycosides-suppress-the-maintenance-of-stemness-and-malignancy-via-inhibiting-hif-1%C3%AE-in-human-glioma-stem-cells
#17
Dae-Hee Lee, Sang Cheul Oh, Amber J Giles, Jinkyu Jung, Mark R Gilbert, Deric M Park
Tissue hypoxia contributes to solid tumor pathogenesis by activating a series of adaptive programs. We previously showed that hypoxia promotes the preferential expansion and maintenance of CD133 positive human glioma stem cells (GSC) in a hypoxia inducible factor 1 alpha (HIF-1α)-dependent mechanism. Here, we examined the activity of digitoxin (DT), a cardiac glycoside and a putative inhibitor of HIF-1α, on human GSC in vitro and in vivo. During hypoxic conditions (1% O2), we observed the effect of DT on the intracellular level of HIF-1α and the extracellular level of vascular endothelial growth factor (VEGF) in human GSC...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410212/hypoxia-induced-plod2-promotes-proliferation-migration-and-invasion-via-pi3k-akt-signaling-in-glioma
#18
Ye Song, Shihao Zheng, Jizhou Wang, Hao Long, Luxiong Fang, Gang Wang, Zhiyong Li, Tianshi Que, Yi Liu, Yilei Li, Xi'an Zhang, Weiyi Fang, Songtao Qi
Gliomas are the most common form of malignant primary brain tumors with poor 5-year survival rate. Dysregulation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was observed in gliomas, but the specific role and molecular mechanism of PLOD2 in glioma have not been reported yet. In this study, PLOD2 was found to be frequently up-regulated in glioma and could serve as an independent prognostic marker to identify patients with poor clinical outcome. Knockdown of PLOD2 inhibited proliferation, migration and invasion of glioma cells in vitro and in vivo...
March 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410190/dietary-oleuropein-inhibits-tumor-angiogenesis-and-lymphangiogenesis-in-the-b16f10-melanoma-allograft-model-a-mechanism-for-the-suppression-of-high-fat-diet-induced-solid-tumor-growth-and-lymph-node-metastasis
#19
Hyerim Song, Do Young Lim, Jae In Jung, Han Jin Cho, So Young Park, Gyoo Taik Kwon, Young-Hee Kang, Ki Won Lee, Myung-Sook Choi, Jung Han Yoon Park
Previously, we reported that high-fat-diet (HFD)-induced obesity stimulates melanoma progression in the B16F10 allograft model. In this study, we examined whether oleuropein (OL), the most abundant phenolic compound in olives, inhibits HFD-induced melanoma progression. Four-week-old male C57BL/6N mice were fed a HFD-diet with or without OL. After 16 weeks of feeding, B16F10-luc cells were subcutaneously injected and the primary tumor was resected 3 weeks later. OL suppressed HFD-induced solid tumor growth. In the tumor tissues, OL reduced HFD-induced expression of angiogenesis (CD31, VE-cadherin, VEGF-A, and VEGFR2), lymphangiogenesis (LYVE-1, VEGF-C, VEGF-D, and VEGFR3), and hypoxia (HIF-1α and GLUT-1) markers as well as HFD-induced increases in lipid vacuoles and M2 macrophages (MΦs)...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405689/differential-effects-of-sulforaphane-in-regulation-of-angiogenesis-in-a-co-culture-model-of-endothelial-cells-and-pericytes
#20
Yichong Wang, Zhigang Zhou, Wei Wang, Ming Liu, Yongping Bao
Aberrant neovascularization supports nutrients and the oxygen microenvironment in tumour growth, invasion and metastasis. Recapitulation of functional microvascular structures in vitro could provide a platform for the study of vascular conditions. Sulforaphane (SFN), an isothiocyanate, has been reported to possess chemopreventive properties. In the present study, the effects of SFN on cell proliferation and tubular formation have been investigated using endothelial cells (ECs) and pericytes in coculture. SFN showed a dose-dependent inhibition on the growth of ECs and pericytes with IC50 values 46...
May 2017: Oncology Reports
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