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https://www.readbyqxmd.com/read/29454386/telomere-elongation-protects-heart-and-lung-tissue-cells-from-fatal-damage-in-rats-exposed-to-severe-hypoxia
#1
Yaping Wang, Zhen Zhao, Zhiyong Zhu, Pingying Li, Xiaolin Li, Xiaohong Xue, Jie Duo, Yingcai Ma
BACKGROUND: The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues. METHODS: Forty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30)...
February 17, 2018: Journal of Physiological Anthropology
https://www.readbyqxmd.com/read/29435131/pd-l1-confers-resistance-to-egfr-mutation-independent-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer-via-upregulation-of-yap1-expression
#2
Jai-Nien Tung, Po-Lin Lin, Yao-Chen Wang, De-Wei Wu, Chi-Yi Chen, Huei Lee
Programmed death ligand (PD-L1) expression was associated with tumor immune escape and subsequent poor prognosis in non-small cell lung cancer (NSCLC). This expression was higher in patients with EGFR-mutated NSCLC tumors than in those with EGFR-wild-type (WT) NSCLC tumors. We therefore hypothesized that poor prognosis mediated by higher PD-L1 may be partially through conferring resistance to tyrosine kinase inhibitor (TKI) in NSCLC regardless of EGFR mutation. The change in PD-L1 expression following gene manipulation corresponded with changes in expression of HIF-1α and YAP1...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29434884/endostatin-reverses-immunosuppression-of-the-tumor-microenvironment-in-lung-carcinoma
#3
Xiaolin Liu, Weiwei Nie, Qi Xie, Guoling Chen, Xingyu Li, Yanrui Jia, Beibei Yin, Xun Qu, Yan Li, Jing Liang
Endostatin has previously been demonstrated to efficiently inhibit the angiogenesis and growth of endothelial cells. However, the role of endostatin in the tumor microenvironment remains to be elucidated. To investigate the antitumor effect of endostatin in lung cancer, the present study was designed to explore the alterations of microvessel density in Lewis lung cancer models and the expression of vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-17, interferon (IFN)-γ and hypoxia inducible factor (HIF)-1α, following endostatin therapy...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29433520/intermittent-hypoxia-promotes-melanoma-lung-metastasis-via-oxidative-stress-and-inflammation-responses-in-a-mouse-model-of-obstructive-sleep-apnea
#4
Lian Li, Fangyuan Ren, Chao Qi, Leiqian Xu, Yinshan Fang, Maoli Liang, Jing Feng, Baoyuan Chen, Wen Ning, Jie Cao
BACKGROUND: Recently, increased tumor incidence and cancer-related mortality have been reported among patients with obstructive sleep apnea (OSA). Intermittent hypoxia (IH), the hallmark feature of OSA, contributes to the metastasis of tumors. However, the molecular mechanisms by which tumor metastasis is accelerated by OSA-like IH remain to be elucidated. METHODS: C57BL/6 J male mice were subjected to intravenous injection of B16F10 melanoma cells before receiving IH treatment...
February 12, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29426911/hypoxia-induces-pulmonary-fibroblast-proliferation-through-nfat-signaling
#5
Lakmini Kumari Senavirathna, Chaoqun Huang, Xiaoyun Yang, Maria Cristina Munteanu, Roshini Sathiaseelan, Dao Xu, Craig A Henke, Lin Liu
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and typically fatal lung disease with a very low survival rate. Excess accumulation of fibroblasts, myofibroblasts and extracellular matrix creates hypoxic conditions within the lungs, causing asphyxiation. Hypoxia is, therefore, one of the prominent features of IPF. However, there have been few studies concerning the effects of hypoxia on pulmonary fibroblasts. In this study, we investigated the molecular mechanisms of hypoxia-induced lung fibroblast proliferation...
February 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29423017/aerosolized-deferoxamine-administration-in-mouse-model-of-bronchopulmonary-dysplasia-improve-pulmonary-development
#6
Yanru Chen, Sha Gao, Yufei Yan, Jihong Qian, Hao Chen
Bronchopulmonary dysplasia (BPD) is the most common complication in preterm newborns. It occurs due to early exposure to high-oxygen and ventilation therapy. The mechanisms of disrupted alveolarization and vascular development associated with BPD were unclear. Deferoxamine (DFO) has been reported to reduce mortality and lung injury in mice after chlorine exposure. The effect of DFO in the treatment of BPD has not been explored. This study aimed to investigate the effect of aerosolized DFO administration in a mouse model of BPD...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29416769/roles-of-malat1-in-development-and-migration-of-triple-negative-and-her-2-positive-breast-cancer
#7
Zhang Xiping, Chen Bo, Yang Shifeng, Yu Feijiang, Yang Hongjian, Cheng Qihui, Tang Binbin
Background: As a type of new targets for prognosis of malignancies, long non-coding RNA MALAT1 (metastasis-associated lung adenocarcinoma transcription 1) is associated with proliferation and metastatic abilities of several malignancies. However, its relations to development and migration of triple negative and human epidermal growth factor receptor 2 (Her-2) positive breast cancers haven't been reported. Objectives: In this paper, we aimed to discuss how MALAT1 is connected with and affects proliferation and invasion abilities of cells in Her-2 positive and triple-negative breast cancers (TNBC)...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29397612/-effect-of-hif-2%C3%AE-on-the-biological-characteristics-of-breast-cancer-stem-cells
#8
Y Q Liu, N Li, H F Huang, H X Li
Objective: To explore the effect of hypoxia inducible factor (HIF)-2α on biological characteristics of breast cancer stem cells (BCSCs). Methods: Stem cells were isolated and purified from MCF-7 cells by using the immunomagnetic microbeads. HIF-2α ORF/shRNA lentiviral vectors were transduced into MCF-7 stem cells respectively, and then the stable stem cell lines were detected and gained. Using the method of Cell Counting Kit-8 (CCK-8) and flow cytometry, the effect of HIF-2α on cell vitality and apoptosis of MCF-7 cancer stem cells (CSCs) were tested...
January 23, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29394091/hypoxia-up-regulates-estrogen-receptor-%C3%AE-in-pulmonary-artery-endothelial-cells-in-a-hif-1%C3%AE-dependent-manner
#9
Andrea L Frump, Mona Selej, Jordan A Wood, Marjorie Albrecht, Bakhtiyor Yakubov, Irina Petrache, Tim Lahm
17β-estradiol (E2) attenuates hypoxia-induced pulmonary hypertension (HPH) through estrogen receptor (ER)-dependent effects, including inhibition of hypoxia-induced endothelial cell proliferation; however, the mechanisms responsible remain unknown. We hypothesized the protective effects of E2 in HPH are mediated through hypoxia-inducible factor 1α (HIF-1α)-dependent increases in ERβ expression. Sprague Dawley rats or ERα or ERβ knockout mice were exposed to hypobaric hypoxia for 2-3 weeks. The effects of hypoxia were also studied in primary rat or human pulmonary artery endothelial cells (PAECs)...
February 2, 2018: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29393397/development-of-single-nanometer-sized-ultrafine-oxygen-bubbles-to-overcome-the-hypoxia-induced-resistance-to-radiation-therapy-via-the-suppression-of-hypoxia-inducible-factor%C3%A2-1%C3%AE
#10
Misaki Iijima, Navchaa Gombodorj, Yoshiaki Tachibana, Kohsuke Tachibana, Takehiko Yokobori, Kyoko Honma, Takashi Nakano, Takayuki Asao, Ryusuke Kuwahara, Kazuhiro Aoyama, Hidehiro Yasuda, Matthew Kelly, Hiroyuki Kuwano, Dai Yamanouchi
Radiation therapy can result in severe side-effects, including the development of radiation resistance. The aim of this study was to validate the use of oxygen nanobubble water to overcome resistance to radiation in cancer cell lines via the suppression of the hypoxia-inducible factor 1-α (HIF‑1α) subunit. Oxygen nanobubble water was created using a newly developed method to produce nanobubbles in the single-nanometer range with the ΣPM-5 device. The size and concentration of the oxygen nanobubbles in the water was examined using a cryo-transmission electron microscope...
January 18, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29370315/lipid-droplet-formation-in-mycobacterium-tuberculosis-infected-macrophages-requires-ifn-%C3%AE-hif-1%C3%AE-signaling-and-supports-host-defense
#11
Matthew Knight, Jonathan Braverman, Kaleb Asfaha, Karsten Gronert, Sarah Stanley
Lipid droplet (LD) formation occurs during infection of macrophages with numerous intracellular pathogens, including Mycobacterium tuberculosis. It is believed that M. tuberculosis and other bacteria specifically provoke LD formation as a pathogenic strategy in order to create a depot of host lipids for use as a carbon source to fuel intracellular growth. Here we show that LD formation is not a bacterially driven process during M. tuberculosis infection, but rather occurs as a result of immune activation of macrophages as part of a host defense mechanism...
January 25, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29339541/phd3-controls-lung-cancer-metastasis-and-resistance-to-egfr-inhibitors-through-tgf%C3%AE
#12
Higinio Dopeso, Hui-Ke Jiao, Angel M Cuesta, Anne-Theres Henze, Liane Jurida, Michael Kracht, Amparo Acker-Palmer, Boyan K Garvalov, Till Acker
Lung cancer is the leading cause of cancer-related death worldwide, in large part due to its high propensity to metastasize and develop therapy resistance. Adaptive responses to hypoxia and epithelial-mesenchymal transition (EMT) are linked to tumor metastasis and drug resistance, but little is known about how oxygen sensing and EMT intersect to control these hallmarks of cancer. Here we show that the oxygen sensor PHD3 links hypoxic signaling and EMT regulation in the lung tumor microenvironment. PHD3 was repressed by signals that induce EMT and acted as a negative regulator of EMT, metastasis and therapeutic resistance...
January 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29339479/hif-signaling-in-osteoblast-lineage-cells-promotes-systemic-breast-cancer-growth-and-metastasis-in-mice
#13
Claire-Sophie Devignes, Yetki Aslan, Audrey Brenot, Audrey Devillers, Koen Schepers, Stéphanie Fabre, Jonathan Chou, Amy-Jo Casbon, Zena Werb, Sylvain Provot
Bone metastasis involves dynamic interplay between tumor cells and the local stromal environment. In bones, local hypoxia and activation of the hypoxia-inducible factor (HIF)-1α in osteoblasts are essential to maintain skeletal homeostasis. However, the role of osteoblast-specific HIF signaling in cancer metastasis is unknown. Here, we show that osteoprogenitor cells (OPCs) are located in hypoxic niches in the bone marrow and that activation of HIF signaling in these cells increases bone mass and favors breast cancer metastasis to bone locally...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29317756/non-coding-rnas-predict-recurrence-free-survival-of-patients-with-hypoxic-tumours
#14
Victor D Martinez, Natalie S Firmino, Erin A Marshall, Kevin W Ng, Brennan J Wadsworth, Christine Anderson, Wan L Lam, Kevin L Bennewith
Hypoxia promotes tumour aggressiveness and reduces patient survival. A spectrum of poor outcome among patients with hypoxic tumours suggests that additional factors modulate how tumours respond to hypoxia. PIWI-interacting RNAs (piRNAs) are small non-coding RNAs with a pivotal role in genomic stability and epigenetic regulation of gene expression. We reported that cancer type-specific piRNA signatures vary among patients. However, remarkably homogenous piRNA profiles are detected across patients with renal cell carcinoma, a cancer characterized by constitutive upregulation of hypoxia-related signaling induced by common mutation or loss of von Hippel-Lindau factor (VHL)...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29300322/mutations-in-emt-related-genes-in-alk-positive-crizotinib-resistant-non-small-cell-lung-cancers
#15
Jiacong Wei, Anthonie J van der Wekken, Ali Saber, Miente M Terpstra, Ed Schuuring, Wim Timens, T Jeroen N Hiltermann, Harry J M Groen, Anke van den Berg, Klaas Kok
Crizotinib is an effective drug for patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), but upon treatment, the tumors inevitably become crizotinib resistant in time. The resistance mechanisms are only partly understood. In this study, we aim to identify gene mutations associated with resistance in ALKpositive advanced non-squamous NSCLC treated with crizotinib. Four ALK positive patients with progressive disease following crizotinib treatment were identified with paired pre- and post-crizotinib tumor tissue from our previously published cohort...
January 4, 2018: Cancers
https://www.readbyqxmd.com/read/29251629/hif-1%C3%AE-promotes-autophagic-proteolysis-of-dicer-and-enhances-tumor-metastasis
#16
Hui-Huang Lai, Jie-Ning Li, Ming-Yang Wang, Hsin-Yi Huang, Carlo M Croce, Hui-Lung Sun, Yu-Jhen Lyu, Jui-Wen Kang, Ching-Feng Chiu, Mien-Chie Hung, Hiroshi I Suzuki, Pai-Sheng Chen
HIF-1α, one of the most extensively studied oncogenes, is activated by a variety of microenvironmental factors. The resulting biological effects are thought to depend on its transcriptional activity. The RNAse enzyme Dicer is frequently downregulated in human cancers, which has been functionally linked to enhanced metastatic properties; however, current knowledge of the upstream mechanisms regulating Dicer is limited. In the present study, we identified Dicer as a HIF-1α-interacting protein in multiple types of cancer cell lines and different human tumors...
December 18, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29245898/a-novel-small-molecule-arylsulfonamide-causes-energetic-stress-and-suppresses-breast-and-lung-tumor-growth-and-metastasis
#17
Xin Dai, Stefan Kaluz, Ying Jiang, Lei Shi, DeAngelo Mckinley, Yingzhe Wang, Binghe Wang, Erwin G Van Meir, Chalet Tan
Neoplastic cells display reprogrammed metabolism due to the heightened energetic demands and the need for biomass synthesis of a growing tumor. Targeting metabolic vulnerabilities is thus an important goal for cancer therapy. Here, we describe a novel small-molecule arylsulfonamide (N-cyclobutyl-N-((2,2-dimethyl-2H-pyrano[3,2-b]pyridin-6-yl)methyl)-3,4-dimethoxybenzenesulfonamide) that exerts potent cytotoxicity and energetic stress on tumor cells while largely sparing non-cancerous human cells. In tumor cells, it stimulates glycolysis and accelerates glucose consumption...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29233858/enhancement-of-glycolysis-by-inhibition-of-oxygen-sensing-prolyl-hydroxylases-protects-alveolar-epithelial-cells-from-acute-lung-injury
#18
Kentaro Tojo, Nao Tamada, Yusuke Nagamine, Takuya Yazawa, Shuhei Ota, Takahisa Goto
Cellular bioenergetic failure caused by mitochondrial dysfunction is a key process of alveolar epithelial injury during acute respiratory distress syndrome (ARDS). Prolyl hydroxylases (PHDs) act as cellular oxygen sensors, and their inhibition activates hypoxia-inducible factor (HIF), resulting in enhanced cellular glycolytic activity, which could compensate for impaired mitochondrial function and protect alveolar epithelial cells from ARDS. Here, we evaluated the effects of pharmacological PHD inhibition with dimethyloxalylglycine (DMOG) on alveolar epithelial cell injury using in vitro and in vivo ARDS models...
December 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29212260/bioenergetics-of-acquired-cisplatin-resistant-h1299-non-small-cell-lung-cancer-and-p31-mesothelioma-cells
#19
Fintan Geoghegan, Robert J Buckland, Eric T Rogers, Karima Khalifa, Emma B O'Connor, Mary F Rooney, Parviz Behnam-Motlagh, Torbjörn K Nilsson, Kjell Grankvist, Richard K Porter
Acquired cisplatin resistance is a common feature of tumours following cancer treatment with cisplatin and also of non-small cell lung cancer (H1299) and mesothelioma (P31) cell lines exposed to cisplatin. To elucidate the cellular basis of acquired cisplatin resistance, a comprehensive bioenergetic analysis was undertaken. We demonstrate that cellular oxygen consumption was significantly decreased in cisplatin resistant cells and that the reduction was primarily due to reduced mitochondrial activity as a result of reduced mitochondrial abundance...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209144/targeting-the-long-noncoding-rna-malat1-blocks-the-pro-angiogenic-effects-of-osteosarcoma-and-suppresses-tumour-growth
#20
Zhi-Chang Zhang, Chun Tang, Yang Dong, Jing Zhang, Ting Yuan, Shi-Cong Tao, Xiao-Lin Li
Osteosarcoma (OS), the commonest primary malignant tumour originating from bone, affects a substantial number of people, mostly during adolescent growth, and leads to a very poor prognosis as a result of the high rate of early metastases. Consequently, there is urgent demand for a novel treatment for this disease. There are growing concerns focused on OS-induced pro-angiogenic effects, but to date, the mechanism of OS-induced pro-angiogenesis is still insufficiently well-understood. Long noncoding RNAs (lncRNAs) have attracted increasing interest due to their strong correlation with a variety of diseases and their powerful capacity for epigenetic regulation...
2017: International Journal of Biological Sciences
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