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https://www.readbyqxmd.com/read/28521397/regulation-of-angiogenic-factors-by-the-pi3k-akt-pathway-in-a549-lung-cancer-cells-under-hypoxic-conditions
#1
Youbang Xie, Yali Qi, Yanmiao Zhang, Jiayi Chen, Tianyi Wu, Yuhai Gu
The aim of the present study was to investigate the influence of hypoxia and PI3K inhibition on angiogenic factors in A549 lung cancer cells. A549 cells were treated with the PI3K inhibitor LY294002 under normoxic and hypoxic conditions. Untreated cells were used as the control group and those treated by the inhibitor, as the suppression group. The cells were further divided based on normoxic or hypoxic conditions and named: Normoxic control group, normoxic suppression group, hypoxic control group and hypoxic suppression group...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28463588/the-lactate-dehydrogenase-inhibitor-gossypol-inhibits-radiation-induced-pulmonary-fibrosis
#2
Jennifer L Judge, Shannon H Lacy, Wei-Yao Ku, Kristina M Owens, Eric Hernady, Thomas H Thatcher, Jacqueline P Williams, Richard P Phipps, Patricia J Sime, R Matthew Kottmann
Exposure of the lung to ionizing radiation that occurs in radiotherapy, as well as after accidental or intentional mass casualty incident can result in pulmonary fibrosis, which has few treatment options. Pulmonary fibrosis is characterized by an accumulation of extracellular matrix proteins that create scar tissue. Although the mechanisms leading to radiation-induced pulmonary fibrosis remain poorly understood, one frequent observation is the activation of the profibrotic cytokine transforming growth factor-beta (TGF-β)...
May 2, 2017: Radiation Research
https://www.readbyqxmd.com/read/28462372/hypoxia-inducible-factor-hif-hydroxylases-as-regulators-of-intestinal-epithelial-barrier-function
#3
REVIEW
Mario C Manresa, Cormac T Taylor
Human health is dependent on the ability of the body to extract nutrients, fluids, and oxygen from the external environment while at the same time maintaining a state of internal sterility. Therefore, the cell layers that cover the surface areas of the body such as the lung, skin, and gastrointestinal mucosa provide vital semipermeable barriers that allow the transport of essential nutrients, fluid, and waste products, while at the same time keeping the internal compartments free of microbial organisms. These epithelial surfaces are highly specialized and differ in their anatomic structure depending on their location to provide appropriate and effective site-specific barrier function...
May 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28457380/overexpression-of-hypoxia-inducible-factor-1%C3%AE-in-primary-graft-dysfunction-developing-in-an-orthotopic-lung-transplantation-rat%C3%A2-model
#4
F Lunardi, D Zampieri, M Vadori, D Bernardini, S E Vuljan, N Nannini, F Rea, E Cozzi, F Calabrese
BACKGROUND: Primary graft dysfunction (PGD) is the major cause of early morbidity and mortality after transplantation. A high rate of PGD is a frequent complication in orthotopic lung transplantation (OLT) models, which are currently used to investigate acute and chronic rejection pathways. Hypoxia-inducible factor (HIF)-1α is a heterodimeric αβ transcription factor that mediates tissue response to hypoxia. In other solid organ transplantations, a significant correlation between HIF-1α expression and PGD was detected...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28446589/antifibrotic-effects-of-cyclosporine-a-on-tgf-%C3%AE-1-treated-lung-fibroblasts-and-lungs-from-bleomycin-treated-mice-role-of-hypoxia-inducible-factor-1%C3%AE
#5
Risa Yamazaki, Yoshitoshi Kasuya, Tetsuo Fujita, Hiroki Umezawa, Madoka Yanagihara, Hiroyuki Nakamura, Ichiro Yoshino, Koichiro Tatsumi, Toshihiko Murayama
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder that is characterized by aberrant tissue remodeling and the formation of fibroblastic foci that are composed of fibrogenic myofibroblasts. TGF-β1 is one of the factors that are responsible for fibrosis as it promotes fibroblast to myofibroblast differentiation (FMD) and is associated with up-regulation of α-smooth muscle actin. Therefore, inhibition of FMD may represent an effective strategy for the treatment of IPF. Here, we describe the treatment of human lung fibroblasts (WI-38 and HFL-1 cells) with cyclosporine A (CsA), which reduces TGF-β1-induced FMD via degradation of hypoxia-inducible factor-1α (HIF-1α)...
April 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28443025/honokiol-induces-apoptosis-g1-arrest-and-autophagy-in-kras-mutant-lung-cancer-cells
#6
Lian-Xiang Luo, Ying Li, Zhong-Qiu Liu, Xing-Xing Fan, Fu-Gang Duan, Run-Ze Li, Xiao-Jun Yao, Elaine Lai-Han Leung, Liang Liu
Aberrant signaling transduction induced by mutant KRAS proteins occurs in 20∼30% of non-small cell lung cancer (NSCLC), however, a direct and effective pharmacological inhibitor targeting KRAS has not yet reached the clinic to date. Honokiol, a small molecular polyphenol natural biophenolic compound derived from the bark of magnolia trees, exerts anticancer activity, however, its mechanism remains unknown. In this study, we sought to investigate the in vitro effects of honokiol on NSCLC cell lines harboring KRAS mutations...
2017: Frontiers in Pharmacology
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
#7
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/28435457/tumor-hypoxia-regulates-forkhead-box-c1-to-promote-lung-cancer-progression
#8
Yu-Jung Lin, Woei-Cherng Shyu, Chi-Wei Chang, Chi-Chung Wang, Chung-Pu Wu, Hsu-Tung Lee, Liang-Jwu Chen, Chia-Hung Hsieh
Forkhead box C1 (FOXC1) is a member of the forkhead family of transcription factors that are characterized by a DNA-binding forkhead domain. Increasing evidence indicates that FOXC1 is involved in tumor progression. However, the role of tumor hypoxia in FOXC1 regulation and its impact on lung cancer progression are unclear. Here, we report that FOXC1 was upregulated in hypoxic areas of lung cancer tissues from rodents or humans. Hypoxic stresses significantly induced FOXC1 expression. Moreover, hypoxia activated FOXC1 transcription via direct binding of hypoxia-inducible factor-1α (HIF-1α) to the hypoxia-responsive element (HRE) in the FOXC1 promoter...
2017: Theranostics
https://www.readbyqxmd.com/read/28430666/myc-induced-glutaminolysis-bypasses-hif-driven-glycolysis-in-hypoxic-small-cell-lung-carcinoma-cells
#9
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/28426124/propofol-suppresses-lps-induced-nuclear-accumulation-of-hif-1%C3%AE-and-tumor-aggressiveness-in-non-small-cell-lung-cancer
#10
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...
May 2017: Oncology Reports
https://www.readbyqxmd.com/read/28424745/distinguishing-the-unique-neuropathological-profile-of-blast-polytrauma
#11
W Brad Hubbard, Shaylen Greenberg, Carly Norris, Joseph Eck, Erin Lavik, Pamela VandeVord
Traumatic brain injury sustained after blast exposure (blast-induced TBI) has recently been documented as a growing issue for military personnel. Incidence of injury to organs such as the lungs has decreased, though current epidemiology still causes a great public health burden. In addition, unprotected civilians sustain primary blast lung injury (PBLI) at alarming rates. Often, mild-to-moderate cases of PBLI are survivable with medical intervention, which creates a growing population of survivors of blast-induced polytrauma (BPT) with symptoms from blast-induced mild TBI (mTBI)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28409544/hypoxia-and-the-hypoxia-regulated-transcription-factor-hif-1%C3%AE-suppress-the-host-defence-of-airway-epithelial-cells
#12
Markus Polke, Frederik Seiler, Philipp M Lepper, Andreas Kamyschnikow, Frank Langer, Dominik Monz, Christian Herr, Robert Bals, Christoph Beisswenger
Chronic diseases of the respiratory tract, such as cystic fibrosis, are associated with mucosal and systemic hypoxia. Innate immune functions of airway epithelial cells are required to prevent and control infections of the lung parenchyma. The transcription factor hypoxia-inducible factor 1α (HIF-1α) regulates cellular adaptation to low oxygen conditions. Here, we show that hypoxia and HIF-1α regulate innate immune mechanisms of cultured human bronchial epithelial cells (HBECs). Exposure of primary HBECs to hypoxia or the prolyl hydroxylase inhibitor dimethyloxaloylglycine (DMOG) resulted in a significantly decreased expression of inflammatory mediators (IL-6, IFN-γ-induced protein 10) in response to ligands for TLRs (flagellin, polyI:C) and Pseudomonas aeruginosa, whereas the expression of inflammatory mediators was not affected by hypoxia or DMOG in the absence of microbial factors...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28394654/inhibiting-igf-1r-attenuates-cell-proliferation-and-vegf-production-in-igf-1r-over-expressing-egfr-mutant-non-small-cell-lung-cancer-cells
#13
Chang Dong Yeo, Young Ae Kim, Hwa Young Lee, Jin Woo Kim, Sang Haak Lee, Seung Joon Kim, Soon Seog Kwon, Yong Hyun Kim, Seok Chan Kim
PURPOSE: The aim of the present study was to demonstrate the role of insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase inhibitors (TKIs) in IGF-1R expressed epidermal growth factor receptor (EGFR) mutant cells. MATERIALS AND METHODS: Human lung adenocarcinoma PC9, HCC827, and H1975 cells were exposed to a combination of IGF-1, gefitinib, or linsitinib. Cell viability was assessed by the MTT assay. The expression of EGFR, IGF-1R, AKT, extracellular regulated kinases 1 and 2 (ERK1/2), cleaved poly ADP ribose polymerase (PARP), cleaved caspase 3, and hypoxia-inducible factor (HIF)-1α were measured by Western blot...
February 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28386380/wheatgrass-extract-inhibits-hypoxia-inducible-factor-1-mediated-epithelial-mesenchymal-transition-in-a549-cells
#14
Nam Yong Do, Hyun-Jae Shin, Ji-Eun Lee
BACKGROUND/OBJECTIVES: Epithelial-mesenchymal transition (EMT) is involved in not only cancer development and metastasis but also non-cancerous conditions. Hypoxia is one of the proposed critical factors contributing to formation of chronic rhinosinusitis or nasal polyposis. Wheatgrass (Triticum aestivum) has antioxidant, anti-aging, and anti-inflammatory effects. In this study, we analyzed whether wheatgrass has an inhibitory effect on the EMT process in airway epithelial cells. MATERIALS/METHODS: A549 human lung adenocarcinoma cells were incubated in hypoxic conditions (CO2 5%/O2 1%) for 24 h in the presence of different concentrations of wheatgrass extract (50, 75, 100, and 150 µg/mL) and changes in expression of epithelial or mesenchymal markers were evaluated by immunoblotting and immunofluorescence...
April 2017: Nutrition Research and Practice
https://www.readbyqxmd.com/read/28381639/gestational-exposure-to-sidestream-secondhand-cigarette-smoke-promotes-transgenerational-epigenetic-transmission-of-exacerbated-allergic-asthma-and-bronchopulmonary-dysplasia
#15
Shashi P Singh, Hitendra S Chand, Raymond J Langley, Neerad Mishra, Ted Barrett, Karin Rudolph, Carmen Tellez, Piotr T Filipczak, Steve Belinsky, Ali I Saeed, Aryaz Sheybani, Vernat Exil, Hemant Agarwal, Venkataramana K Sidhaye, Thomas Sussan, Shyam Biswal, Mohan Sopori
Embryonic development is highly sensitive to xenobiotic toxicity and in utero exposure to environmental toxins affects physiological responses of the progeny. In the United States, the prevalence of allergic asthma (AA) is inexplicably rising and in utero exposure to cigarette smoke increases the risk of AA and bronchopulmonary dysplasia (BPD) in children and animal models. We reported that gestational exposure to sidestream cigarette smoke (SS), or secondhand smoke, promoted nicotinic acetylcholine receptor-dependent exacerbation of AA and BPD in mice...
May 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28364627/protective-role-of-rhapontin-in-experimental-pulmonary-fibrosis-in-vitro-and-in-vivo
#16
Lijun Tao, Juan Cao, Wencheng Wei, Haifeng Xie, Mian Zhang, Chaofeng Zhang
BACKGROUND: Pulmonary fibrosis is a scaring process related to chronic lung injury of all causes. The treatment options for pulmonary fibrosis are very limited. Rhapontin has anti-inflammatory effect and anti-proliferative activity which is widely distributed in the medicinal plants of Rheum genus in China. However, the anti-fibrotic activities of rhapontin have not been previously investigated. METHODS: The effect of rhapontin on TGF-β1-mediated extracellular matrix (ECM) deposition in primary lung fibroblast (PLF) cells, on TGF-β1 secretion in LPS-stimulated human THP-1 derived macrophages in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis was investigated in vivo...
March 29, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28360450/renal-medullary-carcinoma-a-rare-entity
#17
Selahattin Çalışkan, Ali Murat Gökçe, Gülistan Gümrükçü, Mine Önenerk
Renal medullary carcinoma (RMC) is an uncommon aggressive neoplasm of the kidney. RMC is biologically aggressive with a very poor prognosis, and metastasis is seen in up to 95% of the patients at diagnosis or shortly thereafter. The common sites of metastasis are respectively lymph nodes, lungs, livers, and adrenal glands in order of frequency. The presence of poorly differentiated eosinophilic cells in a characteristic fibro-inflammatory stroma is seen in histological examination. The origin and pathogenesis of RMC are unclear...
March 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28356955/ursolic-acid-sensitizes-radioresistant-nsclc-cells-expressing-hif-1%C3%AE-through-reducing-endogenous-gsh-and-inhibiting-hif-1%C3%AE
#18
Bing Song, Qian Zhang, Maohu Yu, Xinrong Qi, Gang Wang, Linlin Xiao, Qiyi Yi, Wensen Jin
In previous studies, the present authors demonstrated that effective sensitization of ionizing radiation-induced death of tumor cells, including non-small cell lung cancer (NSCLC) cells, could be produced by oleanolic acid (OA), a pentacyclic triterpenoid present in plants. In the present study, it was investigated whether ursolic acid (UA), an isomer of OA, had also the capacity of sensitizing radioresistant NSCLC cells. The radioresistant cell line H1299/M-hypoxia inducible factor-1α (HIF-1α) was established by transfection with a recombinant plasmid expressing mutant HIF-1α (M-HIF-1α)...
February 2017: Oncology Letters
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
#19
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...
May 2017: Oncology Reports
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
#20
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
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