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https://www.readbyqxmd.com/read/28430666/myc-induced-glutaminolysis-bypasses-hif-driven-glycolysis-in-hypoxic-small-cell-lung-carcinoma-cells
#1
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
#2
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/28424745/distinguishing-the-unique-neuropathological-profile-of-blast-polytrauma
#3
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
#4
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
#5
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
#6
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
#7
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...
April 5, 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
#8
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
#9
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
#10
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
#11
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/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
#12
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/28318025/maternal-chronic-hypoxia-increases-expression-of-genes-regulating-lung-liquid-movement-and-surfactant-maturation-in-male-fetuses-in-late-gestation
#13
Erin V McGillick, Sandra Orgeig, Beth J Allison, Kirsty L Brain, Youguo Niu, Nozomi Itani, Katie L Skeffington, Andrew D Kane, Emilio A Herrera, Dino A Giussani, Janna L Morrison
Chronic fetal hypoxaemia is a common pregnancy complication that may arise from maternal, placental and/or fetal factors. Respiratory outcome of the infant at birth likely depends on the duration, timing and severity of the hypoxaemic insult. We have isolated the effect of maternal chronic hypoxia (MCH) for a month in late gestation on fetal lung development. Pregnant ewes were exposed to normoxia (21% O2 ) or hypoxia (10% O2 ) from 105-138 d gestation (term ∼145 d). At 138 d, gene expression in fetal lung tissue was determined by qRT-PCR...
March 20, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28302721/involvement-of-notch1-signaling-in-malignant-progression-of-a549-cells-subjected-to-prolonged-cadmium-exposure
#14
Kota Fujiki, Hisako Inamura, Takamitsu Miyayama, Masato Matsuoka
Cadmium exposure is known to increase lung cancer risk, but the underlying molecular mechanisms in cadmium-stimulated progression of malignancy are unclear. Here, we examined the effects of prolonged cadmium exposure on the malignant progression of A549 human lung adenocarcinoma cells and the roles of Notch1, hypoxia-inducible factor 1α (HIF-α), and insulin-like growth factor 1 receptor (IGF-1R)/Akt/extracellular signal-regulated kinase (ERK)/p70 S6 kinase 1 (S6K1) signaling pathways. Exposing A549 cells to 10 or 20 μM cadmium chloride (CdCl2) for 9-15 weeks induced a high proliferative potential, the epithelial-mesenchymal transition (EMT), stress fiber formation, high cell motility, and resistance to anti-tumor drugs...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28302670/modelling-pulmonary-microthrombosis-coupled-to-metastasis-distinct-effects-of-thrombogenesis-on-tumorigenesis
#15
Colin E Evans, Asis Palazon, Jingwei Sim, Petros A Tyrakis, Alice Prodger, Xiao Lu, Saria Chan, Pär-Ola Bendahl, Mattias Belting, Love Von Euler, Helene Rundqvist, Randall S Johnson, Cristina Branco
Thrombosis can cause localized ischemia and tissue hypoxia, and both of these are linked to cancer metastasis. Vascular micro-occlusion can occur as a result of arrest of circulating tumor cells in small capillaries, giving rise to microthrombotic events that affect flow, creating localized hypoxic regions. To better understand the association between metastasis and thrombotic events, we generated an experimental strategy whereby we model the effect of microvascular occlusion in metastatic efficiency, by using inert microbeads to obstruct lung microvasculature before, during and after intravenous tumor cell injection...
March 16, 2017: Biology Open
https://www.readbyqxmd.com/read/28302216/-association-of-indoor-air-pollution-single-nucleotide-polymorphism-of-hif-1%C3%AE-gene-with-susceptibility-to-lung-cancer-in-han-population-in-fujian-province
#16
Fei He, Qi Qi, Xu Li, Rendong Xiao, Qiuping Xu, Weimin Xiong, Zhiqiang Liu, Lin Cai
BACKGROUND: Hypoxia inducible factor-1α (HIF-1α) is associated with the progression and metastasis of lung cancer. There are, however, few studies on the relationship between the single nucleotide polymorphisms of HIF-1α and susceptibility to lung cancer. Therefore, we aimed to investigate the relationship between indoor air pollution, HIF-1α rs2057482, and the susceptibility to primary lung cancer of the Fujian Han population. METHODS: The present study is a hospital-based case-control study...
March 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28263966/lncrna-meg3-downregulation-mediated-by-dnmt3b-contributes-to-nickel-malignant-transformation-of-human-bronchial-epithelial-cells-via-modulating-phlpp1-transcription-and-hif-1%C3%AE-translation
#17
C Zhou, C Huang, J Wang, H Huang, J Li, Q Xie, Y Liu, J Zhu, Y Li, D Zhang, Q Zhu, C Huang
Long noncoding RNAs (lncRNAs) are emerging as key factors in various fundamental cellular biological processes, and many of them are likely to have functional roles in tumorigenesis. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 that encodes a lncRNA, and the decreased MEG3 expression has been reported in multiple cancer tissues. However, nothing is known about the alteration and role of MEG3 in environmental carcinogen-induced lung tumorigenesis. Our present study, for the first time to the best of our knowledge, discovered that environmental carcinogen nickel exposure led to MEG3 downregulation, consequently initiating c-Jun-mediated PHLPP1 transcriptional inhibition and hypoxia-inducible factor-1α (HIF-1α) protein translation upregulation, in turn resulting in malignant transformation of human bronchial epithelial cells...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28259980/genistein-decreases-a549-cell-viability-via-inhibition-of-the-pi3k-akt-hif%C3%A2-1%C3%AE-vegf-and-nf%C3%A2-%C3%AE%C2%BAb-cox%C3%A2-2-signaling-pathways
#18
Juan Zhang, Hongzheng Su, Qingfeng Li, Jing Li, Qianfeng Zhao
Genistein is an important chemopreventive agent against atherosclerosis and cancer. However, whether genistein is effective in the treatment of lung cancer, and its underlying mechanism, remains to be determined. The present study demonstrated that genistein treatment of A549 lung cancer cells decreased viability in a dose‑ and time‑dependent manner, and induced apoptosis. Additionally, A549 cells exhibited significantly increased reactive oxygen species formation and cytochrome‑c leakage, and activated caspase‑3, B‑cell lymphoma 2‑associated X protein and apoptosis inducing factor expression levels, which are involved in the mitochondrial apoptosis pathway...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28225008/anticancer-osmium-complex-inhibitors-of-the-hif-1%C3%AE-and-p300-protein-protein-interaction
#19
Chao Yang, Wanhe Wang, Guo-Dong Li, Hai-Jing Zhong, Zhen-Zhen Dong, Chun-Yuen Wong, Daniel W J Kwong, Dik-Lung Ma, Chung-Hang Leung
The hypoxia inducible factor (HIF) pathway has been considered to be an attractive anti-cancer target. One strategy to inhibit HIF activity is through the disruption of the HIF-1α-p300 protein-protein interaction. We report herein the identification of an osmium(II) complex as the first metal-based inhibitor of the HIF-1α-p300 interaction. We evaluated the effect of complex 1 on HIF-1α signaling pathway in vitro and in cellulo by using the dual luciferase reporter assay, co-immunoprecipitation assay, and immunoblot assay...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216876/wheatgrass-extract-ameliorates-hypoxia-induced-mucin-gene-expression-in-a549-cells
#20
Ju Hwan Sim, Moon-Hee Choi, Hyun-Jae Shin, Ji-Eun Lee
BACKGROUND: Wheatgrass is known to have antioxidant, antiaging, and anti-inflammatory effect. However, its protective effect against hypoxia is not yet evaluated. OBJECTIVE: In this study, we evaluated the protective and anti-inflammatory effect of wheatgrass against the hypoxia in airway epithelial cells. MATERIALS AND METHODS: A549 human lung adenocarcinoma cells were incubated in a hypoxic condition (CO2 5%/O2 1%) for 24 hr in the presence of different concentration of wheatgrass 50, 75, 100, and 150 μg/mL, and the magnitude of each immunologic response produced by the A549 cells was compared...
January 2017: Pharmacognosy Magazine
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