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https://www.readbyqxmd.com/read/28618253/hypoxia-inducible-factor-1%C3%AE-signaling-promotes-repair-of-the-alveolar-epithelium-after-acute-lung-injury
#1
Jazalle McClendon, Nicole L Jansing, Elizabeth F Redente, Aneta Gandjeva, Yoko Ito, Sean P Colgan, Aftab Ahmad, David W H Riches, Harold A Chapman, Robert J Mason, Rubin M Tuder, Rachel L Zemans
During acute respiratory distress syndrome, epithelial cells, primarily alveolar type (AT) I cells, die and slough off the basement membrane, resulting in enhanced permeability. ATII cells proliferate and spread onto the denuded basement membrane to reseal the barrier. Repair of the alveolar epithelium is critical for clinical recovery; however, the mechanisms underlying ATII cell proliferation and spreading are not well understood. We hypothesized that hypoxia-inducible factor (HIF)1α promotes proliferation and spreading of ATII cells during repair after lung injury...
June 12, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28610954/feedback-regulation-of-aldoa-activates-the-hif-1%C3%AE-mmp9-axis-to-promote-lung-cancer-progression
#2
Yu-Chan Chang, Yung-Chieh Chan, Wei-Ming Chang, Yuan-Feng Lin, Chih-Jen Yang, Chia-Yu Su, Ming-Shyan Huang, Alexander T H Wu, Michael Hsiao
Distant metastasis and recurrence are the greatest challenges in the clinical management of lung cancer. Despite advances in targeted therapies, high mortality rates persist. Therefore, alternative therapeutic interventions are urgently required. Accumulating evidence indicates that normalizing tumor metabolism may be a way to increase therapeutic efficacy and to reduce tumor malignancy. Here, we analyzed integrated transcriptomics data and an shRNA library against glycolytic enzymes and found that elevated Aldolase A expression is highly correlated with metastatic potential and a poor prognosis in patients with non-small cell lung cancer (NSCLC)...
June 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28572533/haf-mediates-the-evasive-resistance-of-anti-angiogenesis-tki-through-disrupting-hif-1%C3%AE-and-hif-2%C3%AE-balance-in-renal-cell-carcinoma
#3
Xiang-Me Lai, Shu-Yu Liu, Yi-Ta Tsai, Guang-Huan Sun, Sun-Yran Chang, Shih-Ming Huang, Tai-Lung Cha
Anti-angiogenesis has emerged as a standard of care for metastatic renal cell carcinoma. However, long-lasting efficacy is seldom reached, and evasive resistance eventually occurs under anti-angiogenic tyrosine kinase inhibitor (TKI) therapy. To establish new therapeutic strategies, investigating the molecular mechanism of resistance is critically important. In our study, human umbilical vascular endothelial cells (HUVECs) were incubated with TKI treatment in conditioned medium derived from renal cancer cells (RCCs) to demonstrate cell viability...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28565876/effects-of-17%C3%AE-estradiol-and-2-methoxyestradiol-on-the-oxidative-stress-hypoxia-inducible-factor-1-pathway-in-hypoxic-pulmonary-hypertensive-rats
#4
Li Wang, Quan Zheng, Yadong Yuan, Yanpeng Li, Xiaowei Gong
The present study aimed to investigate the effects of 17β-estradiol (E2) and 2-methoxyestradiol (2ME) on the oxidative stress-hypoxia inducible factor-1 (OS-HIF-1) pathway in hypoxic pulmonary hypertensive rats. Female Sprague-Dawley rats were divided randomly into 4 groups, as follows: i) Control (Group A); ii) ovariectomy (OVX) + hypoxia (Group B); iii) OVX + hypoxia + E2 injection (Group C); and iv) 2ME injection (Group D). The rats were maintained under hypoxic conditions for 8 weeks, and mean pulmonary artery pressure (mPAP) and pulmonary arteriole morphology were measured...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28562340/cell-type-dependent-hif1-%C3%AE-mediated-effects-of-hypoxia-on-proliferation-migration-and-metastatic-potential-of-human-tumor-cells
#5
Enikő Tátrai, Alexandra Bartal, Alexandra Gacs, Sándor Paku, István Kenessey, Tamás Garay, Balázs Hegedűs, Eszter Molnár, Mihály T Cserepes, Zita Hegedűs, Nóra Kucsma, Gergely Szakács, József Tóvári
Tumor hypoxia promotes neoangiogenesis and contributes to the radio- and chemotherapy resistant and aggressive phenotype of cancer cells. However, the migratory response of tumor cells and the role of small GTPases regulating the organization of cytoskeleton under hypoxic conditions have yet to be established. Accordingly, we measured the proliferation, migration, RhoA activation, the mRNA and protein levels of hypoxia inducible factor-1alpha (HIF-1α) and three small G-proteins, Rac1, cdc42 and RhoA in a panel of five human tumor cell lines under normoxic and hypoxic conditions...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28558148/glucosamine-has-an-antiallergic-effect-in-mice-with-allergic-asthma-and-rhinitis
#6
Ah-Yeoun Jung, Min-Jeong Heo, Young Hyo Kim
BACKGROUND: Glucosamine (GlcN) is generally used as a dietary supplement because of its antiinflammatory effects. We evaluated the antiallergic effect of GlcN in mice with allergic asthma and rhinitis. METHODS: Thirty-two mice were allocated equally into 4 groups (n = 8). In group A (control), we performed intraperitoneal/intranasal challenge using sterile saline. In group B (asthma/rhinitis), we used ovalbumin for intraperitoneal/intranasal challenge to induce allergic asthma and rhinitis...
May 30, 2017: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/28537679/mir-15a-expression-analysis-in-non-small-cell-lung-cancer-a549-cells-under-local-hypoxia-microenvironment
#7
X-G Jing, T-F Chen, C Huang, H Wang, L An, Z Cheng, G-J Zhang
OBJECTIVE: Lung cancer is a common tumor in the clinic. Hypoxia is an important biological characteristic in the solid malignant tumor. MiRNA participates in cell proliferation, differentiation, and apoptosis. This study tested hypoxia-inducible factor 1-α (HIF-1α) in lung cancer patients and analyzed the microRNA-15a (miR-15a) expression in A549 cells under different local hypoxia microenvironments. PATIENTS AND METHODS: A total of 40 non-small cell lung cancer (NSCLC) patients in First Affiliated Hospital of Zhengzhou University between Jan 2015 and Jan 2016 were involved in this study...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28536364/hypoxia-and-inflammation-in-cancer-focus-on-hif-and-nf-%C3%AE%C2%BAb
#8
REVIEW
Laura D'Ignazio, Michael Batie, Sonia Rocha
Cancer is often characterised by the presence of hypoxia and inflammation. Paramount to the mechanisms controlling cellular responses under such stress stimuli, are the transcription factor families of Hypoxia Inducible Factor (HIF) and Nuclear Factor of κ-light-chain-enhancer of activated B cells (NF-κB). Although, a detailed understating of how these transcription factors respond to their cognate stimulus is well established, it is now appreciated that HIF and NF-κB undergo extensive crosstalk, in particular in pathological situations such as cancer...
May 9, 2017: Biomedicines
https://www.readbyqxmd.com/read/28521397/regulation-of-angiogenic-factors-by-the-pi3k-akt-pathway-in-a549-lung-cancer-cells-under-hypoxic-conditions
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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