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Hif lung

Wei Zhang, Shanfeng Zhang, Bing Li, Mingyang Sun, Jiaqiang Zhang
BACKGROUND: To investigate the effect of paravertebral dexmedetomidine as an adjuvant to ropivacaine on independent lung injury during one-lung ventilation. METHODS: In total, 120 patients who underwent elective radical resection of pulmonary carcinoma were randomly assigned to one of six groups (n = 20): normal saline (C group), ropivacaine (R group), intravenous dexmedetomidine (Div group), 0.5 μg/kg paravertebral dexmedetomidine as an adjuvant to ropivacaine (RD0...
June 15, 2018: BMC Anesthesiology
Hongjun Zhu, Shuanglin Zhang
Like other tumors, lung cancer must induce angiogenesis as it grows. Hypoxia-inducible factor 1α (HIF-1α) is the inducible subunit of the HIF-1 transcription factor that regulates genes involved in the response to hypoxia, some of which contributes to angiogenesis. Vascular endothelial growth factor (VEGF) is one of the genes upregulated by HIF-1 and is the primary cytokine in relation to angiogenesis. In this study we tested whether aberrant activation of hypoxia inducible factor-1α/vascular endothelial growth factor (HIF-1α/VEGF) pathway correlates with response to radiotherapy and examined the response of lung cancer cells to hypoxia in vitro...
June 15, 2018: Journal of Cellular Biochemistry
Tianxiao Gong, Liuqing Cui, Haili Wang, Haoxun Wang, Na Han
BACKGROUND: Hypoxia-mediated chemoresistance has been regarded as an important obstacle in the development of cancer treatment. Knockdown of krüppel-like factor 5 (KLF5) was reported to inhibit hypoxia-induced cell survival and promote cell apoptosis in non-small cell lung cancer (NSCLC) cells via direct regulation of hypoxia inducible factor-1α (HIF-1α) expression. However, the roles of KLF5 in the development of hypoxia-induced cisplatin (DDP) resistance and its underlying mechanism in NSCLC cells remain to be further elucidated...
June 14, 2018: Journal of Translational Medicine
Hong-Wei Lei, Jie Cai, Cheng-Ming Li, Fang Yang, Wan-Qing Shi, Wan-Qing Shi, Li-Ping Wang, You-Ying Feng
INTRODUCTION AND AIM: To investigate the effect of mTOR inhibitor Rapamycin combined with transcatheter arterial embolization (TAE) on the growth, metastasis, and prognosis of hepatocellular carcinoma (HCC) in rat model. MATERIAL AND METHOD: McARH7777 cells were used to construct rat models of HCC, which were randomly divided into Model, Rapamycin, TAE, and Rapamycin + TAE groups. Quantitative reverse transcription-PCR (qRT-PCR) and Western Blot were used to detect the expression of Epithelial-Mesenchymal Transition (EMT)-related molecules, and immunohistochemical staining to determine the expression of EMTrelated proteins, angiogenic factors as well as microvessel density (MVD)-CD34...
July 2018: Annals of Hepatology
David E Lee, Kinan Alhallak, Samir V Jenkins, Isaac Vargas, Nicholas P Greene, Kyle P Quinn, Robert J Griffin, Ruud P M Dings, Narasimhan Rajaram
Treatment failure caused by a radiation-resistant cell phenotype remains an impediment to the success of radiation therapy in cancer. We recently showed that a radiation-resistant isogenic line of human A549 lung cancer cells had significantly elevated expression of hypoxia-inducible factor (HIF-1α), and increased glucose catabolism compared with the parental, radiation-sensitive cell line. The objective of this study was to investigate the longitudinal metabolic changes in radiation-resistant and sensitive A549 lung cancer cells after treatment with a combination of radiation therapy and YC-1, a potent HIF-1 inhibitor...
June 11, 2018: Scientific Reports
Andrés A Urrutia, Julián Aragonés
Cellular responses to oxygen fluctuations are largely mediated by hypoxia-inducible factors (HIFs). Upon inhalation, the first organ inspired oxygen comes into contact with is the lungs, but the understanding of the pulmonary HIF oxygen-sensing pathway is still limited. In this review we will focus on the role of HIF1α and HIF2α isoforms in lung responses to oxygen insufficiency. In particular, we will discuss novel findings regarding their role in the biology of smooth muscle cells and endothelial cells in the context of hypoxia-induced pulmonary vasoconstriction...
June 6, 2018: Biomedicines
Jie Wang, Ruochen Wang, Niannian Li, Xi Shen, Gang Huang, Jun Zhu, Dannong He
Background: Hypoxemia is one of the most common pathological processes in various clinical diseases. Methods: A novel emulsion of poly(lactide-co-glycolide)-poly(ethylene glycol)/perfluorooctyl bromide has been developed to improve arterial hypoxemia through pulmonary drug delivery. Hypoxia-reoxygenation experiment was used to investigate the ability of the emulsion to supply oxygen and the saline lavage acute lung injury model was established to evaluate oxygen supply of the emulsion...
2018: International Journal of Nanomedicine
Xu Chen, Lei Wu, Dezhi Li, Yanmei Xu, Luping Zhang, Kai Niu, Rui Kong, Jiaoyang Gu, Zihan Xu, Zhengtang Chen, Jianguo Sun
Lung cancer is one of the main causes of cancer mortality globally. Most patients received radiotherapy during the course of disease. However, radioresistance generally occurs in the majority of these patients, leading to poor curative effect, and the underlying mechanism remains unclear. In the present study, miR-18a-5p expression was downregulated in irradiated lung cancer cells. Overexpression of miR-18a-5p increased the radiosensitivity of lung cancer cells and inhibited the growth of A549 xenografts after radiation exposure...
June 2, 2018: Cancer Medicine
Zhaoxi Wang, Yongyue Wei, Ruyang Zhang, Li Su, Stephanie M Gogarten, Geoffrey Liu, Paul Brennan, John K Field, James D McKay, Jolanta Lissowska, Beata Swiatkowska, Vladimir Janout, Ciprian Bolca, Milica Kontic, Ghislaine Scelo, David Zaridze, Cathy C Laurie, Kimberly F Doheny, Elizabeth K Pugh, Beth A Marosy, Kurt N Hetrick, Xiangjun Xiao, Claudio Pikielny, Rayjean J Hung, Christopher I Amos, Xihong Lin, David C Christiani
Recent technological advancements have permitted high-throughput measurement of the human genome, epigenome, metabolome, transcriptome, and proteome at the population level. We hypothesized that subsets of genes identified from omic studies might have closely related biological functions and thus might interact directly at the network level. Therefore, we conducted an integrative analysis of multi-omic datasets of non-small cell lung cancer (NSCLC) to search for association patterns beyond the genome and transcriptome...
May 30, 2018: EBioMedicine
Shuyan Meng, Guorui Wang, Yang Lu, Zhen Fan
OBJECTIVE: Hypoxia-inducible factor 1 (HIF-1) and activator protein 1 (AP-1) are important transcription factors regulating expression of genes involved in cell survival. HIF-1α and c-Jun are key components of HIF-1 and AP-1, respectively, and are regulated by epidermal growth factor receptor (EGFR)-mediated cell signaling and tumor microenvironmental cues. The roles of HIF-1α and c-Jun in development of resistance to EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) with activating mutation of EGFR have not been explored...
July 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Zhuo Chen, Liang Zhao, Feng Zhao, Guanghai Yang, Jian Jun Wang
The present study investigated the effect of tetrandrine on lung cancer cell growth and apoptosis, and its possible underlying molecular mechanism. A549 human lung cancer cells were incubated with between 2.5 and 10 µM tetrandrine for 12, 24 and 48 h, following which the effect of tetrandrine on cell viability and apoptosis were assessed using an MTT assay and flow cytometry. ELISA and western blotting were used to analyze VEGF activity, and the expression of poly (ADP-ribose) polymerase (PARP), phosphorylated protein kinase B (Akt), Bcl-2-associated X protein (Bax), hypoxia inducible factor (HIF)-1α and inter-cellular adhesion molecule-1 (ICAM-1)...
May 2018: Oncology Letters
Rongtao Zhu, Yipu Zhao, Xiaobo Li, Tao Bai, Shuai Wang, Weijie Wang, Yuling Sun
Penehyclidine hydrochloride (PHC) is a selective M1 and M3 receptor antagonist. This study was designed to investigate the effect of PHC on acute lung injury (ALI) induced by severe acute pancreatitis (SAP) and the expression of hypoxia-inducible factor-1α (HIF-1α) in rats. A total of 45 healthy adult male SD rats were randomly divided into 3 groups: an S group, sham operation; an ALI group, pancreatitis-associated acute lung injury (PALI); and a P group, PALI treated with PHC. Rats from the ALI and P groups were used to establish a model of acute lung injury associated with SAP by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct...
January 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Naveen Gupta, Victor Nizet
Bone marrow-derived mesenchymal stem cells (MSCs) have therapeutic effects in experimental models of lung injury. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcriptional regulator that influences cellular metabolism, energetics, and survival under hypoxic conditions. The current study investigated the effects of stabilizing HIF-1α on the therapeutic capacity of MSCs in an experimental mouse model of bacterial pneumonia. HIF-1α stabilization was achieved by the small molecule prolyl-hydroxlase inhibitor, AKB-4924 (Aerpio Therapeutics, Inc...
2018: Frontiers in Medicine
Ruijuan Guan, Jian Wang, Ziying Li, Mingjing Ding, Defu Li, Guihua Xu, Tao Wang, Yuqin Chen, Qian Yang, Zhen Long, Zhou Cai, Chenting Zhang, Xue Liang, Lian Dong, Li Zhao, Haiyun Zhang, Dejun Sun, Wenju Lu
Aberrant activation of hypoxia-inducible factor (HIF)-1α is frequently encountered and promotes oxidative stress and inflammation in chronic obstructive pulmonary disease (COPD). The present study investigated whether sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, can mediate its effect through inhibiting HIF-1α-induced oxidative stress and inflammation in cigarette smoke (CS)-induced COPD in mice. Here, we found that STS improved pulmonary function, ameliorated emphysema and decreased the infiltration of inflammatory cells in the lungs of CS-exposed mice...
2018: Frontiers in Pharmacology
Yung-Ting Kuo, Jhong-Huei Jheng, Mei-Chen Lo, Wei-Lu Chen, Shyang-Guang Wang, Horng-Mo Lee
Iron or oxygen regulates the stability of hypoxia inducible factor-1α (HIF-1α). We investigated whether ferrous glycinate would affect HIF-1α accumulation, aerobic glycolysis and mitochondrial energy metabolism in human A549 lung cancer cells. Incubation of A549 cells with ferrous glycinate decreased the protein levels of HIF-1α, which was abrogated by proteosome inhibitor, or prolyl hydroxylase inhibitor. Addition of ferrous glycinate decreased protein levels of glucose transporter-1, hexokinase-2, and lactate dehydrogenase A, and decreased pyruvate dehydrogenase kinase-1 (PDK-1) and pyruvate dehydrogenase (PDH) phosphorylation in A549 cells...
May 15, 2018: Free Radical Research
Silvia Uccella, Stefano La Rosa, Debora Scaldaferri, Laura Monti, Roberta Maragliano, Elisa Sorrenti, Marzia Gariboldi, Roberto Taramelli, Fausto Sessa, Francesco Acquati
Ribonuclease T2 (RNASET2) is a pleiotropic and polyfunctional protein, which exerts several different activities in neoplastic cells since the early steps of tumor development. Besides having an antitumorigenic activity, RNASET2 inhibits both bFGF-induced and VEGF-induced angiogenesis and has a role as a stress-response, alarmin-like, protein. In this study, we investigated RNASET2 expression in well-differentiated and poorly differentiated neuroendocrine neoplasms of the lung (Lu-NENs), which are known to show clear-cut differences in morphology, biology and clinical behavior...
May 12, 2018: Human Pathology
E T Zakharova, A V Sokolov, N N Pavlichenko, V A Kostevich, I N Abdurasulova, A V Chechushkov, I V Voynova, A Yu Elizarova, N N Kolmakov, M G Bass, I V Semak, A I Budevich, P M Kozhin, N K Zenkov, V M Klimenko, O V Kirik, D E Korzhevskii, E B Menshchikova, V B Vasilyev
Among the properties of lactoferrin (LF) are bactericidal, antianemic, immunomodulatory, antitumour, antiphlogistic effects. Previously we demonstrated its capacity to stabilize in vivo HIF-1-alpha and HIF-2-alpha, which are redox-sensitive multiaimed transcription factors. Various tissues of animals receiving recombinant human LF (rhLF) responded by expressing the HIF-1-alpha target genes, hence such proteins as erythropoietin (EPO), ceruloplasmin, etc. were synthesized in noticeable amounts. Among organs in which EPO synthesis occurred were brain, heart, spleen, liver, kidneys and lungs...
May 10, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Zhiqiang Chen, Xueliang Zuo, Yao Zhang, Guoyong Han, Long Zhang, Jindao Wu, Xuehao Wang
Glucose metabolic reprogramming from oxidative to aerobic glycolysis, referred as the Warburg effect, is a hallmark of tumor cells. Accumulating evidence suggests that a subset of microRNAs play pivotal roles in modulating such reprogramming of glucose metabolism in cancer cells. miR-3662 has been implicated previously in both pro-tumorigenic and anti-tumorigenic effects in several types of cancer. The expression level of miR-3662 is downregulated in acute myeloid leukemia, whereas increased miR-3662 expression is observed in lung adenocarcinoma...
May 10, 2018: Cell Death & Disease
Salvador Pérez, Isabela Finamor, Pablo Martí-Andrés, Javier Pereda, Ana Campos, Rosário Domingues, Fawaz Haj, Luis Sabater, Enrique de-Madaria, Juan Sastre
BACKGROUND/OBJECTIVES: A high body mass index increases the risk of severe pancreatitis and associated mortality. Our aims were: (1) To determine whether obesity affects the release of extracellular nucleosomes in patients with pancreatitis; (2) To determine whether pancreatic ascites confers lipotoxicity and triggers the release of extracellular nucleosomes in lean and obese rats. METHODS: DNA and nucleosomes were determined in plasma from patients with mild or moderately severe acute pancreatitis either with normal or high body mass index (BMI)...
May 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Astrid A Glück, Eleonora Orlando, Dominic Leiser, Michaela Poliaková, Lluís Nisa, Aurélie Quintin, Jacopo Gavini, Deborah M Stroka, Sabina Berezowska, Lukas Bubendorf, Andree Blaukat, Daniel M Aebersold, Michaela Medová, Yitzhak Zimmer
Poor oxygenation is a common hallmark of solid cancers that strongly associates with aggressive tumor progression and treatment resistance. While a hypoxia-inducible factor 1α (HIF-1α)-associated transcriptional overexpression of the hepatocyte growth factor (HGF) receptor tyrosine kinase (RTK) MET has been previously documented, any regulation of the HIF-1α system through MET downstream signaling in hypoxic tumors has not been yet described. By using MET-driven in vitro as well as ex vivo tumor organotypic fresh tissue models we report that MET targeting results in depletion of HIF-1α and its various downstream targets...
May 2, 2018: Oncogene
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