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Hif-1 lung cancer

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https://www.readbyqxmd.com/read/29764240/ferrous-glycinate-regulates-cell-energy-metabolism-by-restricting-hypoxia-induced-factor-1%C3%AE-expression-in-human-a549-cells
#1
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
https://www.readbyqxmd.com/read/29763721/new-insights-into-hypoxia-related-mechanisms-involved-in-different-microvascular-patterns-of-bronchopulmonary-carcinoids-and-poorly-differentiated-neuroendocrine-carcinomas-role-of-ribonuclease-t2-rnaset2-and-hif-1-alpha
#2
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
https://www.readbyqxmd.com/read/29716919/abemaciclib-a-selective-cdk4-6-inhibitor-enhances-the-radiosensitivity-of-non-small-cell-lung-cancer-in-vitro-and-in-vivo
#3
Sarwat Naz, Anastasia L Sowers, Rajani Choudhuri, Maria F Wissler, Janet Gamson, Askale Mathias, John A Cook, James B Mitchell
PURPOSE: To characterize the ionizing radiation (IR) enhancing effects and underlying mechanisms of CDK4/6 inhibitor, Abemaciclib in Non-Small Cell Lung Cancer cells (NSCLC) in vitro and in vivo Experimental Design: IR enhancement by Abemaciclib in a variety of NSCLC cell lines was assessed by in vitro clonogenic assay, flow cytometry, and target inhibition verified by immunoblotting. IR-induced DNA damage repair was evaluated by γ-H2AX analysis. Global metabolic alterations by Abemaciclib and IR combination was evaluated by LC/MS mass spectrometry and YSI-Bioanalyzer...
May 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29690507/hypoxia-induced-cisplatin-resistance-in-non-small-cell-lung-cancer-cells-is-mediated-by-hif-1%C3%AE-and-mutant-p53-and-can-be-overcome-by-induction-of-oxidative-stress
#4
Christophe Deben, Vanessa Deschoolmeester, Jorrit De Waele, Julie Jacobs, Jolien Van den Bossche, An Wouters, Marc Peeters, Christian Rolfo, Evelien Smits, Filip Lardon, Patrick Pauwels
The compound APR-246 (PRIMA-1MET ) is a known reactivator of (mutant) p53 and inducer of oxidative stress which can sensitize cancer cells to platinum-based chemotherapeutics. However, the effect of a hypoxic tumor environment has been largely overlooked in this interaction. This study focusses on the role of hypoxia-inducible factor-1α (HIF-1α) and the p53 tumor suppressor protein in hypoxia-induced cisplatin resistance in non-small cell lung cancer (NSCLC) cells and the potential of APR-246 to overcome this resistance...
April 21, 2018: Cancers
https://www.readbyqxmd.com/read/29629903/zmynd8-acetylation-mediates-hif-dependent-breast-cancer-progression-and-metastasis
#5
Yan Chen, Bo Zhang, Lei Bao, Lai Jin, Mingming Yang, Yan Peng, Ashwani Kumar, Jennifer E Wang, Chenliang Wang, Xuan Zou, Chao Xing, Yingfei Wang, Weibo Luo
Altered epigenetic reprogramming contributes to breast cancer progression and metastasis. How the epigenetic reader mediates breast cancer progression remains poorly understood. Here, we showed that the epigenetic reader zinc finger MYND-type containing 8 (ZMYND8) is induced by HIF-1 and HIF-2 in breast cancer cells and also upregulated in human breast tumors, and is correlated with poor survival of patients with breast cancer. Genetic deletion of ZMYND8 decreases breast cancer cell colony formation, migration, and invasion in vitro, and inhibits breast tumor growth and metastasis to the lungs in mice...
April 9, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29616117/correlation-of-hypoxia-status-with-radiosensitizing-effects-of-sodium-glycididazole-a-preclinical-study
#6
Yang Yu, Xiaolin Li, Hengwei Xu, Jing Liu, Min Dong, Jia Yang, Lu Sun, Xiaorong Sun, Ligang Xing
The correlation of pretreatment hypoxia status with the radiosensitization effect of sodium glycididazole (CMNa) was not previously defined. The purpose of the present study was to evaluate the tumor hypoxia status in various cancer xenografts and to investigate the correlation between tumor hypoxia status and radiosensitizing effects of CMNa based on the pharmacokinetic and pharmacodynamic parameters. Human esophageal cancer (EC109), head and neck cancer (FaDu) and lung cancer (A549) nude mice xenografts were used...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29608508/tumor-heterogeneity-hypoxia-and-immune-markers-in-surgically-resected-non-small-cell-lung-cancer
#7
Angelo Castello, Fabio Grizzi, Luca Toschi, Sabrina Rossi, Daoud Rahal, Federica Marchesi, Carlo Russo, Giovanna Finocchiaro, Egesta Lopci
OBJECTIVES: This study aimed to determine the prognostic role of textural features and their association with metabolic parameters, hypoxia, and cancer-related immune markers in non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: The trial was registered at http://www.clinicaltrials.gov (NCT02519062). From January 2010 to May 2014, 44 patients (male : female=33 : 11; median age: 69.5 years), referred to our Institution for NSCLC resection, were enrolled...
March 30, 2018: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/29568362/the-metal-nonoate-ni-salpipnono-inhibits-in-vitro-tumor-growth-invasiveness-and-angiogenesis
#8
Valerio Ciccone, Martina Monti, Enrico Monzani, Luigi Casella, Lucia Morbidelli
Nitric oxide (NO) exerts conflicting effect on tumor growth and progression, depending on its concentration. We aimed to characterize the anti-cancer activity of a new NO donor, Ni(SalPipNONO) belonging to the class of metal-nonoates, in epithelial derived tumor cells, finally exploring its antiangiogenic properties. Tumor epithelial cells were screened to evaluate the cytotoxic effect of Ni(SalPipNONO), which was able to inhibit cell proliferation in a dose dependent manner, being more effective than the commercial DETA/NO...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29560113/hypoxic-induced-truncation-of-voltage-dependent-anion-channel-1-is-mediated-by-both-asparagine-endopeptidase-and-calpain-1-activities
#9
Hadas Pahima, Simona Reina, Noa Tadmor, Daniella Dadon-Klein, Anna Shteinfer-Kuzmine, Nathalie M Mazure, Vito De Pinto, Varda Shoshan-Barmatz
The voltage-dependent anion channel 1 (VDAC1), an outer mitochondria membrane (OMM) protein, serves as a mitochondrial gatekeeper, mediating the transport of nucleotides, Ca2+ and other metabolites across the OMM. VDAC1 also plays a central role in mitochondria-mediated apoptosis by facilitating the release of apoptotic proteins and by association with both pro- and anti-apoptotic proteins. Tumor cells, which are constantly exposed to hypoxic conditions, affect the cell via the transcription factor hypoxia-inducible factor (HIF) that induces transcriptional activity...
February 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29469087/downregulation-of-hif-2%C3%AE-reverse-the-chemotherapy-resistance-of-lung-adenocarcinoma-a549-cells-to-cisplatin
#10
Zhao-Jia Gao, Wei-Dong Yuan, Jun-Qiang Yuan, Kai Yuan, Yong Wang
BACKGROUND Cisplatin (DDP)-based systemic chemotherapy has been widely used in the treatment of postoperative or advanced NSCLC patients, however, its effective rate is only 14~40%. HIF-2α can upregulate drug-resistant-related genes expression and lead to chemotherapy resistance in many tumors. However, little is known about the relationship between HIF-2α and chemotherapy resistance of lung cancer cells. MATERIAL AND METHODS In our study, the siRNA expression vectors targeting the HIF-2α gene were designed, constructed, and transfected into A549 cells...
February 22, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29467870/hif-1%C3%AE-promotes-zeb1-expression-and-emt-in-a-human-bladder-cancer-lung-metastasis-animal-model
#11
Jianning Zhu, Zhixin Huang, Mengzhao Zhang, Weiyi Wang, Hua Liang, Jin Zeng, Kaijie Wu, Xinyang Wang, Jer-Tsong Hsieh, Peng Guo, Jinhai Fan
Lung is one of the most common sites for bladder cancer to metastasize. Although the involvement of the epithelial-to-mesenchymal transition (EMT) in bladder cancer progression has been established, the mechanism of EMT induction remains unclear. In order to investigate this, T24-parental (P) and T24-lung (L) bladder cancer cells were obtained from primary tumors and lung metastatic sites of an animal model with orthotopic spontaneous metastatic bladder cancer, according to a protocol previously described. Compared with T24-P cells, mesenchymal-like T24-L cells exhibited an increased ability in tumor invasion and metastasis, as well as an increased expression of hypoxia-inducible factor (HIF)-1α, zinc finger E-box-binding homeobox 1 (ZEB1), vimentin and N-cadherin and lower level of cytokeratin 18 were observed...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29416769/roles-of-malat1-in-development-and-migration-of-triple-negative-and-her-2-positive-breast-cancer
#12
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/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
#13
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...
March 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29300322/mutations-in-emt-related-genes-in-alk-positive-crizotinib-resistant-non-small-cell-lung-cancers
#14
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/29245898/a-novel-small-molecule-arylsulfonamide-causes-energetic-stress-and-suppresses-breast-and-lung-tumor-growth-and-metastasis
#15
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-2 H -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/29212260/bioenergetics-of-acquired-cisplatin-resistant-h1299-non-small-cell-lung-cancer-and-p31-mesothelioma-cells
#16
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/29207023/macrophage-migration-inhibitory-factor-promotes-warburg-effect-via-activation-of-the-nf%C3%A2-%C3%AE%C2%BAb-hif%C3%A2-1%C3%AE-pathway-in-lung-cancer
#17
Jun Li, Junhua Zhang, Fengjiao Xie, Jiangzhou Peng, Xu Wu
Macrophage migration inhibitory factor (MIF) is upregulated in various solid tumors, a process that is associated with tumor progression and metastasis. The present study aimed to investigate the role and the underlying mechanism of MIF in human lung cancer. Human lung cancer H358, H460, H524, H1650, H838, H1975 and A549 cell lines were used to examine the expression of MIF by real time‑quantitative polymerase chain reaction and western blotting. The lentivirus was used to overexpress MIF and the expression of MIF and hypoxia‑inducible factor 1‑α (HIF‑1α) were knocked down by shRNA or siRNA...
February 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29190880/enhancement-of-the-anti-tumor-activity-of-fgfr1-inhibition-in-squamous-cell-lung-cancer-by-targeting-downstream-signaling-involved-in-glucose-metabolism
#18
Claudia Fumarola, Daniele Cretella, Silvia La Monica, Mara A Bonelli, Roberta Alfieri, Cristina Caffarra, Federico Quaini, Denise Madeddu, Angela Falco, Andrea Cavazzoni, Graziana Digiacomo, Giulia Mazzaschi, Valentina Vivo, Elisabetta Barocelli, Marcello Tiseo, Pier Giorgio Petronini, Andrea Ardizzoni
Fibroblast Growth Factor Receptor (FGFR) signaling is a complex pathway which controls several processes, including cell proliferation, survival, migration, and metabolism. FGFR1 signaling is frequently deregulated via amplification/over-expression in NSCLC of squamous histotype (SQCLC), however its inhibition has not been successfully translated in clinical setting. We determined whether targeting downstream signaling implicated in FGFR1 effects on glucose metabolism potentiates the anti-tumor activity of FGFR1 inhibition in SQCLC...
November 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29173495/inflammation-and-the-chemical-carcinogen-benzo-a-pyrene-partners-in-crime
#19
REVIEW
Q Shi, R W L Godschalk, F J van Schooten
Exposure to benzo[a]pyrene (B[a]P) is known to play a role in lung carcinogenesis and the underlying processes can be modified by the presence of inflammation. The inflammatory process can for instance enhance the concentration of reactive metabolites that bind to DNA and may also diminish DNA repair. Additionally, during the inflammatory process mediators are released that create a microenvironment which is suitable for further stimulation of cancer development. Various transcriptional pathways are activated by inflammation, including pathways that are mediated via nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), signal transducer and activator of transcription 3 (STAT-3), and hypoxia-inducible factor-1 (HIF-1)...
October 2017: Mutation Research
https://www.readbyqxmd.com/read/29152147/microrna-370-inhibits-the-growth-and-metastasis-of-lung-cancer-by-down-regulating-epidermal-growth-factor-receptor-expression
#20
Xin Liu, You-Guang Huang, Cong-Guo Jin, Yong-Chun Zhou, Xiao-Qun Chen, Jia Li, Yan Chen, Mei Li, Qian Yao, Ke Li, Min Lan, Jia-Gui Ye, Xi-Cai Wang
Abnormal microRNA-370 (miR-370) expression has been frequently reported in several types of cancers, including lung cancer. However, the role and molecular mechanisms of miR-370 in regulating the growth and metastasis of lung cancer have not been clarified. Here, we show higher levels of epidermal growth factor receptor (EGFR), but lower levels of miR-370 expression in most human lung cancer cells and non-tumor cells. Induction of miR-370 over-expression significantly reduced the levels of EGFR expression and the EGFR 3'untranslated region (UTR)-regulated luciferase activity in XWLC-05 and H157 cells, suggesting that miR-370 may bind to the 3'UTR of EGFR mRNA...
October 20, 2017: Oncotarget
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