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Hif-1 lung cancer

Minghui Ou, Xuezhi Sun, Jiancheng Liang, Fei Liu, Liqin Wang, Xiaomin Wu, Jie Tu
A water-soluble polysaccharide (STPC2) was isolated from the boiling-water extract of Sargassum thunbergii, purified by CaCl2 precipitation and chromatography on DEAE-cellulose and Sephacryl S-300 column. It was found that STPC2, with a molecular weight of 57kD, was composed of fucose, xylose, galactose and glucuronic acid, in a ratio of 8.1: 3.8: 2.1: 1.0. Additionally, we found that STPC2 significantly inhibited endothelial cell migration and tube formation without toxicity. Moreover, STPC2 significantly inhibited lung cancer cell A549 migration and proliferation...
October 17, 2016: International Journal of Biological Macromolecules
Elizabeth J Campbell, Margreet C M Vissers, Christina Wohlrab, Kevin O Hicks, R Matthew Strother, Stephanie M Bozonet, Bridget A Robinson, Gabi U Dachs
Despite recent evidence for an anti-tumour role for high-dose ascorbate, potential mechanisms of action are still unclear. At mM concentrations that are achieved with high-dose intravenous administration, autoxidation of ascorbate can generate cytotoxic levels of H2O2. Ascorbate is also a required co-factor for the hydroxylases that suppress the transcription factor hypoxia-inducible factor (HIF-1). HIF-1 supports an aggressive tumour phenotype and is associated with poor prognosis, and previous studies have shown that optimizing intracellular ascorbate levels down-regulates HIF-1 activation...
August 24, 2016: Free Radical Biology & Medicine
Alberto Grandi, Alice Santi, Susanna Campagnoli, Matteo Parri, Elisa De Camilli, Chaojun Song, Boquan Jin, Aurelien Lacombe, Serenella Castori-Eppenberger, Paolo Sarmientos, Guido Grandi, Giuseppe Viale, Luigi Terracciano, Paola Chiarugi, Piero Pileri, Renata Grifantini
Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are highly activated in cancer and involved in tumorigenesis and resistance to anti-cancer therapy. UPR is becoming a promising target of anti-cancer therapies. Thus, the identification of UPR components that are highly expressed in cancer could offer new therapeutic opportunity.In this study, we demonstrate that Endoplasmic Reticulum Metallo Protease 1 (ERMP1) is broadly expressed in a high percentage of breast, colo-rectal, lung, and ovary cancers, regardless of their stage and grade...
August 23, 2016: Oncotarget
Cheng-Cheng Wang, Jia-Rui Yuan, Chun-Fei Wang, Nan Yang, Juan Chen, Dan Liu, Jie Song, Liang Feng, Xiao-Bin Tan, Xiao-Bin Jia
BACKGROUND: Phyllanthus emblica L (PEL), a well-known medical plant, has been used in Asian countries for a long time. Increasing evidence suggests that it can prevent the tumorigenesis of cancer associated with nonresolving inflammation. However, the possible anti-inflammatory mechanism responsible for preventing tumorigenesis of precancerous lung lesions is not well elucidated. MATERIALS AND METHODS: Male A/J mice were randomly divided into 5 groups with 10 mice in each group: (1) blank group (saline), (2) benzo(a)pyrene [B(a)P] group, (3) and (4) B(a)P + PEL (5 g/kg/d, 10 g/kg/d, administered by gavage), (5) B(a)P + celecoxib (30 mg/kg/d, administered by gavage)...
August 24, 2016: Integrative Cancer Therapies
Yasuyuki Ikezawa, Jun Sakakibara-Konishi, Hidenori Mizugaki, Satoshi Oizumi, Masaharu Nishimura
BACKGROUND: The Notch receptor plays an important role in various cell fate decisions during development and in cancer. We have previously reported that Notch3 is upregulated by radiation in non-small cell lung cancer (NSCLC) cell lines and that the Notch pathway inhibitor γ secretase inhibitor GSI (gamma-secretase inhibitor), when combined with radiation therapy, significantly suppressed the growth of lung cancer cells. However, little is known about the mechanism of Notch upregulation induced by radiation...
August 23, 2016: International Journal of Clinical Oncology
Sandrine Sallé-Lefort, Stéphanie Miard, Marc-André Nolin, Louise Boivin, Marie-Ève Paré, Richard Debigaré, Frédéric Picard
Increased expression levels of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) have been associated with enhanced proliferation and metastasis of several cancer cell types. Hypoxia, a hallmark characteristic of solid tumors, has been linked to an increase in the activity of the ATP-generating AMPK protein. Since Malat1 was recently shown to be upregulated during hypoxia, the objective of this study was to determine the contribution of AMPK in the mechanistic pathways regulating Malat1 expression in low oxygen conditions...
October 2016: International Journal of Oncology
Chihiro Takasaki, Masashi Kobayashi, Hironori Ishibashi, Takumi Akashi, Kenichi Okubo
Hypoxia-inducible factor (HIF)-1 is a transcription factor that allows cells to adapt to hypoxic situations. HIF-1 is known to control tissue proliferation, antiapoptosis, angiogenesis and glucose metabolism. Furthermore, HIF-1 is involved in the growth of numerous cancer types. The present study aimed to examine the expression of HIF-1α immunohistochemically in resected lung cancers. The present study included 216 consecutive patients with lung cancer who underwent resection between April 2013 and January 2015...
August 2016: Molecular and Clinical Oncology
Masahiro Yanagawa, Eiichi Morii, Akinori Hata, Maki Fujiwara, Tomoko Gyobu, Ken Ueda, Osamu Honda, Noriyuki Tomiyama
OBJECTIVES: To compare iodine content (IC) of solitary lung cancer using dynamic measurements of CT attenuation (Hounsfield Units, HU) and to correlate their quantitative CT data with expressions of vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and hypoxia-inducible factor-1α (HIF-1α) using immunostaining methods. METHODS: This study included 18 patients with adenocarcinoma, who undergone dual energy dynamic multiphase CT to examine solitary lung nodules (6 part-solid and 12 solid nodules)...
August 2016: European Journal of Radiology
J P Phelan, F J Reen, N Dunphy, R O'Connor, F O'Gara
BACKGROUND: The role of the microbiome has become synonymous with human health and disease. Bile acids, as essential components of the microbiome, have gained sustained credibility as potential modulators of cancer progression in several disease models. At physiological concentrations, bile acids appear to influence cancer phenotypes, although conflicting data surrounds their precise physiological mechanism of action. Previously, we demonstrated bile acids destabilised the HIF-1α subunit of the Hypoxic-Inducible Factor-1 (HIF-1) transcription factor...
2016: BMC Cancer
Sheng-Li Yang, Quan-Guang Ren, Lu Wen, Jian-Li Hu
Hypoxia-inducible factor-1 alpha (HIF-1α) plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. PubMed and Embase were searched from their inception to January 2015 for observational studies...
June 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Stephen L Archer
There is no cure for non-small-cell lung cancer (NSCLC) or pulmonary arterial hypertension (PAH). Therapies lack efficacy and/or are toxic, reflecting a failure to target disease abnormalities that are distinct from processes vital to normal cells. NSCLC and PAH share reversible mitochondrial-metabolic abnormalities which may offer selective therapeutic targets. The following mutually reinforcing, mitochondrial abnormalities favor proliferation, impair apoptosis, and are relatively restricted to PAH and cancer cells: (1) Epigenetic silencing of superoxide dismutase-2 (SOD2) by methylation of CpG islands creates a pseudohypoxic redox environment that causes normoxic activation of hypoxia inducible factor (HIF-1α)...
2016: Advances in Experimental Medicine and Biology
So Young Park, Soo Jin Kwon, Soon Sung Lim, Jin-Kyu Kim, Ki Won Lee, Jung Han Yoon Park
Licorice extracts containing glycyrrhizin exhibit anti-carcinogenic properties. Because glycyrrhizin induces severe hypokalemia and hypertension, we prepared a hexane/ethanol extract of Glycyrrhiza uralensis (HEGU) that lacks glycyrrhizin, and showed that HEGU induces apoptosis and G1 cell cycle arrest and inhibits migration of DU145 human prostate cancer cells. Our previous in vitro studies identified two active components in HEGU: isoangustone A, which induces apoptosis and G1 cycle arrest, and licoricidin, which inhibits metastasis...
2016: International Journal of Molecular Sciences
Yu-Lun Chen, Tsung-Ying Yang, Kun-Chieh Chen, Chieh-Liang Wu, Shih-Lan Hsu, Chi-Mei Hsueh
BACKGROUND: Non-small cell lung cancers (NSCLCs) frequently exhibit resistance to therapeutic drugs, which seriously hampers their treatment. Here, we set out to assess the roles of the multidrug resistance protein 1 (MRP1) and P-glycoprotein (P-gp) in the doxorubicin (DOX) resistance of NSCLC cells, as well as the putative therapeutic efficacy of MRP1 and P-gp blockers on DOX-treated NSCLC cells. METHODS: The impact of DOX on cell survival, DOX efflux and MRP1 and P-gp expression was assessed in 5 different NSCLC-derived cell lines (parental CH27, A549, H1299, H460, and DOX resistant CH27) in the absence or presence of MK571 (MRP1 inhibitor) or Verapamil (P-gp inhibitor), under both normoxic and hypoxic conditions...
June 15, 2016: Cellular Oncology (Dordrecht)
Jun Wan, Wei Wu, Yunlong Huang, Wei Ge, Shandong Liu
Radiofrequency ablation (RFA) therapy has been proved effective and feasible for lung cancer. However, the molecular mechanisms of local lung cancer recurrence following RFA are poorly understood. The present study aimed to evaluate the ability of HSP70/HIF-1α to affect the proliferation and angiogenesis of non-small cell lung cancers (NSCLCs) following insufficient RFA to uncover the molecular mechanisms of local recurrence. In vitro heat treatment was used to establish sublines of NCI-H1650 cells. The NCI-H1650 subline that was established by heat treatment at 54˚C had a relatively higher viability and significantly elevated heat tolerance (compared to the parental strain)...
August 2016: Oncology Reports
Amir Abbas Momtazi, Amirhossein Sahebkar
BACKGROUND: Curcumin, a polyphenol from turmeric, is a dietary phytochemical with a diversity of health benefits including strong anti-tumor effects. Curcumin undergoes a rapid metabolism resulting in a low oral bioavailability. 3, 4-difluorobenzylidene curcumin or (CDF) is a novel fluorinated curcumin analogue which has been shown to be about 3 times more bioavailable than curcumin. This review aimed to summarize the findings of studies related to pharmacokinetic and pharmacological characteristics of CDF...
2016: Current Pharmaceutical Design
L Y Guo, P Zhu, X P Jin
The goal of this study was to investigate the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in primary liver cancer (PLC) and their association with prognosis. Tumor tissue, non-tumor tissue, and blood samples of 75 PLC patients were collected. Blood samples of 20 volunteers were also collected as healthy controls. Real-time quantitative reverse transcription-polymerase chain reaction was used to analyze the mRNA levels of HIF-1α and VEGF in the tissues...
2016: Genetics and Molecular Research: GMR
Jaemoon Koh, Ji-Young Jang, Bhumsuk Keam, Sehui Kim, Moon-Young Kim, Heounjeong Go, Tae Min Kim, Dong-Wan Kim, Chul-Woo Kim, Yoon Kyung Jeon, Doo Hyun Chung
Programmed cell death (PD)-1/PD-1 ligand-1 (PD-L1)-targeted therapy has emerged as a promising therapeutic strategy for lung cancer. However, whether EML4-ALK regulates PD-L1 expression in lung cancer remains unknown. A total of 532 pulmonary adenocarcinomas (pADCs), including 58 ALK-translocated tumors, were immunohistochemically evaluated for PD-L1 and PD-1. H23 (EGFR(Wild-type)EML4-ALK(-)PD-L1(Low)) and H2228 (EGFR(Wild-type)EML4-ALK(+)PD-L1(High)) cells were transfected with EML4-ALK or ALK short interfering RNAs and used to investigate the alterations in PD-L1 expression...
March 2016: Oncoimmunology
Anna Tosatto, Roberta Sommaggio, Carsten Kummerow, Robert B Bentham, Thomas S Blacker, Tunde Berecz, Michael R Duchen, Antonio Rosato, Ivan Bogeski, Gyorgy Szabadkai, Rosario Rizzuto, Cristina Mammucari
Triple-negative breast cancer (TNBC) represents the most aggressive breast tumor subtype. However, the molecular determinants responsible for the metastatic TNBC phenotype are only partially understood. We here show that expression of the mitochondrial calcium uniporter (MCU), the selective channel responsible for mitochondrial Ca(2+) uptake, correlates with tumor size and lymph node infiltration, suggesting that mitochondrial Ca(2+) uptake might be instrumental for tumor growth and metastatic formation. Accordingly, MCU downregulation hampered cell motility and invasiveness and reduced tumor growth, lymph node infiltration, and lung metastasis in TNBC xenografts...
May 2, 2016: EMBO Molecular Medicine
Hui Xia, Ying-Nan Zhao, Chang-Hai Yu, Yun-Long Zhao, Yang Liu
Metabotropic glutamate receptor 1 (mGlu1 receptor) is expressed in many cancer cell types as compared to normal counterparts underscoring its potential role in tumor behavior. The aim of present study was to test the role of mGlu1 receptor in experimental non-small cell lung cancer (NSCLC). First, protein expression of mGlu1 receptor was higher in human NSCLC cell lines, including both adenocarcinoma and squamous carcinoma subtypes, when compared to normal bronchial epithelial cells. Inhibition of mGlu1 receptor by BAY36-7620 (an mGlu1 receptor-specific inhibitor) inhibited tumor growth and prolonged survival of mice with tumors of A549 or H1299...
July 15, 2016: European Journal of Pharmacology
Yih-Leong Chang, Ching-Yao Yang, Mong-Wei Lin, Chen-Tu Wu, Pan-Chyr Yang
BACKGROUND: Pulmonary pleomorphic carcinomas (PPCs) are uncommon malignant tumours characterised by an aggressive clinical course and poor survival. These neoplasms frequently exhibit marked confluent necrosis, in which hypoxia levels are extremely high, causing low responsiveness to chemotherapy and conferring basic resistance to anti-cancer drugs. Programmed death ligand 1 (PD-L1)-mediated immune escape may be an underlying source of resistance and a suitable target for specific therapy, but its role in PPCs is unclear...
June 2016: European Journal of Cancer
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