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Hepatocellular carcinoma mtor

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https://www.readbyqxmd.com/read/28314268/clinical-significance-of-fancd2-gene-expression-and-its-association-with-tumor-progression-in-hepatocellular-carcinoma
#1
Hisateru Komatsu, Takaaki Masuda, Tomohiro Iguchi, Sho Nambara, Kuniaki Sato, Quingjang Hu, Hidenari Hirata, Shuhei Ito, Hidetoshi Eguchi, Keishi Sugimachi, Hidetoshi Eguchi, Yuichiro Doki, Masaki Mori, Koshi Mimori
BACKGROUND/AIM: Fanconi anemia complementation group D2 (FANCD2) gene is vitally involved in DNA damage responses. We investigated the clinical significance of FANCD2 expression in hepatocellular carcinoma (HCC). PATIENTS AND METHODS: FANCD2 mRNA expression of resected HCC tissues was assessed in two HCC cohorts; Our cases (n=111), and The Cancer Genome Atlas (TCGA; n=371). Gene set enrichment analysis (GSEA) was conducted using the TCGA dataset. Proliferation and invasion assays were performed using siRNAs, and the effect of inhibition of the mechanistic target of rapamycin (mTOR) pathway was evaluated...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28284560/computational-discovery-of-niclosamide-ethanolamine-a-repurposed-drug-candidate-that-reduces-growth-of-hepatocellular-carcinoma-cells-in-vitro-and-in-mice-by-inhibiting-cdc37-signaling
#2
Bin Chen, Wei Wei, Li Ma, Bin Yang, Ryan M Gill, Mei-Sze Chua, Atul J Butte, Samuel So
BACKGROUND & AIMS: Drug repositioning offers a shorter approval process than new drug development. We therefore searched large public datasets of drug-induced gene expression signatures to identify agents that might be effective against hepatocellular carcinoma (HCC). METHODS: We searched public databases of mRNA expression patterns reported from HCC specimens from patients, HCC cell lines, and cells exposed to various drugs. We identified drugs that might specifically increase expression of genes that are downregulated in HCCs and reduce expression of genes upregulated in HCCs using a non-parametric, rank-based pattern-matching strategy based on the Kolmogorov-Smirnov statistic...
March 8, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28276313/inhibition-of-mmp-2-expression-enhances-the-anti-tumor-effect-of-sorafenib-in-hepatocellular-carcinoma-by-suppressing-pi3k-akt-mtor-pathway
#3
Wenliang Tan, Sicong Zhu, Jun Cao, Lei Zhang, Wenda Li, Kairui Liu, Jinyi Zhong, Changzhen Shang, Yajin Chen
Sorafenib has been globally approved as the standard treatment for patients with advanced Hepatocellular carcinoma (HCC). However, the response rate of HCC patients to sorafenib is limited due to tumor recurrence and metastasis. Therefore, seeking combined therapeutic strategies with sorafenib is necessary to improve the anti-tumor efficiency. Here we demonstrated that expression of MMP-2 positively correlated with the migration ability of HCC cells. Cells with higher MMP-2 expression (SK-HEP-1 cells) were less sensitive to sorafenib than those with lower MMP-2 expression (HepG2 cells)...
March 8, 2017: Oncology Research
https://www.readbyqxmd.com/read/28266023/astragaloside-ii-sensitizes-human-hepatocellular-carcinoma-cells-to-5-fluorouracil-via-suppression-of-autophagy
#4
Meng Wang, Can Huang, Yong Su, Cui Yang, Quan Xia, Du-Juan Xu
OBJECTIVES: Inhibition of autophagy has been increasingly recognized as a potential therapeutic approach against cancer. Our previous reports showed that Astragaloside II improves hepatic cancer cells resistance by downregulating MDR1 and P-gp .The purpose of this study was to further investigated the effect of autophagy on AS-II reversing multidrug resistance and its molecular mechanism in hepatocellular carcinoma cells in vitro. METHODS: Bel-7402 and Bel-7402/FU cell lines were used in this study...
March 7, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28259820/bclb-methylated-in-hepatocellular-carcinoma-is-a-starvation-stress%C3%A2-sensor-that-induces-apoptosis-and-autophagy-through-the%C3%A2-ampk-mtor-signaling-cascade
#5
Xiaolong Liu, Xiaotong Hu, Yeye Kuang, Peijian Yan, Lili Li, Chen Li, Qian Tao, Xiujun Cai
Epigenetic disruption of tumor suppressor genes (TSGs), particularly DNA methylation, plays a key role in hepatocellular carcinoma (HCC) pathogenesis. Through methylome study, we identified BCLB as a methylated gene in HCC. BCLB was methylated in all tumor cell lines with silenced or reduced expression. BCLB was further found to be silenced in 55.2% (58/105) of HCC samples, while 91.4% (96/105) of paired non-tumor tissues showed high BCLB expression. BCLB protein expression was significantly correlated with HBV status (p = 0...
March 2, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28199961/proteomic-analysis-of-laser-capture-microdissected-focal-lesions-in-a-rat-model-of-progenitor-marker-positive-hepatocellular-carcinoma
#6
Adeola O Adebayo Michael, Nagib Ahsan, Valerie Zabala, Heather Francois-Vaughan, Stephanie Post, Kate E Brilliant, Arthur R Salomon, Jennifer A Sanders, Philip A Gruppuso
We have shown previously that rapamycin, the canonical inhibitor of the mechanistic target of rapamycin (mTOR) complex 1, markedly inhibits the growth of focal lesions in the resistant hepatocyte (Solt-Farber) model of hepatocellular carcinoma (HCC) in the rat. In the present study, we characterized the proteome of persistent, pre-neoplastic focal lesions in this model. One group was administered rapamycin by subcutaneous pellet for 3 weeks following partial hepatectomy and euthanized 4 weeks after the cessation of rapamycin...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28195035/pre-s2-mutant-induced-mammalian-target-of-rapamycin-signal-pathways-as-potential-therapeutic-targets-for-hepatitis-b-virus-associated-hepatocellular-carcinoma
#7
Chiao-Fang Teng, Han-Chieh Wu, Woei-Cherng Shyu, Long-Bin Jeng, Ih-Jen Su
Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Pre-S2 mutant represents an HBV oncoprotein that is accumulated in the endoplasmic reticulum (ER) and manifests as type II ground glass hepatocytes (GGHs). Pre-S2 mutant can induce ER stress and initiate multiple ER stress-dependent or -independent cellular signal pathways, leading to growth advantage of type II GGH. Importantly, the mammalian target of rapamycin (mTOR) signal pathways are consistently activated throughout the liver tumorigenesis in pre-S2 mutant transgenic mice and in human HCC tissues, leading to hepatocyte proliferation, metabolic disorders, and HCC tumorigenesis...
February 14, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28128716/immunosuppression-strategies-in-liver-transplantation-patient-patients-with-hepatocellular-carcinoma
#8
Alexander E Giakoustidis, Dimitrios E Giakoustidis
Hepatocellular carcinoma (HCC) consists the main primary malignant tumor of the liver. There is an underlining liver cirrhosis mainly attributed to chronic hepatitis B virus or hepatitis C virus, alcoholic liver disease, nonalcoholic steatohepatitis and other pathologic conditions. Liver transplantation consists a radical management, treating both cancer and cirrhosis. By introducing the Milan Criteria for liver transplantation in HCC patients there was a 5-year survival escalation. Even though there is a careful selection of patients with HCC for transplantation, recurrent disease is still high...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/28121478/mitoq-regulates-autophagy-by-inducing-a-pseudo-mitochondrial-membrane-potential-pmmp
#9
Chao Sun, Xiongxiong Liu, Cuixia Di, Zhenhua Wang, Xiangquan Mi, Yang Liu, Qiuyue Zhao, Aihong Mao, Weiqiang Chen, Lu Gan, Hong Zhang
During the process of oxidative phosphorylation, protons are pumped into the mitochondrial intermembrane space to establish a mitochondrial membrane potential (MMP). The electrochemical gradient generated allows protons to return to the matrix through the ATP synthase complex and generates ATP in the process. MitoQ is a lipophilic cationic drug that is adsorbed to the inner mitochondrial membrane; however, the cationic moiety of MitoQ remains in the intermembrane space. We found that the positive charges in MitoQ inhibited the activity of respiratory chain complexes I, III, and IV, reduced proton production, and decreased oxygen consumption...
January 25, 2017: Autophagy
https://www.readbyqxmd.com/read/28101201/diosmetin-inhibits-cell-proliferation-and-induces-apoptosis-by-regulating-autophagy-via-the-mammalian-target-of-rapamycin-pathway-in-hepatocellular-carcinoma-hepg2-cells
#10
Jie Liu, Hao Ren, Bin Liu, Qingyu Zhang, Mingyi Li, Runzhi Zhu
Hepatocellular carcinoma (HCC), which is a type of malignant tumor, is the fifth most common cancer in men and ninth in women worldwide. The aim of the present study was to investigate the antitumor effect of diosmetin (DIOS) in hepatocellular carcinoma HepG2 cells. The proliferation, apoptosis and autophagy rates of HepG2 cells were measured following treatment with DIOS. The effects of DIOS treatment on HepG2 cell proliferation and apoptosis rates were analyzed using MTT assays and Annexin V staining, respectively...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28098858/mir-345-inhibits-tumor-metastasis-and-emt-by-targeting-irf1-mediated-mtor-stat3-akt-pathway-in-hepatocellular-carcinoma
#11
Miao Yu, Huanzhou Xue, Yadong Wang, Quan Shen, Qingfeng Jiang, Xiao Zhang, Ke Li, Meng Jia, Jiangkun Jia, Jian Xu, Yuwei Tian
MicroRNAs (miRNAs) have been reported to play critical roles in tumor progression including hepatocellular carcinoma (HCC). Thus, the underlying mechanisms need further investigation. Previous study reported that loss of miR-345 expression indicated a poor prognosis of HCC patients. This study evaluated whether loss of miR-345 could promote the tumor metastasis and epithelial-mesenchymal-transition (EMT) of HCC by targeting interferon regulatory factor 1 (IRF1)-mediated mTOR/STAT3/AKT signaling. Underexpression of miR-345 was identified in 65 cases of human HCC compared to matched tumor-adjacent tissues by qRT-PCR...
March 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28073184/functional-lipidomics-palmitic-acid-impairs-hepatocellular-carcinoma-development-by-modulating-membrane-fluidity-and-glucose-metabolism
#12
Ling Lin, Ying Ding, Yi Wang, Zhenxin Wang, Xuefei Yin, Guoquan Yan, Lei Zhang, Pengyuan Yang, Huali Shen
Lipids are essential cellular components and energy sources of living organisms, altered lipid composition is increasingly recognized as a signature of cancer. We performed the lipidomic analysis in a series of hepatocellular carcinoma (HCC) cells and identified over 1700 intact lipids originating from 3 major lipid categories. Comparative lipidomic screening revealed 93 significantly changed lipids and decreased palmitic acyl (C16:0)-containing glycerophospholipids (GPs) were positively associated with metastatic abilities of HCC cells...
January 10, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28065789/choline-kinase-alpha-mediates-interactions-between-the-epidermal-growth-factor-receptor-and-mtorc2-in-hepatocellular-carcinoma-cells-to-promote-drug-resistance-and-xenograft-tumor-progression
#13
Xi-Meng Lin, Liang Hu, Jin Gu, Ruo-Yu Wang, Liang Li, Jing Tang, Bao-Hua Zhang, Xing-Zhou Yan, Yan-Jing Zhu, Cong-Li Hu, Wei-Ping Zhou, Shao Li, Jing-Feng Liu, Frank J Gonzalez, Meng-Chao Wu, Hong-Yang Wang, Lei Chen
BACKGROUND & AIMS: Choline kinase alpha (CHKA) catalyzes conversion of choline to phosphocholine and can contribute to carcinogenesis. Little is known about the role of CHKA in the pathogenesis of hepatocellular carcinoma (HCC). METHODS: We performed whole-exome and transcriptome sequence analyses of 9 paired HCC and non-tumor adjacent tissues. We performed tissue chip analyses of 120 primary HCC and non-tumor adjacent tissues from patients who received surgery in Shanghai, China from January 2006 through December 2009; 48 sets of specimens (HCC and non-tumor adjacent tissues) were also analyzed...
January 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28036295/identification-of-mtor-as-a-primary-resistance-factor-of-the-iap-antagonist-at406-in-hepatocellular-carcinoma-cells
#14
Mao-Chuan Zhen, Fu-Qiang Wang, Shao-Feng Wu, Yi-Lin Zhao, Ping-Guo Liu, Zhen-Yu Yin
Dysregulation of inhibitor of apoptosis (IAP) proteins (IAPs) in hepatocellular carcinoma (HCC) is often associated with poor prognosis. Here we showed that AT406, an IAP antagonist, was cytotoxic and pro-apoptotic to both established (HepG2, SMMC-7721 lines) and primary HCC cells. Activation of mTOR could be a key resistance factor of AT406 in HCC cells. mTOR inhibition (by OSI-027), kinase-dead mutation or knockdown remarkably enhanced AT406-induced lethality in HCC cells. Reversely, forced-activation of mTOR by adding SC79 or exogenous expressing a constitutively active S6K1 (T389E) attenuated AT406-induced cytotoxicity against HCC cells...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28018099/understanding-the-role-of-pin1-in-hepatocellular-carcinoma
#15
REVIEW
Chi-Wai Cheng, Ka-Wai Leong, Eric Tse
PIN1 is a peptidyl-prolyl cis/trans isomerase that binds and catalyses isomerization of the specific motif comprising a phosphorylated serine or threonine residue preceding a proline (pSer/Thr-Pro) in proteins. PIN1 can therefore induce conformational and functional changes of its interacting proteins that are regulated by proline-directed serine/threonine phosphorylation. Through this phosphorylation-dependent prolyl isomerization, PIN1 fine-tunes the functions of key phosphoproteins (e.g., cyclin D1, survivin, β-catenin and x-protein of hepatitis B virus) that are involved in the regulation of cell cycle progression, apoptosis, proliferation and oncogenic transformation...
December 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27998765/mir-223-modulates-hepatocellular-carcinoma-cell-proliferation-through-promoting-apoptosis-via-the-rab1-mediated-mtor-activation
#16
Zheng Dong, Ruizhao Qi, Xiaodong Guo, Xin Zhao, Yinyin Li, Zhen Zeng, Wenlin Bai, Xiujuan Chang, Liyan Hao, Yan Chen, Min Lou, Zhiwei Li, Yinying Lu
Hepatocellular carcinoma (HCC) is a common digestive malignancy. MiR-223, a well-identified miRNA, exhibits diverse properties in different cancers. In this study, we demonstrated that miR-223 could suppress cell growth and promote apoptosis in HepG2 and Bel-7402 HCC cell lines. We screened and identified a novel miR-223 target, Ras-related protein Rab-1(Rab1). Upregulation of miR-223 would specifically and markedly down-regulate Rab1 expression. In addition, miR-223-overexpressing subclones showed significant cell growth inhibition by increasing cell apoptosis in HepG2 and Bel-7402 cells...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27993818/long-noncoding-rna-malat1-promotes-hepatocellular-carcinoma-development-by-srsf1-upregulation-and-mtor-activation
#17
Pushkar Malakar, Asaf Shilo, Adi Mogilevsky, Ilan Stein, Eli Pikarsky, Yuval Nevo, Hadar Benyamini, Sharona Elgavish, Xinying Zong, Kannanganattu V Prasanth, Rotem Karni
Several long noncoding RNAs (lncRNA) are abrogated in cancer but their precise contributions to oncogenesis are still emerging. Here we report that the lncRNA MALAT1 is upregulated in hepatocellular carcinoma and acts as a proto-oncogene through Wnt pathway activation and induction of the oncogenic splicing factor SRSF1. Induction of SRSF1 by MALAT1 modulates SRSF1 splicing targets, enhancing the production of antiapoptotic splicing isoforms and activating the mTOR pathway by modulating the alternative splicing of S6K1...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/27974549/tsc1-2-mutations-define-a-molecular-subset-of-hcc-with-aggressive-behaviour-and-treatment-implication
#18
Daniel W H Ho, Lo K Chan, Yung T Chiu, Iris M J Xu, Ronnie T P Poon, Tan T Cheung, Chung N Tang, Victor W L Tang, Irene L O Lo, Polly W Y Lam, Derek T W Yau, Miao X Li, Chun M Wong, Irene O L Ng
OBJECTIVE: We investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate mutation-dependent mechanism of mTOR hyperactivation in hepatocarcinogenesis. DESIGN: We performed next-generation sequencing on human HCC samples and cell line panel. Systematic mutational screening of mTOR pathway-related genes was undertaken and mutant genes were evaluated based on their recurrence...
December 14, 2016: Gut
https://www.readbyqxmd.com/read/27959383/combination-of-metformin-and-sorafenib-suppresses-proliferation-and-induces-autophagy-of-hepatocellular-carcinoma-via-targeting-the-mtor-pathway
#19
Sunbin Ling, Lei Song, Ning Fan, Tingting Feng, Lu Liu, Xu Yang, Mingjie Wang, Yanling Li, Yu Tian, Feng Zhao, Ying Liu, Qihong Huang, Zhaoyuan Hou, Fei Xu, Lei Shi, Yan Li
The multi‑kinase inhibitor sorafenib is the only drug for which randomized control trials have shown improved patient survival in advanced hepatocellular carcinoma (HCC). However, life expectancy is extended in these cases by only a few months. The anti‑type II diabetes agent metformin was used in this study in an effort to find a more efficient approach to HCC treatment. Sorafenib effectively reversed the activation status of mTORC2 induced by metformin and enhanced the suppression of the mTORC1 and MAPK pathway by metformin in HCC cells, which may be responsible for reduced proliferation upon combined treatment...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27938509/sorafenib-and-2-deoxyglucose-synergistically-inhibit-proliferation-of-both-sorafenib-sensitive-and-resistant-hcc-cells-by-inhibiting-atp-production
#20
Ryan Reyes, Nissar A Wani, Kalpana Ghoshal, Samson T Jacob, Tasneem Motiwala
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. Sorafenib is the only first-line systemic drug for advanced HCC, but it has very limited survival benefits because patients treated with sorafenib either suffer from side effects or show disease progression after initial response. Thus, there is an urgent need to develop novel strategies for first-line and second-line therapies. The association between sorafenib resistance and glycolysis prompted us to screen several drugs with known antiglycolytic activity to identify those that will sensitize cells to sorafenib...
February 10, 2017: Gene Expression
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