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Hepatocellular carcinoma mtor

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https://www.readbyqxmd.com/read/27906498/st3gal6-mediates-the-effect-of-mir-26a-on-cell-growth-migration-and-invasion-in-hepatocellular-carcinoma-via-the-akt-mtor-pathway
#1
Mingming Sun, Xuzi Zhao, Leilei Liang, Xufeng Pan, Hao Lv, Yongfu Zhao
Aberrant sialylation profiles on the cell surface have been recognized for their potential diagnostic value in identifying the regulation of tumor properties in several cancers, including hepatocellular carcinoma (HCC). Recently, increasing evidence has suggested that the deregulation of microRNA (miRNA) is a common feature in human cancers. In this study, we found obvious up-regulation of ST3GAL6 both in HCC cell lines and in tissue samples. The altered expression of ST3GAL6 was found to correlate with cell proliferation, migration and invasion ability in HCC...
December 1, 2016: Cancer Science
https://www.readbyqxmd.com/read/27884331/inhibition-of-acquired-resistance-hepatocellular-carcinoma-cell-growth-by-combining-sorafenib-with-phosphoinositide-3-kinase-and-rat-sarcoma-inhibitor
#2
Chang-Hao Wu, Xiang Wu, Hong-Wei Zhang
BACKGROUND: To provide support for combined usage of phosphoinositide 3-kinase (PI3K) inhibitors or mitogen-activated protein kinase pathway inhibitors together with sorafenib in treatment of sorafenib-resistant hepatocellular carcinoma. MATERIALS AND METHODS: The sorafenib-resistant cell lines were established to evaluate the effects of MK-2206 2HCL, a dual PI3K/mammalian target of rapamycin (mTOR) inhibitor, and PD0325901, an rat sarcoma (RAS) and/or extracellular signal-regulated kinase (ERK) inhibitor, on cell proliferation and apoptosis, as both single and combined treatments with sorafenib...
December 2016: Journal of Surgical Research
https://www.readbyqxmd.com/read/27871897/sauchinone-exerts-anticancer-effects-by-targeting-ampk-signaling-in-hepatocellular-carcinoma-cells
#3
Young Woo Kim, Eun Jeong Jang, Chang-Hyun Kim, Ju-Hee Lee
Sauchinone is a pharmacologically active compound isolated from Saururus chinensis, which has been used as a traditional Oriental medicine to treat fever, jaundice, and various inflammatory diseases. In this study, we investigated the effect of sauchinone against hepatocellular carcinoma (HCC) and sought to elucidate the mechanism involved. Cell viability was measured by an MTT assay. Cell cycle distributions and the mitochondrial membrane potential were analyzed using flow cytometry. Cell death was analyzed by annexin V assay, 4',6-diamidino-2-phenylindole staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay...
November 18, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27863926/combination-of-temsirolimus-and-adriamycin-exhibits-an-enhanced-antitumor-effect-in-hepatocellular-carcinoma
#4
Hong-Gang Kang, Bao-Zhong Wang, Jing Zhang, Mei-Rong Liu, Ying-Xue Li
OBJECTIVE: The oncogenic PI3K/Akt/mTOR pathway is frequently activated in hepatocellular carcinoma (HCC). The aim of this study is to investigate the anti-HCC effect of combination of temsirolimus, an mTOR inhibitor, and adriamycin, a routinely used drug for treating HCC. METHODS AND MATERIALS: Proliferation of HCC cells exposure to temsirolimus, adriamycin, and their combination was determined using MTT assay in vitro as well as in a nude mice model in vivo. Cell apoptosis was examined using flow cytometry...
November 15, 2016: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/27818634/oncological-impact-of-m-tor-inhibitor-immunosuppressive-therapy-after-liver-transplantation-for-hepatocellular-carcinoma-review-of-the-literature
#5
REVIEW
Giuseppe Tarantino, Paolo Magistri, Roberto Ballarin, Raffaele Di Francia, Massimiliano Berretta, Fabrizio Di Benedetto
Background: Hepatocellular Carcinoma (HCC) represents the fifth most common malignancy and the third cancer-related cause of death worldwide. Hepatitis B (HBV) and C (HCV) viral infections and alcohol abuse are the principal etiological factors for HCC. Liver transplantation (LT) is oncologically the preferable approach to HCC, as it can remove all the intrahepatic tumor foci, and also the oncogenic cirrhotic liver. The use of mTOR inhibitors (mTORi) for immunosuppression after LT for HCC has been proposed due to rapamycin antitumor activity...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27808117/evaluation-of-uttroside-b-a-saponin-from-solanum-nigrum-linn-as-a-promising-chemotherapeutic-agent-against-hepatocellular-carcinoma
#6
Lekshmi R Nath, Jaggaiah N Gorantla, Arun Kumar T Thulasidasan, Vinod Vijayakurup, Shabna Shah, Shabna Anwer, Sophia M Joseph, Jayesh Antony, Kollery Suresh Veena, Sankar Sundaram, Udaya K Marelli, Ravi S Lankalapalli, Ruby John Anto
We report, for the first time, the remarkable efficacy of uttroside B, a potent saponin from Solanum nigrum Linn, against liver cancer. The compound has been isolated and characterized from the leaves of Solanum nigrum Linn, a plant widely used in traditional medicine and is a rich resource of several anticancer molecules. Uttroside B, that comprises of β-D-glucopyranosyl unit at C-26 of the furostanol and β-lycotetraosyl unit at C-3, is ten times more cytotoxic to the liver cancer cell line, HepG2 (IC50: 0...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27807662/c2-ceramide-enhances-sorafenib-induced-caspase-dependent-apoptosis-via-pi3k-akt-mtor-and-erk-signaling-pathways-in-hcc-cells
#7
Shanshan Jiang, Qian Wang, Meiqing Feng, Jiyang Li, Zhongbin Guan, Duopeng An, Mengxue Dong, Yuzhe Peng, Kudelaidi Kuerban, Li Ye
Sorafenib as an effective multikinase inhibitor has been approved for the clinical treatment against advanced hepatocellular carcinoma (HCC). HCC treatment requires usually combined therapy because of its complex pathogenesis. Ceramide has been confirmed to induce remarkable apoptosis in human tumor cells and has attracted increasing attention in investigations on combination therapy. In this paper, the anti-HCC effect of sorafenib combined with C2-ceramide was investigated on cell vitality, apoptosis, and migration, and the underlying mechanism was examined using flow cytometry and western blot...
November 2, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27807479/everolimus-and-malignancy-after-solid-organ-transplantation-a-clinical-update
#8
REVIEW
Hallvard Holdaas, Paolo De Simone, Andreas Zuckermann
Malignancy after solid organ transplantation remains a major cause of posttransplant mortality. The mammalian target of rapamycin (mTOR) inhibitor class of immunosuppressants exerts various antioncogenic effects, and the mTOR inhibitor everolimus is licensed for the treatment of several solid cancers. In kidney transplantation, evidence from registry studies indicates a lower rate of de novo malignancy under mTOR inhibition, with some potentially supportive data from randomized trials of everolimus. Case reports and small single-center series have suggested that switch to everolimus may be beneficial following diagnosis of posttransplant malignancy, particularly for Kaposi's sarcoma and nonmelanoma skin cancer, but prospective studies are lacking...
2016: Journal of Transplantation
https://www.readbyqxmd.com/read/27803295/strong-antineoplastic-effects-of-metformin-in-preclinical-models-of-liver-carcinogenesis
#9
François Cauchy, Mouniya Mebarki, Benjamin Leporq, Samira Laouirem, Miguel Albuquerque, Simon Lambert, Pierre Bourgoin, Olivier Soubrane, Bernard van Beers, Sandrine Faivre, Pierre Bedossa, Valerie Paradis
Studies suggest that metformin, widely used for treating type 2 diabetes, possesses innate antineoplastic properties. For metabolic syndrome patients with hepatocellular carcinoma, metformin may provide antitumoral effects  We evaluated the impact of metformin on tumor growth and visceral fat composition using relevant preclinical models of metabolic syndrome.  EXPERIMENTAL DESIGN: Studies were performed in three hepatoma cell lines, in HepG2 xenograft mice fed with standard chow-diet (SC), 60% high-fat diet (HFD) or 30% fructose diet (FR), and an ex vivo model of human cultured hepatocellular carcinoma slices...
November 1, 2016: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27802188/metformin-enhances-the-radiosensitivity-of-human-liver-cancer-cells-to-%C3%AE-rays-and-carbon-ion-beams
#10
Eun Ho Kim, Mi-Sook Kim, Yoshiya Furusawa, Akiko Uzawa, Soorim Han, Won-Gyun Jung, Sei Sai
The purpose of this study was to investigate the effect of metformin on the responses of hepatocellular carcinoma (HCC) cells to γ-rays (low-linear energy transfer (LET) radiation) and carbon-ion beams (high-LET radiation). HCC cells were pretreated with metformin and exposed to a single dose of γ-rays or carbon ion beams. Metformin treatment increased radiation-induced clonogenic cell death, DNA damage, and apoptosis. Carbon ion beams combined with metformin were more effective than carbon ion beams or γ-rays alone at inducing subG1 and decreasing G2/M arrest, reducing the expression of vimentin, enhancing phospho-AMPK expression, and suppressing phospho-mTOR and phospho-Akt...
October 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27779641/akt-mtor-signaling-pathway-is-involved-in-salvianolic-acid-b-induced-autophagy-and-apoptosis-in-hepatocellular-carcinoma-cells
#11
Ling Gong, Chunhong Di, Xiaofang Xia, Jie Wang, Gongying Chen, Junping Shi, Pengshuai Chen, Hui Xu, Weibing Zhang
Chinese medicines are emerging as an attractive new generation of anticancer drugs. Here, we explored the impact of salvianolic acid B (Sal B), the major water-soluble compounds of Danshen, on apoptosis and autophagy of human hepatocellular carcinoma cells (HCC). We also investigated the related molecular mechanisms. We found that Sal B exhibits potent ability to inhibit HCC cells viability in a concentration-dependent manner, and to induce apoptosis via the mitochondrial apoptosis pathway. Additionally, Sal B could also induce autophagy...
October 24, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27773936/a-novel-matrine-derivate-inhibits-differentiated-human-hepatoma-cells-and-hepatic-cancer-stem-like-cells-by-suppressing-pi3k-akt-signaling-pathways
#12
Ying Liu, Yang Qi, Zhi-Hui Bai, Chen-Xu Ni, Qi-Hui Ren, Wei-Heng Xu, Jing Xu, Hong-Gang Hu, Lei Qiu, Jian-Zhong Li, Zhi-Gao He, Jun-Ping Zhang
AIM: Matrine is an alkaloid extracted from a Chinese herb Sophora flavescens Ait, which has shown chemopreventive potential against various cancers. In this study, we evaluated the anticancer efficacy of a novel derivative of matrine, (6aS, 10S, 11aR, 11bR, 11cS)-10- methylamino-dodecahydro- 3a,7a-diaza-benzo (de) (MASM), against human hepatocellular carcinoma (HCC) cells and their corresponding sphere cells in vitro and in vivo. METHODS: Human HCC cell lines (Hep3B and Huh7) were treated with MASM...
October 24, 2016: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/27770558/expression-of-scavenger-receptor-ai-promotes-alternative-activation-of-murine-macrophages-to-limit-hepatic-inflammation-and-fibrosis
#13
Adam C Labonte, Sun-Sang J Sung, Lucas T Jennelle, Aditya P Dandekar, Young S Hahn
: The liver maintains an immunologically tolerant environment as a result of continuous exposure to food and bacterial constituents from the digestive tract. Hepatotropic pathogens can take advantage of this niche and establish lifelong chronic infections causing hepatic fibrosis and hepatocellular carcinoma. Macrophages (Mϕ) play a critical role in regulation of immune responses to hepatic infection and regeneration of tissue. However, the factors crucial for Mϕ in limiting hepatic inflammation or resolving liver damage have not been fully understood...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27756618/autophagy-prevention-sensitizes-akti-1-2-induced-anti-hepatocellular-carcinoma-cell-activity-in-vitro-and-in-vivo
#14
Qi Zhang, Manyi Yang, Zhan Qu, Jixiang Zhou, Qin Jiang
Molecule-targeted therapy has become the research focus for hepatocellular carcinoma (HCC). Persistent PI3K-AKT activation is often detected in HCC, representing a valuable oncotarget for treatment. Here, we tested the anti-HCC activity by a potent AKT inhibitor: AKT inhibitor 1/2 (AKTi-1/2). In both established (HepG2 and Huh-7) and primary human HCC cells, treatment with AKTi-1/2 inhibited cell survival and proliferation, but induced cell apoptosis. AKTi-1/2 blocked AKT-mTOR activation, yet simultaneously provoked cytoprotective autophagy in HCC cells...
October 15, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27751352/loss-of-tuberous-sclerosis-complex-2-tsc2-as-a-predictive-biomarker-of-response-to-mtor-inhibitor-treatment-in-patients-with-hepatocellular-carcinoma
#15
Jinhyun Cho, Jeeyun Lee, Jusun Kim, Seung Tae Kim, Sujin Lee, Sun Young Kim, Sang Yun Ha, Cheol-Keun Park, Ho Yeong Lim
BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death globally. Mechanistic target of rapamycin (mTOR) is frequently up-regulated in HCC and plays an important role in HCC tumorigenesis. Tumors with loss of tuberous sclerosis complex 2 (TSC2), a negative regulator of mTOR signaling, tend to respond well to mTOR inhibitors. We analyzed TSC2 expression status in Korean patients with HCC and evaluated the correlation between TSC2 loss and response to the mTOR inhibitor, everolimus...
October 2016: Translational Oncology
https://www.readbyqxmd.com/read/27711074/p300-cbp-associated-factor-pcaf-inhibits-the-growth-of-hepatocellular-carcinoma-by-promoting-cell-autophagy
#16
Yu-Li Jia, Meng Xu, Chang-Wei Dou, Zhi-Kui Liu, Yu-Mo Xue, Bo-Wen Yao, Ling-Long Ding, Kang-Sheng Tu, Xin Zheng, Qing-Guang Liu
Aberrant autophagic processes have been found to have fundamental roles in the pathogenesis of different kinds of tumors, including hepatocellular carcinoma (HCC). P300/CBP-associated factor (PCAF), a histone acetyltransferase (HAT), performs its function by acetylating both histone and non-histone proteins. Our previous studies showed that PCAF was downregulated in HCC tissues and its high expression was significantly associated with patient survival after surgery, serving as a prognostic marker. In this study we found that overexpression of PCAF induced autophagy of HCC cells and its knockdown depressed autophagy...
October 6, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27698829/microrna-486-5p-enhances-hepatocellular-carcinoma-tumor-suppression-through-repression-of-igf-1r-and-its-downstream-mtor-stat3-and-c-myc
#17
Rana Ahmed Youness, Hend Mohamed El-Tayebi, Reem Amr Assal, Karim Hosny, Gamal Esmat, Ahmed Ihab Abdelaziz
The insulin-like growth factor (IGF)-axis has been paradigmatically involved in hepatocellular carcinoma (HCC) tumor initiation, progression and drug resistance. Consequently, members of the IGF-axis and most importantly, IGF-1 receptor (IGF-1R) have been considered as intriguing targets for HCC therapy. Few miRNAs have been recently reported to be associated with IGF-1R regulation. The present study aimed to investigate the role of microRNA (miRNA/miR)-486-5p in the regulation of IGF-1R and its downstream signaling cascades...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27696512/melatonin-prevents-deregulation-of-the-sphingosine-kinase-sphingosine-1-phosphate-signaling-pathway-in-a-mouse-model-of-diethylnitrosamine-induced-hepatocellular-carcinoma
#18
Diana I Sánchez, Bárbara González-Fernández, Beatriz San-Miguel, Juan Ortiz de Urbina, Irene Crespo, Javier González-Gallego, María J Tuñón
The sphingosine kinase (SphK)/sphingosine1-phosphate (S1P) pathway is involved in multiple biological processes, including carcinogenesis. Melatonin shows beneficial effects in cell and animal models of hepatocellular carcinoma (HCC), but it is unknown if they are associated with the modulation of the SphK/S1P system, along with different downstream signaling pathways modified in cancer. We investigated effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight i.p) once a week for 8 weeks...
October 1, 2016: Journal of Pineal Research
https://www.readbyqxmd.com/read/27678524/a-microtubule-inhibitor-abt-751-induces-autophagy-and-delays-apoptosis-in-huh-7-cells
#19
Ren-Jie Wei, Su-Shuan Lin, Wen-Ren Wu, Lih-Ren Chen, Chien-Feng Li, Han-De Chen, Chien-Ting Chou, Ya-Chun Chen, Shih-Shin Liang, Shang-Tao Chien, Yow-Ling Shiue
The objective was to investigate the upstream mechanisms of apoptosis which were triggered by a novel anti-microtubule drug, ABT-751, in hepatocellular carcinoma-derived Huh-7 cells. Effects of ABT-751 were evaluated by immunocytochemistry, flow cytometric, alkaline comet, soft agar, immunoblotting, CytoID, green fluorescent protein-microtubule associated protein 1 light chain 3 beta detection, plasmid transfection, nuclear/cytosol fractionation, coimmunoprecipitation, quantitative reverse transcription-polymerase chain reaction, small-hairpin RNA interference and mitochondria/cytosol fractionation assays...
September 24, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27648358/targeting-pcdh20-gene-by-microrna-122-confers-5-fu-resistance-in-hepatic-carcinoma
#20
Wei Wang, Wen Bin Liu, Da Bing Huang, Wei Jia, Chu Shu Ji, Bing Hu
Drug resistance is one of the main hurdles for the successful treatment of hepatic carcinoma. However, the detailed mechanisms underlying resistance remain largely unknown and therapeutic approaches are limited. In the present study, we show that miR-122 confers resistance to 5-fluorouracil induced hepatocellular carcinoma cell apoptosis in vitro and reduces the potency of 5-fluorouracil in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicate that miR-122 modulates drug resistance through down-regulation of expression of PCDH20, which belongs to the protocadherin gene family and negatively regulates Akt activation...
2016: American Journal of Cancer Research
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