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https://www.readbyqxmd.com/read/29348495/preclinical-evaluation-of-antitumor-activity-of-the-proteasome-inhibitor-mln2238-ixazomib-in-hepatocellular-carcinoma-cells
#1
Giuseppa Augello, Martina Modica, Antonina Azzolina, Roberto Puleio, Giovanni Cassata, Maria Rita Emma, Caterina Di Sano, Antonella Cusimano, Giuseppe Montalto, Melchiorre Cervello
Hepatocellular carcinoma (HCC) is one of the common malignancies and is an increasingly important cause of cancer death worldwide. Surgery, chemotherapy, and radiation therapy extend the 5-year survival limit in HCC patients by only 6%. Therefore, there is a need to develop new therapeutic approaches for the treatment of this disease. The orally bioavailable proteasome inhibitor MLN2238 (ixazomib) has been demonstrated to have anticancer activity. In the present study, we investigated the preclinical therapeutic efficacy of MLN2238 in HCC cells through in vitro and in vivo models, and examined its molecular mechanisms of action...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29332449/mir-452-3p-a-potential-tumor-promoter-that-targets-the-cpeb3-egfr-axis-in-human-hepatocellular-carcinoma
#2
Hui Tang, Jianwen Zhang, Zhenyu Yu, Linsen Ye, Kun Li, Fan Ding, Xiao Feng, Wei Meng
PURPOSE: We proposed to investigate the effects of miR-452-3p on the proliferation and mobility of hepatocellular carcinoma (HCC) cells by targeting cytoplasmic polyadenylation element binding protein 3/estimated glomerular filtration rate (CPEB3/EGFR) axis. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect miR-452-3p expression in 84 pairs of HCC tissues and adjacent tissues. Luciferase reporter assay was employed to examine the relationship between miR-452-3p and CPEB3...
December 2017: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29332347/genetically-engineered-bone-marrow-derived-mesenchymal-stem-cells-co-expressing-ifn-%C3%AE-and-il-10-inhibit-hepatocellular-carcinoma-by-modulating-mapk-pathway
#3
Hao Wang, Jun Wang, Xiaolei Shi, Yitao Ding
PURPOSE: One of the major challenges in delivering cytokines for the treatment of hepatocellular carcinoma (HCC) is the mode of delivery. This study hypothesized that genetically engineered bone marrow derived mesenchymal stem cells (BMSCs) co-expressing IFN-γ and IL-10 can serve as a potential therapeutic strategy in the treatment of HCC by inhibiting cell proliferation. METHODS: Male Sprague-Dawley rats (n=5, 200-250 g) for BMSCs isolation and Nude/SCID mice (n=35,12-20g) to develop liver cancer xenograft model were used...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29285212/tumor-suppressive-effect-of-s-adenosylmethionine-supplementation-in-a-murine-model-of-inflammation-mediated-hepatocarcinogenesis-is-dependent-on-treatment-longevity
#4
Evgeniy Stoyanov, Lina Mizrahi, Devorah Olam, Temima Schnitzer-Perlman, Eithan Galun, Daniel S Goldenberg
Chronic inflammation precedes the majority of hepatocellular carcinoma (HCC) cases. We investigated the chemopreventive potential of S-adenosylmethionine (SAM), an essential donor for all methylation reactions in the cell, at the late precancerous stage of HCC development using the Mdr2-knockout (Mdr2-KO, Abcb4-/-) mice, a model of inflammation-mediated hepatocarcinogenesis. Previously, we revealed down-regulation of the genes regulating SAM metabolism in the liver of these mice at the precancerous stages. Now, we have supplied Mdr2-KO mice at the late precancerous stage with SAM during either a short-term (17 days) or a long-term (51 days) period and explored the effects of such supplementation on tumor development, DNA methylation and gene expression in the liver...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29214213/therapeutic-potential-of-arsenic-trioxide-ato-in-treatment-of-hepatocellular-carcinoma-role-of-oxidative-stress-in-ato-induced-apoptosis
#5
Erika B Dugo, Clement G Yedjou, Jacqueline J Stevens, Paul B Tchounwou
Hepatocellular carcinoma (HCC), the dominant form of primary liver cancer, is the sixth most common cancer in the world with more than 700,000 people diagnosed annually. Arsenic trioxide (ATO) has been shown to be a potent anticancer agent in various carcinomas, proving particularly effective in the clinical treatment of relapsed and refractory acute promyelocytic leukemia. However, its bioactivity and molecular mechanisms against HCC has not been fully studied. Using human HCC (HepG2) cells as a test model, we studied the effects of ATO and examined the role of oxidative stress (OS) and apoptosis in cytotoxicity...
2017: Annals of Clinical Pathology
https://www.readbyqxmd.com/read/29213215/cmtm5-is-downregulated-and-suppresses-tumour-growth-in-hepatocellular-carcinoma-through-regulating-pi3k-akt-signalling
#6
Gang Xu, Chengxue Dang
Background: Human chemokine like factor (CKLF)-like MAL and related proteins for vesicle trafficking transmembrane, domain-containing member 5 (CMTM5) has been shown to involved and may function as a tumour suppressor in tumorigenesis. The current study aimed to investigate the expression and function of CMTM5 in human hepatocellular carcinoma (HCC). Methods: CMTM5 expression was examined by immunohistochemistry, and its clinical significance was analysed in 76 HCC specimens...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29175329/inhibition-of-cip2a-attenuates-tumor-progression-by-inducing-cell-cycle-arrest-and-promoting-cellular-senescence-in-hepatocellular-carcinoma
#7
Xue Yang, Kai Qu, Jie Tao, Guozhi Yin, Shaoshan Han, Qingguang Liu, Hao Sun
CIP2A is a recent identified oncogene that inhibits protein phosphatase 2A (PP2A) and stabilizes c-Myc in cancer cells. To investigate the potential oncogenic role and prognostic value of CIP2A, we comprehensively analyzed the CIP2A expression levels in pan-cancer and observed high expression level of CIP2A in majority cancer types, including hepatocellular carcinoma (HCC). Based on a validation cohort including 60 HCC and 20 non-tumorous tissue samples, we further confirmed the high mRNA and protein expression levels of CIP2A in HCC, and found high CIP2A mRNA expression level was associated with unfavorable overall and recurrence-free survival in patients with HCC...
November 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29117881/downregulated-trophinin-associated-protein-plays-a-critical-role-in-human-hepatocellular-carcinoma-through-upregulation-of-tumor-cell-growth-and-migration
#8
Yifan Lian, Weiming Fan, Yanlin Huang, Hongbo Wang, Jialiang Wang, Liang Zhou, Xiaojuan Wu, Meihai Deng, Yuehua Huang
Trophinin Associated Protein (TROAP) was a protein first identified to mediate the process of embryo transplantation and later found to be involved in microtubule regulation. However, little is known about the role of TROAP in hepatocellular carcinoma (HCC). In the present study, we reported that both TROAP mRNA and protein expressions were downregulated in human HCC samples as well as cell lines. High level of TROAP was associated with small tumor size (P < 0.05), minor tumor nodules (P < 0.01) and mild vein invasion (P < 0...
November 8, 2017: Oncology Research
https://www.readbyqxmd.com/read/29093516/thyroid-hormone-inhibits-growth-of-hepatoma-cells-through-induction-of-mir-214
#9
Po-Shuan Huang, Yang-Hsiang Lin, Hsiang-Cheng Chi, Pei-Yu Chen, Ya-Hui Huang, Chau-Ting Yeh, Chia-Siu Wang, Kwang-Huei Lin
Thyroid hormone (TH) plays a role in regulating the metabolic rate, heart functions, muscle control and maintenance of bones. 3,3'5-tri-iodo-L-thyronine (T3) displays high affinity to nuclear thyroid hormone receptors (TRs), which mediate most TH actions. Recent studies have shown hypothyroidism in patients with an increased risk of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs), a class of non-protein-coding RNA, are suggested to control tumor growth by interacting with target genes. However, the clinical significance of T3/TR-regulated miRNAs in tumors has yet to be established...
November 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29080747/trip6-promotes-cell-proliferation-in-hepatocellular-carcinoma-via-suppression-of-foxo3a
#10
Wenhui Zhao, Yubin Dai, Ting Dai, Tian Xie, Xiaobo Su, Jing Li, Xiang Zhou, Kewei Meng, Xiaohui Zhao
Thyroid hormone receptor-interacting protein 6 (TRIP6), a member of LIM family, acts as an adaptor protein and is overexpressed in several tumor types. However, the clinical significance and biological role of TRIP6 in HCC remains unknown. In our study, we found that TRIP6 was markedly overexpressed in HCC cells and clinical specimens compared with normal hepatocytes and adjacent non-tumor tissues. Immunohistochemical and statistical analysis showed that the expression of TRIP6 significantly correlated with HCC patients' clinical stage and poor survival...
October 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29018945/-nuclear-her2-expression-in-hepatocytes-in-liver-disease
#11
REVIEW
P Döring, G M Pilo, D F Calvisi, F Dombrowski
BACKGROUND: Her2 is a well-known member of the epidermal growth factor receptor (EGFR) superfamily, a group of transmembrane receptors that mediate effects of proliferation and survival and thus play an important role in tumorigenesis. EGFRs can translocate to the nucleus and may mediate DNA repair and cell cycle arrest. OBJECTIVES: The aim of this study was to characterize hepatocellular Her2 expression in different liver diseases. MATERIALS AND METHODS: Her2 expression was analyzed by immunohistochemistry in 674 liver biopsies...
October 10, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28993733/lncrna-uc002mbe-2-interacting-with-hnrnpa2b1-mediates-akt-deactivation-and-p21-up-regulation-induced-by-trichostatin-in-liver-cancer-cells
#12
Ting Chen, Chengxin Gu, Cailin Xue, Tao Yang, Yun Zhong, Shiming Liu, Yuqiang Nie, Hui Yang
Long non-coding RNAs (lncRNAs) have been implicated in liver carcinogenesis. We previously showed that the induction of lncRNA-uc002mbe.2 is positively associated with the apoptotic effect of trichostatin A (TSA) in hepatocellular carcinoma (HCC) cells. The current study further analyzed the role of uc002mbe.2 in TSA-induced liver cancer cell death. The level of uc002mbe.2 was markedly increased by TSA in the cytoplasm of HCC cells. Knockdown of uc002mbe.2 prohibited TSA-induced G2/M cell cycle arrest, p21 induction, and apoptosis of Huh7 cells and reversed the TSA-mediated decrease in p-AKT...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28990231/ifi16-restoration-in-hepatocellular-carcinoma-induces-tumour-inhibition-via-activation-of-p53-signals-and-inflammasome
#13
Wei Lin, Zhiguang Zhao, Zhonglin Ni, Yaxin Zhao, Wenjun Du, Shijun Chen
OBJECTIVE: Interferon-inducible 16 (IFI16) is known to involve in p53-dependent tumour suppression and also the formation of inflammasome, which function, however, remains controversy during carcinogenesis as a pattern recognition receptor for tumour death-derived free DNA. In this study, we investigated the anti-tumour role of IFI16 in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Hepatocellular carcinoma tissues (n = 20) and corresponding non-neoplastic tissues (n = 20) were collected to determine the expression of IFI16...
October 8, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28978114/microrna-18a-promotes-proliferation-and-metastasis-in-hepatocellular-carcinoma-via-targeting-klf4
#14
Li Liu, Xun Cai, Enqiang Liu, Xia Tian, Chuan Tian
MicroRNAs (miRNAs) are short, non-coding and endogenous RNAs that played as important roles in the proliferation and metastasis of tumors. In this study, we determined the role of miR-18a in the regulation of HCC cell motility. We showed that miR-18a expression was upregulated in human HCC tissues and cell lines. Moreover, Elevated expression of miR-18a promoted the HCC cell proliferation and migration. KLF4 was identified as a direct target of miR-18a in HCC cells. Furthermore, overexpression of KLF4 attenuated the effects of miR-18a on the regulation of HCC cell motility...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977851/downregulation-of-serum-rab27b-confers-improved-prognosis-and-is-associated-with-hepatocellular-carcinoma-progression-through-pi3k-akt-p21-signaling
#15
Xue Yang, Xieqiong Ye, Le Sun, Fangyuan Gao, Yuxin Li, Xiaomin Ji, Xuejiang Wang, Ying Feng, Xianbo Wang
Previous study revealed that elevated expression of RAB27B in tissues is correlated with hepatocellular carcinoma (HCC) progression; however, the mechanisms involved in promoting HCC development are still unclear. Moreover, HCC tissues are not readily obtained during routine diagnosis. Therefore, to further explore its potential value in early diagnosis, we examined RAB27B expression in patient sera. First, the correlation between serum RAB27B expression and survival, as well as TNM and Barcelona Clinic Liver Cancer stages, were evaluated in patients with HCC...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969053/induction-of-socs3-by-liver-x-receptor-suppresses-the-proliferation-of-hepatocellular-carcinoma-cells
#16
Haojun Xiong, Yan Zhang, Shan Chen, Zhenhong Ni, Jintao He, Xinzhe Li, Bo Li, Kai Zhao, Fan Yang, Yijun Zeng, Bingbo Chen, Fengtian He
Liver X receptor (LXR), a member of nuclear receptor superfamily, is involved in the regulation of glucose, lipid and cholesterol metabolism. Recently, it has been reported that LXR suppress different kinds of cancers including hepatocellular carcinoma (HCC). However, the corresponding mechanism is still not well elucidated. In the present study, we found that activation of LXR downregulated cyclin D1 while upregulated p21 and p27 by elevating the level of suppressor of cytokine signaling 3 (SOCS3), leading to the cell cycle arrest at G1/S phase and growth inhibition of HCC cells...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938844/mcur1-mediated-mitochondrial-calcium-signaling-facilitates-cell-survival-of-hepatocellular-carcinoma-via-reactive-oxygen-species-dependent-p53-degradation
#17
Tingting Ren, Jiaojiao Wang, Hui Zhang, Peng Yuan, Jianjun Zhu, Yousheng Wu, Qichao Huang, Xu Guo, Jing Zhang, Lele Ji, Jibin Li, Hongxin Zhang, Hushan Yang, Jinliang Xing
AIMS: Levels of the mitochondrial calcium uniporter regulator 1 (MCUR1) increases during development of hepatocellular carcinoma (HCC). However, mechanisms of how mitochondrial Ca(2+) homeostasis is modulated and its function remain limited in cancers. RESULTS: MCUR1 was frequently upregulated in HCC cells to enhance the Ca(2+) uptake into mitochondria in an MCU-dependent manner, which significantly facilitated cell survival by inhibiting mitochondria-dependent intrinsic apoptosis and promoting proliferation of HCC cells, and thus led to poor prognosis...
November 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28935368/ube2t-promotes-hepatocellular-carcinoma-cell-growth-via-ubiquitination-of-p53
#18
Li-Ping Liu, Mei Yang, Quan-Zhou Peng, Ming-Yue Li, Yu-Sen Zhang, Yue-Hua Guo, Yang Chen, Shi-Yun Bao
Deregulation of Ubiquitin-conjugating enzyme E2T (UBE2T) contributes to the progression of human cancers. However, its clinical significance and role in hepatocellular carcinoma (HCC) remain unclear. Here, we show that UBE2T is up-regulated in HCC and exerts oncogenic activities via ubiquitination of p53. High UBE2T expression was correlated with higher pathological grade, advanced TNM stage, tumor vascular invasion, and poor overall and disease-free survivals in two independent cohorts containing 827 patients with HCC...
November 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28919514/hz-6d-targeted-herc5-to-regulate-p53-isgylation-in-human-hepatocellular-carcinoma
#19
Yang Wang, Qi Ding, Tao Xu, Chang-Yao Li, Dan-Dan Zhou, Lei Zhang
Manipulating the posttranslational modulator of p53 is central in the regulation of its activity and function. ISGylated p53 can be degraded by the 20S proteasome. During this process, HERC5/Ceb1, an IFN-induced HECT-type E3 ligase, mediated p53 ISGylation. In this study, we indicated that HERC5 was over-expressed in both HCC tissue samples and cell lines. Knockdown of HERC5 significantly induced the expression of p53, p21 and Bax/Bcl-2 in HCC cells, resulting in apoptosis augment. Whereas, opposite results were obtained by using HERC5 over-expression...
November 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28903351/preoperative-transcatheter-arterial-chemotherapy-may-suppress-oxidative-stress-in-hepatocellular-carcinoma-cells-and-reduce-the-risk-of-short-term-relapse
#20
Hao Su, Guangzhi Zhu, Ketut Indra Djaja P, Yi Lin, Yizhen Gong, Xiaoguang Liu, Jiaquan Li, Zhiming Liu, Xiao Qin, Lequn Li, Tangwei Liu, Zili Lu, Minyi Wei, Lunan Yan, Cheryl Ann Winkler, Stephen J O'Brien, Jing Li, Kaiyin Xiao, Tao Peng
In this study, we aim to investigate oxidative stress in hepatocellular carcinoma (HCC) tissues in patients receiving preoperative transcatheter arterial chemotherapy (TAC) and its association with prognosis. A total of 89 HCC patients enrolled in this study, 39 received preoperative TAC 1 week before surgery (pTAC group) and 50 did not (non-pTAC group). All patients underwent hepatectomy and postoperative TAC and were followed up to 400 weeks. Samples of liver tissue without HCC and hepatitis (n = 15) served as normal controls...
August 15, 2017: Oncotarget
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