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https://www.readbyqxmd.com/read/28087069/safety-tolerability-and-antiviral-effect-of-rg-101-in-patients-with-chronic-hepatitis-c-a-phase-1b-double-blind-randomised-controlled-trial
#1
Meike H van der Ree, J Marleen de Vree, Femke Stelma, Sophie Willemse, Marc van der Valk, Svend Rietdijk, Richard Molenkamp, Janke Schinkel, Ad C van Nuenen, Ulrich Beuers, Salah Hadi, Marten Harbers, Eva van der Veer, Kai Liu, John Grundy, Amy K Patick, Adam Pavlicek, Jacqueline Blem, Michael Huang, Paul Grint, Steven Neben, Neil W Gibson, Neeltje A Kootstra, Hendrik W Reesink
BACKGROUND: miR-122 is an important host factor for hepatitis C virus (HCV) replication. The aim of this study was to assess the safety and tolerability, pharmacokinetics, and antiviral effect of a single dose of RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated oligonucleotide that antagonises miR-122, in patients with chronic HCV infection with various genotypes. METHODS: In this randomised, double-blind, placebo-controlled, multicentre, phase 1B study, patients were randomly assigned to RG-101 or placebo (7:1)...
January 10, 2017: Lancet
https://www.readbyqxmd.com/read/28081155/evaluation-of-bufadienolides-as-the-main-antitumor-components-in-cinobufacin-injection-for-liver-and-gastric-cancer-therapy
#2
Xiaolu Wei, Nan Si, Yuefei Zhang, Haiyu Zhao, Jian Yang, Hongjie Wang, Lianmei Wang, Linyu Han, Baolin Bian
BACKGROUND: Cinobufacin injection, also known as huachansu, is a preparation form of Cinobufacini made from Cinobufacin extract liquid. Despite that Cinobufacin injection is shown to shrink liver and gastric tumors, improving patient survival and life quality, the effective components in Cinobufacin remain elusive. In this study, we aim to screen antitumor components from Cinobufacin injection to elucidate the most effective antitumor components for treatment of liver and gastric cancers...
2017: PloS One
https://www.readbyqxmd.com/read/28079796/serum-microrna-panel-for-early-diagnosis-of-the-onset-of-hepatocellular-carcinoma
#3
Ying Zhang, Tao Li, Yumin Qiu, Tao Zhang, Pengbo Guo, Xiaomin Ma, Qing Wei, Lihui Han
Unique change of circulating microRNAs (miRNAs) was recognized to occur in early oncogenesis, which conferred it the potential as biomarkers for early detection of cancer. However, its diagnostic capability for hepatocellular carcinoma (HCC) has not been fully understood. In this study, microarray analysis was applied to screen the initial candidate miRNA from both the supernatants of anoikis-resistant cellular models and the sera samples of HCC patients. The selected differentially expressed miRNAs were further verified in 115 HCC patients and 40 health controls by qRT-PCR...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28079114/discovering-potential-serological-biomarker-for-chronic-hepatitis-b-virus-related-hepatocellular-carcinoma-in-chinese-population-by-mal-associated-serum-glycoproteomics-analysis
#4
Tianhua Liu, Denghe Liu, Riqiang Liu, Hucong Jiang, Guoquan Yan, Wei Li, Lu Sun, Shu Zhang, Yinkun Liu, Kun Guo
The accuracy of current biomarkers for the diagnosis of hepatocellular carcinoma (HCC), especially chronic Hepatitis B Virus (HBV)-related HCC, is limited. Recent progress in glycoproteomics has provided a novel platform for screening novel serological biomarkers of HCC. In this study, lectin affinity chromatography by Maackia amurensis lectin (MAL) and iTRAQ combined with mass spectrometric analysis were performed to enrich and identify the glycoprotein fractions in serum samples from HBV-related HCC patients and from healthy controls...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28073423/-research-advances-in-application-of-isobaric-tags-for-relative-and-absolute-quantitation-in-proteomics-of-hepatocellular-carcinoma
#5
Y Z Qi, L S Chen, P Xu
Due to the features of strong heterogeneity, difficult early diagnosis, poor prognosis, and high fatality rate, hepatocellular carcinoma (HCC) has become an important disease which threatens the health of the Chinese population. Accurate early diagnosis is crucial to improving the success rate of liver cancer resection and reducing postoperative recurrence and metastasis, and its core is the screening and validation of biomarkers for early diagnosis. Isobaric tags for relative and absolute quantitation (iTRAQ) and stable isotope labeling with amino acids in cell culture are important parts of proteomics technology, and iTRAQ has become the most important technique in quantitative proteomics technology due to its advantages of high throughput, high quantitative accuracy, and no limitation by sample source...
December 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28073184/functional-lipidomics-palmitic-acid-impairs-hepatocellular-carcinoma-development-by-modulating-membrane-fluidity-and-glucose-metabolism
#6
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/28061012/serum-microrna-profiles-as-diagnostic-biomarkers-for-hbv-positive-hepatocellular-carcinoma
#7
Hao-Tu Zhu, Rong-Bin Liu, Ya-Yong Liang, Abdulbaqi M E Hasan, Hai-Yun Wang, Qiong Shao, Zi-Chen Zhang, Jing Wang, Cai-Yun He, Fang Wang, Jian-Yong Shao
BACKGROUND & AIMS: The discovery of effective and reliable biomarkers to detect hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC) at an early stage may improve the survival of HCC. The aim of this study was to establish serum microRNA (miRNA) profiles as diagnostic biomarkers for HBV-positive HCC. METHODS: We used deep sequencing to screen serum miRNAs in a discovery cohort (n=100). Quantitative polymerase chain reaction (qPCR) assays were then applied to evaluate the expression of selected miRNAs...
January 6, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28060762/eukaryotic-elongation-factor-2-is-a-prognostic-marker-and-its-kinase-a-potential-therapeutic-target-in-hcc
#8
Leona L Pott, Sascha Hagemann, Henning Reis, Kristina Lorenz, Thilo Bracht, Thomas Herold, Boris V Skryabin, Dominik A Megger, Julia Kälsch, Frank Weber, Barbara Sitek, Hideo A Baba
: Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis. Therefore kinases are valuable targets in cancer therapy. To this end we performed 2D differential gel electrophoresis and mass spectrometry analysis of phosphoprotein-enriched lysates of tumor and corresponding non-tumorous liver samples to detect differentially abundant phosphoproteins to screen for novel kinases as potential drug targets...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28055301/autophagy-orchestrates-adaptive-responses-to-targeted-therapy-in-endometrial-cancer
#9
Núria Eritja, Bo-Juen Chen, Ruth Rodríguez-Barrueco, Maria Santacana, Sònia Gatius, August Vidal, Maria Dolores Martí, Jordi Ponce, Laura Bergadà, Andree Yeramian, Mario Encinas, Joan Ribera, Jaume Reventós, Jeff Boyd, Alberto Villanueva, Xavier Matias-Guiu, Xavier Dolcet, David Llobet-Navàs
Targeted therapies in endometrial cancer (EC) using kinase inhibitors rarely result in complete tumor remission and are frequently challenged by the appearance of refractory cell clones, eventually resulting in disease relapse. Dissecting adaptive mechanisms is of vital importance to circumvent clinical drug resistance and improve the efficacy of targeted agents in EC. Sorafenib is an FDA-approved multitarget tyrosine and serine/threonine kinase inhibitor currently used to treat hepatocellular carcinoma, advanced renal carcinoma and radioactive iodine-resistant thyroid carcinoma...
January 5, 2017: Autophagy
https://www.readbyqxmd.com/read/28052399/molecular-trail-for-the-anticancer-behavior-of-a-novel-copper-carbohydrazone-complex-in-brca1-mutated-breast-cancer
#10
Rakesh Sathish Nair, Easwaran Potti Manoj, Ratheeshkumar Thankappan, Sivakumar Krishnankutty Chandrika, M R Prathapachandra Kurup, Priya Srinivas
Novel chelated metal complexes were synthesized from carbohydrazones and thiocarbohydrazones using metal-based drug designing platforms and their combination effect with Pb, a naphthaquinone were analyzed for anticancer activity in breast cancer cell lines. A panel of BRCA1 wild type and mutated breast cancer cells: MCF-7 (BRCA1(+) / ER(+) ), MDA-MB-231 (BRCA1(+) / ERα(-) ), HCC-1937 (BRCA1(-) / ERα(-) ), HCC1937/wt BRCA1, MX1 (BRCA1(-) / ERα(-) ) and MDA-MB-436 (BRCA1(-) / ERα(-) ) were screened for anti-cancer activity...
January 4, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28049764/the-scf%C3%AE-trcp-e3-ubiquitin-ligase-complex-targets-lipin1-for-ubiquitination-and-degradation-to-promote-hepatic-lipogenesis
#11
Kouhei Shimizu, Hidefumi Fukushima, Kohei Ogura, Evan C Lien, Naoe Taira Nihira, Jinfang Zhang, Brian J North, Ailan Guo, Katsuyuki Nagashima, Tadashi Nakagawa, Seira Hoshikawa, Asami Watahiki, Koji Okabe, Aya Yamada, Alex Toker, John M Asara, Satoshi Fukumoto, Keiichi I Nakayama, Keiko Nakayama, Hiroyuki Inuzuka, Wenyi Wei
The SCF(β-TRCP) E3 ubiquitin ligase complex plays pivotal roles in normal cellular physiology and in pathophysiological conditions. Identification of β-transducin repeat-containing protein (β-TRCP) substrates is therefore critical to understand SCF(β-TRCP) biology and function. We used a β-TRCP-phosphodegron motif-specific antibody in a β-TRCP substrate screen coupled with tandem mass spectrometry and identified multiple β-TRCP substrates. One of these substrates was Lipin1, an enzyme and suppressor of the family of sterol regulatory element-binding protein (SREBP) transcription factors, which activate genes encoding lipogenic factors...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28041651/ultrasound-surveillance-for-hepatocellular-carcinoma-service-evaluation-of-a-radiology-led-recall-system-in-a-tertiary-referral-centre-for-liver-diseases-in-the-uk
#12
C Farrell, A Halpen, T J S Cross, P D Richardson, P Johnson, E C Joekes
AIM: To review the radiology-led ultrasound (US) surveillance programme for the detection of hepatocellular carcinoma (HCC) in cirrhotic patients in a UK tertiary-referral centre. MATERIALS AND METHODS: The radiology information system was searched for patients who had undergone US for surveillance of cirrhosis from September 2009 to May 2013. Patient demographics and cirrhosis aetiology were documented. Data including numbers of surveillance scans, abnormal findings suspicious for HCC, subsequent radiological investigations, numbers of HCC and survival for HCC patients were recorded...
December 29, 2016: Clinical Radiology
https://www.readbyqxmd.com/read/28034876/an-indel-polymorphism-within-pre-mir3131-confers-risk-for-hepatocellular-carcinoma
#13
Chaoqun Wang, Lijuan Li, Zhixia Yin, Qing Zhang, Hua Zhao, Ruiyang Tao, Shouyu Wang, Shuxiang Hu, Yan He, Dayong Wang, Chengtao Li, Suhua Zhang, Jiejie Xu, Xinghong Jiang, Shaohua Zhu, Yuzhen Gao
Polymorphisms in pre-miRNAs may affect its expression, then have effect on its target mRNAs and be associated with cancer susceptibility. In this study, we evaluated the association of an indel polymorphism rs57408770 in pre-miR-3131 with hepatocellular carcinoma (HCC) susceptibility in a Chinese population. The contribution of rs57408770 to HCC risk was investigated in two independent case-control sets (1051 HCC and 1058 controls). Logistic regression analysis showed that the insertion allele of rs57408770 was significantly associated with an increased risk for HCC occurrence in both case-control studies...
December 29, 2016: Carcinogenesis
https://www.readbyqxmd.com/read/28031526/radiolabeled-the-novel-mab-4g1-for-immunospect-imaging-of-egfrviii-expression-in-preclinical-glioblastoma-xenografts
#14
Xujie Liu, Chengyan Dong, Jiyun Shi, Teng Ma, Zhongxia Jin, Bing Jia, Zhaofei Liu, Li Shen, Fan Wang
Epidermal growth factor receptor mutant III (EGFRvIII) is exclusively expressed in tumors, such as glioblastoma, breast cancer and hepatocellular carcinoma, but never in normal organs. Increasing evidence suggests that EGFRvIII has clinical significance in glioblastoma prognosis due to its enhanced tumorigenicity and chemo/radio resistance, thus the development of an imaging approach to early detect EGFRvIII expression with high specificity is urgently needed. To illustrate this point, we developed a novel anti-EGFRvIII monoclonal antibody 4G1 through mouse immunization, cell fusion and hybridoma screening and then confirmed its specificity and affinity by a serial of assays...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28027570/aldehyde-dehydrogenase-2-aldh2-opposes-hcc-progression-by-regulating-ampk-signaling
#15
Guojun Hou, Lei Chen, Gang Liu, Liang Li, Yuan Yang, He-Xin Yan, Hui-Lu Zhang, Jing Tang, Ying Cheng Yang, Ximeng Lin, Xin Chen, Gui Juan Luo, Yanjing Zhu, Shanhua Tang, Jin Zhang, Hui Liu, Qingyang Gu, Ling-Hao Zhao, Yixue Li, Lei Liu, Weiping Zhou, Hongyang Wang
: Potential biomarkers that can be used to determine prognosis and perform targeted therapies are urgently needed to treat patients with hepatocellular carcinoma (HCC). To meet this need, we performed a screen to identify functional genes associated with hepatocellular carcinogenesis and its progression at the transcriptome and proteome levels. We identified Aldehyde Dedydrogenase-2 (ALDH2) as a gene of interest for further study. ALDH2 levels were significantly lower at the mRNA and protein level in tumor tissues than in normal tissues, and they were even lower in tissues that exhibited increased migratory capacity...
December 27, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28012864/germline-and-somatic-dicer1-mutations-in-familial-and-sporadic-liver-tumors
#16
Stefano Caruso, Julien Calderaro, Eric Letouzé, Jean-Charles Nault, Gabrielle Couchy, Anais Boulais, Alain Luciani, Elie-Serge Zafrani, Paulette Bioulac-Sage, Olivier Seror, Sandrine Imbeaud, Jessica Zucman-Rossi
BACKGROUND & AIMS: Growing evidence suggests that genetic predisposition significantly increases the risk of hepatocellular carcinoma (HCC), independently from the presence of other risk factors. Here, we report a novel germline DICER1 mutation associated with familial recurrent liver tumors. Next, we aimed to investigate the contribution of constitutional and somatic DICER1 mutations on HCC occurrence. METHODS: We investigated two individuals of a family that developed recurrent well-differentiated hepatocellular tumors over the years...
December 21, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/28003720/role-of-diffusion-weighted-imaging-dwi-for-hepatocellular-carcinoma-hcc-detection-and-its-grading-on-3t-mri-a-prospective-study
#17
Shiva Shankar, Naveen Kalra, Anmol Bhatia, Radhika Srinivasan, Paramjeet Singh, Radha K Dhiman, Niranjan Khandelwal, Yogesh Chawla
BACKGROUND: Limited studies have evaluated the role of diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) for histologically grading the hepatocellular carcinoma (HCC). OBJECTIVE: To compare the efficacy of DWI with dynamic contrast enhanced magnetic resonance (DCEMR) in detection of HCC in cirrhosis, and to evaluate whether DWI can be used instead of DCEMR. METHODS: 20 patients of either sex with cirrhosis and suspected of having HCC on screening USG were included in this prospective study approved by the Institutional Ethics Committee...
December 2016: Journal of Clinical and Experimental Hepatology
https://www.readbyqxmd.com/read/27999186/lhbs-can-elevate-the-expression-of-mdr1-through-hif-1%C3%AE-in-patients-with-chb-infection-a-comparative-proteomic-study
#18
Shiying Li, Yixuan Yang, Xiangchun Ding, Min Yang, Sha She, Hong Peng, Xiaoming Xu, Xiaoping Ran, Sanglin Li, Peng Hu, Huaidong Hu, Dazhi Zhang, Hong Ren
BACKGROUND AND AIMS: Hepatitis B virus (HBV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC). To gain a better understanding of the pathogenesis of HBV infection, this study aimed to investigate the differentially expressed proteins (DEPs) in liver tissues from patients with chronic hepatitis B (CHB) infection. RESULTS: Seventy-one DEPs were identified. Overexpression of multi-drug resistance protein 1 (MDR1) was validated by RT-qPCR and western blot analyses...
December 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27998765/mir-223-modulates-hepatocellular-carcinoma-cell-proliferation-through-promoting-apoptosis-via-the-rab1-mediated-mtor-activation
#19
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...
December 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27989824/rapid-and-cost-effective-xenograft-hepatocellular-carcinoma-model-in-zebrafish-for-drug-testing
#20
Federica Tonon, Cristina Zennaro, Barbara Dapas, Michele Carraro, Massimo Mariotti, Gabriele Grassi
We developed a novel, rapid and cost-effective Zebrafish xenograft model of hepatocellular carcinoma (HCC) for drug screening in the disease. Following injection into the yolk sack of Zebrafish larvae of the human HCC cell line JHH6 stained by a vital dye, tumor mass growth was followed by fluorescence microscopy and by human Ki67 quantification. Tumor induced neo-angiogenesis was evaluated by alkaline phosphatase staining of the vessels, by using the Tg(fli1:EGFP)y(1) strain of Zebrafish and by the quantification of the zebrafish vascular endothelial growth factor and of its receptor...
October 29, 2016: International Journal of Pharmaceutics
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