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https://www.readbyqxmd.com/read/28323123/circumventing-intratumoral-heterogeneity-to-identify-potential-therapeutic-targets-in-hepatocellular-carcinoma
#1
Ao Huang, Xin Zhao, Xin-Rong Yang, Fu-Qiang Li, Xin-Lan Zhou, Kui Wu, Xin Zhang, Qi-Man Sun, Ya Cao, Hong-Mei Zhu, Xiang-Dong Wang, Huan-Ming Yang, Jian Wang, Zhao-You Tang, Yong Hou, Jia Fan, Jian Zhou
BACKGROUND AND AIMS: Intratumoral heterogeneity (ITH) challenges identifying mutations with target therapy potential whereas circulating cell-free DNAs (cfDNAs) in blood could possibly reflect the entire mutation spectrum in certain tumors. We investigated how to minimize the limit of ITH for profiling hepatocellular carcinoma (HCC). METHODS: Thirty-two multi-regional tumor samples from five patients were subjected to whole exome sequencing (WES) and targeted deep sequencing (TDS); matched preoperative cfDNAs were sequenced accordingly...
March 17, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28322443/all-trans-retinoic-acid-ameliorates-hepatic-stellate-cell-activation-via-suppression-of-thioredoxin-interacting-protein-expression
#2
Hiroki Shimizu, Toshiaki Tsubota, Keita Kanki, Goshi Shiota
Activation of hepatic stellate cells (HSCs) is the effector factor of hepatic fibrosis and hepatocellular carcinoma (HCC) development. Accumulating evidence suggests that retinoic acids (RAs), derivatives of vitamin A, contribute to prevention of liver fibrosis and carcinogenesis, however, regulatory mechanisms of RAs still remain exclusive. To elucidate RA signaling pathway, we previously performed a genome-wide screening of RA-responsive genes by in silico analysis of RA-response elements, and identified 26 RA-responsive genes...
March 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28321157/hsa-mir-183-is-frequently-methylated-and-related-to-poor-survival-in-human-hepatocellular-carcinoma
#3
Sumadi Lukman Anwar, Till Krech, Britta Hasemeier, Elisa Schipper, Nora Schweitzer, Arndt Vogel, Hans Kreipe, Reena Buurman, Britta Skawran, Ulrich Lehmann
AIM: To screen clinically relevant microRNAs (miRNAs) silenced by DNA methylation in human hepatocellular carcinoma (HCC). METHODS: Knockdown of DNA methyltransferases (DNMTs) using siRNAs and miRNA profiling in HCC cell lines were performed to identify DNA hypermethylation-mediated miRNA downregulation. Confirmation using individual quantitative real-time PCR (qRT-PCR) assays was then performed followed by DNA methylation quantification at the promoter of the miRNA genes...
March 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28302149/identification-and-interaction-analysis-of-key-genes-and-micrornas-in-hepatocellular-carcinoma-by-bioinformatics-analysis
#4
Tong Mou, Di Zhu, Xufu Wei, Tingting Li, Daofeng Zheng, Junliang Pu, Zhen Guo, Zhongjun Wu
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common liver malignancy worldwide. However, present studies of its multiple gene interaction and cellular pathways still could not explain the initiation and development of HCC perfectly. To find the key genes and miRNAs as well as their potential molecular mechanisms in HCC, microarray data GSE22058, GSE25097, and GSE57958 were analyzed. METHODS: The microarray datasets GSE22058, GSE25097, and GSE57958, including mRNA and miRNA profiles, were downloaded from the GEO database and were analyzed using GEO2R...
March 16, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28295457/hepatic-ifit3-predicts-interferon-%C3%AE-therapeutic-response-in-patients-of-hepatocellular-carcinoma
#5
Yingyun Yang, Ye Zhou, Jin Hou, Chunmei Bai, Zhenyang Li, Jia Fan, Irene O L Ng, Weiping Zhou, Huichuan Sun, Qiongzhu Dong, Joyce M F Lee, Chung-Mau Lo, Kwan Man, Yun Yang, Nan Li, Guoshan Ding, Yizhi Yu, Xuetao Cao
Adjuvant interferon-α (IFN-α) therapy is used to control certain types of cancer in clinics. For hepatocellular carcinoma (HCC), IFN-α therapy is effective in only a subgroup of HCC patients, therefore identifying biomarkers to predict the response to IFN-α therapy is of high significance and clinical utility. As the induced IFN-stimulated genes (ISGs) expression following IFN-α treatment plays pivotal roles in IFN-α effects, we screened ISGs expression in HCC tissues and found several ISGs were significantly decreased in HCC...
March 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28294533/evaluation-of-donor-workups-and-exclusions-in-a-single-center-experience-of-living-donor-liver-transplantation
#6
Adianto Nugroho, Ok-Kyung Kim, Kwang-Woong Lee, Sanghee Song, Hyeyoung Kim, Suk Kyun Hong, Kyung Chul Yoon, Hyo-Sin Kim, YoungRok Choi, Hae Won Lee, Nam-Joon Yi, Kyung-Suk Suh
The process of evaluating potential donors in liver transplantation is important to ensure donor safety and provide optimal recipient outcome. However, there has been no report about donor exclusion rates and reasons for such exclusion in Korea. In this study, we aimed to elucidate the outcomes of potential live liver donor evaluation in a major LDLT center. From July 2011 to June 2015, prospectively collected data of 726 potential donors for 588 matched recipients were subsequently evaluated. Among 726 potential donors, 374 potential donors (51...
March 14, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28291769/downregulation-of-mir-33a-5p-in-hepatocellular-carcinoma-a-possible-mechanism-for-chemotherapy-resistance
#7
Wei Meng, Yan Tai, Hui Zhao, Binsheng Fu, Tong Zhang, Wei Liu, Hua Li, Yang Yang, Qi Zhang, Yuliang Feng, Guihua Chen
BACKGROUND Multi-drug resistance is one of the major problems limiting the efficacy of cisplatin (CDDP) in treatment of hepatocellular carcinoma (HCC), and abnormal microRNA (miRNA) expression in drug-resistant cell lines plays an important role in liver cancer chemotherapy resistance. MATERIAL AND METHODS We established stable Hep3B and 97L HCC cell strains resistant to CDDP, both in vitro and in vivo. A combination of microRNA microarray and RT-qPCR experiments were used to screen differentially expressed miRNAs in HCC cell strains...
March 14, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28289104/scalp-hair-cortisol-for-diagnosis-of-cushing-s-syndrome
#8
Vincent L Wester, Martin Reincke, Jan Koper, Erica van den Akker, Laura Manenschijn, Christina Maria Berr, Julia Fazel, Yolanda de Rijke, Richard A Feelders, Elisabeth F C van Rossum
OBJECTIVE: Current first-line screening tests for Cushing's syndrome (CS) only measure time-point or short-term cortisol. Hair cortisol content (HCC) offers a non-invasive way to measure long-term cortisol exposure over several months of time. We aimed to evaluate HCC as a screening tool for CS. DESIGN: case-control study in two academic referral centers for CS Methods: Between 2009 and 2016, we collected scalp hair from patients suspected of CS and healthy controls...
March 13, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28288526/performance-of-khorana-risk-score-for-prediction-of-venous-thromboembolism-in-patients-with-hepatocellular-carcinoma
#9
Y Wang, B M Attar, H E Fuentes, J Yu, Huiyuan Zhang, A J Tafur
Cancer-associated venous thromboembolism (VTE) is one of the leading causes of mortality and morbidity among patients with malignancy. The Khorana risk score (KRS) is currently the best validated risk assessment model to stratify risks of VTE development in ambulatory patients with cancer. In the current study, we assessed the performance of KRS in patients with hepatocellular carcinoma (HCC). We retrospectively analyzed patients with diagnosis of HCC (screened by International Classification of Diseases [ ICD-9] and ICD-10 code, confirmed with radiographic examination and/or histopathology) at a large public hospital over 15 years (January 2000 through July 2015)...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28279846/design-synthesis-and-biological-evaluation-of-novel-4-anilinoquinazoline-derivatives-bearing-amino-acid-moiety-as-potential-egfr-kinase-inhibitors
#10
You-Guang Zheng, Jun Su, Cai-Yun Gao, Ping Jiang, Lin An, Yun-Sheng Xue, Jian Gao, Yi Liu
In this study, a series of 4-anilinoquinazoline derivatives bearing amino acid moiety were designed, synthesized and evaluated for biological activities. The synthesized compounds were screened for anticancer activity against human hepatocellular carcinoma cell HepG2 using SRB assay. In vitro cell growth inhibition assays indicated that compound 6m exhibited moderate inhibitory activities only against human hepatocellular carcinoma cells HepG2 with IC50 of 8.3 μM. Synthetic derivatives showed excellent selectivity, such as compound 6m demonstrated a strong inhibition of EGFR (IC50 = 0...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28279536/clinical-characteristics-of-hepatocellular-carcinoma-in-spain-comparison-with-the-2008-2009-period-and-analysis-of-the-causes-of-diagnosis-out-of-screening-programs-analysis-of-686-cases-in-73-centers
#11
Carlos Rodríguez de Lope, María Reig, Ana Matilla, María Teresa Ferrer, Eva Dueñas, Beatriz Mínguez, Javier F Castroagudín, Inmaculada Ortiz, Sonia Pascual, José Luis Lledó, Adolfo Gallego, Juan I Arenas, Carles Aracil, Montserrat Forne, Carolina Muñoz, Fernando Pons, Margarita Sala, Mercedes Iñarrairaegui, Marta Martin-Llahi, Victoria Andreu, Carmen Garre, Paloma Rendón, Javier Fuentes, Javier Crespo, Manuel Rodríguez, Jordi Bruix, María Varela
BACKGROUND AND OBJECTIVE: In 2010 we published that 53% of cases of hepatocellular carcinoma (HCC) detected in Spain were diagnosed outside the context of standard screening programs, which consequently leads to lower survival rates. The aim of this study was to analyze the current situation and the causes of diagnosis out of screening programs. MATERIAL AND METHODS: Prospective registry of 73 second- and third-level Spanish healthcare centers carried out between October 1, 2014 and January 31, 2015...
March 6, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28276727/evaluation-of-prothrombin-induced-by-vitamin-k-absence-macrophage-migration-inhibitory-factor-and-golgi-protein-73-versus-alpha-fetoprotein-for-hepatocellular-carcinoma-diagnosis-and-surveillance
#12
Manar M Ismail, Heba K Morsi, Nahla A B Abdulateef, Maissa K Noaman, Ghada A Abou El-Ella
Hepatocellular carcinoma (HCC) represents a challenging malignancy of worldwide importance. It is the third most common cause of cancer-related death globally as most patients present with unresectable disease. Alpha-fetoprotein (AFP) is the widely and solely used biomarker for HCC diagnosis; yet, its usefulness is hampered by low sensitivity and specificity. We aimed to identify more sensitive biomarkers for HCC diagnosis and a surveillance algorithm that may facilitate early detection of HCC. A total of 305 Egyptian and Saudi participants grouped as healthy controls, cancer controls, benign hepatic lesions, chronic viral hepatitis and HCC were included...
May 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28273073/src-2-mediated-coactivation-of-anti-tumorigenic-target-genes-suppresses-myc-induced-liver-cancer
#13
Shruthy Suresh, Deniz Durakoglugil, Xiaorong Zhou, Bokai Zhu, Sarah A Comerford, Chao Xing, Xian-Jin Xie, Brian York, Kathryn A O'Donnell
Hepatocellular carcinoma (HCC) is the fifth most common solid tumor in the world and the third leading cause of cancer-associated deaths. A Sleeping Beauty-mediated transposon mutagenesis screen previously identified mutations that cooperate with MYC to accelerate liver tumorigenesis. This revealed a tumor suppressor role for Steroid Receptor Coactivator 2/Nuclear Receptor Coactivator 2 (Src-2/Ncoa2) in liver cancer. In contrast, SRC-2 promotes survival and metastasis in prostate cancer cells, suggesting a tissue-specific and context-dependent role for SRC-2 in tumorigenesis...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28267620/cancer-associated-circulating-large-extracellular-vesicles-in-cholangiocarcinoma-and-hepatocellular-carcinoma
#14
Henrike Julich-Haertel, Sabine K Urban, Marcin Krawczyk, Arnulf Willms, Krzysztof Jankowski, Waldemar Patkowski, Beata Kruk, Maciej Krasnodębski, Joanna Ligocka, Robert Schwab, Ines Richardsen, Sebastian Schaaf, Angelina Klein, Sebastian Gehlert, Hanna Sänger, Markus Casper, Jesus M Banales, Detlef Schuppan, Piotr Milkiewicz, Frank Lammert, Marek Krawczyk, Veronika Lukacs-Kornek, Miroslaw Kornek
BACKGROUND AND AIMS: we previously reported that large extracellular vesicles, specifically AnnexinV(+)EpCAM(+)CD147(+) tumour-associated microparticles (taMPs), facilitate the detection of colorectal carcinoma (CRC), non-small cell lung carcinoma (NSCLC) as well as pancreas carcinoma (PaCa). Here we assess the diagnostic value of taMPs for detection and monitoring of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Specifically, we aim to differentiate liver taMPs from other cancer taMPs, such as CRC and NSCLC...
March 3, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28259962/downregulation-of-npm-reverses-multidrug-resistance-in-human-hepatoma-cells-via-inhibition-of-p-glycoprotein-expression
#15
Fei Luo, Huiyu Li, Jianfang Liang, Hongyan Jia, Xiaoyu Li, Hong Xiao, Xuehua He, Jiefeng He, Yanzhang Tian, Haoliang Zhao
Multidrug resistance (MDR) is an important issue in current cancer treatments. In human cancer, drug resistance is primarily associated with the overexpression of multidrug resistance gene 1 (MDR1). Therefore, the human MDR1 gene promoter may be a target for anti‑MDR drug screening. Numerous methods to prevent MDR have been investigated. However, they have been proven to be clinically ineffective. Therefore, the aim of the present study was to investigate whether downregulation of nucleophosmin (NPM) demonstrates any effects on the reversal of MDR in hepatocellular carcinoma (HCC) cells...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28259177/imaging-of-hepatocellular-carcinoma-and-image-guided-therapies-how-we-do-it
#16
REVIEW
Jonathon Willatt, Julie A Ruma, Shadi F Azar, Nara L Dasika, F Syed
Treatment options for hepatocellular carcinoma have evolved over recent years. Interventional radiologists and surgeons can offer curative treatments for early stage tumours, and locoregional therapies can be provided resulting in longer survival times. Early diagnosis with screening ultrasound is the key. CT and MRI are used to characterize lesions and determine the extent of tumour burden. Imaging techniques are discussed in this article as the correct imaging protocols are essential to optimise successful detection and characterisation...
March 4, 2017: Cancer Imaging: the Official Publication of the International Cancer Imaging Society
https://www.readbyqxmd.com/read/28255353/anti-cancer-activity-of-novel-tm4sf5-targeting-antibodies-through-tm4sf5-neutralization-and-immune-cell-mediated-cytotoxicity
#17
Hye-Mi Ahn, Jihye Ryu, Jin Myeong Song, Yunhee Lee, Hye-Jin Kim, Dongjoon Ko, Inpyo Choi, Sang Jick Kim, Jung Weon Lee, Semi Kim
The transmembrane four L6 family member 5 (TM4SF5) protein is a novel molecular target for the prevention and treatment of hepatocellular carcinoma. TM4SF5 is highly expressed in liver, colon, esophageal, and pancreatic cancers and is implicated in tumor progression. Here, we screened monoclonal antibodies that specifically bound to the extracellular loop 2 (EC2) of TM4SF5 from a phage-displayed murine antibody (single-chain variable fragment; scFv) library. We constructed and characterized chimeric antibodies, Ab27 and Ab79, of scFv fused with Fc domain of human IgG1...
2017: Theranostics
https://www.readbyqxmd.com/read/28253902/sulfasalazine-attenuates-evading-anticancer-response-of-cd133-positive-hepatocellular-carcinoma-cells
#18
Yeonhwa Song, Jaewoo Jang, Tae-Hoon Shin, Sang Mun Bae, Jin-Sun Kim, Kang Mo Kim, Seung-Jae Myung, Eun Kyung Choi, Haeng Ran Seo
BACKGROUND: CD133-positive cells in hepatocellular carcinoma (HCC) exhibit cancer stem cell (CSC)-like properties as well as resistance to chemotherapeutic agents and ionizing radiation; however, their function remains unknown. In this paper, we identified a hitherto unknown mechanism to overcome CD133-induced resistance to anticancer therapy. METHODS: We applied an alternative approach to enrich the CD133-positive HCC population by manipulating 3D culture conditions...
March 3, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28252637/hepatitis-c-virus-infection
#19
REVIEW
Michael P Manns, Maria Buti, Ed Gane, Jean-Michel Pawlotsky, Homie Razavi, Norah Terrault, Zobair Younossi
Hepatitis C virus (HCV) is a hepatotropic RNA virus that causes progressive liver damage, which might result in liver cirrhosis and hepatocellular carcinoma. Globally, between 64 and 103 million people are chronically infected. Major risk factors for this blood-borne virus infection are unsafe injection drug use and unsterile medical procedures (iatrogenic infections) in countries with high HCV prevalence. Diagnostic procedures include serum HCV antibody testing, HCV RNA measurement, viral genotype and subtype determination and, lately, assessment of resistance-associated substitutions...
March 2, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28249586/serum-lipid-profile-as-a-marker-of-liver-impairment-in-hepatitis-b-cirrhosis-patients
#20
Sadia Qamar Arain, Farah Naz Talpur, Naseem Aslam Channa, Muhammad Shahbaz Ali, Hassan Imran Afridi
BACKGROUND: Chronic HBV infection is a major cause of Cirrhosis and an important risk factor to develop hepatocellular carcinoma. The study is conducted to find out the changes in the lipid metabolism of HBV-cirrhosis patients. METHODS: In the present study, serum lipid profiles of patients with HBV-cirrhosis were assessed by utilizing micro-lab and gas chromatography, while risk factors for transmission of HBV-cirrhosis studied through the standard questionnaire...
March 1, 2017: Lipids in Health and Disease
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