Academic Journal
Clinical significance of CHD1L in hepatocellular carcinoma and therapeutic potentials of virus-mediated CHD1L depletion
العنوان: | Clinical significance of CHD1L in hepatocellular carcinoma and therapeutic potentials of virus-mediated CHD1L depletion |
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المؤلفون: | Guan, XY, Chen, L, Yuan, YF, Li, Y, Chan, THM, Zheng, BJ, Huang, J |
بيانات النشر: | //gut.bmjjournals.com/ United Kingdom |
سنة النشر: | 2011 |
المجموعة: | University of Hong Kong: HKU Scholars Hub |
مصطلحات موضوعية: | Medical sciences, Gastroenterology, DNA Helicases - genetics - metabolism - physiology, Carcinoma, Hepatocellular - drug therapy - metabolism, Apoptosis - drug effects, Antineoplastic Combined Chemotherapy Protocols - therapeutic use, Animals, Aged, Adult, Adenoviridae - genetics, Young Adult, Xenograft Model Antitumor Assays, Tumor Markers, Biological - metabolism, Tumor Cells, Cultured, Treatment Outcome, Neoplasm Proteins - genetics - metabolism - physiology, Prognosis, Retrospective Studies, Signal Transduction, Middle Aged, Mice, Nude, Liver Neoplasms - drug therapy - metabolism, Male, Humans, Genetic Vectors, Gene Therapy - methods |
الوصف: | Background: Hepatocellular carcinoma (HCC) is among the most lethal of human malignancies. It is difficult to detect early, has a high recurrence rate and is refractory to chemotherapies. Amplification of 1q21 is one of the most frequent genetic alterations in HCC. CHD1L is a newly identified oncogene responsible for 1q21 amplification. This study aims to investigate the role of CHD1L in predicting prognosis and chemotherapy response of patients with HCC, its chemoresistant mechanism and whether virus-mediated CHD1L silencing has therapeutic potentials for HCC treatment. Methods: The clinical significance of CHD1L in a cohort of 109 HCC cases including 50 cases who received transarterial chemoembolisation treatment was assessed by clinical correlation and Kaplan-Meier analyses. A CHD1L-overexpressing cell model was generated and the mechanism of chemoresistance involving CHD1L was investigated. An adenovirus-mediated silencing method was used to knockdown CHD1L, and its effects on tumorigenicity and chemoresistance were investigated in vivo and in vitro. Results: Overexpression of CHD1L was significantly associated with tumour microsatellite formation (p=0.045), advanced tumour stage (p=0.018), overall survival time (p=0.002), overall survival time of patients who received transarterial chemoembolisation treatment (p=0.028) and chemoresistance (p=0.020) in HCC. Interestingly, CHD1L could inhibit apoptosis induced by 5-fluorourail (5-FU) but not doxorubicin. The mechanistic study revealed that the involvement of the Nur77-mediated pathway in chemotherapeutic agent-induced apoptosis can dictate if CHD1L could confer resistance to chemotherapy. Furthermore, an adenoviral vector containing short hairpin RNAs against CHD1L (CHD1L-shRNAs) could suppress cell growth, clonogenicity and chemoresistance to 5-FU. An in vivo study found that CHD1L-shRNAs could inhibit xenograft tumour growth and increase the sensitivity of tumour cells to 5-FU in nude mice. Conclusions: This study highlighted for the first time the ... |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
تدمد: | 0017-5749 |
Relation: | Gut; Liver Transplantation Research Centre: A Multidisciplinary Study for Liver Graft Injury; http://www.scopus.com/mlt/select.url?eid=2-s2.0-79952532633&selection=ref&src=s&origin=recordpage; Gut, 2011, v. 60 n. 4, p. 534-543; 543; 188643; WOS:000288010600019; http://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0017-5749&volume=60&issue=4&spage=534&epage=543&date=2010&atitle=Clinical+significance+of+CHD1L+in+hepatocellular+carcinoma+and+therapeutic+potentials+of+virus-mediated+CHD1L+depletion; eid_2-s2.0-79952532633; 534; http://hdl.handle.net/10722/135283; 60 |
DOI: | 10.1136/gut.2010.224071 |
الاتاحة: | https://doi.org/10.1136/gut.2010.224071 http://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0017-5749&volume=60&issue=4&spage=534&epage=543&date=2010&atitle=Clinical+significance+of+CHD1L+in+hepatocellular+carcinoma+and+therapeutic+potentials+of+virus-mediated+CHD1L+depletion http://hdl.handle.net/10722/135283 |
Rights: | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. ; Gut. Copyright © B M J Publishing Group. |
رقم الانضمام: | edsbas.67949BF0 |
قاعدة البيانات: | BASE |
تدمد: | 00175749 |
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DOI: | 10.1136/gut.2010.224071 |