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Tan X.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Tan X.,George Washington University | Wang H.,Peking University | Luo G.,Case Western Reserve University | And 6 more authors.
International Journal of Biological Sciences | Year: 2015

Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal adjacent tissues were collected at the time of surgery. DNA, RNA and protein samples were isolated from GC specimens and cell lines. Mutations were detected by PCR-RFLP/DHPLC and sequencing analysis. POLB gene expression was examined by RT-PCR, tissue microarray, Western blotting and immunofluorescence assays. The function of the mutation was evaluated by chemosensitivity, MTT, Transwell matrigel invasion and host cell reactivation assays. The T889C mutation was detected in 18 (10.17%) of 177 GC patients. And the T889C mutation was associated with POLB overexpression, lymph nodes metastases and poor tumor differentiation. In addition, patients with- the mutation had significantly shorter survival time than those without-, following postoperative chemotherapy. Furthermore, cell lines with T889C mutation in POLB gene were more resistant to the treatment of 5-fluorouracil, cisplatin and epirubicin than those with wild type POLB. Forced expression of POLB gene with T889C mutation resulted in enhanced cell proliferation, invasion and resistance to anticancer drugs, along with increased DNA repair capability. These results suggest that POLB gene with T889C mutation in surgically resected primary gastric tissues may be clinically useful for predicting responsiveness to chemotherapy in patients with GC. The POLB gene alteration may serve as a prognostic biomarker for GC. © Ivyspring International Publisher. Source


Dai N.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Xu D.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Zhong X.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Li L.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | And 3 more authors.
Journal of Thoracic Disease | Year: 2014

We have entered an open access publishing era. The impact and significance of open access is still under debate after two decades of evolution. Open access journals benefit researchers and the general public by promoting visibility, sharing and communicating. Non-mainstream journals should turn the challenge of open access into opportunity of presenting best research articles to the global readership. Open access journals need to optimize their business models to promote the healthy and continuous development. Source


Li Z.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Li Z.,Peking University | Zhu W.-G.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Zhu W.-G.,Peking University | Zhu W.-G.,Tsinghua University
International Journal of Biological Sciences | Year: 2014

Genetic abnormalities have been conventionally considered as hallmarks of cancer. However, studies over the past decades have demonstrated that epigenetic regulation also participates in the development of cancer. The fundamental patterns of epigenetic components, such as DNA methylation and histone modifications, are frequently altered in tumor cells. Acetylation is one of the best characterized modifications of histones, which is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are a group of enzymes which catalyze the removal of the acetyl groups of both histones and non-histone proteins. HDACs are involved in modulating most key cellular processes, including transcriptional regulation, apoptosis, DNA damage repair, cell cycle control, autophagy, metabolism, senescence and chaperone function. Because HDACs have been found to function incorrectly in cancer, various HDAC inhibitors are being investigated to act as cancer chemotherapeutics. The primary purpose of this paper is to summarize recent studies of the links between HDACs and cancer, and further discuss the underlying mechanisms of anti-tumor activities of HDAC inhibitors and clinical implications. © Ivyspring International Publisher. Source


Jin K.-M.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Gu J.,Peking University | Du X.-J.,Peking University | Xing B.-C.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education
Chinese Journal of Cancer Research | Year: 2010

Objective: To investigate cortactin expression in hepatocellular carcinoma (HCC) and explore its significance in the prognosis of HCC patients. Methods: Immunohistochemistry was performed for paraffin samples of 119 pairs of HCC tissues (HCCs) and paratumorous liver tissues (PTLTs) to evaluate cortactin expression. The cortactin expression difference in HCCs and PTLTs were analyzed by the McNemar's test. The relationship of cortactin expressions in HCCs and clinicopathologic factors was analyzed with Mann-Whitney U test. The Kaplan-Meier method and log-rank test were employed to compare the overall survival between Cortactin negative expression group, weak expression group and strong expression group. Expression of cortactin was further determined in 19 pairs of fresh HCCs and PTLTs specimens with Western blotting. Results: Cortactin expression rate was significantly higher in HCCs (53/119, 44.5%) than that in PTLTs (2/119, 1.7%) (P<0.001). The upregulated cortactin expression in HCCs was significantly correlated to absence of capsule formation (P=0.012), vascular invasion (P=0.037) and high Edmondson-Steiner grade (P=0.020), and predicted shorter overall survival. Western blotting demonstrated that cortactin expression was upregulated in 9 out of 19 HCCs (47.4%) compared to corresponding PTLTs. Conclusion: Cortactin expression is upregulated in HCC and is related to shorter overall survival of patients, suggesting that cortactin might play roles in the metastasis of HCC and predict a poor prognosis of HCC patients. © Chinese Anti-Cancer Association and Springer-Verlag Berlin Heidelberg 2010. Source


Bu Z.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Bu Z.,Peking University | Ji J.,Key Laboratory of Carcinogenesis and Translational Research Ministry of Education | Ji J.,Peking University
Current Cancer Drug Targets | Year: 2013

Gastric cancer remains one of the most common types of cancer worldwide, and most patients present with advanced disease. Sixty percent of these patients eventually relapse after curative surgical resection, and combination chemotherapy regimens only provide limited survival benefits. Mammalian target of rapamycin (mTOR) is a new target of cancer therapies. Preclinical data suggest that the suppression of the mTOR pathway inhibits the progression of gastric cancer in vitro and in animal models. In clinical trials, the mTOR inhibitor, everolimus, was well tolerated in phase I/II studies on patients with metastatic gastric cancer. The efficacy of everolimus was promising in a phase II clinical trial, but in a recently published phase III clinical trial everolimus monotherapy do not significantly improve the overall survival of patients with advanced gastric cancer who had been previously treated with one or two lines of systemic chemotherapy. Phosphoinositide 3-kinase/mTOR dual inhibitors have not yet entered early-stage clinical trials in patients with advanced gastric cancer. Further studies are needed to establish the role of mTOR inhibitors for the treatment of gastric cancer. © 2013 Bentham Science Publishers. Source

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