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The Sequence-Dependent Cytotoxic Effect of Trastuzumab in Combination With 5-Fluorouracil or Cisplatin on Gastric Cancer Cell Lines

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机构: [1]Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, China, [2]Cancer Center, Beijing 307 Hospital, Beijing, China, [3]State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China, [4]The Second Affiliated Hospital, Dalian Medical University, Dalian, China
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关键词: Trastuzumab 5-Fluorouracil Cisplatin Gastric cancer HER-2/neu

摘要:
The effect of trastuzumab on patients with HER-2/neu (HER2)-positive gastric cancer has been confirmed in a phase III clinical trial (ToGA study). However, the optimized sequence and synergic mechanism of trastuzumab and chemotherapy are not clear. Our study investigated the effects and mechanisms of trastuzumab in combination with 5-Fluorouracil (5-Fu) or cisplatin (DDP) on gastric cancer cell lines. Flow cytometry was used to determine HER2 expression and cell cycle. MTT assay was performed to evaluate cytotoxicity. Western blotting and RT-PCR were used to analyze signaling transduction and mRNA expression. Sequential 5-Fu followed by trastuzumab and trastuzumab plus DDP followed by trastuzumab produced the best inhibitory effects. Inhibition of HER2-PI3K-AKT signal transduction, downregulation of nucleotide excision repair cross-complementation 1 (ERCC1), and interference with cell cycle distribution may elucidate the synergism between trastuzumab and chemotherapy. These results provide some evidence for designing a rational regime when trastuzumab is being considered to be used in patients with gastric cancer.

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出版当年[2009]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
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出版当年[2008]版:
Q3 ONCOLOGY
最新[2023]版:
Q3 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2008版] 出版当年五年平均 出版前一年[2007版] 出版后一年[2009版]

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第一作者机构: [1]Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, China, [2]Cancer Center, Beijing 307 Hospital, Beijing, China,
通讯作者:
通讯机构: [*]Cancer Center, Beijing 307 Hospital 8 Dongdajie, Fengtai, Beijing 100071, China
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