p53 mutation, but not in vitro predictor genes of therapeutic efficacy of cisplatin, is clinically relevant in comparing partial and complete responder cases of maxillary squamous cell carcinoma

p53 mutation, but not in vitro predictor genes of therapeutic efficacy of cisplatin, is clinically relevant in comparing partial and complete responder cases of maxillary squamous cell carcinoma
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DOI:
10.3892/or_00000929
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发表时间:
2010-10-01
期刊:
影响因子:
4.2
通讯作者:
Ikeda, Minoru
Ikeda, Minoru
中科院分区:
医学3区
文献类型:
--
作者:
Kudo, Itsuhiro;Esumi, Mariko;Ikeda, Minoru

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为了预测顺铂和放射治疗对上颌鳞状细胞癌的疗效,我们检测了14个顺铂耐药基因的mRNA表达和p53突变,从患者开始治疗前活检标本。10例患者中有5例p53基因突变,其中4例在放化疗后病理学上有残留肿瘤(p=0.0476)。在检测的14个基因中,ATP 7 B的mRNA表达在对放化疗耐药的病例中显著降低。多药耐药蛋白1(MDR-1)、多药耐药相关蛋白1(MRP-1)、Cu++转运β多肽(ATP 7 B)、着色性干皮病互补组A(XPA)、切除修复交叉互补啮齿类修复缺陷互补组1(ERCC-1)和B细胞CLL/淋巴瘤2(BCL 2)等6个基因在复发癌中表达下调。这些结果表明,p53突变的评估提供了最有用的预测治疗效果。在应答者病例中,通过培养在细胞系中确定的耐药基因不一定转化为临床相关性。
To predict the efficacy of cisplatin and radiation therapy for maxillary squamous cell carcinoma, we examined the mRNA expression of 14 cisplatin-resistant genes and p53 mutation in specimens biopsied from patients prior to initiation of therapy. Five of 10 patients had mutations in the p53 gene, of whom four had residual tumors pathologically following chemoradiotherapy (p=0.0476). Of 14 genes examined, the mRNA expression of ATP7B was significantly lower in cases that were resistant to chemoradiotherapy. Six genes including multidrug resistance protein 1 (MDR-1), multidrug resistance associated protein 1 (MRP-1), Cu++ transporting, beta polypeptide (ATP7B), xeroderma pigmentosum, complementation group A (XPA), excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC-1) and B-cell CLL/lymphoma 2 (BCL2) were down-regulated in cases of recurrent cancers. These results show that the evaluation of p53 mutation provides the most useful predictor of therapeutic effects. In responder cases, the drug-resistant genes that were determined in cell lines by culture do not necessarily translate into clinical relevance.