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目的:通过对肿瘤组织P14ARF、突变型p53基因蛋白表达状态与E1B-55K缺陷型腺病毒(简称H101)治疗头颈部鳞癌疗效关系研究,进一步探讨H101基因治疗的作用机制。方法:应用免疫组化法对36例H101治疗的晚期头颈部鳞癌病例进行肿瘤组织P14ARF、突变型p53基因蛋白进行检测,分析肿瘤组织P14ARF、突变型p53基因蛋白表达与H101临床疗效的关系。结果:突变型p53和P14ARF基因蛋白在36例头颈部鳞癌中总阳性表达率分别为55·6%(20/36)和44·4%(16/36)。突变型p53-+P14ARF+(即P14ARF基因蛋白无缺失)患者均无有效病例;突变型p53-+P14ARF-(即P14ARF基因蛋白有缺失)患者8例中有4例有效(P>0·05)。结论:对于p53基因无突变的恶性肿瘤,P14ARF基因异常可能是H101能在肿瘤细胞内有效复制并杀死肿瘤细胞的一个重要影响因素。
OBJECTIVE: To further investigate the mechanism of H101 gene therapy by studying the relationship between the expression of P14ARF, mutant p53 gene and the therapeutic effect of E1B-55K-deficient adenovirus (H101) on squamous cell carcinoma of head and neck. Methods: Immunohistochemical method was used to detect the expression of P14ARF and mutant p53 gene in 36 cases of advanced head and neck squamous cell carcinoma of H101 treated with H101. The relationship between the expression of P14ARF and mutant p53 gene protein and the clinical efficacy of H101 . Results: The positive rates of mutant p53 and P14ARF protein in 36 cases of head and neck squamous cell carcinoma were 55.6% (20/36) and 44.4% (16/36), respectively. There were no effective cases in patients with mutant p53- + P14ARF + (P14ARF gene protein was absent); 4 of 8 patients with mutant p53- + P14ARF- (deletion of P14ARF gene) were effective (P> 0.05) . CONCLUSION: Abnormal P14ARF gene may be an important factor for H101 to efficiently replicate and kill tumor cells in tumor cells without p53 mutation.