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目的:观察肿瘤组织p14ARF、突变型p53蛋白表达状态与E1B缺陷型腺病毒治疗鼻咽癌疗效的关系,探讨E1B缺陷型腺病毒(简称H101)基因治疗的作用机制。方法:应用免疫组织化学方法对36例H101治疗的晚期鼻咽鳞癌病例进行肿瘤组织p14ARF、突变型p53蛋白检测,分析肿瘤组织p14ARF、突变型p53蛋白表达与H101临床疗效的关系;结果:突变型p53和p14ARF蛋白在36例晚期鼻咽鳞癌中总阳性表达率分别为55.6%和44.4%;突变型p53+p14ARF+(即p14ARF蛋白无缺失)患者均无治疗有效病例;突变型p53+p14ARF-(即p14ARF蛋白有缺失)患者中有4例有效;结论:对于p53基因无突变的恶性肿瘤,p14ARF基因缺失可能是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 observe the relationship between the expression of p14ARF, mutant p53 protein and the efficacy of E1B-deficient adenovirus in the treatment of nasopharyngeal carcinoma (NPC), and to explore the mechanism of the gene therapy of E1B-deficient adenovirus (H101). Methods: Immunohistochemistry was used to detect the expression of p14ARF and mutant p53 protein in 36 cases of H101-treated advanced nasopharyngeal squamous cell carcinoma. The relationship between the expression of p14ARF, mutant p53 protein and the clinical efficacy of H101 was analyzed. Results: The positive rates of p53 and p14ARF protein in 36 cases of advanced nasopharyngeal squamous cell carcinoma were 55.6% and 44.4%, respectively. No mutation in p53 + p14ARF + (p14ARF protein) - (ie, lack of p14ARF protein) were found in 4 patients. CONCLUSION: The deletion of p14ARF gene may be an important factor for H101 to efficiently replicate and kill tumor cells in malignant tumors without p53 gene mutation.