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子宫颈癌患者的化学敏感性及p53 - Bax通路介导的细胞凋亡

Chemosensitivity and p53-Bax pathway-mediated apoptosis in patients with uterine cervical cancer.

作者信息

Sultana H, Kigawa J, Kanamori Y, Itamochi H, Oishi T, Sato S, Kamazawa S, Ohwada M, Suzuki M, Terakawa N

机构信息

Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan.

出版信息

Ann Oncol. 2003 Feb;14(2):214-9. doi: 10.1093/annonc/mdg071.

Abstract

OBJECTIVES

To determine whether and how apoptosis through the p53-Bax pathway affects sensitivity to chemotherapy in cervical cancer.

MATERIALS AND METHODS

Thirty patients with cervical squamous cell carcinoma, who had human papilloma virus (HPV) and underwent neoadjuvant chemotherapy, were entered in the present study. Tumor specimens were obtained before and after chemotherapy. HPV was detected by polymerase chain reaction. The expression of Ki-67, p53, Bax and Bcl-2 proteins was determined by immunohistochemical staining. Apoptotic cells were identified by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling method.

RESULTS

Of 30 patients, 18 responded to chemotherapy and 12 did not. The apoptotic index in tumors of responders was significantly higher than in non-responders after chemotherapy. The Ki-67 labeling index (LI) in responders was significantly higher than in non-responders before chemotherapy. Patients with tumors >33% of the LI, which was determined by a receiver operating characteristic curve, had a better survival rate. The incidence of p53 protein expression did not differ between responders and non-responders. After chemotherapy, the expression of Bax protein in responders was more frequent and Bcl-2 protein expression was less frequent than in non-responders.

CONCLUSIONS

Chemosensitivity in cervical cancer may be associated with apoptosis via the p53-Bax pathway.

摘要

目的

确定通过p53 - Bax途径的细胞凋亡是否以及如何影响宫颈癌对化疗的敏感性。

材料与方法

本研究纳入30例患有人类乳头瘤病毒(HPV)且接受新辅助化疗的宫颈鳞状细胞癌患者。在化疗前后获取肿瘤标本。通过聚合酶链反应检测HPV。采用免疫组织化学染色法测定Ki-67、p53、Bax和Bcl-2蛋白的表达。通过末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸生物素缺口末端标记法鉴定凋亡细胞。

结果

30例患者中,18例对化疗有反应,12例无反应。化疗后,有反应者肿瘤中的凋亡指数显著高于无反应者。化疗前,有反应者的Ki-67标记指数(LI)显著高于无反应者。根据受试者工作特征曲线确定LI>33%的肿瘤患者生存率更高。有反应者和无反应者之间p53蛋白表达发生率无差异。化疗后,有反应者中Bax蛋白表达比无反应者更常见,而Bcl-2蛋白表达比无反应者更少见。

结论

宫颈癌的化疗敏感性可能与通过p53 - Bax途径的细胞凋亡有关。

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