华西口腔医学杂志

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重组人p53腺病毒注射液治疗口腔黏膜白斑的生物学反应观察

张松涛1,2, 张媛媛3, 李小玉2, 李龙江2,4, 李一2, 高宁2, 张壮2   

  1. 1.河南省肿瘤医院头颈肿瘤外科, 河南郑州450008; 2.口腔疾病研究国家重点实验室, 四川大学, 四川成都610041;3.郑州大学口腔医院口腔内科, 河南郑州450052; 4.四川大学华西口腔医院头颈肿瘤外科, 四川成都610041
  • 收稿日期:2008-12-25 修回日期:2008-12-25 出版日期:2008-12-20 发布日期:2008-12-20
  • 通讯作者: 李龙江,Tel: 028-85501428
  • 作者简介: 张松涛(1979-),男,河南人,主治医师,博士
  • 基金资助:

    国家自然科学基金资助项目(30471903)

Biologic analysis of recombinant human adenovirus-p53 injection in patients with oral leukoplakia

ZHANG Song-tao1,2, ZHANG Yuan-yuan3, LI Xiao-yu2, LI Long-jiang2,4, LI Yi2, GAO Ning2, ZHANG Zhuang2   

  1. 1. Dept. of Head and Neck Oncology Surgery, Henan Province Tumor Hospital, Zhengzhou 450008, China; 2. State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, China; 3. Dept. of Oral Medicine, College of Stomatology, Zhengzhou University, Zhengzhou 450052, China; 4. Dept. of Head and Neck Oncology Surgery, West China College of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2008-12-25 Revised:2008-12-25 Online:2008-12-20 Published:2008-12-20
  • Contact: LI Long-jiang,Tel: 028-85501428

摘要:

目的观察重组人p53腺病毒注射液Ad-p53治疗上皮异常增生型口腔白斑引起的生物学反应。方法对18例上皮异常增生型口腔白斑患者进行为期15 d的Ad-p53局部黏膜内注射治疗。每3 d注射1次,以1 cm2作为一个注射点,每点注射1×108 vp,0.5 mL。在最后一次注射后24~48 h内行病变组织活检,并用免疫组化法检测Ad-p53治疗前后组织内P53蛋白和P21CIP/WAF蛋白的表达。结果P53蛋白和P21CIP/WAF蛋白在Ad-p53治疗后组织内的阳性表达率分别为100%和89.9%,明显高于治疗前的表达,并且二者的高表达呈正相关(r=0.598,P<0.01)。结论Ad-p53治疗上皮异常增生型口腔白斑有良好的生物学反应,有广阔的临床应用前景。

关键词: 腺病毒, 基因治疗, 口腔白斑

Abstract:

Objective Advances in tumor biology and clinical trials indicate that p53 transfer is an alternative therapy for head and neck squamous cell carcinoma. The aim of this study is to evaluate the biologic activity of multiple intraepithelial injections of Ad-p53 in patients with dysplastic oral leukoplakia, which is the most common premalignant lesion of the oral squamous cell carcinoma. Methods From 2006 to 2007, 18 Chinese patientsclinically and histopathologically diagnosed as dysplastic oral leukoplakia were recruited for this study. On a 15-day cycle, intraepithelial injections of Ad-p53 were administered once every three days at dose levels dependent upon lesion size/dose escalation sequence(1×108 vp). 24-48 h after the last injection, incisional biopsy were performed, and immunohistochemistry was used to examine the protein expression of P53 and P21CIP/WAF. Results In the postreatment patients, P53 protein and P21CIP/WAF protein expression were significantly enhanced(100%, 89.9%, respectively) and statistical analysis revealed the expression of P53 protein had a positive correlation with that of P21CIP/WAF protein(r=0.598, P<0.01). Conclusion Intraepithelial injections of gendicine is biologically active in patients with dysplastic oral leukoplakia. It may be a promising treatment for oral leukoplakia.

Key words: adenovirus, gene therapy, oral leukoplakia