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p53与类维生素A对口腔癌发生的化学预防作用

p53 and retinoid chemoprevention of oral carcinogenesis.

作者信息

Lippman S M, Shin D M, Lee J J, Batsakis J G, Lotan R, Tainsky M A, Hittelman W N, Hong W K

机构信息

Department of Thoracic/Head and Neck Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.

出版信息

Cancer Res. 1995 Jan 1;55(1):16-9.

PMID:7805028
Abstract

We studied p53 protein's pattern of expression, association with retinoid response or resistance, and modulation by retinoid intervention in oral premalignancy. These p53 analyses were included in a prospective trial of the retinoid isotretinoin (1.5 mg/kg/day for 3 months) in 40 patients (45 oral premalignant lesions). Seven nonsmoking subjects (eight oral biopsies) were included as a control. Protein levels of p53 were determined separately for the whole epithelium and the basal, parabasal, and superficial layers. A wide range of accumulated p53 protein levels occurred in 40 (89%) of 45 lesions in basal and parabasal but not superficial layers. No p53 protein was detected in any normal controls. Accumulation of p53 increased in direct association with histological grade (P = 0.0004). An inverse relationship occurred between the levels of accumulated p53 protein and response to isotretinoin (P = 0.006). High-dose isotretinoin did not modulate accumulated p53 protein expression.

摘要

我们研究了p53蛋白在口腔癌前病变中的表达模式、与维甲酸反应或耐药性的关联以及维甲酸干预对其的调节作用。这些p53分析纳入了一项针对40例患者(45个口腔癌前病变)的维甲酸异维甲酸(1.5mg/kg/天,共3个月)前瞻性试验。纳入7名非吸烟受试者(8次口腔活检)作为对照。分别测定全层上皮以及基底层、副基底层和表层的p53蛋白水平。在45个病变中的40个(89%)的基底层和副基底层而非表层出现了广泛的p53蛋白积累水平。在任何正常对照中均未检测到p53蛋白。p53的积累与组织学分级直接相关(P = 0.0004)。积累的p53蛋白水平与对异维甲酸的反应呈负相关(P = 0.006)。高剂量异维甲酸未调节积累的p53蛋白表达。

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