Development of differentiation therapy for oral with vitamin D analogue.

开发口服维生素 D 类似物的分化疗法。

• 批准号: 14571896
• 负责人: IGA Hiroki
• 金额: $ 2.18万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571896/
• 关键词: oral leukoplakia; vitamin D analogue; differentiation therapy

It is known that Oral leukoplakia is one of the precancerous diseases and it is frequently converted into oral cancer. It has been reported that a vitamin D analogue, 22-oxa-1,25-dihydroxyvitamin D_3 (OCT) is capable of promoting differentiation and inhibiting proliferation of psoriasis which is pathologically similar to oral leuplakia. In this study, we examined the effects of OCT on oral mucosa in order to develop the new therapeutic method for oral leukoplakia.It was found by RT-PCR and westernblotting that vitamin D receptor (VDR), subtype of retinoic acid receptor (RXR) and transcriptional coactivator(TIF2) were detected both in keratinocytes and fibroblasts isolated from the patients of oral leukoplakia. The growth of keratinocytes and fibroblasts were inhibited by the treatment of 10^<-7> 〜10^<-9> M OCT for 4days in dose dependent mannar. Thease above findings indicate that oral leukoplakia might be a clinical target of OCT.The expression of involcrine and cytokeratin were increased in a certain type of keratinocytes by the treatment with OCT. This results indicate that OCT induces the differentiation of keratinocytes. Although we examined the expressions of VDR, RXR, or TIF2 mRNA by in situ hybridization in biopsy materials, any relationship between the expression and those pathological diagnosis could not be detected.These findings indicate that OCT might be a clinically useful pharmaceutical agent in the differentiation therapy for oral leukoplakia.

口腔白斑是癌前病变之一，易转化为口腔癌。据报道，维生素D类似物22-oxa-1,25-二羟基维生素D_3 （OCT）能够促进银屑病的分化和抑制银屑病的增殖，银屑病的病理类似于口腔白斑病。本研究探讨了OCT对口腔黏膜的影响，以期为口腔白斑的治疗开辟新的途径。RT-PCR和westernblotting检测发现，口腔白斑患者的角质形成细胞和成纤维细胞中均检测到维生素D受体（VDR）、维甲酸受体（RXR）亚型和转录辅激活因子（TIF2）。10^<-7> ~ 10^<-9> M OCT以剂量依赖性方式处理4天，可抑制角质形成细胞和成纤维细胞的生长。以上结果提示口腔白斑可能是OCT治疗的临床靶点。OCT治疗后，某类型角质形成细胞中内参碱和细胞角蛋白的表达增加，提示OCT诱导了角质形成细胞的分化。虽然我们通过原位杂交检测了活检材料中VDR、RXR或TIF2 mRNA的表达，但无法检测到表达与病理诊断之间的任何关系。提示OCT在口腔白斑的鉴别治疗中可能是一种临床有用的药物。