2003 Fiscal Year Final Research Report Summary

Development of differentiation therapy for oral with vitamin D analogue.

Research Project

Project/Area Number	14571896
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Surgical dentistry
Research Institution	The University of Tokushima
Principal Investigator	IGA Hiroki The University of Tokushima university Hospital, 2nd Dept.of oral and Maxillofacial Surgery, Assistant Professor, 医学部・歯学部附属病院, 講師 (40175188)
Project Period (FY)	2002 – 2003
Keywords	oral leukoplakia / vitamin D analogue / differentiation therapy
Research Abstract	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.