Viewing Study NCT00166946



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Study NCT ID: NCT00166946
Status: UNKNOWN
Last Update Posted: 2005-12-21
First Post: 2005-09-12

Brief Title: Effects of Arsenic on Keratinocytes in a Skin Equivalent Model
Sponsor: National Taiwan University Hospital
Organization: National Taiwan University Hospital

Study Overview

Official Title: Effects of Arsenic on Keratinocytes in a Skin Equivalent Model
Status: UNKNOWN
Status Verified Date: 2004-11
Last Known Status: RECRUITING
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: None
Brief Summary: We popose that arsenic-induced lymphocytes dysfunction plays an important role in biological mechanisms of arsenical Bowens disease
Detailed Description: Arsenical cancers comprising skin bladder kidney lung colon and liver malignancies were prevalent in southwestern coast of Taiwan where the artesian water was contaminated with high concentration of arsenic Skin is a main target of arsenical poisoning The cutaneous manifestations of chronic arsenism can take form as hyperpigmentation hypopigmentation arsenical keratosis and arsenical skin cancers The most popular arsenical skin cancer is Bowens disease which is a carcinoma in situ of skin and often confined to sun-protected skin Pathologically there are several characteristics present in Bowens disease 1 abnormal cell proliferation and carcinogenesis in keratinocytes 2 dysplasia and apoptosis at the lesion 3 integrin deficiencydefect in the basal cells of the skin 4 dysfunctions in peripheral immune cells Our pervious results indicated that arsenic affected cell cycle regulation by influencing the proliferation and apoptosis of keratinocytes Furthermore we found that integrins were deficient in basal layer of lesional and perilesional sites of Bowens disease as demonstrated by immunohistochemistry The integrin deficiency in Bowens disease might lead to abnormality of cell cycle regulation differentiation and carcinogenesis In addition arsenic can destruct lymphocytes to cytokine regulation and induce lymphocytes apoptosis We propose that arsenic-induced lymphocytes dysfunction plays an important role in biological mechanisms of arsenical Bowens disease There are many regulatory mechanisms involved in progression of chemical carcinogenesis including the reactions among carcinogen and target cells supporting cells and immune interactions Therefore this study is to investigate these skin cell-cell interactions induced by arsenic using an organotypic epidermis culture model By using this model we can mimic the mechanism of arsenic-induced skin diseases Which will give us much more information that similar to carcinogenesis progesee in human body as compared to cell culture model The effects of arsenic on epidermis formation the effects of UVB and arsenic on arsenical carcinogenesis and the interactions between immune cells and skin cells will be studied in this 3-year proposal as described below

The 1st year Study of arsenical effects on integrin expression cell proliferation differentiation and apoptosis in organotypic epidermis

The 2nd year Study of arsenic andor UVB -induced biological changes in organotypic epidermis and Bowens disease

The 3rd year Study of the interactions between immune cells and epidermal cells induced by arsenic

This study will give us much more information that similar to carcinogenesis progesee in human body as compaired to cell culture model We hope the result of this study can provide a useful model in chemical carcinogenesis investigation field

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: None
Is a FDA Regulated Device?: None
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None