This project is an application to use genetic therapy directed against KS apoptotic mechanisms. Based on preliminary evidence found by this and other groups, the Bcl-2 and Bcl-xl gene products are expressed by KS cells in vivo and in vitro. The approach is to inactivate these gene products with a repressor, Bcl-xs. An adenovirus vector expressing Bcl-xs has been constructed. Thus far it has been lethal to all KS cells examined, presumably by induction of apoptosis. The hypothesis is that this or a similar virus vector may be a useful novel therapeutic agent for KS treatment.
The specific aims are to: (1) determine the molecular mechanism by which the Bcl-xs adenovirus kills KS cells; (2) to determine whether expression of Bcl-2, Bcl-xl or the HIV tat gene product in KS cells affect the efficiency of killing by the bcl-xs adenovirus vector; (3) to determine the effect of the bcl-xs adenovirus on a spectrum of normal cells and KS cells; and (4) to assess the possible in vivo therapeutic utility of the bcl-xs adenovirus in an animal model of KS.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA070057-04
Application #
2748836
Study Section
AIDS and Related Research Study Section 3 (ARRC)
Program Officer
Cremer, Kenneth J
Project Start
1995-09-30
Project End
2000-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Pathology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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