Determining whether tumors are sensitive to a particular form of therapy is a major problem. changes in tumor volume as a result of treatment are often difficult to quantitate accurately and require long periods of time (weeks) to become evident, and the diagnosis of resistance is usually dependent on assessment o response to several courses of therapy. It is therefore, the overall aim of this research program is to develop molecular strategies for assessing tumor injury in vivo. Developments in PCR technology and immunohistochemistry have made it possible to quantitate the level of mRNA expression and/or gene products in very small tumor samples. It is our hypothesis that the magnitude of transcriptional activation of genes induced by cellular injury, when measured 24 hours after treatment by these novel techniques, can provide a direct measure of the effectiveness of treatment since it reflects the extent to which the tumor itself believes it has been injured rather than an indirect measure of likely response such as plasma drug levels or the extent of drug uptake. As prototype treatment, we have selected radiation therapy (XRT) and chemotherapy (cisplatin and taxol), and as a prototypic tumor we have selected head and neck carcinoma.
The specific aims are: 1) to determine whether there is a correlation between the extent of exposure to cisplatin (cDDP) taxol and XRT, the extent of tumor cell kill, and the magnitude of the induction of gaddl53 and c-jun; 2) to determine whether the magnitude of induction of either gaddl53 or c-jun can be used to quantitate the emergence of resistance; 3) to determine whether immunohistochemical techniques can be used to quantitate the level of the products of either the gaddl53 or c-jun genes and correlate them to tumor cell kill and tumor response; 4) to identify and characterize additional gene(s) which are even more lushly induced than gadd153 or c-jun, using the new technique of differential display PCR. Gene expression, measured at the mRNA and protein levels, will be studied in the human head and neck cancer cell lines UMSCC10b and UMSCC5, in needle biopsies from a xenograft model established in nude mice from the UMSCC10b cell line and in needle biopsies from human tumors of the head and neck region.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21CA067269-01
Application #
2110908
Study Section
Special Emphasis Panel (ZRG3-ET-2 (02))
Project Start
1995-05-01
Project End
1997-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Surgery
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093