Abstract

The goal of this proposal is to investiage the Etiology of Osteosarcoma, Radiation Induced Sacroma and Soft Tissue Sarcoma. We will investigate the hypothesis that some spontaneous and radiation induced sarcoma arise subsequent to genetic changes causing loss or inactivation of both homologous copies of a gene on chromosome 13 band q14, resulting in malignant transformation of target cells. We will also investigate the hypothesis that oncogene expression/activation may be important in the etiology of spontaneous and radiation induced sarcomas. We will employ DNA transfection to identify and analyze oncogene activation in these sarcomas. We will perform karyotypic analysis on early passage tumor cell lines established from spontaneous and radiation induced sarcomas to study non-random chromosome anomalies associated with these tumors. Molecular and cytogenetic data will be analyzed in conjunction with patient outcome since oncogene amplification and specific chromosomal abnormalities have been correlated with prognosis in other human cancers. Non-random chromsome anomalies may also provide clues as to the location of genes involved in the transformation process.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA041068-03
Application #
3181369
Study Section
Radiation Study Section (RAD)
Project Start
1985-05-01
Project End
1992-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637

  Publications

Chmura, S J; Dolan, M E; Cha, A et al. (2000) In vitro and in vivo activity of protein kinase C inhibitor chelerythrine chloride induces tumor cell toxicity and growth delay in vivo. Clin Cancer Res 6:737-42
Fortunato, J E; Mauceri, H J; Kocharyan, H et al. (2000) Gene therapy enhances the antiproliferative effect of radiation in intimal hyperplasia. J Surg Res 89:155-62
Advani, S J; Chung, S M; Yan, S Y et al. (1999) Replication-competent, nonneuroinvasive genetically engineered herpes virus is highly effective in the treatment of therapy-resistant experimental human tumors. Cancer Res 59:2055-8
Gorski, D H; Beckett, M A; Jaskowiak, N T et al. (1999) Blockage of the vascular endothelial growth factor stress response increases the antitumor effects of ionizing radiation. Cancer Res 59:3374-8
Seetharam, S; Staba, M J; Schumm, L P et al. (1999) Enhanced eradication of local and distant tumors by genetically produced interleukin-12 and radiation. Int J Oncol 15:769-73
Chung, T D; Mauceri, H J; Hallahan, D E et al. (1998) Tumor necrosis factor-alpha-based gene therapy enhances radiation cytotoxicity in human prostate cancer. Cancer Gene Ther 5:344-9
Staba, M J; Mauceri, H J; Kufe, D W et al. (1998) Adenoviral TNF-alpha gene therapy and radiation damage tumor vasculature in a human malignant glioma xenograft. Gene Ther 5:293-300
Epperly, M; Bray, J; Kraeger, S et al. (1998) Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy. Gene Ther 5:196-208
Hanna, N N; Mauceri, H J; Wayne, J D et al. (1997) Virally directed cytosine deaminase/5-fluorocytosine gene therapy enhances radiation response in human cancer xenografts. Cancer Res 57:4205-9
Chmura, S J; Nodzenski, E; Beckett, M A et al. (1997) Loss of ceramide production confers resistance to radiation-induced apoptosis. Cancer Res 57:1270-5

Showing the most recent 10 out of 57 publications