The overall objective of this proposal is to determine whether the combination of suicide gene therapy and radiation therapy is superior to single modality therapy in the treatment of human tumors. Based on the investigators' in vitro cell culture studies with the HSV-tk transduced human glioma cells, three specific approaches will be used to accomplish the objective. The first approach will test the hypothesis that tumors which contain wild type (wt) p53 function will be more sensitive to the combination of suicide gene therapy and radiation than tumors which lack wt-p53 or contain mutated (mut) p53 genes. Two other important questions relevant to the combined therapy to be answered are: 1) Is there sufficient radiosensitization to produce an increased tumor cure rate? and 2) Can an appropriate delivery system be developed? This group will use a genetically well characterized human glioma cell line, U-251 cells, growing in nude rat brains. The major significance of this approach would be to determine whether the use of suicide genes in combination with radiation would improve the cure rates of radioresistant human tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA064323-03
Application #
2748765
Study Section
Radiation Study Section (RAD)
Program Officer
Stone, Helen B
Project Start
1996-08-01
Project End
2000-03-31
Budget Start
1998-08-01
Budget End
2000-03-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Henry Ford Health System
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
073134603
City
Detroit
State
MI
Country
United States
Zip Code
48202
Kim, Jae Ho; Lew, Young S; Kolozsvary, Andrew et al. (2003) Arsenic trioxide enhances radiation response of 9L glioma in the rat brain. Radiat Res 160:662-6
Shah, Tushar; Ryu, Samuel; Lee, Ho Jun et al. (2002) Pronounced radiosensitization of cultured human cancer cells by COX inhibitor under acidic microenvironment. Int J Radiat Oncol Biol Phys 53:1314-8
Ryu, Samuel; Brown, Stephen L; Kolozsvary, Andrew et al. (2002) Noninvasive detection of radiation-induced optic neuropathy by manganese-enhanced MRI. Radiat Res 157:500-5
Lew, Young S; Kolozsvary, Andrew; Brown, Stephen L et al. (2002) Synergistic interaction with arsenic trioxide and fractionated radiation in locally advanced murine tumor. Cancer Res 62:4202-5
Ryu, S; Stein, J P; Chung, C T et al. (2001) Enhanced apoptosis and radiosensitization by combined 13-cis-retinoic acid and interferon-alpha2a; role of RAR-beta gene. Int J Radiat Oncol Biol Phys 51:785-90
Paielli, D L; Wing, M S; Rogulski, K R et al. (2000) Evaluation of the biodistribution, persistence, toxicity, and potential of germ-line transmission of a replication-competent human adenovirus following intraprostatic administration in the mouse. Mol Ther 1:263-74
Khil, M S; Kolozsvary, A; Apple, M et al. (2000) Increased tumor cures using combined radiosurgery and BCNU in the treatment of 9l glioma in the rat brain. Int J Radiat Oncol Biol Phys 47:511-6
Xie, Y; Gilbert, J D; Kim, J H et al. (1999) Efficacy of adenovirus-mediated CD/5-FC and HSV-1 thymidine kinase/ganciclovir suicide gene therapies concomitant with p53 gene therapy. Clin Cancer Res 5:4224-32
Kim, J H; Khil, M S; Kolozsvary, A et al. (1999) Fractionated radiosurgery for 9L gliosarcoma in the rat brain. Int J Radiat Oncol Biol Phys 45:1035-40
Kim, S H; Brown, S L; Kim, J H (1998) The potentiation of radiation response in human colon carcinoma cells in vitro and murine lymphoma in vivo by AG337 (Thymitaq), a novel thymidylate synthase inhibitor. Int J Radiat Oncol Biol Phys 42:789-93

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