The Basic Study for Mn-SOD Gene Therapy

Research Project

Project/Area Number	08044290
Research Category	Grant-in-Aid for international Scientific Research
Allocation Type	Single-year Grants
Section	Joint Research
Research Institution	Okayama University
Principal Investigator	KURODA Masahiro Okayama University Hospital attached to Medical School, Department of Radiology, Assistant professor, 医学部附属病院, 助手 (50225306)
Co-Investigator(Kenkyū-buntansha)	DARET K.St.C Medical Center, University of Kentucky, 助教授 KAWASAKI Shoji School of Health Sciences, Okayama University Professor, 医療技術短期大学部, 教授 (20034952) DARET.K St Clair University of Kentucky Medical Center Associate professor
Project Period (FY)	1996
Project Status	Completed (Fiscal Year 1996)
Budget Amount *help	¥1,300,000 (Direct Cost: ¥1,300,000) Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywords	Mn-SOD / Radiation / Chemotherapy / Gene-therapy / Gene transfection / Multidisciplinary troatment
Research Abstract	The objective of this study is to test the in vivo potential tumor suppressive effect of human manganese superoxide dismutase (MuSOD) for the combined treatments with radiation, chemotherapeutic agents and hyperthermia. Tumor cells studied were an in vitro line derived from a murine spontaneous fibrosarcoma, FSa-ll. These cells were transfected with pSV2-NEO plasmid (NEO line) or co-transfected with MnSOD plasmid plus pSV2-NEO plasmid (SOD line). The cell lines used was SOD-H,which expressed high MnSOD activities after transfection, and NEO as control. The SOD-H cell line was slightly more resistant to ^<60>Co gamma-ray than NEO cell line when irradiated in vitro in the presence of oxygen. However both SOD-H and NEO had the almost same radiosensitivity for 290MeV/u carbon beam. These data were analyzed with the previous data of TCD50, that is the radiation dose to control one-half of the irradiated tumors. This analysis predicted TCD50 values of NEO and SOD-H with carbon beam under oxic condition to be 7.1 Gy and 3.0 Gy, respectively. The SOD-H cell line was more resistant than NEO cell line for in vitro MMC treatment. The in vivo effect for ADR was almost same in SOD-H as in NEO,although in vitro effects for ADR and 5FU were slightly high in SOD-H than in NEO.As a result, it was predicted that the elevated activity of MnSOD might enhance the in vivo effects of radiation, chemotherapeutic agents such as 5FU and MMC.Following these predicted data, the in vivo multidisciplinary treatment with MnSOD gene-transfection and radiotherapy and chemotherapy are now on going.