2000 Fiscal Year Final Research Report Summary
The Basic Study of Multidisciplinary Treatment for Malignant Tumors using MnSOD Gene Therapy
| Project/Area Number |
10470196
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
KURODA Masahiro Medical School, Hospital, OKAYAMA UNIVERSITY, Lecturer, 医学部・附属病院, 講師 (50225306)
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| Project Period (FY) |
1998 – 2000
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| Keywords | MnSOD / gene therapy / radiotherapy / hyperthermia / chemotherapy / tumorigenicity / apoptosis / multidisciplinary treatment |
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| Research Abstract |
1) We confirmed that MnSOD gene overexpression increased the in vivo effects of radiotherapy, hyperthermia, and chemotherapy, using MnSOD gene-tranfected fibrosarcoma cell line, FSa-II.
2) Experiments using scid mice revealed that overexpression of MnSOD gene suppressed spontaneous apoptosis without a resultant alteration in in vivo growth of the mouse fibrosarcoma, FSa-II.
3) Newly developed microscopic system was available to indicate that MnSOD gene overexpression increased apoptosis after hyperthermic treatments.
4) In vitro timelapse microscopic observation of cellular moving ability did not show any difference by MnSOD gene overexpression.
5) Intracellular MnSOD activity following gene-transfection by in vivo electroporation increased as concentration of DNA increased from 5 to 5Oμg/6μl, and reached peak at third day after transfection.
6) MnSOD gene-transfection by in vivo electroporation increased the in vivo effects of radiotherapy and hyperthermia. MnSOD gene was transfected by in vivo electroporation for FSa-II tumor in C3H/He mice. Tumors were irradiated at graded doses or heated at 44℃ for 60 min at third day after gene-transfection. The effects of treatments were analyzed by tumor growth-50 method and tumor control dose-50 method.
This study indicated that MnSOD overexpression increased thermosensitivity of cells in vitro, and substantially reduces the tumorigenicity, resulting in a significant increase in tumor growth time in vivo. Reduced tumorigenicity by MnSOD overexpression also resulted in a significant increase in tumor control rate by radiotherapy in vivo.
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