2000 Fiscal Year Final Research Report Summary
CONTROL MECHANISM OF RADIORESISTANT HYPOXIC CELLS IN MUTICELLULAR TUMOR SPHEROIDS
| Project/Area Number |
10470399
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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 |
病態科学系歯学(含放射線系歯学)
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| Research Institution | TOKYO MEDICAL AND DENTAL UNIVERSITY(TMDU) |
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Principal Investigator |
SASAKI Takehito TOKYO MEDICAL AND DENTAL UNIVERSITY Graduate School Professor, 大学院・医歯学総合研究科, 教授 (90013896)
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| Co-Investigator(Kenkyū-buntansha) |
MIURA Masahiko TOKYO MEDICAL AND DENTAL UNIVERSITY Graduate School Assoc Prof., 大学院・医歯学総合研究科, 助教授 (10272600)
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| Project Period (FY) |
1998 – 2000
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| Keywords | radioresistance / spheroid / apoptosis / IGF-IR / hypoxic cells / knockout mouse / glioblastoma cells |
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| Research Abstract |
Human glioblastoma cells(A-7)transfected with plasmid containing human IGF-IR cDNA(A7(R)), or co-transfected with that containing only puromycin-resistant gene(A7(puro))were established in this study. Overexpression of IGF-IR resulted in the loss of necrotic zone in A7(R)spheroids, whereas spheroids of A7(puro)cells showed a central necrosis. Together with faster growth rate in the spheroids of A7(R)cells, it was suggested that tumors consisting cells with overexpression of IGF-IR grow faster with reduced formation of necrosis. A7(R)cells in spheroids, however, showed a higher radiosensitivity than A7(puro)cells and the radiosensitivity was dependent on a size of dose fraction.
Role of IGF-IR in severely hypoxic cells was studied using fibroblasts derived from knockout mouse of IGF-IR(R-), or cells transfected with human IGF-IR cDNA(R+). (R+)cells survived longer than(R-)cells in a hypoxic condition of less than 3 mm Hg of partial oxygen pressure, and were more radioresistant than(R-)cells in the hypoxic condition. (R+)cells grown in confluent state exfoliated in a short time from the surface of petri dish, indicating that these cells tend to die rapidly depending on the cell density in a severely hypoxic condition.
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