2002 Fiscal Year Final Research Report Summary
Gene therapy for the treatment of chondrosarcoma
| Project/Area Number |
12470306
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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 |
Orthopaedic surgery
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| Research Institution | Mie University |
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Principal Investigator |
UCHIDA Atsumasa Mie University, Faculty of Medicine, Professor, 医学部, 教授 (40176681)
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| Project Period (FY) |
2000 – 2002
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| Keywords | chondrosarcoma / gene therapy / suicide gene / bystander effect / apoptosis |
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| Research Abstract |
Gene therapy for the treatment of chondrosarcoma was studied in vitro and in vivo using cell culture and an experimental animal model developed originally. Cell culture study showed cytocidal effect of chondrosarcoma cells incorporated suicide gene (thymidine kinase gene of herpes simplex virus) by addition of anti-virus agent (Ganciclovir). The bystander effect was also confirmed with the ratio of 1:50. The bystander effect in chondrosarcoma cells seems to be caused by the presence of the structure as gap junction which was demonstrated electron microscopically. These effects were enhanced by the addition of some cytocidal cytokines TRAIL and TNF α. Cell death was caused by apoptosis.
Growth of the tumor implanted into the mice subcutaneously was markedly inhibited by injection of suicide gene into the tumor and thereafter intraabdominal administration of anti-virus agent. The tumor size after administration of suicide gene and anti-virus agent was one fifth of control after 4 weeks.
These results suggest that gene therapy by suicide gene is useful for the treatment of chondrosarcoma which does not have effective treatments except surgery. Improvement of survival rate in chondrosarcoma by gene therapy will contribute to those in other malignant bone and soft tissue sarcomas.
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