| Project/Area Number |
10470140
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B).
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Nara Medical University |
|---|
Principal Investigator |
KURIYAMA Shigeki Nara Medical University, Third Dept.of Internal Medicine, Assistant Professor, 医学部, 講師 (50244710)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TOMINAGA Kentaro Nara Medical University, Third Dept.of Internal Medicine, Research Fellow, 医学部, 医員
KOJIMA Hideyuki Nara Medical University, Third Dept.of Internal Medicine, Research Associate, 医学部, 助手 (60326345)
YOSHIKAWA Masahide Nara Medical University, Department of Parasitology, Associate Professor, 医学部, 助教授 (50230701)
TSUJINOUE Hirohisa Nara Medical University, Third Dept.of Internal Medicine, Research Fellow, 医学部, 医員
YOSHIJI Hitoshi Nara Medical University, Third Dept.of Internal Medicine, Research Fellow, 医学部, 医員
菊川 政次 奈良県立医科大学, 医学部, 医員
|
|---|
| Project Period (FY) |
1998 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2000: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1999: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1998: ¥4,700,000 (Direct Cost: ¥4,700,000)
|
|---|
| Keywords | gene therapy / retrovirus / adenovirus / hepatocellular carcinoma / colorectal carcinoma / suicide gene / cytokine gene / in vivo |
|---|
| Research Abstract |
(1) We have shown that retroviral packaging cells introduced with the polyoma virus early regions could produce high-titer recombinant retroviruses compared with conventional retroviral packaging cells.
(2) We have shown that intratumoral injections of retroviruses carrying the herpes simplex virus thymidine kinase (HSV-tk) gene under the control of the albumin promoter could induce complete cure of subcutaneously established hepatocellular carcinoma in mice. We have also shown that intraperitoneal injections of retroviruses carrying the HSV-tk gene under the control of the albumin promoter could profoundly prolong the survival periods of mice with carcinomatous peritonitis due to invasion of hepatocellular carcinoma.
(3) We have shown that the addition of the 5' sequences of the α-fetoprotein gene to the retroviral long terminal repeat promoter or the housekeeping phosphoglycerate kinase promoter could induce hepatocellular carcinoma cell-selective expression of suicide genes and cytoki
… More
ne genes used for a therapeutic purpose.
(4) We have shown that intraperitoneal injections of retroviruses carrying the bacterial cytosine deaminase (CD) gene under the control of the carcinoembryonic antigen promoter could profoundly prolong the survival periods of mice with peritoneal dissemination of colorectal carcinoma. Furthermore, intraperitoneal injections of the retroviruses followed by 5-fluorocytosine (5-FC) treatment did not cause significant bone marrow suppression, while intraperitoneal injections of retroviruses carrying the CD gene under the control of the retroviral long terminal repeat promoter caused severe bone marrow suppression with 5-FC treatment.
(5) We have shown that intravenous infusion of adenoviruses could induce marked expression of a transgene in the liver not only in mice with normal livers but also in mice with severely damaged livers such as fulminant hepatitis and liver cirrhosis. However, transgene expression was transient and reinfusion of the same adenoviruses could not induce re-expression of the transgene. We have demonstrated that administration of immunosuppressive agents such as cyclophosphamide and FK506 around the time of adenoviral re-infusion could successfully induce expression of the original gene construct. Less
|
