1997 Fiscal Year Final Research Report Summary
Establishment of gene therapy for hepatocellular carcinoma by transfer of suicide genes
| Project/Area Number |
07457141
|
|---|
| 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, Medicine, Assistant, 医学部, 講師 (50244710)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TOMINAGA Kentaro Nara Medical University, Medicine, Staff, 医学部, 医員
MASUI Kazuhiro Nara Medical University, Medicine, Assistant, 医学部, 助手 (10295800)
YOSHIKAWA Masahide Nara Medical University, Medicine, Assistant, 医学部, 助手 (50230701)
|
|---|
| Project Period (FY) |
1995 – 1997
|
| Keywords | gene therapy / hepatoma / retrovirus / suicide gene / thymidine kinase / cytosine deaminase |
|---|
| Research Abstract |
We have previously reported that a reporter gene directed by the albumin gene promoter in a retroviral vector is expressed solely in hepatoma cells but not in non-hepatoma cells. This year, we have got the following additional results.
1)Transduction of the herpes simplex virus thymidine kinase (HSV-tk) gene under the control of albumin promoter can render hepatoma cells, but not non-hepatoma cells, susceptible to ganciclovir (GCV) toxicity.
2)Established subcutaneous tumors consisting of HSV-tk gene-transduced hepatoma cells were abrogated completely by GCV treatment in 11 of 14 mice. However, in the remaining 3 mice, tumors did not regress completely despite GCV treatment due to methylation of the HSV-tk gene.
3)Bacterial cytosine deaminase (CD) gene/5-fluorocytosine (5-FC) system can cause profound bystander killing on neighboring untransduced cells without direct cell-to-cell contact. This bystander killing effect was shown to be mediated by 5-fluorouracil (5-FU) produced from 5-FC by CD gene-transduced hepatoma cells.
4)CD-5-FC system can induce substantial bystander effect in vivo. This in vivo bystander effect was mainly caused by host's tumor immunity elicited by the CD/5-FC system but not by 5-FU produced by the CD/5-FC system.
|
