2004 Fiscal Year Final Research Report Summary
Research of increase radiosensitivity targeting DNA repair mechanism in treatment-resistant cells
| Project/Area Number |
15591276
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Radiation science
|
|---|
| Research Institution | Kobe University |
|---|
Principal Investigator |
SASAKI Ryohei Kobe University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 講師 (30346267)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SUGIMURA Kazuro Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00136384)
ONO Yoshiharu Kobe University, Graduate School of Medicine, Research Fellow, 大学院・医学系研究科, 産学官連携研究員 (30324924)
MURAKAMI Masao Hyogo Ion Beam Center, Associate Professor, 科長(研究職)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | Resistant tumor / Rad51 / Radiosensitivity / Radioresistance / FDG-PET / Prostate Cancer / Combination therapy / Isofravinol |
|---|
| Research Abstract |
Inhibition of Rad51, a DNA repair protein in homologus recombination after DNA damage, leads to an increase of radiosensitivity in prostate cancer cells in vitro. In this study, we used several antisense oligonucleotide to decrease Rad51 protein function, and evaluate Rad51 dysfunction with using comet assay, which is an analysis for DNA repair ability after DNA damage.
In the next step, we first established several radioresistant clones from parental colon cancer cell lines (HCT116 p53+/+, p53 -/-). We are now applying Rad51 inhibition to those sets of parental and radioresistant clones.
On the other hand, we investigated an novel combination therapy, which are consisted of natural product of isoflavinol and ionizing radiation. We found that treatment of an isoflavinol, genistein, increase radiosensitivity in radioresistant prostate cancer cells by promoting apoptosis (Asian J Androl. 2004;6(4):285-290.)
To apply these findings, we investigated efficacy of FDG-PET in non-small cell lung cancer as an clinical model. We found and reported that tumor in which FDG were accumulated showed radioresistant characteristics, and metastatized frequently.(J Clin Oncol. 2005;23(6): 1136-1143).
|
