2006 Fiscal Year Final Research Report Summary
Molecular targeting therapy for anticancer drug-resistant cancer cells derived from uterus and ovary
| Project/Area Number |
17591752
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Obstetrics and gynecology
|
|---|
| Research Institution | Wakayama Medical University |
|---|
Principal Investigator |
TANAKA Tetsuji Wakayama Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (80275255)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YUKAWA Kazunori Wakayama Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (20301434)
UTSUNOMIYA Hirotoshi Wakayama Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (60264876)
MINAMI Sawako Wakayama Medical University, School of Medicine, Assistant Professor, 医学部, 講師 (90219692)
UTSUNOMIYA Tomoko Wakayama Medical University, School of Medicine, Assistant, 医学部, 助手 (60382355)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Keywords | Uterine cancer / Ovarian cancer / Anticancer drug / Drug resistance |
|---|
| Research Abstract |
[1] Epigenetic regulation and changes in anticancer drug-sensitivities of the cancer cells.
(1) Promoter hypermethylation and anticancer drug-sensitivities: We have recently reported the novel mechanism in acquired CDDP-resistance, an extremely strong impairment of RNA translation in CDDP-resistant cells, which was investigated with the CDDP-resistant cervical cancer cell lines established originally in our lab. Next, we have examined de-methylation effects and other anticancer drug-resistances in the cervical cancer cells, de-methylation effects and CDDP-resistances in endometrial cancer cells and ovarian cancer cells. As a result, demethylation treatment partially suppressed the resistance to topoisomelase I inhibitor in the cervical cancer cells (preparation in submission). Resistance to topoisomelase I inhibitor showed a positive relation to the promoter hypermethylation, as found in the CDDP-resistant cervical cancer cell variants. mRNA profiling study did not revealed any recovery
… More
factors related to drug-sensitivity modulation by hypermethylation treatment. Experiments with intracellular signaling inhibitors and demethylation treatments have not identified any drug-sensitivity recovery molecules yet.
(2) Analysis of relationships of DAPK expression and anticancer drug-sensitivities: DAPK expression can be easily regulated by promoter-methylation and have some relations to CDDP-resistance mechanisms. Therefore, relationships of DAPK expression and demethylation effects, and of siRNA-DAPK knockdown and CDDP-sensitivity, were examined. Demethylation treatment inhibited drug-resistance while DAPK expression was increased. Recovered drug-sensitivity was thought to be regulated unknown methylation-regulated molecules except for DAPK. DAPK knockdown partially inhibited CDDP-resistance and VP16-resistance, and completely suppressed 5-FU-resistance.
[2] Identification of antiapoptotic signals in some Kampo medicine components against anticancer drugs to establish molecular targeting therapy for drug-resistant cancers: In some Kampo medicine components, several molecules with strong suppressive activities against anticancer drugs were identified (preparation for submission). And then, further experiments were done to identify the intracellular signalings in anti-apoptotic phenomena.
(1) Identification of intracellular signaling in the cells stimulated with Kampo medicine components. Either MAPKK and DAPK may have some association with the signals, which are now under investigation. Both mRNA profiling analysis and siRNA experiments are now under investigations. Less
|
Research Products
(6 results)
