The investigation of new treatment for ovarian clear cell carcinoma with TOP2A amplification
| Project/Area Number |
16H06907
|
|---|
| Research Category |
Grant-in-Aid for Research Activity Start-up
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Obstetrics and gynecology
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2016-08-26 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
|---|
| Keywords | 卵巣明細胞癌 / 染色体17番長腕増幅 / シスプラチン耐性 / PDK2 / 染色体17番長腕 / プラチナ抵抗性 / stemness / TP53 / TOP2A |
|---|
| Outline of Final Research Achievements |
Ovarian clear cell carcinoma (CCC) has poor prognosis owing to its chemoresistance. Here we aimed to identify a biomarker of this drug resistance and the therapeutic target of CCC. Whole exome sequencing and expression microarray were conducted using 39 CCC clinical samples and 13 CCC cell lines. IC50 values and apoptosis of 13 CCC cell lines against cisplatin were measured by cleaved caspase-3. Chr17q21-24 amplification correlated positively with IC50 values for cisplatin in 13 CCC cell lines (r>0.4). The expression levels of 59 genes located on chr17q21-24 are positively correlated with Chr17q21-24 amplification in 13 CCC cell lines and 18 CCC patients (r>0.4). Of these 59 genes, we focused on pyruvate dehydrogenase kinase isoform 2(PDK2). A PDK inhibitor and suppression of PDK2 decreased the IC50 values for cisplatin by increasing cleaved caspase-3 expression. PDK2 inhibition is a promising therapeutic strategy against CCC.
|
Report
(3 results)
Research Products
(3 results)
-
[Presentation] Is the mesenchymal transition subtype more responsive to dose dense taxane chemotherapy combined with carboplatin (ddTC) than to conventional taxane and carboplatin chemotherapy (TC) in high grade serous ovarian carcinoma? A survey of Japanese Gynecology Oncology Group study (JGOG3016A1)2017
Author(s)
Ryusuke Murakami, Noriomi Matsumura, Hiroshi Tanabe, Hirofumi Michimae, Mayu Yunokawa, Haruko Iwase, Motoi Sasagawa, Toshiaki Nakamura, Osamu Tokuyama, Masashi Takano, Toru Sugiyama, Takashi Sawasaki, Seiji Isonishi, Kazuhiro Takehara, Hidekatsu Nakai, Aikou Okamoto, Masaki Mandai, Ikuo Konishi
Organizer
ASCO2017, J Clin Oncol 35, 2017
Related Report
Int'l Joint Research
-
-
