Eradication of radioresistant cancer stem cells by inhibiting the AKT survival signaling pathway.
| Project/Area Number |
24510063
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Risk sciences of radiation/Chemicals
|
|---|
| Research Institution | National Institute of Public Health |
|---|
Principal Investigator |
SHIMURA Tsutomu 国立保健医療科学院, その他部局等, その他 (40463799)
|
|---|
| Project Period (FY) |
2012-04-01 – 2015-03-31
|
| Project Status |
Completed (Fiscal Year 2014)
|
| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
|---|
| Keywords | 放射線 / がん |
|---|
| Outline of Final Research Achievements |
Radioresistance, which is a major cause of failure of radiotherapy (RT), is proposed as one of the intrinsic characteristics of cancer stem cells (CSCs) whose unique DNA damage response (DDR), efficient DNA repair and resistance to apoptosis are thought to confer the phenotype. We have isolated surviving CSCs by exposure to long-term fractionated radiation for 82 days from HepG2 cells (82FR-31NR cells). 82FR-31NR cells exhibited CSC properties, such as high expression of CSC marker CD133 and the ABC transporters (MDR1 and BCRP1), and high tumorigenic potential after transplantation into nude mice. 82FR-31NR cells showed efficient DNA repair of radiation-induced DNA damage and radioresistance with activation of the AKT signaling pathway. Therefore, inhibition of the AKT pathway by an AKT inhibitor, resulted in radiosensitization of 82FR-31NR cells. Combination of fractionated RT and reagents targeting the AKT pathway to eradicate CSCs would be effective therapeutic modality.
|
Report
(4 results)
Research Products
(24 results)
-
-
[Journal Article] RAD18 Activates the G2/M Checkpoint through DNA Damage Signaling to Maintain Genome Integrity after Ionizing Radiation Exposure.2015
Author(s)
Sasatani M, Xu Y, Kawai H, Cao L, Tateishi S, Shimura T, Li J, Iizuka D, Noda A, Hamasaki K, Kusunoki Y, Kamiya K.
-
Journal Title
PLoS One
Volume: 10
Issue: 2
Pages: 1-16
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Distribution of artificial radionuclides in abandoned cattle in theeva cuation zone of the Fukushima Daiichi nuclear power plant2013
Author(s)
Fukuda T, Kino Y, Abe Y, Yamashiro H, Kuwahara Y, Nihei H, Sano Y, Irisawa A, Shimura T, Fukumoto M, Shinoda H, Obata Y, Saigusa S, Sekine T, Isogai E, Fukumoto M.
-
Journal Title
PLoS One
Volume: 8(1)
Issue: 1
Pages: 1-7
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
