Identification of radio-resistance factors for glioblastoma and construction of personalized treatment aimed at overcoming them
| Project/Area Number |
18K08957
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 56010:Neurosurgery-related
|
|---|
| Research Institution | Chiba Cancer Center (Research Institute) |
|---|
Principal Investigator |
Iuchi Toshihiko 千葉県がんセンター(研究所), 脳神経外科, 部長 (80370881)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 神経膠芽腫 / 放射線耐性 / 細胞周期チェックポイント / NFkB / microglia / 間葉系分化誘導 / 放射線治療抵抗性 / DNA修復関連遺伝子 / NF-kB / マイクログリア / 遺伝子発現 / TNF alpha / cell cycle checkpoint / irradiation / temozolomide / DNA damage repair / glioblastoma / radiation / molecule / personalized treatment |
|---|
| Outline of Final Research Achievements |
The changes in gene expression levels before and after radiotherapy in glioblastoma were verified by enrichment analysis. The expression of DNA repair-related genes was rather reduced by radiation therapy. On the other hand, in addition to the upregulation of inflammatory genes such as IFNa / IFNb, upregulation of TNFa via NFkB was confirmed, and upregulation of IL6 / JAK / STST3 was also observed. From these results, radiation therapy induces the activity of NKkB and the accompanying increase in TNFa expression from microglia, and the increased expression of IL6 / JAK / STAT3 induces the differentiation of tumor stem cells from the anterior nervous system to the mesenchymal system. It was suggested that such changes in the induction of tumor stem cell differentiation play a certain role in radiation resistance.
|
| Academic Significance and Societal Importance of the Research Achievements |
放射線治療に対する治療抵抗性は、これまでDNA修復の観点から主に研究されてきた。今回の検討で、これとは別に放射線被曝後にマイクログリアの誘導を介して腫瘍幹細胞の分化誘導を前神経系から間葉系に変化させることも、放射線耐性の獲得とその後の治療抵抗性に関与していることが示唆され、その課程に於いて NFkBの活性化が重要な役割を担っていることが判明した。この様に、単に DNAが修復されることのみならず、腫瘍の微小環境の変化が放射線耐性に関与していることが判明して事により、今後治療抵抗性克服の標的分子として、NFkBをはじめとしたいくつかの分子を同定することができた。
|
Report
(4 results)
Research Products
(6 results)
