| Project/Area Number |
20K17627
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 55020:Digestive surgery-related
|
|---|
| Research Institution | Nara Medical University |
|---|
Principal Investigator |
Nakade Hiroshi 奈良県立医科大学, 医学部附属病院, 研究員 (90745796)
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Project Status |
Completed (Fiscal Year 2022)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | ユビキチン・プロテアソーム / 食道癌 / ユビキチン・プロテアソーム系 / Cullin4A / cullin4A / ユビキチンプロテアソーム |
|---|
| Outline of Research at the Start |
最難治癌である食道癌を対象疾患とし，従来とは異なる視点から新規癌治療法の開発および臨床応用に向けた基礎実験を行う点にある．腫瘍は様々な機序で増殖能や薬物治療抵抗性を獲得していることが明らかとなっているが，その機序の一つとしてユビキチン修飾系機能異常が挙げられる．腫瘍細胞増殖抑制や細胞死が効率的に誘導され，有効な抗腫瘍効果が発揮されるのみならず，転移抑制効果や抗癌剤，放射線療法感受性増強効果が得られると期待される． 悪性腫瘍のなかでも極めて予後不良である食道癌を対象として，癌の進展機序を解明するとともに，新規癌治療法としての有用性・安全性を検証し，臨床応用の実現を本研究の目的とする．
|
| Outline of Final Research Achievements |
We confirmed that CUL4A overexpression affects tumors' proliferative, invasive, and migratory capacities. Next, we examined the effect of combining CUL4A overexpression with chemotherapy or radiotherapy to inhibit tumor growth. At the time of planning, we thought that the addition of chemotherapeutic agents or radiotherapy to a cell line with CUL4A activity inhibition would have a significantly favorable therapeutic effect due to their synergistic effects, but such a result was not achieved. However, this was not the case. The reason for this is thought to be that each treatment has its mechanism of action. We planned to create a liver metastasis model, but it did not grow well after transplantation. We will continue to investigate the cause and continue the experiment. We plan to summarize the above results and discuss them in a future issue.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究ではヒト食道癌においてCUL4Aの発現と癌の進展機序を解明し，臨床応用可能な新たな集学的治療戦略の開発を目的である．CUL4Aは腫瘍増殖や浸潤，転移の重要な役割を担い，治療抵抗性の一因であるがゆえ，治療標的になりうるのではないかという点が本研究の成果の学術的意義や社会的意義と考える。
|
