Research Project
Grant-in-Aid for Scientific Research (B)
膵癌では術前化学放射線療法が推奨されているが,ほかの癌にくらべて効果は低い.その理由に,治療に対する感受性の低さがあげられる.したがい,耐性メカニズムの解明は予後改善のブレイクスルーになる.一方,我々は,抗癌剤や放射線耐性を有する膵癌細胞株の樹立に成功し,網羅的な遺伝子解析の結果IL-1RIに着目した.我々は既に,IL-1RIを介するシグナルが膵癌の浸潤や転移に関与することを世界に先駆けて報告した.IL-1RIの拮抗薬IL-1raは他疾患で認可されており,膵癌臨床への応用が可能と考える.本研究では,抗癌剤及び放射線耐性のメカニズムの解明と,IL-1RIの機能解析および新規治療薬の開発を目指す.
The prognosis for pancreatic cancer is extremely poor, and recurrence occurs quickly even after radical surgery. Currently, preoperative chemoradiotherapy is recommended, but it is less effective than for other cancers. One reason for this is low sensitivity to treatment. Therefore, elucidating the resistance mechanism and increasing the sensitivity of preoperative treatment will lead to truly curative surgery and will be a breakthrough in improving prognosis. Meanwhile, we succeeded in establishing a pancreatic cancer cell line that is resistant to anticancer drugs and radiation, and as a result of comprehensive genetic analysis, we focused on IL-1RI, a cell membrane receptor for pancreatic cancer. In this study, we revealed that IL-1RI expression increases with resistance, and that it contributes to the tumor progression of pancreatic cancer through NF-κB signaling.
今回着目したIL-1RIの拮抗薬であるIL-1R antagonist(IL-1ra)はすでに欧米で関節リウマチに対して使用されており,膵癌においても臨床応用への実現性が高いと考えている.我々の研究室ではこれまでにIL-1/ IL-1RIシグナルが転写因子NF-κBを活性化し,血管新生因子や接着能や浸潤能を制御していることを世界に先駆けて報告しているが,抗癌剤耐性化によるこれらの機能の変化は未知数である.IL-1/ IL-1RIシグナルを制御することでGem感受性を高め,浸潤や微小転移を術前に今まで以上に制御することができれば,手術の根治性が高まりさらなる予後の改善につながると考える。
All 2024 2023 2022 2021
All Journal Article (23 results) (of which Open Access: 21 results, Peer Reviewed: 15 results) Presentation (22 results) (of which Int'l Joint Research: 3 results)
Cancer Science
Volume: - Issue: 6 Pages: 1964-1978
10.1111/cas.16173
Nutrients
Volume: 16 Issue: 5 Pages: 705-705
10.3390/nu16050705
Molecular and Clinical Oncology
Volume: 20 Issue: 1
10.3892/mco.2023.2700
Volume: 15 Issue: 24 Pages: 5064-5064
10.3390/nu15245064
Volume: 114 Issue: 12 Pages: 4571-4582
10.1111/cas.15980
Oncology Reports
Volume: 50 Issue: 3
10.3892/or.2023.8606
10.3892/or.2023.8601
Anticancer Research
Volume: 43 Issue: 5 Pages: 2333-2341
10.21873/anticanres.16398
BMC Surgery
Volume: 23 Issue: 1
10.1186/s12893-023-01949-0
Volume: 49 Issue: 3
10.3892/or.2023.8489
Scientific Reports
Volume: 12 Issue: 1 Pages: 419-419
10.1038/s41598-021-04335-z
Pancreas
Volume: 51 Issue: 4 Pages: e69-e71
10.1097/mpa.0000000000002038
Volume: 47 Issue: 4 Pages: 68-68
10.3892/or.2022.8279
Volume: 42 Issue: 3 Pages: 1277-1288
10.21873/anticanres.15594
Indoor Air
Volume: 32 Issue: 2
10.1111/ina.12988
Volume: 47 Issue: 6
10.3892/or.2022.8323
Volume: 47 Issue: 4
10.3892/or.2022.8289
Volume: 47 Issue: 3
10.3892/or.2022.8259
Volume: 14 Issue: 1 Pages: 42-42
10.3390/nu14010042
Carcinogenesis
Volume: - Issue: 7 Pages: 940-950
10.1093/carcin/bgab017
World Journal of Surgical Oncology
Volume: 19 Issue: 1
10.1186/s12957-021-02290-7
Volume: 45 Issue: 5 Pages: 1-9
10.3892/or.2021.8006
Volume: 21 Issue: 1
10.1186/s12893-021-01096-4