Treatment strategy of ovariam cancer, targeting the new programed all dezth, "Ferroptosis".
| Project/Area Number |
18K09257
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
|
|---|
| Research Institution | Gifu University |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
竹中 基記 岐阜大学, 医学部附属病院, 助教 (20566484)
上田 陽子 岐阜大学, 医学部附属病院, 医員 (20795075)
鈴木 紀子 岐阜大学, 大学院医学系研究科, 助教 (40642096)
森 美奈子 岐阜大学, 医学部附属病院, 助教 (60585610)
|
|---|
| 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: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | 卵巣癌 / フェントン反応 / フェロトーシス / オートファジー / フェリチン / 二価鉄 / 卵巣がん / 鉄依存性 / 細胞死 / RAS変異 / エラスチン / 活性酸素 |
|---|
| Outline of Final Research Achievements |
The mechanism of action of elastin, an inducer of ferrotosis, is to inhibit the function of the cystine transporter, thereby suppressing cystine uptake into the cell, leading to a decrease in intracellular glutathione and consequently an increase in the amount of intracellular reactive oxygen species produced by the Fenton reaction from divalent iron, resulting in lipid oxidation and cell death. This is the mechanism that induces lipid oxidation and cell death. This effect was also observed with sulfasalazine.
On the other hand, artesunate did not affect the cystine transporter activity, but promoted ferritin-specific autophagy (ferritinophagy), which released ferritin-bound iron, increased intracellular divalent iron, and increased the amount of intracellular ROS produced by the Fenton reaction.
|
| Academic Significance and Societal Importance of the Research Achievements |
卵巣がんでは粘液性癌、（低異型）漿液性癌、明細胞癌などの一部にRas変異が認められており、これらは抗がん剤抵抗性である。これらの化学療法抵抗性腫瘍に対して有用な抗がん剤を見つけ出すためにはがんの原因となるドライバー変異の解析だけでなく、異なるプログラム細胞死を誘導する抗がん剤の開発が重要となる。その点においてRas変異卵巣がんにおけるフェロトーシスの解析と誘導薬の研究は抗がん剤抵抗性の卵巣がん治療薬の開発につながりうるものである。
|
Report
(4 results)
Research Products
(23 results)
-
[Journal Article] Efficacy and safety of 5 mg olanzapine combined with aprepitant, granisetron and dexamethasone to prevent carboplatin-induced nausea and vomiting in patients with gynecologic cancer: A multi-institution phase II study.2020
Author(s)
Iihara H, Shimokawa M, Hayasaki Y, Fujita Y, Abe M,Takenaka M, Yamamoto S, Arai T, Sakurai M, Mori M, Nakamura K, Kado N, Murase S, Shimaoka R, Suzuki A, Morishige KI
-
Journal Title
Gynecol Oncol
Volume: 156
Issue: 3
Pages: 629-635
DOI
Related Report
Peer Reviewed
-
-
-
-
[Journal Article] Study protocol for an open-label, single-arm, multicentre phase II trial to evaluate the efficacy and safety of combined triplet therapy and olanzapine for prevention of carboplatin-induced nausea and vomiting in gynaecological cancer patients2019
Author(s)
Iihara H, Shimokawa M, Abe M, Hayasaki Y, Fujita Y, Nagasawa Y, Sakurai M, Matsuoka R, Suzuki A, Morishige K-I
-
Journal Title
BMJ Open 2019
Volume: 9
Issue: 1
Pages: e024357-e024357
DOI
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
