Analysis of lysosome in pancreatic cancer
| Project/Area Number |
17K16584
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | Jikei University School of Medicine |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | 膵臓癌 / Lysosome / オートファジー / 酸性αグルコシダーゼ / 酸性さらみだーぜ / アデノウイルスベクター / 抗癌剤耐性 / 遺伝子治療 / ライソゾーム |
|---|
| Outline of Final Research Achievements |
Anticancer drug resistance in unresectable pancreatic cancer was investigated focusing on lysosomal enzymes. We used human pancreatic cancer cell line and an animal model. Microarray analysis identified a group of lysosomal enzymes whose requirements were increased by anticancer drugs. Above all, elevated levels of enzymes related to glucose and lipid metabolism such as acid α-glucosidase and acid ceramidase were observed. RNA interference was performed with these enzymes as targets, and the cell growth inhibitory effect was confirmed. Inhibition of acid α-glucosidase caused abnormal mitochondrial accumulation and cell apoptosis. Inhibition of acid ceramidase caused cell death by intracellular accumulation of ceramide and ROS. Gene therapies using an adeno virus vector were verified in a mouse model, and the tumor growth inhibitory effects were confirmed.
|
| Academic Significance and Societal Importance of the Research Achievements |
切除不能膵臓癌には塩酸ゲムシタビンを中心とした化学療法が適応されている。生存期間中央値は7-9カ月と予後不良であり、抗癌剤耐性を示す症例に対する新たな治療法の開発が必要である。我々は抗癌剤耐性に関与するオートファジー機構の実態であるライソゾーム酵素に着目し、抗癌剤投与によって細胞内の要求が上昇する酵素群を特定し、その酵素を阻害することで抗癌体制を改善する方法を培養細胞および動物実験モデルで明らかにした。当該研究の結果は将来的に抗癌剤耐性を改善させ、膵臓癌化学療法の奏功率を大きく改善させる可能性がある。
|
Report
(4 results)
Research Products
(7 results)
-
[Presentation] Inhibition of lysosomal enzyme activity enhances antitumor effect of gemcitabine in pancreatic cancer cells.2019
Author(s)
Ryoga Hamura, Yoshihiro Shirai, Nobuhiro Saito, Tomohiko Taniai, Yohta Shimada, Takashi Horiuchi, Hiroshi Sugano, Naoki Takada, Yumi Kanegae, Toya Ohashi, Katsuhiko Yanaga
Organizer
14th Annual Academic Surgical Congress
Related Report
Int'l Joint Research
-
[Presentation] 抗癌剤耐性膵癌におけるライソソーム酵素の機能解析と遺伝子制御による塩酸ゲムシタビンの抗腫瘍効果増強の試み2019
Author(s)
羽村凌雅, 矢永勝彦, 白井祥睦, 谷合 智彦, 斉藤庸博, 嶋田洋太, 堀内 尭, 菅野 宏, 高田直樹, 鐘ヶ江裕美, 大橋十也, 大木隆生
Organizer
第119回 日本外科学会定期学術集会
Related Report
-
[Presentation] Down-regulation of acid-α glucosidase induce antitumor effect via mitochondrial dysfunction in pancreatic cancer cell2019
Author(s)
Ryoga Hamura, Yoshihiro Shirai, Nobuhiro Saito, Tomohiko Taniai, Yohta Shimada, Takashi Horiuchi, Hiroshi Sugano, Naoki Takada, Yumi Kanegae, Toya Ohashi, Katsuhiko Yanaga
Organizer
第78回 日本癌学会学術集会
Related Report
-
-
[Presentation] Inhibition of lysosomal enzyme activity enhances antitumor effect of gemcitabine in pancreatic cancer cells.2019
Author(s)
Hamura R, Shirai Y, Saito N, Taniai T, Shimada Y, Horiuchi T, Sugano H, Takada N, Kanegae Y, Ohashi T, Yanaga K.
Organizer
14th Annual Academic Surgical Congress (ASC)
Related Report
Int'l Joint Research
-
[Presentation] 抗癌剤耐性膵癌におけるライソソーム酵素の機能解析と遺伝子制御による塩酸ゲムシタビンの抗腫瘍効果増強の試み2019
Author(s)
羽村凌雅, 矢永勝彦, 白井祥睦, 谷合 智彦, 斉藤庸博, 嶋田洋太, 堀内 尭, 菅野 宏, 高田直樹, 鐘ヶ江裕美, 大橋十也, 大木隆生.
Organizer
第119回 日本外科学会定期学術集会
Related Report
-
[Presentation] Suppression of lysosomal enzyme improves chemoresistance in pancreatic cancer cells.2018
Author(s)
Hamura R, Shirai Y, Saito N, Taniai T, Shimada Y, Horiuchi T, Sugano H, Takada N, Kanegae Y, Ohashi T, Yanaga K
Organizer
第77回 日本癌学会学術総会
Related Report
