Development of new treatments of non-viral hepatocellular carcinoma through targeting microbiota
| Project/Area Number |
20K17658
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 55020:Digestive surgery-related
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
Mima Kosuke 熊本大学, 病院, 特任助教 (00546559)
|
|---|
| Project Period (FY) |
2020-04-01 – 2022-03-31
|
| Project Status |
Completed (Fiscal Year 2021)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 肝細胞癌 / 肝転移 / 腸内細菌 / 免疫細胞 / フレイル / Fusobacterium nucleatum / 日常生活自立度 / 非B非C型 / 糖尿病 / 免疫 |
|---|
| Outline of Research at the Start |
熊本大学消化器外科では年間500例以上の消化器癌手術が行われ、600例以上の肝癌切除例の切除標本が凍結組織、パラフィン包埋組織として管理されている。さらに手術のみならず、患者背景、腫瘍因子、手術因子、化学療法、生活背景、予後がデータベースに管理されている。本研究では多数例のヒト非B非C型肝細胞癌組織中の細菌叢や腸内細菌叢を網羅的に解析し、臨床データと組み合わせて解析することで非B非C型肝細胞癌の進展や抗腫瘍免疫応答に関わる細菌の同定を試みる。さらにマウスモデルを用いて、そのメカニズムを解明する。本研究結果は細菌を標的とした非B非C肝細胞癌に対する新たな治療法の開発につながることが期待される。
|
| Outline of Final Research Achievements |
Evidence suggests that the gut microbiome inhibits antitumor immune responses and promotes the development of gastrointestinal cancer. The liver is exposed to bacteria via blood through the portal vein has many immune cells such as T-cells and macrophages. We found that high TAN (tumor associated neutrophils) (p=0.0398), low CD8+ cells (p=0.0275), and high TAM (tumor associated macrophages) (p=0.001) were significantly associated with worse overall survival (OS), and that high TAN (p=0.010), and high TAM (p=0.00125) were significantly associated with worse disease-free survival (DFS).
|
| Academic Significance and Societal Importance of the Research Achievements |
肝細胞癌は、本邦はもちろん国際的に罹患数・死亡数が多い癌で、予後不良の疾患である。近年本邦において 肝炎ウイルス感染を伴わない肝細胞癌が増加している。本研究により、肝細胞癌組織中の免疫細胞が肝細胞癌の発育進展に重要な役割を果たしていることが明らかとなり、本研究の成果は細菌を標的とした非B非C型肝細胞癌の新たな治療法の開発のための有益な情報となることが期待される。
|
Report
(3 results)
Research Products
(22 results)
-
-
-
-
[Journal Article] The Sulfur Microbial Diet and Risk of Colorectal Cancer by Molecular Subtypes and Intratumoral Microbial Species in Adult Men2021
Author(s)
Sikavi DR, Nguyen LH, Haruki K, Ugai T, Ma W, Wang DD, Thompson KN, Yan Y, Branck T, Wilkinson JE, Akimoto N, Zhong R, Lau MC, Mima K, Kosumi K, Morikawa T, Rimm EB, Garrett WS, Izard J, Cao Y, Song M, Huttenhower C, Ogino S, Chan AT.
-
Journal Title
Clinical and Translational Gastroenterology
Volume: 12
Issue: 8
Pages: e00338-e00338
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
[Journal Article] Frailty is an independent risk factor for recurrence and mortality after curative resection in patients with stage I-III colorectal cancer2020
Author(s)
Mima K, Kurashige J, Miyanari N, Morito A, Yumoto S, Matsumoto T, Kosumi K, Inoue M, Mizumoto T, Kubota T, Baba H
-
Journal Title
Ann Gastroenterol Surg
Volume: -
Issue: 4
Pages: 405-412
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
[Presentation] Preoperative impairment of activities of daily living is a risk factor for mortality following resection of hepatocellular carcinoma2021
Author(s)
Kosuke Mima, Katsunori Imai, Shigeki Nakagawa, Takashi Matsumoto, Shotaro Kinoshita, Kazuki Matsumura, Fumimasa Kitamura, Norio Uemura, Takayoshi Kaida, Hiromitsu Hayashi, Yo-ichi Yamashita, Hideo Baba
Organizer
第80回日本癌学会学術総会
Related Report
-
-
-
-
-
