Pathogenesis and management of carcinogenic cholangiopathy induce by deteriorated lipids
| Project/Area Number |
16K09396
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Hiroshima University |
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Principal Investigator |
Tazuma Susumu 広島大学, 病院(医), 教授 (80201614)
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| Co-Investigator(Kenkyū-buntansha) |
菅野 啓司 広島大学, 病院(医), 准教授 (30448237)
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| Research Collaborator |
Kishikawa Nobusuke
Kobayashi Tomoki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 変性脂質 / EMT / ペリオスチン / ＥＭＴ / アポトーシス / コランギオパチー / 胆管 / 劣化脂質 / 腫瘍性コランギオパチー / 硬化性胆管炎 / 胆道がん |
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| Outline of Final Research Achievements |
Whether deteriorated lipids (DLs)induce carcinogenic cholangiopathy was studied in order to determine in part the pathogenesis and management of biliary carcinogenesis following cholangiopathy in biliary systems. As a result, DLs induced apoptosis of human bile duct cells in a dose-dependent, time-dependent manner, along with the enhanced expression of periostin and SASP factors, leading to epitherial-mesenchymal transition (EMT). These changes were cancelled by neutralized antibody for integrins, suggesting a future therapeutic strategy.
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| Academic Significance and Societal Importance of the Research Achievements |
変性脂質が惹起する腫瘍性コランギオパチーにおけるペリオスチンの役割が明らかとなり、
１）SASPを介すること、２）EMT関連遺伝子およびタンパク発現増強と連動しており肝胆道系発がんとの関連が示唆されたこと、３）上記はインテグリンを介する現象であり、その中和抗体により抑制されたことから、①脂質に関する食生活習慣制御、②脂質吸収阻害薬（NPC1L1阻害薬）による治療介入、③SASP因子やインテグリンに対する生物製剤などが治療戦略として提案されることを示唆した。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Periostin promotes malignant potential by induction of epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma2017
Author(s)
Mino M, Kanno K, Okimoto K, Sugiyama A, Kishikawa N, Kobayashi T, Ono J, Izuhara K, Kobayashi T, Ohigashi T, Ohdan H, Tazuma S
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Journal Title
Hepatol Commun
Volume: 1
Issue: 10
Pages: 1099-1109
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Periostin promotes malignant potential by induction of epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma.2017
Author(s)
Sugiyama A, Mino M, Kanno K, Ono J, Kishikawa N, Kobayashi T, Kobayashi T, Ohdan H, Tazuma S.
Organizer
The 118th AGA meeting (May 6-9, 2017, Chicago, Illinois)
Place of Presentation
Chicago, USA
Related Report
Int'l Joint Research
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