Analysis of carcinogenesis originated from chronic inflammation in malignant lymphoma

• Project/Area Number: 17K09920
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Gifu University
• Principal Investigator: Tsurumi Hisashi 岐阜大学, 大学院医学系研究科, 非常勤講師 (00313891)
• Co-Investigator(Kenkyū-buntansha): 原 武志 岐阜大学, 大学院医学系研究科, 非常勤講師 (10456501) ; 齋藤 邦明 藤田医科大学, 保健学研究科, 教授 (80262765) ; 後藤 尚絵 岐阜大学, 大学院医学系研究科, 非常勤講師 (80444280)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 悪性リンパ腫 / GP88 / progranulin / 悪性リンパ;腫 / ＴＮＦ / GP８８ / 慢性炎症

Outline of Final Research Achievements

We investigated the role of GP88 (progranulin), which binds to the TNF receptor in the patients with malignant lymphoma. Serum levels of GP88 was measured by the ELISA. GP88 protein expression was examined by immunohistochemistry. We found a case in which GP88 was strongly expressed in lymphoma cells. High levels of serum GP88 was a significantly poor prognosis factor in the patients with diffuse large B-cell lymphoma.

Academic Significance and Societal Importance of the Research Achievements

悪性リンパ腫の慢性炎症からの発がんは疫学的に証明されているが、その分子的機序については、本質的な発がんと慢性炎症を線引きするような決定的な分子の発見には至っていない。本研究にて、TNFαと結合を同じくするGP88が血液中で上昇している悪性リンパ腫は予後不良であることを明らかにした。GP88をターゲットとした悪性リンパ腫の、あらたな分子標的薬剤の開発に寄与するものと考えられる。さらには、同じくGP88高発現による難治性悪性腫瘍などへの応用も十分可能である。

Research Products

• [Journal Article] Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy. (2020)
  • Author(s): Ninomiya S, Nakamura N, Nakamura H, Mizutani T, Kaneda Y, Yamaguchi K, Matsumoto T, Kitagawa J, Kanemura N, Shiraki M, Hara T, Shimizu M, Tsurumi H.
  • Journal Title: Nutrients Volume: 12 Issue: 4 Pages: 978-978
  • DOI: 10.3390/nu12040978
  • Peer Reviewed / Open Access
• [Journal Article] Association between increased serum GP88 (progranulin) concentrations and prognosis in patients with malignant lymphomas. (2017)
  • Author(s): Yamamoto Y, Goto N, Takemura M, Yamasuge W, Yabe K, Takami T, Miyazaki T, Takeuchi T, Shiraki M, Shimizu M, Adachi S, Saito K, Shibata Y, Nakamura N, Hara T, Serrero G, Saito K, Tsurumi H.
  • Journal Title: Clin Chim Acta Volume: 473 Pages: 139-146
  • DOI: 10.1016/j.cca.2017.07.024
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Indoleamine 2, 3-dioxygenasase (IDO) as a prognostic factor of hematological malignancies. (2018)
  • Author(s): Hara T, Shibata Y, Mabuchi R, Matsumoto T, Nakamura N, Nakamura H, Ninomiya S, Kitagawa J, Kanemura N, Fukuno K, Tsurumi H.
  • Organizer: 第80回日本血液学会学術集会