Elucidation of the role of Wnt in tumor immunity of malignant glioma and its application to therapy

• Project/Area Number: 15K10338
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kagoshima University
• Principal Investigator: HIRANO Hirofumi 鹿児島大学, 医歯学域医学系, 准教授 (00264416)
• Co-Investigator(Kenkyū-buntansha): 岸田 昭世 鹿児島大学, 医歯学域医学系, 教授 (50274064) ; 米澤 大 鹿児島大学, 医学部・歯学部附属病院, その他 (50550076) ; 内田 裕之 鹿児島大学, 医学部・歯学部附属病院, その他 (80404482) ; 有田 和徳 鹿児島大学, 医歯学総合研究科, 客員研究員 (90212646)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: Wnt-5a / グリオーマ / 相互作用 / 免疫 / PD-L1 / 膠芽腫 / 生存期間 / マクロファージ / Wnt5a

Outline of Final Research Achievements

We studied the relationship between intratumoral expression of Wnt and expression of PDL-1 and therapeutic effect, but the correlation between Wnt5a and PD-L1 expression in glioblastoma was weak, and the expression level of PD-L1 in patients with glioblastoma did not show the difference in survival time.
In the analysis of Gene Expression Omnibus Database, there was PD-1 as a highly correlated gene candidate with Wnt-5a, but in vitro study the gene expression change related to immunosuppression of tumor cells by Wnt5a stimulation could not detected, and macrophage-mediated influence was no obvious in expression of immunity checkpoint-related genes.

Research Products

• [Journal Article] ATP7B expression in human glioblastoma is related to temozolomide resistance. (2018)
  • Author(s): Moinuddin FM, Hirano H, Shinsato Y, Higa N, Arita K, Furukawa T.
  • Journal Title: Oncology Letter Volume: 14 Pages: 7777-7782
  • DOI: 10.3892/ol.2017.7249
  • Peer Reviewed / Open Access
• [Journal Article] Antitumor activity of gemcitabine against high-grade meningioma in vitro and in vivo. (2017)
  • Author(s): Takeda H, Okada M, Kuramoto K, Suzuki S, Sakaki H, Sanomachi T, Seino S, Yoshioka T, Hirano H, Arita K, Kitanaka C.
  • Journal Title: Oncotarget. Volume: 8 Issue: 53 Pages: 90996-91008
  • DOI: 10.18632/oncotarget.18827
  • Peer Reviewed / Open Access
• [Journal Article] Anaplastic astrocytoma cells not detectable on autopsy following long-term temozolomide treatment: A case repor (2017)
  • Author(s): Hirano H, Kawahara T, Niiro M, Yonezawa H, Takajou T, Ohi Y, Kitazono I, Sakae K, Arita K
  • Journal Title: Molecular and Clinical Oncology Volume: 6 Issue: 3 Pages: 321-326
  • DOI: 10.3892/mco.2017.1160
  • Peer Reviewed / Open Access
• [Presentation] 悪性グリオーマに対する分子標的治療 (2017)
  • Author(s): 平野宏文
  • Organizer: 第22回 脳腫瘍レビュー
  • Invited
• [Presentation] 術中MRI使用経験と術中MRIの意義. (2017)
  • Author(s): 平野宏文，内田裕之，米澤大，羽生未佳，比嘉那優大，花田朋子，細山浩史，大吉達樹，花谷亮典，有田和徳
  • Organizer: 第22回日本脳腫瘍の外科学会
• [Presentation] Malignant brain tumor and the treatment (2017)
  • Author(s): 平野宏文
  • Organizer: International Conference on Translational Medicine and Health Sciences 2017
  • Int'l Joint Research
• [Presentation] 膠芽腫におけるPD-L1、MIB-1 LIと生存期間に関する検討 (2016)
  • Author(s): 比嘉那優大，平野宏文，米澤 大，内田裕之，大吉達樹，花谷亮典，有田和徳
  • Organizer: 第75回日本脳神経外科学会総会
  • Place of Presentation: 福岡国際会議場（福岡県福岡市博多区）
  • Year and Date: 2016-09-30
• [Presentation] 膠芽腫治療前後のMIB-1, PD-L1染色性と生存期間に関する検討 (2016)
  • Author(s): 平野宏文，比嘉那優大，米澤 大，内田裕之，羽生未佳，大吉達樹，花谷亮典，東拓一郎，有田和徳
  • Organizer: 第34回日本脳腫瘍病理学会
  • Place of Presentation: 東京コンファレンスセンター・有明（東京都江東区）
  • Year and Date: 2016-05-27