Elucidation of new testing method in refractory multiple myeloma

• Project/Area Number: 20K08746
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Asahikawa Medical College
• Principal Investigator: Shindo Motohiro 旭川医科大学, 医学部, 講師 (10396377)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 多発性骨髄腫

Outline of Research at the Start

多発性骨髄腫は再発・難治性で、複数の新規薬剤が登場しているが未だ十分な生命予後を得ているとは言えず、更なる治療法の開発が求められている。多発性骨髄腫マウスでは骨髄低酸素環境で骨髄腫細胞増殖が増強されることから、治療戦略として骨髄低酸素の解除が有用である可能性がある。申請者の教室では、癌微小環境における腫瘍血管の重要性に着目し、マウス腫瘍モデルへの健常血管前駆細胞(VPC)移植が、腫瘍血流是正の結果、癌の低酸素応答を解除し腫瘍退縮も来すという事実を明らかにしている。本研究ではVPC移植によって腫瘍血流是正・低酸素解除を引き出し、骨髄腫難治例に対する治療法開発の糸口とする。

Outline of Final Research Achievements

Cell-free DNA (cfDNA) is an extracellular free DNA fragment that contains circulating tumor DNA (ctDNA). Recent studies have shown that cfDNA is useful for diagnosis and examining treatment efficacy in neoplastic disease. In this study, we investigated the genetic mutation of ctDNA in multiple myeloma patients and followed test results over time. From this study, we have found that the analysis of cfDNA is useful for monitoring disease status in patients with KRAS mutation. This finding suggests that cfDNA obtained from a blood test can be used to study disease status instead of bone marrow aspiration, which is more invasive.

Academic Significance and Societal Importance of the Research Achievements

本研究では、侵襲の大きい骨髄穿刺検査に代わり、より侵襲の少ない血液検査による検体を用いることが特色である。血漿由来のcfDNAを用いた経時的解析が多発性骨髄腫の治療評価に有用である可能性が示された。

Research Products

• [Journal Article] Centrally administered GLP-1 analogue improves intestinal barrier function through the brain orexin and the vagal pathway in rats. (2023)
  • Author(s): Funayama T, Nozu T, Ishioh M, Igarashi S, Sumi C, Saito T, Toki Y, Hatayama M, Yamamoto M, Shindo M, Tanabe H, Okumura T.
  • Journal Title: Brain Res. Volume: 1809 Pages: 148371-148371
  • DOI: 10.1016/j.brainres.2023.148371
  • Peer Reviewed
• [Journal Article] Ghrelin prevents lethality in a rat endotoxemic model through central effects on the vagal pathway and adenosine A2B signaling : Brain ghrelin and anti-septic action. (2023)
  • Author(s): Igarashi S, Nozu T, Ishioh M, Funayama T, Sumi C, Saito T, Toki Y, Hatayama M, Yamamoto M, Shindo M, Tanabe H, Okumura T.
  • Journal Title: J Physiol Biochem. Volume: - Issue: 3 Pages: 625-634
  • DOI: 10.1007/s13105-023-00962-4
  • Peer Reviewed
• [Journal Article] Cytomegalovirus infection in patients with malignant lymphomas who have not received hematopoietic stem cell transplantation. (2022)
  • Author(s): Sato K, Igarashi S, Tsukada N, Inamura J, Yamamoto M, Shindo M, Moriichi K, Mizukami Y, Fujiya M, Torimoto Y.
  • Journal Title: BMC Cancer. Volume: 22 Issue: 1 Pages: 944-944
  • DOI: 10.1186/s12885-022-10008-5
  • Peer Reviewed / Open Access
• [Journal Article] Late-onset posttransplant Epstein-Barr virusrelated lymphoproliferative disease after cord blood transplantation for chronic active Epstein Barr virus infection: A case report. (2022)
  • Author(s): Yamamoto M, Shindo M, Funayama T, Sumi C, Saito T, Toki Y, Hatayama M, Imadome KI, Mizukami Y, Okumura T.
  • Journal Title: Medicine (Baltimore). Volume: 101 Issue: 12 Pages: e29055-e29055
  • DOI: 10.1097/md.0000000000029055
  • Peer Reviewed / Open Access
• [Presentation] Liquid biopsy with cfDNA in plasma could predict disease progression in a case of multiple myeloma (2022)
  • Author(s): 山本昌代、進藤基博、船山拓也、鷲見千紘、齋藤豪志、畑山真弓、土岐康通、小野裕介、水上裕輔、谷野美智枝、奥村利勝
  • Organizer: 第84回日本血液学会学術集会