Elucidation of the mechanism of the refractory neuroblastoma using Patient-Derived Orthotopic Xenograft

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18022
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Chiba University
• Principal Investigator: Shinno Yoshitaka 千葉大学, 大学院医学研究院, 特任研究員 (90815094)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 神経芽腫 / PDOX / がん幹細胞

Outline of Final Research Achievements

We performed a transplantation of tumor experiment derived from patients using an immunodeficiency mouse, but did not engraft. Therefore, we transplanted the thing which concentrated cancer stem cells by the Neurosphere formation method, but, after all, did not engraft. We paid our attention to EZH1 which is one of the polycomb complex PRC2 subunits. EZH1 expression was increased when neuroblastoma cell line changed in sphere. The knockdown of EZH1 resulted in cell death by the apoptosis in the several cell line. By the microarrays method and the ChIP sequence method, EZH1 coordinated the expression of gene cluster about cell cycle in collaboration with MYCN. We can develop a new therapy for the refractory neuroblastoma by EZH1 inhibition.

Free Research Field

小児外科

Academic Significance and Societal Importance of the Research Achievements

神経芽腫は小児悪性固形腫瘍としては脳腫瘍に次いで多く、良性に近いものから極めて悪性度の高いものまで、多彩なcharacterを示す腫瘍である。進行神経芽腫は集学的治療により約７割が寛解となるが、その約半数は再発をきたす。再発腫瘍は治療抵抗性を獲得し、様々なサルベージ治療が奏功せずに不幸な転帰をたどる場合が多い。今回の研究では神経芽腫の難治性に関わるとされる、がん幹細胞を標的とした治療の可能性を示した。今後標的遺伝子の同定と阻害効果を検討したい。