| Project/Area Number |
17K16696
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | エリブリン / 低酸素 / Hypoxia-inducible factor / 薬剤耐性 / 悪性末梢神経鞘腫瘍 / 平滑筋肉腫 / Tubulin / 骨軟部腫瘍 / 肉腫 / 微小管 / HIF-1α / 癌 / 化学療法 |
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| Outline of Final Research Achievements |
Primary MPNST cases showed the negative correlation between the nuclear expression of HIF-1α and prognosis. We also clarified that inhibition of HIF-1α signaling suppressed growth and caused apoptosis in MPNST cells. Thus, we believe that the status of HIF-1α nuclear expression will provide useful prognostic information in patients with MPNSTs, and that HIF-1α signaling is a promising molecular target for novel therapeutic agents for MPNSTs.
An eribulin-resistant leiomyosarcoma cell line was developed which lead to the finding that TUBB3 overexpression induced chemoresistance to eribulin and knockdown of TUBB3 expression by siRNA led to chemosensitization. TUBB3 has the potential to be a therapeutic target to overcome eribulin resistance and a biomarker for selection of drug treatment.
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| Academic Significance and Societal Importance of the Research Achievements |
エリブリンは腫瘍増殖を抑えるだけでなく腫瘍内の低酸素環境を改善することが知られている。HIFは低酸素で誘導される増殖因子であるが悪性末梢神経鞘腫瘍においてHIF-1αが恒常的に発現かつ予後不良と関係し、これを抑えると悪性末梢神経鞘腫瘍の増殖を抑制することが可能であることを示した。また、エリブリン耐性平滑筋肉腫株を作成しエリブリンの作用点であるTubulinのサブユニットのうちTubulinβ3の高発現が耐性化に関与していることを示しエリブリン感受性マーカーとなり得る可能性を見出した。
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