| Project/Area Number |
17K07237
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor therapeutics
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| Research Institution | Shizuoka Institute of Environment and Hygiene |
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Principal Investigator |
Ando Takayuki 静岡県環境衛生科学研究所, 医薬食品部, 主査 (40402226)
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| Co-Investigator(Kenkyū-buntansha) |
秋山 靖人 静岡県立静岡がんセンター(研究所), その他部局等, 研究員 (70222552)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 悪性脳腫瘍 / グリオーマ / 脳腫瘍 / 増殖抑制 / 低分子化合物 / 類縁体合成 / 抗がん剤 |
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| Outline of Final Research Achievements |
Novel glioblastoma multiforme (GBM) stem cell was isolated and identified by Dr Akiyama et al in Shizuoka Cancer Center. We found a salysilic acid derivative having the growth inhibition of adobe cell. The optimization of salycilic acid derivative which had inhibitory activity of Glioma cell of malignant brain tumor patient. Over two hundred analogs were designed and synthesized for the clarification of pharmacophore. Unfortunately, any analogs did not show the inhibitory activity. Unexpectedly, the heterocycles with bicycle aromatic ring containing nitrogen atom showed 10 times stronger activity than initial compound. Furthermore, that compound also showed the selective growth inhibition between normal and GBM stem cell.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性脳腫瘍は、未だに極めて難治性で予後の悪い疾患であり、手術後の集学的治療（放射線照射＋化学療法）にもかかわらず、再発や転移が発生する。現行のテモゾロミド(TMZ)の薬効は十分ではなく、TMZ 耐性となった症例では、現在有効な治療法は確立されていない。我々は、TMZ 耐性を示す要因としての悪性グリオーマがん性幹細胞(GBM)に着目し、創薬探索研究を目指した。TMZ 耐性GBMに直接作用し、死滅させるかもしくは増殖を完全に抑制する事が可能な化合物を見出すことに成功すれば、画期的な新規脳腫瘍治療薬へと応用可能であり、学術的にも社会的にも意義のある研究といえる。
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