2018 Fiscal Year Final Research Report
An attempt to achieve both controlling local tumors and repressing distant metastases through exploiting analytical findings concerning characteristics of intratumor microenvironment
| Project/Area Number |
15H04295
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
永澤 秀子 岐阜薬科大学, 薬学部, 教授 (90207994)
田野 恵三 京都大学, 複合原子力科学研究所, 准教授 (00183468)
真田 悠生 京都大学, 複合原子力科学研究所, 助教 (50738656)
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| Research Collaborator |
TAKEDA Shun-ichi
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 休止期腫瘍細胞 / 腫瘍内微小環境 / 中性子捕捉療法 / 転移 / ゲノム改変操作 |
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| Outline of Final Research Achievements |
The p53 status of tumor cells in the local tumor influenced the distribution efficiency of 10B from 10B compounds, which are essential for neutron capture therapy, and the sensitivity to gamma-ray irradiation. The effect on the sensitivity to gamma-rays were efficiently suppressed by irradiation using high linear energy transfer radiation or reactor neutron beams. In addition, large recovery capacity from gamma-ray-induced damage in oxygenated quiescent tumor cells was efficiently suppressed with antidiabetic drug metformin. Hypoxia-inducible factor 1-alpha deficiency in tumor cells increased the metformin sensitivity under glucose deprivation or hypoxia, and the sensitivity to gamma-ray irradiation in combination with metformin. On the other hand, the higher the operation power of the reactor at the time of neutron capture therapy for the tumors implanted in the experimental animal, the higher the therapeutic effect.
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| Free Research Field |
放射線腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍細胞のp53 statusや低酸素誘導因子の欠損の有無などゲノム特性によって、癌治療効果が変化し、悪性腫瘍に多いp53変異型腫瘍細胞では、その効果が低下する。高線エネルギー付与放射線照射はこの低下を効率よく抑制し、中性子捕捉療法では、全腫瘍細胞と休止期腫瘍細胞との間の10B分布量の差が、p53 statusの変異によってp53野生型より小さくなるために、腫瘍全体としてより均一な線量の付与が可能となり病変部全体としての制御可能性が高まる。さらには、中性子捕捉療法施行時に用いる原子炉の運転出力は高い方が、殺腫瘍細胞効果も高まるので、治療に必要な照射時間は短くても十分な治療効果を期待できる。
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