| Project/Area Number |
22K16307
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | Senolysis / 抗がん剤 / senolysis / 悪性リンパ腫 |
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| Outline of Research at the Start |
グルタミン代謝阻害による老化細胞除去に関する最近の発見に着想を得て高齢者血液悪性疾患における化学療法の有害事象軽減と抗腫瘍効果向上を最適化する学術基盤を構築する。老化細胞由来の種々の老化促進物質を減少させ、全身の生体機能が向上する可能性が注目されている。申請者は、リンパ腫モデル老齢マウスに抗がん剤治療であるCHOP療法とグルタミン代謝阻害薬を併用することにより、CHOP療法単独群と比較し、老化に伴い顕在化しやすい抗がん剤による臓器障害・副作用を軽減し、抗腫瘍効果が増強出来る可能性を検証する。
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| Outline of Final Research Achievements |
Old mice were injected subcutaneously EL4 T-cell lymphoma cells. Mice were treated either with BPTES (an inhibitor of glutaminase 1) +CHOP, BPTES, CHOP or PBS as control. Survival and counts of peripheral blood cell were evaluated. CHOP groups were received three cycles of chemotherapy. BPTES groups were received BPTES three times a week from day 0 to day 22.
Counts of white blood cell and platelet in the CHOP+BPTES group were significantly higher than those in the CHOP group (p<0.05). There was no significant difference in survival between the CHOP+BPTES group and CHOP group, but a prolongation of survival was observed in the BPTES group compared with the control group (Hazard Ratio 0.53). <Conclusion>Our results raise a possibility that combined use of BPTES with CHOP would reduce cytopenia caused by chemotherapy. In addition, the BPTES group showed a prolongation of survival compared to the control group, suggesting the potential antitumor effect of BPTES.
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| Academic Significance and Societal Importance of the Research Achievements |
造血器腫瘍高齢患者では臓器予備能や併存疾患から抗がん剤を減量せざるを得ない場合、血球減少時の感染症の併発に伴い治療再開が遷延し、dose intensityが維持できない場合、十分な治療ができずに再発する場合も多く、高齢化が著しい我が国において、安全で有効性の高い高齢血液悪性腫瘍患者の治療戦略の確立は急務の課題である。
グルタミン代謝阻害薬によるsenolysisを活用し、高齢造血器腫瘍患者の臓器機能改善を介して、化学療法の有害事象や合併症を軽減し、若年者と同等の強度の治療を行なうことが期待される。加えて、グルタミン代謝阻害そのものによる抗腫瘍効果によって効果を増強できる可能性も期待できる。
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