KINOSHITA Mariko

写真a

Affiliation

Faculty of Medicine School of Medicine Department of Developmental and Urological-Reproductive Medicine, Pediatrics

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  • 学士(医学) ( 2005.3   宮崎大学 )

 

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  • Steroid-refractory gastrointestinal acute graft-versus-host disease treated with vedolizumab and ruxolitinib in a pediatric patient with therapy-related acute myeloid leukemia

    NAGASAWA Shun, YAMADA Ai, KINOSHITA Mariko, KAMIMURA Sachiyo, TANAKA Hiroyuki, NISHIKAWA Takuro, OKAMOTO Yasuhiro, MORITAKE Hiroshi

    Rinsho Ketsueki   64 ( 1 )   23 - 29   2023

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:The Japanese Society of Hematology  

    A 12-year-old girl developed Philadelphia chromosome-positive acute myeloid leukemia due to therapy-related myelodysplastic syndrome with monosomy 7 following neuroblastoma treatment. She underwent allogenic bone marrow transplantation from a human leukocyte antigens-DR1 locus-mismatched unrelated donor. However, on day 49 post transplantation, she presented with diarrhea due to gastrointestinal acute graft-versus-host disease (aGVHD), and treatments with prednisolone, budesonide rectal foam, and human mesenchymal stem cells were ineffective. Therefore, vedolizumab was administered from day 100, which improved the symptoms from gut stage 3 to gut stage 1. Consequently, prednisolone was withdrawn without any serious adverse effects. However, the symptoms worsened to gut stage 3 again; therefore, ruxolitinib was administered to achieve complete remission. Vedolizumab exhibits gut-selective action without systemic immunosuppressive activity. Hence, vedolizumab administration before other systemic immunosuppressive agents may be recommended in patients with steroid-refractory gastrointestinal aGVHD. Thus far, only a few reports have been published regarding the administration of vedolizumab and ruxolitinib for steroid-refractory gastrointestinal aGVHD in children. Further evidence should be obtained from patients treated with vedolizumab and ruxolitinib to confirm their effectiveness for pediatric steroid-refractory gastrointestinal aGVHD.

    DOI: 10.11406/rinketsu.64.23

    PubMed

    CiNii Research

  • Successful treatment with rituximab for autoimmune cytopenia after autologous hematopoietic stem cell transplantation

    Kinoshita M., Yamada A., Saito Y., Kamimura S., Moritake H.

    Pediatrics international : official journal of the Japan Pediatric Society   64 ( 1 )   e14975   2022.1

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Pediatrics international : official journal of the Japan Pediatric Society  

    DOI: 10.1111/ped.14975

    Scopus

    PubMed

  • Successful treatment of paraspinal/spinal epidural lymphoma by early intervention and local control with proton beam therapy

    Nagasawa S., Yamada A., Kinoshita M., Kamimura S., Moritake H.

    Pediatrics international : official journal of the Japan Pediatric Society   64 ( 1 )   e14970   2022.1

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Pediatrics international : official journal of the Japan Pediatric Society  

    DOI: 10.1111/ped.14970

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  • ヒト脳脊髄液中topotecan濃度のHPLC分析法構築と髄腔内薬物投与後の排泄評価

    吉川 直樹, 山田 愛, 横田 翼, 山田 侑世, 木下 真理子, 盛武 浩, 池田 龍二

    日本臨床薬理学会学術総会抄録集   43 ( 0 )   3-C-P-110   2022

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:一般社団法人 日本臨床薬理学会  

    【目的】抗悪性腫瘍薬の髄腔内投与は、髄液中の薬物濃度を高く維持し、全身性の副作用が最小化される利点を有する。しかし、脳室内薬物のクリアランスは全ての患者で一律ではない。従って、安全な抗悪性腫瘍薬の髄腔内投与のためには、局所薬物動態を評価可能な環境が必要である。髄腔内投与後の髄液中薬物濃度が評価できれば、患者ごとに適切な用法・用量での化学療法が可能となる。Topoisomerase I阻害剤topotecanは、横紋筋肉腫、髄芽腫、神経芽腫などの小児腫瘍の治療に使用され、その有効性が認識されてきている。髄腔内投与後の髄液中topotecan濃度の評価は第I相臨床試験に限定され、髄液中topotecan濃度モニタリングに基づく個別化医療については未だ議論されていない。そこで本研究では、HPLCを使用した簡便かつ再現性の高い髄液中topotecan濃度測定法を開発し、その臨床応用性を確認した。【方法】脳脊髄液中topotecan濃度を測定するためのHPLC法には、Prominence UFLCシステムおよびC18カラムを使用した。Topotecanは生理的条件下にてラクトン環が閉環したラクトン型と開環したカルボキシレート型が可逆的に平衡状態で存在する。本法では総topotecan濃度を定量するために、分析対象試料のラクトン環の状態をpH調整処理により制御した後、除蛋白処理を施した。Topotecanは蛍光検出により定量した(励起波長380 nm、発光波長520 nm)。さらに、topotecan髄腔内投与中の1歳児より脳脊髄液を採取し、本法にて脳脊髄液中topotecan濃度をモニタリングした。【結果・考察】脳脊髄液中topotecanは試料調製時のシンプルなpH調整により、閉環型および開環型への変換が確認された。この2形態は構築した分析法により明確に分離することができ、開環型と閉環型の保持時間はそれぞれ1.3分と3.2分であった。髄液が吸収不良により停滞する患者にトポテカンを髄腔内投与後、本法を用いて、投与24、48、72時間後の脳脊髄液中topotecan濃度をモニタリングした。投与24、48時間後において、投与量を反映した脳脊髄液中濃度の定量に成功した。従って本法は、髄腔内投与後のtopotecan排泄遅延を検出可能と考える。【結論】日常的なtopotecanモニタリングを実現することで、topotecanの髄腔内投与における投与量および投与間隔の適時調整が可能となった。本研究成果は、抗悪性腫瘍薬の髄腔内投与における個別化治療法の実現に貢献するものである。

    DOI: 10.50993/jsptsuppl.43.0_3-c-p-110

    CiNii Research

  • Development and validation of an HPLC method for analysis of topotecan in human cerebrospinal fluid and its application in elimination evaluation of topotecan after intraventricular injection

    Yoshikawa N., Yamada A., Yokota T., Yamada Y., Kinoshita M., Moritake H., Ikeda R.

    Cancers   13 ( 18 )   2021.9

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Cancers  

    Intrathecal administration of anticancer drugs is an effective dosage strategy, but the elimination of intraventricular drugs is not uniform in all patients. For safety, a system to evaluate local pharmacokinetics in the ventricles after administration is desired. In this study, we developed a simple and reproducible method to measure topotecan concentration in the cerebrospinal fluid (CSF) and confirmed its clinical applicability. High-performance liquid chromatography (HPLC) analysis was performed using a C18 column to measure the total topotecan concentration in the CSF. Clinical CSF samples were obtained from a 1-year old child with poor CSF absorption and stagnation. The patient received topotecan via an intraventricular subcutaneous reservoir. The HPLC method complied with the validation criteria. The lower limit of quantitation of this method was 0.04 µM. Using the developed method, we could determine the difference in topotecan CSF concentrations at 24 and 48 h after administration. The patient’s topotecan elimination rate was extremely low, and signs of adverse effects were observed at high CSF concentration of topotecan. The developed method could detect the delay in topotecan elimination after intrathecal injection. The findings of this study are valuable for the development of personalized treatments for the intrathecal administration of anticancer drugs.

    DOI: 10.3390/cancers13184643

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