研究者業績
基本情報
- 所属
- 藤田医科大学 橋渡し研究シーズ探索センター 准教授
- 学位
- 社会健康医学 修士(2002年3月 京都大学)
- J-GLOBAL ID
- 201801012345530637
- researchmap会員ID
- B000306689
研究キーワード
2論文
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JMIR research protocols 15 e87907 2026年2月12日BACKGROUND: Cisplatin-induced nephrotoxicity (CIN) is a major dose-limiting adverse event that can lead to both acute and chronic kidney injury. The formation of thiol-cisplatin conjugates within renal tubular cells has been implicated as a key mechanism underlying CIN. Flopropione is an inhibitor of cysteine conjugate β-lyase 1, an enzyme that catalyzes the formation of the thiol-cisplatin conjugate, which might prevent CIN. OBJECTIVE: We designed a clinical trial to evaluate the safety of flopropione in patients receiving cisplatin-based chemotherapy and explore its efficacy in preventing CIN. METHODS: This is a phase 1 and 2a, single-center, randomized, open-label trial conducted in patients undergoing cisplatin therapy. Participants are randomized in a 5:2 ratio per cohort to receive either flopropione or no treatment. On the day of cisplatin administration, the flopropione group receives oral flopropione twice daily (80 mg in cohort 1, 160 mg in cohort 2, and 240 mg in cohort 3). On the following day, all cohorts receive 3 doses of 80 mg of oral flopropione. A step-up dose escalation design is adopted, progressing from cohort 1 to 3 after confirming safety at each level. The primary end point is the safety of flopropione use in combination with cisplatin; the secondary end points include changes in the levels of urinary biomarkers of nephrotoxicity such as neutrophil gelatinase-associated lipocalin, liver-type fatty acid-binding protein, and kidney injury molecule-1. Blood and urine samples are collected within 48 hours before cisplatin administration and at 24 hours, 48 hours, and 1 week after its initiation for safety and efficacy assessments. RESULTS: The first participant was registered in July 2024. As of January 2026, participant registration is ongoing. The final participant will complete the study by March 2026. Publication of results is expected by March 2027. CONCLUSIONS: This study is expected to contribute to advances in preventive strategies for CIN by providing evidence that inhibition of cysteine conjugate β-lyase 1 by flopropione may attenuate CIN. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs041220021; https://jrct.mhlw.go.jp/en-latest-detail/jRCTs041220021. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/87907.
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Cancer science 2025年12月28日Clinical development of crizotinib in children with ALK-positive anaplastic large cell lymphoma (ALCL) was advanced in the US but not in Japan. The objectives of phase 1 part of a clinical study in Japan were to assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of crizotinib in children with relapsed/refractory (R/R) ALK-positive ALCL or neuroblastoma (NB). Two dose levels (165 and 280 mg/m2 twice daily (BID)) were planned to be evaluated. The aim of phase 2 part of the study was to assess the antitumor activity of crizotinib at the RP2D in children with R/R ALK-positive ALCL. Seven patients were eligible for phase 1 part, 5 with ALCL and 2 with NB. All 7 patients received crizotinib at a starting dose of 165 mg/m2 BID, with 1 dose-limiting toxicity observed (grade 3 gamma-glutamyltransferase increased). The most common grade 3 or 4 adverse event was neutropenia (71%). The steady-state Cmax and AUCtau of crizotinib at 165 mg/m2 BID were higher than expected. Considering the risk of a greater incidence of severe neutropenia, we decided that the 165 mg/m2 BID be the RP2D without evaluation at 280 mg/m2 BID. A total of 11 patients with ALK-positive ALCL were enrolled in the phase 2 part. The objective response rate was 72.7% (90% CI, 43.6%-92.1%). One patient permanently discontinued crizotinib due to disease progression. Crizotinib at 165 mg/m2 BID was well tolerated and showed favorable antitumor activity in children with R/R ALK-positive ALCL. Trial Registration: UMIN-CTR: UMIN000028075.
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JMIR Formative Research 9 e71265-e71265 2025年10月16日Abstract Background Various digital biomarkers have been explored to detect cognitive impairment in community-dwelling older individuals, among which electricity consumption (EC) data obtained from smart meters are novel and promising because they pose no burden to the individuals. Objective The study aimed to explore the potential of EC as a digital biomarker to screen older individuals with cognitive impairment living alone. Methods We recruited 40 older individuals living alone and recorded their 1-year daily household EC data. We used the Japanese version of the Montreal Cognitive Assessment to categorize participants into 2 groups: those with and without cognitive impairment. As the pattern of daily household EC is different between lower and higher temperature ranges because of the use of heating and cooling equipment, we divided the daily household EC into 3 temperature ranges. Using a linear mixed model, we evaluated the association between daily household EC, daily outside temperature, and the groups. Results After excluding 12 participants, they were categorized into 2 groups: those with (10/28, 36%) and without cognitive impairment (18/28, 64%). The daily household EC data consisting of 9391 points showed two characteristics: (1) daily household EC was significantly lower in the group with cognitive impairment than in the group without cognitive impairment in the high temperature range (2.158 kWh at 25 °C, P=.02; 3.712 kWh at 30 °C, P<.001). The increase in EC with rising temperature from 25 °C to 30 °C was less in the group with cognitive impairment (2.387 kWh, P<.001) than in the group without cognitive impairment (3.940 kWh, P<.001); and (2) a tendency for lower daily household EC in the group with cognitive impairment was observed in the moderate temperature range (1.795 kWh at 15 °C, P=.06; 1.582 kWh at 20 °C, P=.08). Conclusions The group with cognitive impairment may use less cooling equipment in the high temperature range and fewer home appliances in the moderate temperature range. Daily household EC might be useful in screening cognitive impairment in older individuals living alone.
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Journal of clinical oncology : official journal of the American Society of Clinical Oncology JCO2400811 2024年11月12日PURPOSE: The JCCG ALL-B12 clinical trial aimed to evaluate the effectiveness of unvalidated treatment phases for pediatric ALL and develop a safety-focused treatment framework. PATIENTS AND METHODS: Patients age 1-19 years with newly diagnosed B-ALL were enrolled in this study. These patients were stratified into standard-risk (SR), intermediate-risk (IR), and high-risk (HR) groups. Randomized comparisons assessed the effectiveness of vincristine (VCR)/dexamethasone pulses in the SR group, evaluated the effects of L-asparaginase (ASP) intensification in the IR group, and compared standard consolidation including block-type treatment with experimental consolidation with high-dose methotrexate (HD-MTX) intensified with VCR and ASP in the HR group. RESULTS: Of 1,936 patients enrolled, 1,804 were eligible for the experimental treatment. The overall 5-year event-free survival and overall survival rates were 85.2% (95% CI, 83.5 to 86.8) and 94.3% (95% CI, 93.1 to 95.3), respectively. The cumulative incidence of relapse and postremission nonrelapse mortality was 13.2% (95% CI, 11.6 to 14.8) and 0.6% (95% CI, 0.3 to 1.0), respectively. Random assignment in the SR group showed no significant benefit from pulse therapy. In the IR group, ASP intensification had limited effects. In the HR group, standard block therapy and HD-MTX yielded equivalent outcomes. CONCLUSION: The ALL-B12 trial achieved favorable outcomes in a nationwide cohort by stratifying treatment on the basis of risk and balancing treatment intensity. This study not only demonstrated that existing standard of care can be further refined but also indicated that improvement in outcomes with intensified chemotherapy has reached a plateau.
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International Journal of Hematology 120(5) 631-638 2024年8月27日
MISC
48-
日本血液学会学術集会 83回 OS3-3 2021年9月
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日本血液学会学術集会 83回 OS3-4 2021年9月
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JOURNAL OF CLINICAL ONCOLOGY 39(15) 2021年5月
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精神医学 62(1) 71-72 2020年1月
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脳神経外科ジャーナル = Japanese journal of neurosurgery 22(9) 678-687 2013年9月20日厚生労働科学研究費補助金事業「包括的脳卒中センターの整備に向けた脳卒中の救急医療に関する研究」 (研究代表者 飯原弘二) の中で, 日本脳神経外科学会, 日本神経学会および日本脳卒中学会教育訓練施設を対象に, 1) 米国ブレインアタック連合が推奨する脳卒中センターの推奨要件 (専門医, 診断機器, 専門的治療, インフラ, 教育研究) に関する施設調査を施行し, 749病院から回答を得て, 施設ごとの推奨要件の充足率に歴然とした格差が存在すること, 2) 脳卒中診療に従事する専門医の約半数が, 疲労やストレスなどが原因で仕事への意欲が大幅に低下する「燃え尽き症候群」の恐れがあることを明らかとした. 3) 2011年度にはDPC参加病院256施設において2010年度に加療した急性期脳卒中症例53,170例を登録し, 本邦における単年度の調査としては過去最大規模の横断調査を施行し, 死亡率に影響する施設要因, 人的要因について解析を行っている.
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EUROPEAN JOURNAL OF HEART FAILURE 12 S211-S212 2013年5月
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医学のあゆみ 244(13) 1253-1257 2013年3月
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EUROPEAN HEART JOURNAL 33 379-380 2012年8月
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CEREBROVASCULAR DISEASES 34 61-61 2012年
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日本医療薬学会年会講演要旨集 21 396-396 2011年
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日本医療薬学会年会講演要旨集 20 491-491 2010年
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心電図 = Electrocardiology 29(1) 44-49 2009年2月5日【背景】ニフェカラントは,我が国で開発されたIII群静注抗不整脈薬である.治療抵抗性の致死的不整脈(心室頻拍;VT,心室細動;VF)に対して適応があり,その投与は心停止に陥った危機的状態において考えられる最大限の除細動治療の一つといえる.ニフェカラントは,純粋なK+チャネル遮断薬であり,心機能への悪影響が少ない,除細動閾値を改善させるなど,同じIII群薬であるアミオダロンとは異なる特性を有している.【目的】院外心停止症例を対象に電気的除細動(DC)補助手段としてニフェカラント使用実態を調査し,その有効性と安全性について検討する.【方法】多施設共同レジストリ研究(国立循環器病センター,千里救命救急センター,三島救命救急センター,大阪大学高度救命救急センター).対象は,(1)3回のDC,エピネフリン静注およびその処置移行のDCに抵抗を示す院外心停止症例,(2)生存例については患者自身より同意を得られた場合(ただし患者の状態によっては家族などの代諾者からの文書同意でも可)とし,生存入院を主要評価項目として検討した.【結果】2006年2月~2007年2月にかけて23症例(男性21例,女性2例,66±12[SD]歳)が仮登録され,うち2症例は同意が得られず,3症例が除外基準に抵触した.解析対象となった18症例(初期ECG波形:VF13例,心静止3例,その他2例)のうち,Dr. Car使用は8例(61%),生存入院は13症例(72%)であった.覚知からニフェカラント使用までの時間は38.5分,使用量は25mg(いずれも中央値)であった.QT延長に伴うtorsade de pointes(TdP)が認められたのは1例のみであった.【総括】院外心停止例に対するニフェカラント投与後のQT延長・TdPの合併は少数であった.今回の多施設共同レジストリ研究では,ニフェカラント投与はDCの有望な補助手段である可能性が示唆された.
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日本内科学会雑誌 98(Suppl.) 131-131 2009年2月
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Brain and nerve = Shinkei kenkyu no shinpo 60(11) 1357-64 2008年11月Aspirin inhibits platelet activation through the permanent inactivation of the cyclooxygenase (COX) activity of prostaglandin H synthase-1 (referred to as COX-1), and consequently inhibits the biosynthesis of thromboxane A2 (TXA2), a platelet agonist. Recent meta-analysis has revealed that long-term aspirin administration has clear benefits for the secondary prevention of cardiovascular diseases with an odds reduction of 23% and an absolute risk reduction of 3.1% over 2 years. However, this indicates that not all individuals respond equally to aspirin therapy and cardiovascular events may occur during aspirin therapy, this is often denoted as "clinical aspirin resistance". Several reports have, indeed, suggested that the effect of aspirin administration varies considerably among the patients at high risk for cardiovascular events. Approximately one forth of the patients showed persistent platelet reactivity in vitro despite the use of aspirin (denoted "laboratory aspirin resistance"), this was determined by laboratory tests including the test for arachidonic acid-induced platelet aggregation and the assays using point-of-care devices. Recent clinical studies have proposed that resistance to aspirin (laboratory aspirin resistance) can relate to the cardiovascular outcomes in patients treated with aspirin (clinical aspirin resistance). A systematic review and meta-analysis on aspirin resistance have indicated that patients who are resistant to aspirin are at a greater risk (odds ratio: 3.85) of clinically important cardiovascular morbidity than patients who are sensitive to aspirin. However, many issues are yet to be resolved in order to apply the concept of "aspirin resistance" to actual clinical practice. The relevance of the various ex vivo functional indexes of platelet capacity to in vivo platelet activation and the precise mechanisms underlying aspirin resistance are still largely unknown. To assess what kind of laboratory assays is the best predictor for cardiovascular events and the risk factors of aspirin resistance, including non-compliance, concurrent intake of other drugs such as nonsteroid anti-inflammatory drugs, and polymorphism of COX-1, we have conducted a multicenter, prospective cohort study (ProGEAR study). We hope that these results will contribute to an individualized antiplatelet therapy through the identification of aspirin nonresponders as a high-risk group for cardiovascular events.
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Circulation journal : official journal of the Japanese Circulation Society 72 604-604 2008年3月1日
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Circulation journal : official journal of the Japanese Circulation Society 71 153-153 2007年3月1日
講演・口頭発表等
1共同研究・競争的資金等の研究課題
6-
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日本学術振興会 科学研究費助成事業 2013年4月 - 2017年3月