研究等業績 - その他 - 髙橋 直人
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Takahashi N.
International Journal of Hematology ( International Journal of Hematology ) 121 ( 1 ) 5 - 38 2024年
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Kobayashi Takahiro, Honami Sato, Miura Masatomo, Fukushi Yayoi, Kuroki Wataru, Ito Fumiko, Teshima Kazuaki, Watanabe Atsushi, Fujishima Naohito, Kobayashi Isuzu, Kameoka Yoshihiro, Takahashi Naoto
Cancer Chemotherapy and Pharmacology ( Springer Nature ) 2024年
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Cortes J.E.
Future Oncology ( Future Oncology ) 18 ( 38 ) 4161 - 4170 2023年12月
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経口薬で白血病を治す－CMLに対する分子標的療法の挑戦
高橋 直人
日本医療薬学会年会講演要旨集 ( 一般社団法人 日本医療薬学会 ) 33 ( 0 ) 4 - 4 2023年11月
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t(4;14)陽性多発性骨髄腫に対するMMSET阻害剤
松岡 紗恵, 菊池 次郎, 長田 直希, 窪田 浩一, 喜久里 貢, 小山 裕雄, 菊地 正樹, 安井 寛, 池田 翔, 高橋 直人, 梅原 崇史, 仲宗根 秀樹, 古川 雄祐
日本血液学会学術集会 ( (一社)日本血液学会 ) 85回 44 - 44 2023年10月
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Clinical Course of a Rare Epstein-Barr Virus-Associated Smooth Muscle Tumor and Its Genomic Analysis
Miyahara J.
Case Reports in Oncology ( Case Reports in Oncology ) 16 ( 1 ) 577 - 584 2023年08月
Epstein-Barr virus (EBV) can rarely induce smooth muscle tumors (SMTs). A 20-year-old female patient underwent kidney transplantation for renal failure. Since then, she has been treated with immunosuppressants, including a calcineurin inhibitor, tacrolimus, and prednisolone, owing to the immunological rejection. Three years later, she developed large liver tumors (diameter >5 cm) and multiple small lung tumors that were identified as EBV-SMTs based on the results of liver biopsy/histopathology. No intervention was performed except for the addition of a mammalian target of the rapamycin inhibitor, everolimus, which inhibits both immune reaction and SMT growth. Finally, after 8 years, the transplanted kidney became nonfunctional, and immunosuppressant administration became unnecessary as urinary dialysis was started. Under these circumstances, SMT growth was observed despite the absence of immunosuppressant administration. Three months after the cessation of the immunosuppressants, EBV-SMTs in the liver and lungs shrank slightly. To the best of our knowledge, this is the first report on the genomic profile of this rare tumor. The clinical course of our patient indicates that EBV can induce SMTs, and immunological suppression of EBV may inhibit the activity of these tumors.
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Acute Myeloid Leukemia Harboring the t(16;21)(p11;q22) Translocation Treated With Venetoclax Plus Azacitidine After Cord Blood Transplantation.
Kazuaki Teshima, Sho Ikeda, Ko Abe, Masahiro Yamada, Naoto Takahashi
Cureus 15 ( 7 ) e42215 2023年07月
A 62-year-old female was diagnosed with acute myeloid leukemia (AML) with t(16;21)(p11;q22). She achieved complete hematological remission after induction therapy and underwent umbilical cord blood stem cell transplantation (CBT). At 150 days after the CBT, a bone marrow examination revealed relapse. We treated the patient with venetoclax plus azacitidine as salvage therapy. After five cycles of venetoclax and azacitidine therapy, the patient died due to disease progression. The prognosis of AML with t(16;21)(p11;q22) is very poor owing to the high rate of early relapse even after hematopoietic stem cell transplantation. Therefore, a novel therapeutic approach is required to improve patient outcomes.
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保存期CKDにおけるESA初期治療抵抗性と予後に関する検討
金澤 達郎, 齋藤 雅也, 齋藤 綾乃, 阿部 史人, 加賀 一, 高橋 直人
日本腎臓学会誌 ( (一社)日本腎臓学会 ) 65 ( 3 ) 294 - 294 2023年05月
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糖尿病性腎臓病腎組織におけるToll-like receptor 4発現と病理学的検討
齋藤 綾乃, 阿部 史人, 齋藤 雅也, 加賀 一, 金澤 達郎, 高橋 直人
日本腎臓学会誌 ( (一社)日本腎臓学会 ) 65 ( 3 ) 317 - 317 2023年05月
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長田 直希, 菊池 次郎, 安井 寛, 池田 翔, 松岡 紗恵, 高橋 直人, 古川 雄祐
International Journal of Myeloma ( (一社)日本骨髄腫学会 ) 13 ( 3 ) 136 - 136 2023年05月
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Onishi Y.
International Journal of Hematology ( International Journal of Hematology ) 117 ( 5 ) 738 - 747 2023年
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Hosono N.
Cancer Science ( Cancer Science ) 114 ( 5 ) 2098 - 2108 2023年
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難治性食道狭窄を来した同種造血幹細胞移植後の食道粘膜類天疱瘡
藤田 菜々子, 山下 鷹也, 阿部 史人, 奈良 美保, 吉岡 智子, 古賀 浩嗣, 石井 文人, 高橋 直人
臨床血液 ( 一般社団法人 日本血液学会 ) 64 ( 2 ) 107 - 112 2023年
<p>40代女性。AML再発に対し血縁者間HLA半合致移植を施行。移植後day59に食道狭窄症を発症した。GVHDと診断し免疫抑制療法中は定期的な食道拡張術で安定していたが，AML再々発に伴い免疫抑制剤を中止すると食道狭窄の増悪を認めた。食道粘膜は易出血性・易剥離性であり，生検組織で剥脱した重層扁平上皮と上皮下の肉芽組織との離開を認めた。蛍光抗体直接法で基底膜部へのIgGとIgAの線状沈着を認め，蛍光抗体間接法ではIgG陰性，IgAが表皮側で陽性，BP180のC末端部位リコンビナント蛋白を用いた免疫ブロット法ではIgG，IgAが陽性であり，抗BP180型粘膜類天疱瘡と診断した。同種移植後の類天疱瘡はGVHDにより表皮の基底細胞が傷害され基底膜部蛋白が露出し，抗原提示されることにより生じると考えられている。本症例も同様の機序と考えられ，典型的なGVHDと異なる症例では詳細な組織診断が重要である。</p>
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Ono T.
International Journal of Hematology ( International Journal of Hematology ) 116 ( 6 ) 871 - 882 2022年12月
Bosutinib has been evaluated for treatment of chronic-phase chronic myeloid leukemia (CP-CML) in several clinical studies, including in Japan. This open-label, single-arm, phase 2 study evaluated the efficacy and safety of bosutinib at a starting dose of 400 mg once daily in Japanese patients (n = 60) with newly diagnosed CP-CML. The minimum follow-up period was 3 years and median duration of treatment was 35.9 months. At study completion, 60% of patients were still on treatment. Cumulative rates of major molecular response (MMR), molecular response4 (MR4), and MR4.5 at any time were 70.0%, 53.3%, and 48.3%, respectively. No patient who achieved MMR or MR4 had a confirmed loss of response. No patient experienced on-treatment transformation to accelerated/blast phase or died within 28 days of the last bosutinib dose. Any-grade treatment-emergent adverse events (TEAEs) occurred in 100% (grade ≥ 3: 81.7%) of patients. The most common TEAEs were diarrhea (86.7%), increased alanine aminotransferase (55.0%), and increased aspartate aminotransferase (46.7%). No new safety signals emerged during the follow-up period. Bosutinib continues to demonstrate a favorable benefit/risk profile and is an important treatment option for Japanese patients with newly diagnosed CP-CML. Optimal management of TEAEs during initial treatment with bosutinib should be prioritized.Trial Registration: ClinicalTrials.gov ID: NCT03128411.
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Kaga H.
Clinical Proteomics ( Clinical Proteomics ) 19 ( 1 ) 2022年12月
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Evaluation of protein production in rice seedlings under dark conditions
Watanabe A.
Scientific Reports ( Scientific Reports ) 12 ( 1 ) 2022年12月
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Imamura K.
eClinicalMedicine ( eClinicalMedicine ) 53 2022年11月
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Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial
今村 恵子, 和泉 唯信, 永井 真貴子, 西山 和利, 渡辺 保裕, 花島 律子, 江川 斉宏, 綾木 孝, 沖 良祐, 藤田 浩司, 魚住 龍史, 森永 明子, 廣橋 朋子, 藤井 陽介, 山本 拓也, 建部 陽嗣, 徳田 隆彦, 高橋 直人, 森田 智視, 髙橋 良輔, 井上 治久
eClinicalMedicine ( Elsevier BV ) 53 2022年11月
[Background] Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the loss of motor neurons, and development of effective medicines is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified the Src/c-Abl inhibitor bosutinib, which is approved for the treatment of chronic myelogenous leukemia (CML), as a candidate for the molecular targeted therapy of ALS. [Methods] An open-label, multicentre, dose-escalation phase 1 study using a 3 + 3 design was conducted in 4 hospitals in Japan to evaluate the safety and tolerability of bosutinib in patients with ALS. Furthermore, the exploratory efficacy was evaluated using Revised ALS Functional Rating Scale (ALSFRS-R), predictive biomarkers including plasma neurofilament light chain (NFL) were explored, and single-cell RNA sequencing of iPSC-derived motor neurons was conducted. Patients, whose total ALSFRS-R scores decreased by 1–3 points during the 12-week, received escalating doses starting from 100 mg quaque die (QD) up to 400 mg QD based on dose-limiting toxicity (DLT) occurrence, and all participants who received one dose of the study drug were included in the primary analysis. This trial is registered with ClinicalTrials.gov, NCT04744532, as Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic Lateral Sclerosis Medicine (iDReAM) study. [Findings] Between March 29, 2019 and May 7, 2021, 20 patients were enrolled, 13 of whom received bosutinib treatment and 12 were included in the safety and efficacy analyses. No DLTs were observed up to 300 mg QD, but DLTs were observed in 3/3 patients of the 400 mg QD cohort. In all patients receiving 100 mg–400 mg, the prevalent adverse events (AEs) were gastrointestinal AEs in 12 patients (92.3%), liver function related AEs in 7 patients (53.8%), and rash in 3 patients (23.1%). The safety profile was consistent with that known for CML treatment, and ALS-specific AEs were not observed. A subset of patients (5/9 patients) was found to respond well to bosutinib treatment over the 12-week treatment period. It was found that the treatment-responsive patients could be distinguished by their lower levels of plasma NFL. Furthermore, single-cell RNA sequencing of iPSC-derived motor neurons revealed the pathogenesis related molecular signature in patients with ALS showing responsiveness to bosutinib. [Interpretation] This is the first trial of a Src/c-Abl inhibitor, bosutinib, for patients with ALS. The safety and tolerability of bosutinib up to 300 mg, not 400 mg, in ALS were described, and responsiveness of patients on motor function was observed. Since this was an open-label trial within a short period with a limited number of patients, further clinical trials will be required.
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Kuroki W.
International Journal of Hematology ( International Journal of Hematology ) 116 ( 5 ) 712 - 722 2022年11月
Despite the introduction of rituximab-containing regimens, approximately 20% of patients with follicular lymphoma (FL) still experience progression of disease within 24 months (POD24) and have poor overall survival. Therefore, a more accurate risk assessment tool is required. We investigated the predictive value of two new volume-based parameters determined from baseline 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), baseline total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG), in 45 patients with high-tumor-burden FL who underwent baseline PET/CT. We observed that high TMTV, high TLG, and poor initial treatment response (less than complete [metabolic] response [non-CR/CMR] at the end of induction therapy) independently predicted poor PFS. Notably, POD24-positive patients were more common in the high-TLG group than in the high-TMTV group, which suggests that TLG is a stronger predictor of outcomes than TMTV. Combining baseline TLG and initial treatment response showed that patients with both high TLG and non-CR/CMR experienced significantly poorer outcomes, with a 2 year PFS of 0% (hazard ratio 60.39, P = 0.000002). This combination had 56% sensitivity and 100% specificity for detecting patients who would experience POD24. Baseline TLG and initial treatment response can precisely identify patients at high risk of POD24.
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膜性腎症・V型ループス腎炎におけるExostosin1/Exostosin2の検討
今泉 ちひろ, 橋本 眞子, 阿部 史人, 加賀 一, 齋藤 綾乃, 齋藤 雅也, 奈良 瑞穂, 高橋 直人
秋田腎不全研究会誌 ( 秋田腎不全研究会 ) 25 33 - 37 2022年11月