研究等業績 - その他 - 髙橋 直人
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特集 急性白血病の薬物療法のupdate ～最新の診断・治療戦略～ ８.治療薬物モニタリング
三浦昌朋, 高橋直人
医薬ジャーナル ( 医薬ジャーナル社 ) 54 ( 5 ) 1244 - 1248 2018年05月
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治療への基礎的アプローチ 骨髄腫微小環境で発現上昇する解糖系遺伝子群の治療標的としての可能性
池田 翔, 北舘 明宏, 阿部 史人, 小林 敬宏, 高橋 直人, 田川 博之
International Journal of Myeloma ( 日本骨髄腫学会 ) 8 ( 2 ) 92 - 92 2018年05月
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治療への基礎的アプローチ 骨髄腫微小環境で発現上昇する解糖系遺伝子群の治療標的としての可能性
池田 翔, 北舘 明宏, 阿部 史人, 小林 敬宏, 高橋 直人, 田川 博之
International Journal of Myeloma ( 日本骨髄腫学会 ) 8 ( 2 ) 92 - 92 2018年05月
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ANCA関連血管炎における末梢血単核球でのToll-like receptors mRNA発現の検討
齋藤 綾乃, 加賀 一, 阿部 史人, 齋藤 雅也, 奈良 瑞穂, 佐藤 隆太, 奥山 慎, 小松田 敦, 涌井 秀樹, 高橋 直人
日本腎臓学会誌 ( (一社)日本腎臓学会 ) 60 ( 3 ) 374 - 374 2018年04月
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特発性膜性腎症における抗PLA2R抗体の経時的推移の検討
阿部 史人, 澤村 昌人, 齋藤 綾乃, 齋藤 雅也, 加賀 一, 小澤 政豊, 大谷 浩, 奥山 慎, 小松田 敦, 涌井 秀樹, 高橋 直人
日本腎臓学会誌 ( (一社)日本腎臓学会 ) 60 ( 3 ) 370 - 370 2018年04月
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特集 血液疾患における薬剤の副作用とその対策 １.チロシンキナーゼ阻害薬での対策１)末梢動脈閉塞性疾患(PAOD)(ニロチニブ)
吉岡智子, 高橋直人
血液フロンティア ( 医薬ジャーナル社 ) 28 ( 5 ) 673 - 679 2018年04月
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著明な白血球増多を伴い急速な病状進行と多臓器障害を呈したG-CSF産生ALK陽性ALCL
渡部 敦, 阿部 史人, 奈良 美保, 鵜生川 久美, 藤島 眞澄, 吉岡 智子, 藤島 直仁, 亀岡 吉弘, 高橋 直人, 菅沢 邦江
臨床血液 ( (一社)日本血液学会-東京事務局 ) 59 ( 4 ) 449 - 449 2018年04月
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学会印象記 第59回 米国血液学会議(ASH2017)
池田翔, 髙橋直人
血液フロンティア ( 医薬ジャーナル社 ) 28 ( 4 ) 608 - 611 2018年03月
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Tubulointerstitial nephritis with IgM-positive plasma cells
Takahashi N.
Journal of the American Society of Nephrology ( Journal of the American Society of Nephrology ) 28 ( 12 ) 3688 - 3698 2017年12月
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BCL2、BCL6、MYC遺伝子転座を認めた治療抵抗性triple hit follicular lymphoma
池田 翔, 亀岡 吉弘, 斎藤 綾乃, 小林 五十鈴, 鵜生川 久美, 山下 鷹也, 奈良 美保, 郭 永梅, 渡部 敦, 藤島 眞澄, 藤島 直仁, 吉岡 智子, 高橋 直人
臨床血液 ( (一社)日本血液学会-東京事務局 ) 58 ( 12 ) 2473 - 2473 2017年12月
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High-Throughput Sequencing of IgG B-Cell Receptors Reveals the Frequent Usage of the Rearranged IGHV4-28//IGHJ4 Gene in Primary Immune Thrombocytopenia in Adults
Naohito Fujishima, Masaru Togashi, Ryo Hasegawa, Ken Watanabe, Akiko Saga, Ayumi Omokawa, Tomoo Saga, Shigeharu Ueki, Naoto Takahashi, Kazutaka Kitaura, Ryuji Suzuki, Makoto Hirokawa
BLOOD ( AMER SOC HEMATOLOGY ) 130 2017年12月
研究発表要旨（国際会議）
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Histone Deacetylase Inhibitors Downregulate CCR4 Expression and Decrease Mogamulizumab Efficacy in CCR4-Positive Mature T-Cell Lymphomas
Kitadate Akihiro, Ikeda Sho, Abe Fumito, Takahashi Naoto, Shimizu Norio, Matsue Kosei, Tagawa Hiroyuki
BLOOD 130 2017年12月
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Hypoxia-Inducible KDM3A Addiction in Multiple Myeloma
Ikeda Sho, Kitadate Akihiro, Abe Fumito, Takahashi Naoto, Tagawa Hiroyuki
BLOOD 130 2017年12月
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半月体を形成する糖尿病性腎症の臨床病理学的検討
齋藤 綾乃, 加賀 一, 齋藤 雅也, 阿部 史人, 奈良 瑞穂, 富樫 賢, 小松田 敦, 涌井 秀樹, 高橋 直人
秋田腎不全研究会誌 ( 秋田腎不全研究会 ) 20 43 - 47 2017年11月
腎生検で診断した糖尿病性腎症患者を対象とし、半月体形成を伴う群20例(男性16例、女性4例、36.0〜81.0歳)、伴わない群43例(男性31例、女性12例、18.5〜40.8歳)であった。腎生検時の年齢、BMI、血圧、尿蛋白、尿潜血、eGFR、HbA1c、総コレステロール値、C-reactive protein、糖尿病性網膜症の有無、降圧薬内服の有無、および腎予後について調査した。腎予後は透析導入をエンドポイントとした。臨床データは全ての項目で2群間に有意差を認めなかった。病理学的所見では糸球体病変がClass III(結節病変を伴う糸球体)の割合が半月体形成群で有意に高く、糸球体基底膜のIgG沈着も半月体形成群で有意に高かった。腎生存率は2群間で有意差を認めなかった。
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Niioka T.
Therapeutic Drug Monitoring ( Therapeutic Drug Monitoring ) 39 ( 5 ) 514 - 521 2017年10月
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Relationship Between the CYP2C19 Phenotype Using the Voriconazole-to-Voriconazole N-Oxide Plasma Concentration Ratio and Demographic and Clinical Characteristics of Japanese Patients With Different CYP2C19 Genotypes
Takenori Niioka, Naohito Fujishima, Maiko Abumiya, Takaya Yamashita, Kumi Ubukawa, Miho Nara, Masumi Fujishima, Naoto Takahashi, Masatomo Miura
THERAPEUTIC DRUG MONITORING ( LIPPINCOTT WILLIAMS & WILKINS ) 39 ( 5 ) 514 - 521 2017年10月
Background: Although voriconazole (VRCZ) is metabolized to VRCZ N-oxide principally by CYP2C19, VRCZ clearance is affected by multiple factors. In this study, we investigated the relationship between the CYP2C19 phenotype using the VRCZ-to-VRCZ N-oxide plasma concentration ratio (VRCZ/N-oxide) and demographic and clinical characteristics of Japanese patients taking VRCZ.
Methods: A total of 65 Japanese patients taking VRCZ for prophylaxis or treatment of fungal infection were enrolled in this study. Stepwise selection multiple linear regression analysis was performed to investigate the effect of factors on the VRCZ/N-oxide ratio.
Results: In patients not undergoing concurrent treatment with a drug influencing CYP2C19 activity (n = 54), the VRCZ/N-oxide ratio with definite thresholds for CYP2C19 genotypes, CYP2C19*1/ *1, *1/*2 + *1/*3 + *2/*17, and *2/*2 + *2/*3, was specifically identified in patients taking VRCZ (<0.48, >= 0.48, and <0.82 and >= 0.82). However, the VRCZ/N-oxide ratio could not be predicted based solely on the CYP2C19 genotype (R-2 = 0.053). The route of VRCZ administration, C-reactive protein concentration determined on the same day as VRCZ plasma concentration measurement, CYP2C19 extensive metabolizer, and patient age were independent factors influencing the VRCZ/N-oxide ratio (R-2 = 0.489, standard-ized regression coefficient = 0.385, 0.380, 20.231, and 0.231; P = 0.001, 0.001, 0.032, and 0.036, respectively).
Conclusions: It is possible to comprehensively evaluate CYP2C19 activity using the actual measured value of the VRCZ/N-oxide ratio in patients taking VRCZ. The predictive performance of the VRCZ/ N-oxide ratio was improved by including the route of administration, C-reactive protein level, and patient age in addition to the CYP2C19 genotype as predictive factors. -
Doki N.
Annals of Hematology ( Annals of Hematology ) 96 ( 9 ) 1517 - 1523 2017年09月
Post-transplant microbial diversity in the gastrointestinal tract is closely associated with clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the impact of the fecal microbiota before allo-HSCT. We analyzed fecal samples approximately 2 weeks before conditioning among 107 allo-HSCT recipients between 2013 and 2015. Microbial analysis was performed using 16S rRNA gene sequencing. Operational taxonomic unit-based microbial diversity was estimated by calculating the Shannon index. Patients were classified into three groups based on the diversity index: low (<2), intermediate (2, 3), and high (>3) diversity (18 (16.8%), 48 (44.9%), and 41 (38.3%) patients, respectively). There were no significant differences in the 20-month overall survival, cumulative incidence of relapse, and non-relapse mortality among three groups. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was similar among the three groups (low 55.6%; intermediate 35.4%; high 48.8%, p = 0.339, at day 100). Furthermore, we found no differences in the cumulative incidence of grade II to IV acute gastrointestinal GVHD among the three groups (low 38.9%; intermediate 21.3%; high 24.4%, p = 0.778, at day 100). Regarding the composition of microbiota before allo-HSCT, aGVHD patients showed a significantly higher abundance of phylum Firmicutes (p < 0.01) and a lower tendency for Bacteroidetes (p = 0.106) than non-aGVHD patients. Maintenance of Bacteroidetes throughout allo-HSCT may be a strategy to prevent aGVHD.
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Takahashi N.
International Journal of Hematology ( International Journal of Hematology ) 106 ( 3 ) 398 - 410 2017年09月
This long-term follow-up of a completed phase 1/2 study assessed the safety and efficacy of bosutinib in Japanese Philadelphia chromosome-positive, chronic phase (CP) or advanced phase (ADV) chronic myeloid leukemia patients who were resistant/refractory or intolerant to prior tyrosine kinase inhibitor treatment. This analysis included 63 patients with a median bosutinib follow-up of 132 weeks (range 3aEuro'372). In the CP second-line (2L) cohort, the cumulative major cytogenetic response (MCyR) and major molecular response (MMR) rates throughout the study were 73 and 53%, respectively. In the CP third-line (3L) cohort, the cumulative MCyR and MMR rates throughout the study were 70 and 40%, respectively. Of the eight ADV patients, MCyR was attained or maintained by 50% of patients, and complete hematologic response was attained or maintained by 25% of patients. Progression-free survival rate and overall survival rate at 96 weeks were, respectively, 91 and 98% in CP2L, 88 and 100% in CP3L, and 33 and 50% in ADV patients. The most common adverse events (> 50%) reported were diarrhea (95%), nasopharyngitis (57%), and rash (57%). Bosutinib demonstrated durable efficacy and a manageable tolerability profile over long-term use in Japanese patients.
ClinicalTrials.gov: NCT00811070. -
Ponatinib in Japanese patients with Philadelphia chromosome-positive leukemia, a phase 1/2 study
Tojo A.
International Journal of Hematology ( International Journal of Hematology ) 106 ( 3 ) 385 - 397 2017年09月
In this ongoing Phase 1/2 study (NCT01667133), we evaluated ponatinib and assessed its recommended dose in Japanese patients with chronic myeloid leukemia (CML) resistant/intolerant to dasatinib or nilotinib, or with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) resistant/intolerant to ≥1 tyrosine kinase inhibitor (TKI). The primary endpoints were safety of the recommended dose (Phase 1) and major cytogenetic response (MCyR) by 12 months in chronic-phase CML (CP-CML) patients or major hematologic response (MaHR) by 6 months in patients with advanced phase disease (Phase 2). MCyR was achieved/maintained by 12 months in 65% of CP-CML patients
MaHR was achieved by 6 months in 61% of patients with advanced phase disease. The most common nonhematologic grade 3/4 treatment-emergent adverse event (AE) was hypertension (37%)
common hematologic grade 3/4 AEs were thrombocytopenia (57%), neutropenia (34%), and leukopenia (26%). Overall, five (14%) patients experienced arterial occlusive events (AOEs)
no grade 5 AOEs were reported. The steady-state accumulation ratio of ponatinib (based on area under the curve) ranged from 2.6 (15 mg/day) to 1.3 (45 mg/day). In summary, ponatinib demonstrated efficacy in Japanese patients with CML and Ph+ALL resistant/intolerant to prior TKI treatment
safety data support a recommended starting dose of 45 mg/day in these patients. -
Nara M.
American Journal of Nephrology ( American Journal of Nephrology ) 46 ( 3 ) 187 - 194 2017年09月