2021/10/25 更新

写真a

イマイ チハヤ
今井 千速
IMAI Chihaya
所属
教育研究院 医歯学系 医学系列 准教授
医歯学総合研究科 生体機能調節医学専攻 内部環境医学 准教授
職名
准教授
外部リンク

学位

  • 博士(医学) ( 2005年12月   新潟大学 )

研究キーワード

  • childhood leukemia

  • genetic modification

  • NK cell therapy

  • キメラ抗原受容体

  • 白血病

  • 小児がん

  • NK細胞

研究分野

  • ライフサイエンス / 免疫学  / 腫瘍免疫学

  • ライフサイエンス / 腫瘍生物学

  • ライフサイエンス / 胎児医学、小児成育学  / 血液腫瘍学

  • ライフサイエンス / 血液、腫瘍内科学

経歴(researchmap)

  • 新潟大学   医歯学総合病院 小児科   病院教授

    2020年6月 - 現在

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    国名:日本国

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  • 新潟大学   医歯学総合研究科 生体機能調節医学専攻 内部環境医学   准教授

    2014年8月 - 現在

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  • 新潟大学   医歯学総合研究科 医科学専攻   講師

    2012年7月 - 現在

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  • 新潟大学   医歯学総合病院 小児科   講師

    2012年7月 - 2014年7月

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  • 新潟大学   医歯学総合研究科 生体機能調節医学専攻   講師

    2012年7月 - 2014年7月

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  • 新潟大学   医歯学総合研究科 生体機能調節医学専攻   助教

    2006年1月 - 2012年6月

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  • 医学博士(新潟大学)

    2005年12月

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    国名:日本国

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  • セントジュード小児研究病院   血液腫瘍科   研究員

    2001年10月 - 2005年3月

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    国名:アメリカ合衆国

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  • 新潟大学医歯学総合病院および関連病院   小児科

    1993年4月 - 2001年9月

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    国名:日本国

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経歴

  • 新潟大学   医歯学総合研究科 生体機能調節医学専攻 内部環境医学   准教授

    2014年8月 - 現在

  • 新潟大学   医歯学総合研究科 医科学専攻   講師

    2012年7月 - 2014年7月

  • 新潟大学   医歯学総合病院 小児科   講師

    2012年7月 - 2014年7月

  • 新潟大学   医歯学総合研究科 生体機能調節医学専攻   講師

    2012年7月 - 2014年7月

  • 新潟大学   医歯学総合研究科 生体機能調節医学専攻   助教

    2006年1月 - 2012年6月

学歴

  • 新潟大学   医学部   医学科

    - 1993年3月

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    国名: 日本国

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  • 医学博士(新潟大学)

    2005年12月

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所属学協会

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留学歴

  • セントジュード小児病院   研究員

    2001年10月 - 2005年3月

 

論文

  • Human leukocyte antigen I is significantly downregulated in patients with myxoid liposarcomas. 国際誌

    Naoki Oike, Hiroyuki Kawashima, Akira Ogose, Hiroshi Hatano, Takashi Ariizumi, Tetsuro Yamagishi, Yudai Murayama, Hajime Umezu, Chihaya Imai, Masanori Hayashi, Naoto Endo

    Cancer immunology, immunotherapy : CII   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The characteristics of the tumor immune microenvironment remains unclear in liposarcomas, and here we aimed to determine the prognostic impact of the tumor immune microenvironment across separate liposarcomas subtypes. A total of 70 liposarcoma patients with three subtypes: myxoid liposarcoma (n = 45), dedifferentiated liposarcoma (n = 17), and pleomorphic liposarcoma (n = 8) were enrolled. The presence of tumor infiltrating lymphocytes (CD4+ , CD8+ , FOXP3+ lymphocytes) and CD163+ macrophages and expression of HLA class I and PD-L1 were assessed by immunohistochemistry in the diagnostic samples; overall survival and progression-free survival were estimated from outcome data. For infiltrating lymphocytes and macrophages, dedifferentiated liposarcoma and pleomorphic liposarcoma patients had a significantly higher number than myxoid liposarcoma patients. While myxoid liposarcoma patients with a high number of macrophages were associated with worse overall and progression-free survival, dedifferentiated liposarcoma patients with high macrophage numbers showed a trend toward favorable prognosis. Expression of HLA class I was negative in 35 of 45 (77.8%) myxoid liposarcoma tumors, whereas all dedifferentiated liposarcoma and pleomorphic liposarcoma tumors expressed HLA class I. The subset of myxoid liposarcoma patients with high HLA class I expression had significantly poor overall and progression-free survival, while dedifferentiated liposarcoma patients with high HLA class I expression tended to have favorable outcomes. Only four of 17 (23.5%) dedifferentiated liposarcomas, two of eight (25%) pleomorphic liposarcomas, and no myxoid liposarcoma tumors expressed PD-L1. Our results demonstrate the unique immune microenvironment of myxoid liposarcomas compared to other subtypes of liposarcomas, suggesting that the approach for immunotherapy in liposarcomas should be based on subtype.

    DOI: 10.1007/s00262-021-02928-1

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  • 右房まで到達する腫瘍栓を合併した腎芽腫diffuse anaplasiaの1例

    荒井 勇樹, 木下 義晶, 水田 耕一, 白石 修一, 今井 千速, 小林 隆, 大山 俊之, 横田 直樹, 斎藤 浩一, 岩渕 晴子, 今村 勝, 笠原 靖史, 申 将申, 久保 暢大

    日本小児泌尿器科学会雑誌   29 ( 2 )   185 - 185   2020年12月

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    記述言語:日本語   出版者・発行元:日本小児泌尿器科学会  

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  • 脈絡叢乳頭癌の臨床像と治療経験

    大石 誠, 棗田 学, 吉村 淳一, 塚本 佳広, 今井 千速, 藤井 幸彦

    小児の脳神経   45 ( 3 )   257 - 257   2020年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児神経外科学会  

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  • In-Hospital Management Might Reduce Induction Deaths in Pediatric Patients With Acute Lymphoblastic Leukemia: Results From a Japanese Cohort. 査読 国際誌

    Shunsuke Nakagawa, Motohiro Kato, Toshihiko Imamura, Chihaya Imai, Katsuyoshi Koh, Yoshifumi Kawano, Yasuto Shimomura, Arata Watanabe, Atsushi Kikuta, Akiko Saito, Keizo Horibe, Atsushi Manabe, Akira Ohara, Yasuhiro Okamoto

    Journal of pediatric hematology/oncology   2020年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Induction deaths (ID) remain a critical issue in the treatment of pediatric patients with acute lymphoblastic leukemia (ALL). The reported rate of ID in this population is 1% or higher. We speculate that this proportion might be lower in Japan because of mandatory hospitalization during induction therapy to manage complications. We retrospectively analyzed the incidence of ID among children with ALL enrolled in 4 Japanese study groups between 1994 and 2013. Among 5620 children, 41 (0.73%) cases of ID were noted. The median age was 6.5 years; 24 children were female, and 7 had T-cell ALL. Infection was the most common cause of ID (n=22), but the incidence (0.39%) was lower than that reported in western countries. Mortality within 48 hours from the onset of infection was low, comprising 25% of infection-related deaths. The incidence of infections caused by Bacillus species was low. Only 1 patient died because of Aspergillus infection. Fatal infections mostly occurred during the third week of induction therapy. Our findings suggest that close monitoring, stringent infection control, and immediate administration of appropriate antibiotics through hospitalization might be important strategies in reducing the rate of infection-related ID in pediatric patients with ALL.

    DOI: 10.1097/MPH.0000000000001926

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  • Nationwide study of pediatric B-cell precursor acute lymphoblastic leukemia with chromosome 8q24/MYC rearrangement in Japan. 査読 国際誌

    Kimiyoshi Sakaguchi, Toshihiko Imamura, Sae Ishimaru, Chihaya Imai, Hidemi Shimonodan, Naoto Fujita, Keiko Okada, Takeshi Taketani, Rie Kanai, Hisamichi Tauchi, Motohiro Kato, Yasuko Kojima, Arata Watanabe, Takao Deguchi, Yoshiko Hashii, Nobutaka Kiyokawa, Tomohiko Taki, Akiko M Saito, Keizo Horibe, Atsushi Manabe, Atsushi Sato, Katsuyoshi Koh

    Pediatric blood & cancer   67 ( 7 )   e28341   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Rearrangements of chromosome 8q24/MYC (8q24/MYC-r), resulting from t(8;14)(q24;q32), t(2;8)(p11;q24), or t(8;22)(q24;q11), are mainly associated with Burkitt lymphoma/leukemia (BL) and rarely observed in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The characteristics of BCP-ALL with 8q24/MYC-r are poorly understood. PROCEDURE: A retrospective nationwide study of data from patients with pediatric BCP-ALL with 8q24/MYC-r in Japan was conducted to clarify the clinical and biological characteristics associated with 8q24/MYC-r BCP-ALL. RESULTS: Ten patients with BCP-ALL with 8q24/MYC-r, including three with double-hit leukemia (DHL) (two with t(8;14)(q24;q32) and t(14;18)(q32;q21) and one with t(8;14) and t(3;22)(q27;q11)), were identified. Patients with BCP-ALL with 8q24/MYC-r had higher median age and uric acid and lactate dehydrogenase levels, than those without 8q24/MYC-r. All patients were initially treated with ALL-type chemotherapy; however, four, including one with DHL, were switched to BL-type chemotherapy, based on cytogenetic findings. One patient relapsed after standard-risk ALL-type chemotherapy, and two patients with DHL did not attain complete remission with chemotherapy; all three died within 11 months. The other seven patients treated with BL-type or high-risk ALL-type chemotherapy are alive without disease. CONCLUSIONS: The clinical and laboratory features of BL with IG-MYC rearrangement, displaying a BCP immunophenotype (Wagener et al. and Herbrueggen et al. termed it as pre-BLL), are similar to those of BCP-ALL with 8q24/MYC-r. Low-risk ALL-type chemotherapy may not be appropriate for them, and further studies are required to establish an adequate therapeutic strategy. Further studies of DHL to identify new treatment strategies are also needed.

    DOI: 10.1002/pbc.28341

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  • Spontaneous remission of infant acute myeloid leukemia with a novel four-way translocation. 査読 国際誌

    Nobuhiro Kubo, Haruko Iwabuchi, Masaru Imamura, Akihiko Saitoh, Chihaya Imai

    Pediatric blood & cancer   67 ( 2 )   e28052   2020年2月

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    記述言語:英語  

    DOI: 10.1002/pbc.28052

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  • 夜尿症治療中に発症し内服中止により速やかに改善した薬剤性肺障害の一例

    松下 仁美, 今井 千速, 申 将守, 笠原 靖史, 岩渕 晴子, 今村 勝, 齋藤 昭彦

    日本小児科学会雑誌   124 ( 2 )   444 - 444   2020年2月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • Development and characterisation of NKp44-based chimeric antigen receptors that confer T cells with NK cell-like specificity. 査読 国際誌

    Yasushi Kasahara, Chansu Shin, Nobuhiro Kubo, Keichiro Mihara, Haruko Iwabuchi, Takayuki Takachi, Masaru Imamura, Akihiko Saitoh, Chihaya Imai

    Clinical & translational immunology   9 ( 7 )   e1147   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Objectives: One of the reasons as to why chimeric antigen receptors (CAR)-T cell therapy for malignancies other than CD19- or BCMA-positive tumors has yet to produce remarkable progress is the paucity of targetable antigens. NKp44 is only expressed by activated natural killer cells and detects a variety of transformed cells, while it reportedly does not react with normal tissues. The aim of this study is to develop CAR-T cell that can target multiple types of tumor cells. Methods: We created a series of novel CAR constructs in first-generation (1G) and second-generation (2G) CAR format with the extracellular immunoglobulin-like domain of NKp44 (NKp44-CAR). Results: Transduction of the best 1G construct into human primary T cells led to specific cytotoxic effects and cytokine secretion upon encountering multiple types of neoplastic cells including AML, T-ALL and childhood solid tumors. Replacement of the extracellular hinge domain of NKp44 with that of CD8α resulted in diminished CAR function. The 1G NKp44-CAR-T cells exhibited significantly better tumor control in long-term co-culture assays compared with activated NK cells, as well as with NK cells transduced with identical NKp44-CAR. T cells transduced with the best 2G-CAR construct with 4-1BB co-stimulatory domain proliferated at significantly higher levels upon single antigen exposure and showed significantly better tumor control compared with the 1G-CAR and 2G-CAR with CD28 co-stimulatory domain. Conclusions: NKp44-based CAR endows T cells with NK cell-like anti-tumor specificity. The CAR gene created in this study will be useful for the development of novel gene-modified T-cell immunotherapy.

    DOI: 10.1002/cti2.1147

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  • Fatal Progressive Meningoencephalitis Diagnosed in Two Members of a Family With X-Linked Agammaglobulinemia. 査読 国際誌

    Yasushi Kasahara, Masaru Imamura, Chansu Shin, Hiroshi Shimizu, Jirou Utsumi, Ryosuke Hosokai, Haruko Iwabuchi, Takayuki Takachi, Akiyoshi Kakita, Hirokazu Kanegane, Akihiko Saitoh, Chihaya Imai

    Frontiers in pediatrics   8   579 - 579   2020年

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    記述言語:英語  

    Chronic enteroviral meningoencephalitis is a well-known complication in patients with X-linked agammaglobulinemia (XLA). However, progressive neurodegenerative disorders or chronic neuroinflammatory diseases with no causative microorganisms have been recognized as rare central nervous system (CNS) complications in XLA. We herein report a family in which two of three members with XLA had developed progressive meningoencephalitis with an unknown etiology. A 15-month-old male infant presented with left-sided ptosis. Initially, the family denied any family history of inherited diseases, but later disclosed a family history of agammaglobulinemia previously diagnosed in two family members. In the early 1980s, one of the elder brothers of the index patient's mother who had been treated with intramuscular immunoglobulin [or later intravenous immunoglobulin (IVIG)] for agammaglobulinemia deceased at 10 years of age after showing progressive neurological deterioration during the last several years of his life. The index patient was diagnosed with XLA caused by Bruton tyrosine kinase deficiency (654delG; Val219Leufs*9), and chronic meningoencephalitis with an unknown infectious etiology. Magnetic resonance imaging of the brain demonstrated inflammatory changes in the basal ganglia, hypothalamus, midbrain, and pons, with multiple nodular lesions with ring enhancement, which showed impressive amelioration after the initiation of IVIG replacement therapy. Pleocytosis, which was characterized by an increase in CD4-positive and CD8-positive T cells expressing an activation marker and an elevation in inflammatory cytokines in the cerebrospinal fluid, was identified. No microorganism was identified as a cause of CNS complications. He thereafter developed brain infarction at 19 months of age and fatal status epilepticus at 5 years of age, despite regular IVIG with high trough levels and regular intraventricular immunoglobulin administration. The etiology of this rare CNS complication in XLA is currently unknown. Previous studies have suggested a possible association of IVIG, which was clearly denied in our index case because of the demonstration of his neurological disorder at presentation. In the future, extensive and unbiased molecular methods to detect causative microorganisms, as well as to investigate the possible role of autoimmunity are needed to clarify the etiology of CNS complications.

    DOI: 10.3389/fped.2020.00579

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  • [Current status of cancer immunotherapy for relapsed/refractory acute lymphoblastic leukemia in children and adolescents in Japan].

    Chihaya Imai

    [Rinsho ketsueki] The Japanese journal of clinical hematology   61 ( 6 )   673 - 681   2020年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

    Several novel therapeutics that employ immunological mechanisms have been introduced in recent years for the treatment of hematological malignancies. To date, very few drugs have been introduced for acute lymphoblastic leukemia (ALL). Nonetheless, three novel agents have been approved recently in the US, Europe, Australia, and Japan: blinatumomab, which kills CD19-positive leukemia cells via cytotoxic activity of the patient's autologous T cells; inotuzumab ozogamicin, which delivers the anti-cancer antibiotic calicheamicin via CD22 internalization after antibody binding; and tisagenlecleucel, which uses patient's T cells via anti-CD19 chimeric antigen receptors. Aggressive multi-agent chemotherapy followed by allogeneic hematopoietic cell transplantation has been the only curative strategy for relapsed or refractory ALL. However, treatment strategies for such patients are about to change dramatically. In this article, I review the clinical development of the new therapeutics and discuss their roles in modern therapy for ALL in children and adolescents. An approach for treatment selection has not yet been established. Therefore, it is important to understand the advantages and disadvantages of each treatment for choosing a treatment strategy for each individual.

    DOI: 10.11406/rinketsu.61.673

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  • BRAFV600E-Positive Precursors as Molecular Markers of Bone Marrow Involvement in Pediatric Langerhans Cell Histiocytosis 査読

    Kudo Ko, Kanezaki Rika, Masaru Imamura, Imai Chihaya, Irie Masahiro, Sasahara Yoji, Ando Kumiko, Kakuda Harumi, Doi Takehiko, Kawaguchi Hiroshi, Kudo Kazuko, Kanegane Hirokazu, Kobayashi Akie, Sato Tomohiko, Kamio Takuya, Sasaki Shinya, Terui Kiminori, Toki Tsutomu, Ito Etsuro

    PEDIATRIC BLOOD & CANCER   66   S47   2019年12月

  • 肺炎様症状で発症した横紋筋肉腫の1例と後方視的なエックス線所見の検討

    稲葉 聡, 丸山 馨, 下妻 大毅, 馬場 恵史, 目黒 茂樹, 高橋 勇弥, 添野 愛基, 渡辺 健一, 小林 玲, 沼田 修, 田中 篤, 笠原 靖史, 久保 暢大, 石井 孝規, 岩渕 晴子, 今村 勝, 今井 千速

    長岡赤十字病院医学雑誌   32 ( 1 )   37 - 41   2019年12月

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    記述言語:日本語   出版者・発行元:長岡赤十字病院  

    症例は生来健康な10歳男児であり、発熱、咳嗽、呼吸困難、胸水貯留からマイコプラズマ肺炎が疑われ前医で入院加療されていたが、胸水貯留と呼吸困難が増悪し当院紹介・入院となった。当院入院後撮影したCT検査で中縦隔下部を中心に両側胸腔と腹腔に及び、胸腹膜播種と肝臓への直接浸潤を伴い下大静脈の狭窄をきたす巨大な腫瘤が指摘された。胸水細胞診からは診断に至らず、精査加療目的に新潟大学医歯学総合病院小児科へ転院となった。その後の開胸生検の結果、横紋筋肉腫と診断された。後方視的に初診時の胸部エックス線所見を確認すると、腫瘤性病変を示唆する所見を確認することができた。あらゆる身体部位に発生しうる横紋筋肉腫は初発症状も多様であり、常に鑑別にあげ早期の発見と介入に務めるべきである。日常診療で行われることの多い胸部単純エックス線写真を適切に評価し、より適切に確定診断を行うための検査を進めていくことが肝要である。(著者抄録)

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  • Nationwide survey of pediatric hypodiploid acute lymphoblastic leukemia in Japan. 査読 国際誌

    Sae Ishimaru, Yasuhiro Okamoto, Chihaya Imai, Hirotoshi Sakaguchi, Tomohiko Taki, Daisuke Hasegawa, Yuko Cho, Harumi Kakuda, Hideki Sano, Atsushi Manabe, Toshihiko Imamura, Motohiro Kato, Yuki Arakawa, Hidemi Shimonodan, Atsushi Sato, Souichi Suenobu, Takeshi Inukai, Arata Watanabe, Yoshifumi Kawano, Atsushi Kikuta, Keizo Horibe, Akira Ohara, Katsuyoshi Koh

    Pediatrics international : official journal of the Japan Pediatric Society   61 ( 11 )   1103 - 1108   2019年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Ploidy is a highly significant prognostic factor for pediatric acute lymphoblastic leukemia (ALL). Children with hypodiploid ALL have poor outcomes despite current intensive chemotherapy. Little has been investigated with regard to hypodiploid ALL in Japanese children. METHODS: We retrospectively collected clinical data on hypodiploid ALL cases from the registries of prospective multicenter trials conducted by the four independent clinical study groups in Japan between 1997 and 2012. RESULTS: A total of 117 ALL patients with hypodiploidy were analyzed in this study. There were 101, eight, and eight patients with 45, 44, and fewer than 44 chromosomes, respectively. The 5 year overall survival rates differed significantly: 86.0%, 87.5%, and 62.5% for patients with 45, 44, and fewer than 44 chromosomes, respectively (P = 0.037). Of the eight patients with 44 chromosomes, seven were alive, including five patients who maintained complete remission without undergoing hematopoietic stem cell transplantation (HSCT). Of the eight patients with fewer than 44 chromosomes, six were good responders to prednisolone and none had induction failure, but the relapse rate was high (5/8). No patients had central nervous system relapse. Four patients underwent HSCT after relapse, but only one survived. CONCLUSIONS: Outcomes of Japanese ALL patients with fewer than 44 chromosomes were poor, as previously reported in other countries. Although the sample size was small, patients with 44 chromosomes had better prognoses than those previously reported. Further studies including international collaboration are needed to improve outcomes for pediatric ALL patients with fewer than 44 chromosomes.

    DOI: 10.1111/ped.14006

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  • 手術療法により根治したKasabach-Merritt現象を伴う房状血管腫の1例

    古川 絵美, 申 将守, 笠原 靖史, 岩渕 晴子, 榊原 清一, 有泉 高志, 川島 寛之, 今村 勝, 今井 千速

    日本小児血液・がん学会雑誌   56 ( 4 )   333 - 333   2019年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • 肺炎様症状を契機に診断に至った横紋筋肉腫の1例

    稲葉 聡, 丸山 馨, 下妻 大毅, 馬場 恵史, 目黒 茂樹, 高橋 勇弥, 添野 愛基, 渡辺 健一, 小林 玲, 沼田 修, 田中 篤, 笠原 靖史, 石井 孝規, 久保 暢大, 岩渕 晴子, 今村 勝, 今井 千速

    日本小児科学会雑誌   123 ( 6 )   1063 - 1063   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • NKp44キメラ抗原受容体による新しいがん免疫治療の開発

    笠原 靖史, 久保 暢大, 申 将守, 高地 貴行, 岩渕 晴子, 今村 勝, 今井 千速

    日本小児科学会雑誌   123 ( 6 )   1062 - 1062   2019年6月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • 小児脳腫瘍のトランスレーショナルリサーチと基礎研究 膠芽腫に対する新たなCAR-T療法の基礎的検討(NKp44-based CAR)

    笠原 靖史, 申 将守, 久保 暢大, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    小児の脳神経   44 ( 2 )   142 - 142   2019年4月

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    記述言語:日本語   出版者・発行元:(一社)日本小児神経外科学会  

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  • WHIM症候群の一家系

    石井 孝規, 久保 暢大, 笠原 靖史, 岩渕 晴子, 岡田 賢, 今村 勝, 斎藤 昭彦, 今井 千速

    日本小児科学会雑誌   123 ( 2 )   510 - 510   2019年2月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • 骨病変を有したLangerhans細胞組織球症の3例

    勝見 達也, 新熊 悟, 荻根沢 真帆子, 河合 亨, 加畑 雄大, 折目 真理, 伊藤 明子, 久保 暢大, 岩渕 晴子, 今井 千速, 阿部 理一郎

    臨床皮膚科   73 ( 1 )   78 - 84   2019年1月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    <文献概要>症例1:1歳5ヵ月,女児.頭部に脂漏性湿疹様皮疹,体幹四肢には紫斑,丘疹があり,Langerhans細胞の骨髄浸潤と,CT検査で蝶形骨の破壊像を認めた.症例2:5ヵ月,女児.下腹部や鼠径部に点状紫斑や丘疹があり,CT検査で右下顎骨の骨溶解を伴う腫瘤性病変を認めた.症例3:5歳,女児.鼠径部および大腿内側に褐色調の紅斑,丘疹があり,CT検査で第5頸椎の圧迫骨折を認めた.いずれの症例も皮疹からLangerhans細胞組織球症(Langerhans cell histiocytosis:LCH)を疑い,病理組織学的検査,電子顕微鏡検査にて多臓器型のLCHと診断した.化学療法もしくは経過観察で,皮疹は改善傾向である.LCHの皮疹は多彩であり,視診だけで診断することは困難である.LCHの皮膚病変を疑った場合は積極的に皮膚生検を行い,病型を確定する必要がある.

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  • Detection of BRAF V600E Mutation for Monitoring Residual Disease in LCH 査読

    Kudo Ko, Sato Tomohiko, Kamio Takuya, Sasaki Shinya, Irie Masahiro, Sasahara Yoji, Imamura Masaru, Imai Chihaya, Ando Kumiko, Kakuda Harumi, Doi Takehiko, Kawaguchi Hiroshi, Kanezaki Rika, Toki Tsutomu, Terui Kiminori, Ito Etsuro

    PEDIATRIC BLOOD & CANCER   65   S23   2018年11月

  • CAR-T細胞療法-遺伝子改変T細胞を用いた新しいがん治療 招待

    今井 千速

    小児科   59 ( 10 )   1583 - 1591   2018年10月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Langerhans cell histiocytosisにおけるBRAFV600E変異検出による残存病変の評価(Detection of BRAFV600E mutation for monitoring residual disease in Langerhans cell histiocytosis) 査読

    工藤 耕, 佐藤 知彦, 神尾 卓哉, 佐々木 伸也, 入江 正寛, 笹原 洋二, 今村 勝, 今井 千速, 安藤 久美子, 角田 治美, 土居 岳彦, 川口 浩史, 金崎 里香, 土岐 力, 伊藤 悦朗

    臨床血液   59 ( 9 )   1606 - 1606   2018年9月

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    記述言語:英語   出版者・発行元:(一社)日本血液学会-東京事務局  

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  • PD-1リガンドを標的とした新規キメラ抗原受容体T細胞の作製(Development of novel chimeric antigen receptor targeting PD-1 ligands in cancer cells)

    申 将守, 久保 暢大, 笠原 靖史, 高地 貴行, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    臨床血液   59 ( 9 )   1587 - 1587   2018年9月

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    記述言語:英語   出版者・発行元:(一社)日本血液学会-東京事務局  

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  • 小児血液・腫瘍疾患における菌血症の臨床的検討 患者受け入れ再開後12年の変遷

    久保 暢大, 申 将守, 笠原 靖史, 吉田 咲子, 細貝 亮介, 高地 貴行, 岩渕 晴子, 今村 勝, 今井 千速, 齋藤 昭彦

    日本小児科学会雑誌   122 ( 2 )   359 - 359   2018年2月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • Nationwide Survey of Pediatric Hypodiploid Acute Lymphoblastic Leukemia in Japan 査読

    Ishimaru Sae, Okamoto Yasuhiro, Imai Chihaya, Sakaguchi Hirotoshi, Taki Tomohiko, Hasegawa Daisuke, Cho Yuko, Kakuda Harumi, Sano Hideki, Manabe Atushi, Imamura Toshihiko, Kato Motohiro, Arakawa Yuki, Shimonodan Hidemi, Sato Atsushi, Suenobu So-ichi, Inukai Takeshi, Watanabe Arata, Kawano Yoshifumi, Kikuta Atsushi, Horibe Keizo, Ohara Akira, Koh Katsuyoshi

    BLOOD   130   2017年12月

  • Detection of Somatic Mutations by PCR-based Next-Generation Sequencing from Fixed Clinical Specimens in Childhood LCH 査読

    Ko Kudo, Rika Kanezaki, Akie Kobayashi, Tomohiko Sato, Takuya Kamio, Shinya Sasaki, Kiminori Terui, Atsushi Sato, Masahiro Irie, Yoji Sasahara, Masaru Imamura, Chihaya Imai, Tsutomu Toki, Etsuro Ito

    PEDIATRIC BLOOD & CANCER   64   S14 - S14   2017年11月

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    記述言語:英語   出版者・発行元:WILEY  

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  • Detection of Somatic Mutations by PCR-Based Next-Generation Sequencing from Fixed Clinical Specimens in Childhood LCH 査読

    Ko Kudo, Rika Kanezaki, Akie Kobayashi, Tomohiko Sato, Takuya Kamio, Shinya Sasaki, Kiminori Terui, Atsushi Sato, Masahiro Irie, Yoji Sasahara, Masaru Imamura, Chihaya Imai, Tsutomu Toki, Etsuro Ito

    PEDIATRIC BLOOD & CANCER   64   S19 - S19   2017年11月

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    記述言語:英語   出版者・発行元:WILEY  

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  • 各種治療が無効であったが、発症10年後に自然軽快したびまん性肺リンパ管腫症の1例

    申 将守, 久保 暢大, 笠原 靖史, 高地 貴行, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   54 ( 4 )   330 - 330   2017年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphic IKBKG/NEMO mutations 査読

    Charline Miot, Kohsuke Imai, Chihaya Imai, Anthony J. Mancini, Zeynep Yesim Kucuk, Tokomki Kawai, Ryuta Nishikomori, Etsuro Ito, Isabelle Pellier, Sophie Dupuis Girod, Jeremie Rosain, Shinya Sasaki, Shanmuganathan Chandrakasan, Jana Pachlopnik Schmid, Tsubasa Okano, Estelle Colin, Alberto Olaya-Vargas, Marco Yamazaki-Nakashimada, Waseem Qasim, Sara Espinosa Padilla, Andrea Jones, Alfons Krol, Nyree Cole, Stephen Jolles, Jack Bleesing, Thomas Vraetz, Andrew R. Gennery, Mario Abinun, Tayfun Güngör, Beatriz Costa-Carvalho, Antonio Condino-Neto, Paul Veys, Steven M. Holland, Gulbu Uzel, Despina Moshous, Benedicte Neven, Stéphane Blanche, Stephan Ehl, Rainer Döffinger, Smita Y. Patel, Anne Puel, Jacinta Bustamante, Erwin W. Gelfand, Jean-Laurent Casanova, Jordan S. Orange, Capucine Picard

    Blood   130 ( 12 )   1456 - 1467   2017年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Society of Hematology  

    X-linked recessive ectodermal dysplasia with immunodeficiency is a rare primary immunodeficiency caused by hypomorphic mutations of the IKBKG gene encoding the nuclear factor κB essential modulator (NEMO) protein. This condition displays enormous allelic, immunological, and clinical heterogeneity, and therapeutic decisions are difficult because NEMO operates in both hematopoietic and nonhematopoietic cells. Hematopoietic stem cell transplantation (HSCT) is potentially life-saving, but the small number of case reports available suggests it has been reserved for only the most severe cases. Here, we report the health status before HSCT, transplantation outcome, and clinical follow-up for a series of 29 patients from unrelated kindreds from 11 countries. Between them, these patients carry 23 different hypomorphic IKBKG mutations. HSCT was performed from HLA-identical related donors (n = 7), HLA-matched unrelated donors (n = 12), HLA-mismatched unrelated donors (n = 8), and HLA-haploidentical related donors (n = 2). Engraftment was documented in 24 patients, and graft-versus-host disease in 13 patients. Up to 7 patients died 0.2 to 12 months after HSCT. The global survival rate after HSCT among NEMO-deficient children was 74% at a median follow-up after HSCT of 57 months (range, 4-108 months). Preexisting mycobacterial infection and colitis were associated with poor HSCT outcome. The underlying mutation does not appear to have any influence, as patients with the same mutation had different outcomes. Transplantation did not appear to cure colitis, possibly as a result of cell-intrinsic disorders of the epithelial barrier. Overall, HSCT can cure most clinical features of patients with a variety of IKBKG mutations.

    DOI: 10.1182/blood-2017-03-771600

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  • Successful treatment of histiocytic sarcoma with cladribine and high-dose cytosine arabinoside in a child 査読

    Haruko Iwabuchi, Hiroyuki Kawashima, Hajime Umezu, Takayuki Takachi, Masaru Imamura, Akihiko Saitoh, Akira Ogose, Chihaya Imai

    INTERNATIONAL JOURNAL OF HEMATOLOGY   106 ( 2 )   299 - 303   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    Histiocytic sarcoma, a rare hematopoietic neoplasm with evidence of histiocytic differentiation, is often refractory to conventional chemotherapy and radiotherapy, and its prognosis is generally dismal. The optimal management of this malignancy has not been established. We report a case of 8-year-old girl with histiocytic sarcoma involving the left femur. The tumor rapidly responded to a combination of cladribine and high-dose cytosine arabinoside, an aggressive salvage regimen for refractory Langerhans cell histiocytosis, and became impalpable during the first cycle. The patient has remained in complete remission more than 7 years from diagnosis.

    DOI: 10.1007/s12185-017-2202-8

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  • 2008年以降に新潟県で発生した再生不良性貧血の臨床的検討

    久保 暢大, 高地 貴行, 岩渕 晴子, 今村 勝, 申 将守, 笠原 靖史, 細貝 亮介, 吉田 咲子, 渡辺 輝浩, 小川 淳, 今井 千速, 齋藤 昭彦

    日本小児科学会雑誌   121 ( 8 )   1419 - 1419   2017年8月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • 軟部組織病変を呈し特異な臨床経過を示したランゲルハンス細胞組織球症の1例

    古寺 一樹, 今村 勝, 高地 貴行, 申 将守, 笠原 靖史, 岩渕 晴子, 川島 寛之, 生越 章, 梅津 哉, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   54 ( 2 )   157 - 160   2017年6月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

    ランゲルハンス細胞組織球症(LCH)は、ランゲルハンス細胞様細胞(LCH細胞)のモノクローナルな腫瘍性増殖をきたす疾患である。骨病変の頻度が最も高く、軟部組織単独病変は稀である。今回我々は、胸椎の骨融解病変、胸膜病変、および骨病変に連続しない後頸部の軟部組織病変を伴う多臓器型LCHの5歳女児例を経験した。本例は当初、後頸部皮下膿瘍および化膿性脊椎炎の疑いで抗菌薬が投与され、解熱し病変部位の腫脹が軽減消失したことから、結果的に化学療法の同意が得られず経過観察の方針となった。約9ヵ月間で2回の再燃を観察し、いずれも抗菌薬投与のみで解熱し、局所症状も軽減消失した。最終的に多剤併用化学療法を導入したところ、速やかに寛解が得られ、4年間再発なく経過良好である。本例はLCHでは稀な軟部組織病変を伴うのみならず、抗菌薬による一時的効果が観察された点で、LCHの複雑な病態を考察する上で貴重と思われる。(著者抄録)

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  • Donor Killer Immunoglobulin-Like Receptor Haplotype B/x Induces Severe Acute Graft-versus-Host Disease in the Presence of Human Leukocyte Antigen Mismatch in T Cell-Replete Hematopoietic Cell Transplantation 査読

    Ryosuke Hosokai, Masayoshi Masuko, Yasuhiko Shibasaki, Akihiko Saitoh, Tatsuo Furukawa, Chihaya Imai

    BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION   23 ( 4 )   606 - 611   2017年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Natural killer cells have been identified as a mediator of alloimmune reactions in allogeneic hematopoietic stem cell transplantation (HSCT). Killer immunoglobulin-like receptors (KIRs) are an important determinant of natural killer cell function. The relationship between KIR genotypes/haplotypes and clinical outcomes of allogeneic HSCT is complex and inconsistent among several reports. We assessed the clinical impact of KIR haplotype on T cell-replete allogeneic HSCTs performed in a single Japanese center for hematological malignancies (n = 106). A comparison of 2 groups, donor haplotypes A/A and B/x, revealed no significant differences in overall survival, relapse, and nonrelapse mortality. However, grade III to IV acute graft-versus-host disease (GVHD) occurred significantly more frequently in the KIR haplotype B/x group (A/A versus B/x: 4.9% versus 20.0%; P=.02). This was even more evident when HLA mismatch was present. The highest incidences of grade II to IV and grade III to IV acute GVHD were observed in patients who received allografts from HLAmismatched donors with KIR haplotype B/x. These data highlight the importance of KIR genotyping in donor matching, especially when HLA mismatch allogeneic grafting is planned. (C) 2017 American Society for Blood and Marrow Transplantation.

    DOI: 10.1016/j.bbmt.2016.12.638

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  • 白血病に対する新しい薬物・細胞治療 招待

    今井 千速

    日本医師会雑誌   145 ( 12 )   2600 - 2604   2017年3月

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • B.cereus髄膜炎を合併した急性骨髄性白血病の救命例 TDMの重要性

    久保 暢大, 吉田 咲子, 申 将守, 笠原 靖史, 高地 貴行, 岩渕 晴子, 今村 勝, 今井 千速, 齋藤 昭彦

    日本小児科学会雑誌   121 ( 2 )   467 - 467   2017年2月

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    記述言語:日本語   出版者・発行元:(公社)日本小児科学会  

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  • キメラ抗原受容体 (CAR): 人工受容体遺伝子を導入したリンパ球による新たながん治療. 招待

    今井 千速

    新潟医学会雑誌   131 ( 1 )   7 - 10   2017年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • All-trans retinoic acid enhances cytotoxic effect of T cells with an anti-CD38 chimeric antigen receptor in acute myeloid leukemia. 査読

    Yoshida T, Mihara K, Takei Y, Yanagihara K, Kubo T, Bhattacharyya J, Imai C, Mino T, Takihara Y, Ichinohe T

    Clin Transl Immunology.   5 ( 12 )   e116   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • 本邦において2002年から2011年までに発生した2例の小児BCL2およびMYC dual-hit白血病(Two cases of pediatric BCL2 and MYC dual-hit leukemia between 2002 and 2011 in Japan)

    坂口 公祥, 今村 俊彦, 石丸 紗恵, 今井 千速, 下之段 秀美, 岡田 恵子, 出口 隆生, 橋井 佳子, 清河 信敬, 齋藤 明子, 真部 淳, 佐藤 篤, 康 勝好

    日本小児血液・がん学会雑誌   53 ( 4 )   370 - 370   2016年11月

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    記述言語:英語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • ヒトprimary NK細胞へのインターロイキン21遺伝子の導入は抗白血病作用を増強する(Genetic engineering of primary natural killer cells with human Interleukin-21 enhances their anti-leukemic capacity)

    笠原 靖史, 申 将守, 高地 貴行, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   53 ( 4 )   279 - 279   2016年11月

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    記述言語:英語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • Hematopoietic stem cell transplantation for pediatric mature B-cell acute lymphoblastic leukemia with non-L3 morphology and MLL-AF9 gene fusion: three case reports and review of the literature 査読

    Takeo Sarashina, Haruko Iwabuchi, Naoyuki Miyagawa, Masahiro Sekimizu, Tomoko Yokosuka, Kunio Fukuda, Satoshi Hamanoue, Fuminori Iwasaki, Shoko Goto, Masae Shiomi, Chihaya Imai, Hiroaki Goto

    INTERNATIONAL JOURNAL OF HEMATOLOGY   104 ( 1 )   139 - 143   2016年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER JAPAN KK  

    Mature B-cell acute lymphoblastic leukemia (B-ALL) is typically associated with French-American-British (FAB)-L3 morphology and MYC gene rearrangement. However, rare cases of mature B-ALL with non-L3 morphology and MLL-AF9 fusion have been reported, and such cases are characterized by a rapid and aggressive clinical course. We here report three such cases of pediatric mature B-ALL in female patients respectively aged 15 months, 4 years, and 4 months. Bone marrow smears at diagnosis showed FAB-L1 morphology in all patients. Immunophenotypically, they were positive for cluster of differentiation (CD) 10, CD19, CD20 (or CD22), Human Leukocyte Antigen-DR, and surface immunoglobulin.. No evidence of MYC rearrangement was detected in any of the cases by fluorescent in situ hybridization (FISH) analysis. However, MLL rearrangement was detected by FISH, and MLL-AF9 fusion was confirmed by reverse transcriptase-polymerase chain reaction. All patients achieved complete remission after conventional chemotherapy and subsequently underwent hematopoietic stem cell transplantation as high-risk ALL; patient 3 for infantile ALL with MLL rearrangement and the others for ALL with MLL rearrangement and hyperleukocytosis (white blood cell count at diagnosis >50 x 10(9)/L). At the latest follow-up for each case (12-98 months post-transplantation), complete remission was maintained. Moreover, we discuss the clinical, genetic, and immunophenotypic features of this rare disease.

    DOI: 10.1007/s12185-016-1971-9

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  • Characterization of pediatric Philadelphia-negative B-cell precursor acute lymphoblastic leukemia with kinase fusions in Japan 査読

    T. Imamura, N. Kiyokawa, M. Kato, C. Imai, Y. Okamoto, M. Yano, K. Ohki, Y. Yamashita, Y. Kodama, A. Saito, M. Mori, S. Ishimaru, T. Deguchi, Y. Hashii, Y. Shimomura, T. Hori, K. Kato, H. Goto, C. Ogawa, K. Koh, T. Taki, A. Manabe, A. Sato, A. Kikuta, S. Adachi, K. Horibe, A. Ohara, A. Watanabe, Y. Kawano, E. Ishii, H. Shimada

    BLOOD CANCER JOURNAL   6   e419   2016年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Recent studies revealed that a substantial proportion of patients with high-risk B-cell precursor acute lymphoblastic leukemia (BCP-ALL) harbor fusions involving tyrosine kinase and cytokine receptors, such as ABL1, PDGFRB, JAK2 and CRLF2, which are targeted by tyrosine kinase inhibitors (TKIs). In the present study, transcriptome analysis or multiplex reverse transcriptase-PCR analysis of 373 BCP-ALL patients without recurrent genetic abnormalities identified 29 patients with kinase fusions. Clinically, male predominance (male/female: 22/7), older age at onset (mean age at onset: 8.8 years) and a high white blood cell count at diagnosis (mean: 94 200/mu l) reflected the predominance of National Cancer Institute high-risk (NCI-HR) patients (NCI-standard risk/HR: 8/21). Genetic analysis identified three patients with ABL1 rearrangements, eight with PDGFRB rearrangements, two with JAK2 rearrangements, three with IgH-EPOR and one with NCOR1-LYN. Of the 14 patients with CRLF2 rearrangements, two harbored IgH-EPOR and PDGFRB rearrangements. IKZF1 deletion was present in 16 of the 22 patients. The 5-year event-free and overall survival rates were 48.6 +/- 9.7% and 73.5 +/- 8.6%, respectively. The outcome was not satisfactory without sophisticated minimal residual disease-based stratification. Furthermore, the efficacy of TKIs combined with conventional chemotherapy without allogeneic hematopoietic stem cell transplantation in this cohort should be determined.

    DOI: 10.1038/bcj.2016.28

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  • Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34(+) cells of juvenile myelomonocytic leukemia 査読

    Yozo Nakazawa, Kazuyuki Matsuda, Takashi Kurata, Akane Sueki, Miyuki Tanaka, Kazuo Sakashita, Chihaya Imai, Matthew H. Wilson, Kenichi Koike

    JOURNAL OF HEMATOLOGY & ONCOLOGY   9 ( 1 )   27   2016年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: Juvenile myelomonocytic leukemia (JMML) is a fatal, myelodysplastic/myeloproliferative neoplasm of early childhood. Patients with JMML have mutually exclusive genetic abnormalities in granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor (GMR, CD116) signaling pathway. Allogeneic hematopoietic stem cell transplantation is currently the only curative treatment option for JMML; however, disease recurrence is a major cause of treatment failure. We investigated adoptive immunotherapy using GMR-targeted chimeric antigen receptor (CAR) for JMML.
    Methods: We constructed a novel CAR capable of binding to GMR via its ligand, GM-CSF, and generated piggyBac transposon-based GMR CAR-modified T cells from three healthy donors and two patients with JMML. We further evaluated the anti-proliferative potential of GMR CAR T cells on leukemic CD34(+) cells from six patients with JMML (two NRAS mutations, three PTPN11 mutations, and one monosomy 7), and normal CD34(+) cells.
    Results: GMR CAR T cells from healthy donors suppressed the cytokine-dependent growth of MO7e cells, but not the growth of K562 and Daudi cells. Co-culture of healthy GMR CAR T cells with CD34(+) cells of five patients with JMML at effector to target ratios of 1: 1 and 1: 4 for 2 days significantly decreased total colony growth, regardless of genetic abnormality. Furthermore, GMR CAR T cells from a non-transplanted patient and a transplanted patient inhibited the proliferation of respective JMML CD34(+) cells at onset to a degree comparable to healthy GMR CAR T cells. Seven-day co-culture of GMR CAR T cells resulted in a marked suppression of JMML CD34(+) cell proliferation, particularly CD34(+)CD38(-) cell proliferation stimulated with stem cell factor and thrombopoietin on AGM-S3 cells. Meanwhile, GMR CAR T cells exerted no effects on normal CD34(+) cell colony growth.
    Conclusions: Ligand-based GMR CAR T cells may have anti-proliferative effects on stem and progenitor cells in JMML.

    DOI: 10.1186/s13045-016-0256-3

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  • Augmented Consolidation Therapy Based on Minimal Residual Disease (MRD) and Analysis of the Measurement of Sequential MRD in Childhood Acute Lymphoblastic Leukemia : Children's Cancer and leukemia Study Group of JAPAN (CCLSG), Cclsg ALL 2004 Protocol Study 査読

    Arata Watanabe, Toshinori Hori, Yasuto Shimomura, Chihaya Imai, Atsushi Ogawa, Motoaki Chin, Hiroyuki Shichino, Yasuo Horikoshi, Keiko Nomura, Yutaka Saikawa, Shouhei Yokota, Akiko Inoue, Takashi Taga, Masahiko Okada, Jun-ichi Ueyama, Asayuki Iwai, Michihiro Yano, Yasuhiro Okamoto, Masahito Tsurusawa, Atsushi Kikuta

    BLOOD   126 ( 23 )   2015年12月

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    記述言語:英語   出版者・発行元:AMER SOC HEMATOLOGY  

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  • ニーマンピック病C型に合併した進行期肝細胞がんに対しソラフェニブ投与を行った1例

    笠原 靖史, 江村 重仁, 申 将守, 高地 貴行, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   52 ( 4 )   293 - 293   2015年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • 低ゴナドトロピン性性腺機能低下症を呈した輸血後鉄過剰症女児例

    西崎 淑美, 佐藤 英利, 小川 洋平, 長崎 啓祐, 今井 千速, 齋藤 昭彦

    日本内分泌学会雑誌   91 ( 3 )   841 - 841   2015年10月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • ステロイド抵抗性の消化管GVHDに対して少量メソトレキセートが有効であった一例(Efficacy of weekly low-dose methotrexate pulse therapy for steroid-refractory gut GVHD after unrelated bone marrow transplantation in a child)

    申 将守, 笠原 靖史, 高地 貴行, 岩渕 晴子, 今村 勝, 今井 千速

    日本小児血液・がん学会雑誌   52 ( 4 )   341 - 341   2015年10月

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    記述言語:英語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • 小児・思春期再生不良性貧血にウサギATGを使用した免疫抑制治療後のEBV/CMV再活性化 後方視的解析(EBV/CMV reactivation following immunosuppressive therapy with rabbit ATG for children and adolescents with aplastic anemia: A retrospective chart review)

    久保 暢大, 細貝 亮介, 渡辺 彰浩, 小川 淳, 申 将守, 高地 貴行, 笠原 靖史, 吉田 咲子, 岩渕 晴子, 今村 勝, 齋藤 昭彦, 今井 千速

    日本小児血液・がん学会雑誌   52 ( 4 )   313 - 313   2015年10月

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    記述言語:英語   出版者・発行元:(一社)日本小児血液・がん学会  

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  • 低身長を契機に発見されたCastleman病の1例

    園田 香里, 堀口 祥, 樋浦 誠, 金子 詩子, 今井 千速, 佐藤 英利, 今村 勝, 齋藤 昭彦, 横田 直樹, 大山 俊之, 荒井 勇樹, 窪田 正幸, 梅津 哉

    日本小児リウマチ学会総会・学術集会プログラム・抄録集   25回   150 - 150   2015年10月

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    記述言語:日本語   出版者・発行元:(一社)日本小児リウマチ学会  

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  • Secondary osteosarcoma arising from osteochondroma following autologous stem cell transplantation with total-body irradiation for neuroblastoma: A case report 査読

    Hiroyuki Kawashima, Akira Ogose, Tetsuo Hotta, Chihaya Imai, Masaharu Imamura, Naoto Endo

    ONCOLOGY LETTERS   10 ( 2 )   1026 - 1030   2015年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPANDIDOS PUBL LTD  

    The present study reports the first case of malignant transformation to osteosarcoma arising from osteochondroma following childhood total-body irradiation (TBI). The association between TBI and later development of osteochondroma is well-known; however, malignant degeneration arising from radiation-induced osteochondroma is rare. The current study describes the case of a 17-year-old boy with osteosarcoma arising from osteochondroma of the left distal humerus, which developed following TBI. TBI was administered as part of a conditioning regimen received prior to autologous peripheral hematopoietic stem cell transplantation (HSCT) at the age of 6 years, following an initial diagnosis of neuroblastoma at the age of 5 years. The patient subsequently underwent preoperative chemotherapy followed by wide local excision and reconstruction with an extracorporeally irradiated autograft. Postoperative chemotherapy was administered, and the patient demonstrated no clinical or radiographic evidence of recurrence after 40 months of follow-up. To the best of our knowledge, this is only the second reported case of malignant degeneration of osteochondroma following childhood TBI, and the first reported case of transformation to osteosarcoma. The current case highlights the importance of close observation for secondary malignancies in this patient population.

    DOI: 10.3892/ol.2015.3257

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  • 全脳脊髄照射を要する小児脳腫瘍における術後2週間以内のG-CSF単独自家末梢血幹細胞採取 査読

    細貝亮介, 高地貴行, 吉田咲子, 岩渕晴子, 今村勝, 申将守, 笠原靖史, 齋藤昭彦, 佐野正和, 西山健一, 阿部英輔, 青山英史, 吉村淳一, 今井千速

    日本小児血液・がん学会雑誌   52 ( 2 )   133 - 138   2015年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)   出版者・発行元:(一社)日本小児血液・がん学会  

    悪性脳腫瘍に対する全脳脊髄照射(CSI)では頭蓋骨及び全脊椎の骨髄組織が障害されるため、CSI後の強力な化学療法では骨髄抑制が著しく遷延し、結果的に治療全体の強度が低下することが大きな問題である。そこで我々は、CSI及び強力な化学療法を要する悪性脳腫瘍に対しG-CSF単独の末梢血幹細胞(PBSC)採取を試み、化学療法に自家末梢血幹細胞移植(aPBSCT)を併用することとした。早期にCSIを開始するため、術後2週以内の採取完了を目指した。初発未治療例6例では中央値12.6×10^6/kg(3.9-21.6×10^6/kg)のCD34陽性細胞採取が可能だったが、うち2例では複数回のaPBSCTに十分な細胞数に達しなかった。再発例の2例では少なくとも1回の移植に必要な量は採取できた。これら4例ではaPBSCT併用化学療法1コース終了後に再度PBSC採取を行い十分量が確保できた(13.7-42.1×10^6/kg)。術後2週以内のPBSC採取では白血球数が増加しやすい傾向にあったが、重篤な有害事象はみられなかった。全例で予定した複数回aPBSCTを実施でき、骨髄抑制の遷延をきたすことなく規定の間隔で化学療法を完遂できた。術後2週以内のG-CSF単独PBSC採取は安全に実施できたものの少数例の経験であり、術後早期にCSIを要する悪性脳腫瘍の集学的治療における有効性に関しては更なる検討を要する。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J06030&link_issn=&doc_id=20160106240003&doc_link_id=%2Fex9syoga%2F2015%2F005202%2F003%2F0133-0138%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fex9syoga%2F2015%2F005202%2F003%2F0133-0138%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Autonomous growth and increased cytotoxicity of natural killer cells expressing membrane-bound interleukin-15

    Masaru Imamura, David Shook, Takahiro Kamiya, Noriko Shimasaki, Sally M. H. Chai, Elaine Coustan-Smith, Chihaya Imai, Dario Campana

    Blood   124 ( 7 )   1081 - 1088   2014年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Society of Hematology  

    Natural killer (NK) cell survival and, hence, cytotoxicity requires cytokine support. We determined whether expression of interleukin-15 (IL-15) in a nonsecretory, membranebound form could sustain NK cell growth. We linked the human IL15 gene to that encoding CD8α transmembrane domain (mbIL15). After retroviral transduction, human NK cells expressed mbIL15 on the cell surface
    IL-15 secretion was negligible. Survival of mbIL15-NK cells without interleukin-2 (IL-2) after 7-day culturewas vastly superior to that of mock-transduced NK cells (P &lt
    .001, n = 15) and of NK cells expressing nonmembrane-bound IL-15 (P = .025, n = 9)
    viable mbIL15-NK cells were detectable for up to 2 months. In immunodeficient mice, mbIL15-NK cells expanded without IL-2 and were detectable in all tissues examined (except brain) in much higher numbers than mock-transduced NK cells (P &lt
    .001).Expansion further increasedwith IL-2. The primary mechanism of mbIL15 stimulation was autocrine
    it activated IL-15 signaling and antiapoptotic signaling. NK cells expressing mbIL15 had higher cytotoxicity against leukemia, lymphoma, and solid tumor cells in vitro and against leukemia and sarcoma cells in xenograft models. Thus, mbIL15 confers independent growth to NK cells and enhances their antitumor capacity. Infusion of mbIL15-NK cells would allow NK cell therapy without the potential adverse effects of cytokine administration. © 2014 by The American Society of Hematology.

    DOI: 10.1182/blood-2014-02-556837

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  • Autonomous growth and increased cytotoxicity of natural killer cells expressing membrane-bound interleukin-15 査読

    Masaru Imamura, David Shook, Takahiro Kamiya, Noriko Shimasaki, Sally M. H. Chai, Elaine Coustan-Smith, Chihaya Imai, Dario Campana

    BLOOD   124 ( 7 )   1081 - 1088   2014年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC HEMATOLOGY  

    Natural killer (NK) cell survival and, hence, cytotoxicity requires cytokine support. We determined whether expression of interleukin-15 (IL-15) in a nonsecretory, membrane-bound form could sustain NK cell growth. We linked the human IL15 gene to that encoding CD8 alpha transmembrane domain (mbIL15). After retroviral transduction, human NK cells expressed mbIL15 on the cell surface; IL-15 secretion was negligible. Survival of mbIL15-NK cells without interleukin-2 (IL-2) after 7-day culture was vastly superior to that of mock-transduced NK cells (P < .001, n = 15) and of NK cells expressing nonmembrane-bound IL-15 (P = .025, n=9); viable mbIL 15-NK cells were detectable for up to 2 months. In immunodeficient mice, mbIL15-NK cells expanded without IL-2 and were detectable in all tissues examined (except brain) in much higher numbers than mock-transduced NK cells (P < .001). Expansion further increased with IL-2. The primary mechanism of mbIL15 stimulation was autocrine; it activated IL-15 signaling and antiapoptotic signaling. NK cells expressing mbIL15 had higher cytotoxicity against leukemia, lymphoma, and solid tumor cells in vitro and against leukemia and sarcoma cells in xenograft models. Thus, mbIL15 confers independent growth to NK cells and enhances their antitumor capacity. Infusion of mbIL15-NK cells would allow NK cell therapy without the potential adverse effects of cytokine administration.

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  • T Lymphocytes Expressing a CD16 Signaling Receptor Exert Antibody-Dependent Cancer Cell Killing 査読

    Ko Kudo, Chihaya Imai, Paolo Lorenzini, Takahiro Kamiya, Koji Kono, Andrew M. Davidoff, Wee Joo Chng, Dario Campana

    CANCER RESEARCH   74 ( 1 )   93 - 103   2014年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    To expand applications for T-cell-based immunotherapy in cancer, we designed a receptor that binds the Fc portion of human immunoglobulins and delivers activation signals. The construct included the high-affinity CD16 (FCGR3A) V158 variant, CD8 alpha hinge, and transmembrane domains, along with signaling domains from CD3 zeta and 4-1BB (TNFRSF9), forming a chimeric receptor termed CD16V-BB-zeta. After retrovirus-mediated expression in human T cells, CD16V-BB-zeta bound humanized antibodies with higher affinity than a control receptor containing the more common F158 variant. Engagement of CD16V-BB-zeta provoked T-cell activation, exocytosis of lytic granules, and sustained proliferation, with a mean cell recovery after4-week coculture with Daudi lymphoma cells and rituximab of nearly 70-fold relative to input cells. In contrast, unbound antibody alone produced no effect. CD16V-BB-zeta T cells specifically killed lymphoma cells and primary chronic lymphocytic leukemia cells in combination with rituximab at a low effector target ratio, even when assayed on mesenchymal cells. Trastuzumab triggered CD16V-BB-zeta-mediated killing of HER2 (ERBB2)(+) breast and gastric cancer cells; similar results were obtained with an anti-GD2 antibody in neuroblastoma and osteosarcoma cells. Furthermore, coadministration of CD16V-BB-zeta T cells with immunotherapeutic antibodies exerted considerable antitumor activity in vivo. Signaling mediated by 4-1BB-CD3 zeta induced higher T-cell activation, proliferation, and cytotoxicity than CD3 zeta or Fc epsilon RI gamma, and the receptor was expressed effectively after mRNA electroporation without viral vectors, facilitating clinical translation. Our results offer preclinical proof of concept for CD16V-BB-zeta as a universal, next-generation chimeric receptor with the potential to augment the efficacy of antibody therapies for cancer. (C)2013 AACR.

    DOI: 10.1158/0008-5472.CAN-13-1365

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  • 4-1BB chimeric antigen receptors

    Dario Campana, Herbert Schwarz, Chihaya Imai

    Cancer Journal (United States)   20 ( 2 )   134 - 140   2014年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Lippincott Williams and Wilkins  

    In addition to T-cell receptor signals, T lymphocytes require costimulatory signals for robust activation. Among these, those mediated by 4-1BB (CD137, TNFRSF9) are critical for tumor immunity. 4-1BB is expressed in T-cell receptor-activated lymphocytes as well as natural killer cells and other hematopoietic and nonhematopoietic cells. 4-1BB ligation induces a signaling cascade that results in cytokine production, expression of antiapoptotic molecules, and enhanced immune responses. In line with the described function of 4-1BB, its addition to CD3ζ chimeric antigen receptors (CARs) increases their capacity to provoke T-cell expansion and antitumor activity. The results of preclinical studies with 4-1BB CARs have been corroborated by encouraging results from clinical trials. Advantages and disadvantages of 4-1BB CARs versus CARs bearing other costimulatory components remain to be fully elucidated. In this review, we discuss the properties of 4-1BB, the design of 4-1BB CARs, and the function of T lymphocytes and natural killer cells expressing them. Copyright © 2014 Lippincott Williams &amp
    Wilkins.

    DOI: 10.1097/PPO.0000000000000028

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  • Autoimmunity and persistent RAS-mutated clones long after the spontaneous regression of JMML 査読

    M. Takagi, J. Piao, L. Lin, H. Kawaguchi, C. Imai, A. Ogawa, A. Watanabe, K. Akiyama, C. Kobayashi, M. Mori, K. Ko, M. Sugimoto, S. Mizutani

    Leukemia   27 ( 9 )   1926 - 1928   2013年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1038/leu.2013.82

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  • Alveolar rhabdomyosarcoma after treatment of osteosarcoma

    Yasushi Kasahara, Haruko Iwabuchi, Takayuki Takachi, Ryosuke Hosokai, Sakiko Yoshida, Masaru Imamura, Akihiro Watanabe, Hajime Umezu, Tetsuo Hotta, Akira Ogose, Chihaya Imai

    Pediatrics International   55 ( 4 )   527 - 530   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Secondary rhabdomyosarcoma (RMS) after treatment of osteosarcoma (OS) is rare. Reported here is the case of a metachronous RMS in the nasal cavity, developing 12 years after successful treatment of non-metastatic OS. The patient was diagnosed as having OS of the femur at 2 years of age. Chemotherapy for OS included doxorubicin (cumulative dose, 488 mg/m2). No radiotherapy was given. There was no family history suggestive of cancer predisposition syndrome. At 14 years of age, alveolar RMS was diagnosed on histopathology. PAX3-FKHR fusion transcripts were detected on reverse transcription-polymerase chain reaction. Germline TP53 mutation was not seen on standard DNA sequencing. The occurrence of secondary sarcomas, in the Children's Cancer Survivor study conducted in North America, has been associated with high cumulative doses of anthracyclines, which may also have played a role in the development of RMS in the present case. In the future, novel molecular technologies might uncover genetic cancer predisposition in patients with metachronous cancers. © 2013 The Authors.

    DOI: 10.1111/ped.12070

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  • Alveolar rhabdomyosarcoma after treatment of osteosarcoma 査読

    Yasushi Kasahara, Haruko Iwabuchi, Takayuki Takachi, Ryosuke Hosokai, Sakiko Yoshida, Masaru Imamura, Akihiro Watanabe, Hajime Umezu, Tetsuo Hotta, Akira Ogose, Chihaya Imai

    PEDIATRICS INTERNATIONAL   55 ( 4 )   527 - 530   2013年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Secondary rhabdomyosarcoma (RMS) after treatment of osteosarcoma (OS) is rare. Reported here is the case of a metachronous RMS in the nasal cavity, developing 12 years after successful treatment of non-metastatic OS. The patient was diagnosed as having OS of the femur at 2 years of age. Chemotherapy for OS included doxorubicin (cumulative dose, 488 mg/m(2)). No radiotherapy was given. There was no family history suggestive of cancer predisposition syndrome. At 14 years of age, alveolar RMS was diagnosed on histopathology. PAX3-FKHR fusion transcripts were detected on reverse transcription-polymerase chain reaction. Germline TP53 mutation was not seen on standard DNA sequencing. The occurrence of secondary sarcomas, in the Children's Cancer Survivor study conducted in North America, has been associated with high cumulative doses of anthracyclines, which may also have played a role in the development of RMS in the present case. In the future, novel molecular technologies might uncover genetic cancer predisposition in patients with metachronous cancers.

    DOI: 10.1111/ped.12070

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  • 微小残存病変を用いた急性リンパ性白血病治療戦略 招待

    今井 千速

    小児内科   45 ( 6 )   1134 - 1136   2013年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • ヒトNK細胞の体外増幅と遺伝子改変 ~難治性白血病・がんの征圧に向けて. 招待

    今井 千速

    日本小児血液・がん学会雑誌   50 ( 3 )   341 - 349   2013年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Frequent somatic mosaicism of NEMO in T cells of patients with X-linked anhidrotic ectodermal dysplasia with immunodeficiency 査読

    Tomoki Kawai, Ryuta Nishikomori, Kazushi Izawa, Yuuki Murata, Naoko Tanaka, Hidemasa Sakai, Megumu Saito, Takahiro Yasumi, Yuki Takaoka, Tatsutoshi Nakahata, Tomoyuki Mizukami, Hiroyuki Nunoi, Yuki Kiyohara, Atsushi Yoden, Takuji Murata, Shinya Sasaki, Etsuro Ito, Hiroshi Akutagawa, Toshinao Kawai, Chihaya Imai, Satoshi Okada, Masao Kobayashi, Toshio Heike

    BLOOD   119 ( 23 )   5458 - 5466   2012年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC HEMATOLOGY  

    Somatic mosaicism has been described in several primary immunodeficiency diseases and causes modified phenotypes in affected patients. X-linked anhidrotic ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is caused by hypomorphic mutations in the NF-kappa B essential modulator (NEMO) gene and manifests clinically in various ways. We have previously reported a case of XL-EDA-ID with somatic mosaicism caused by a duplication mutation of the NEMO gene, but the frequency of somatic mosaicism of NEMO and its clinical impact on XL-EDA-ID is not fully understood. In this study, somatic mosaicism of NEMO was evaluated in XL-EDA-ID patients in Japan. Cells expressing wild-type NEMO, most of which were derived from the T-cell lineage, were detected in 9 of 10 XL-EDA-ID patients. These data indicate that the frequency of somatic mosaicism of NEMO is high in XL-ED-ID patients and that the presence of somatic mosaicism of NEMO could have an impact on the diagnosis and treatment of XL-ED-ID patients. (Blood. 2012;119(23):5458-5466)

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  • 家系に複数の脾臓摘出者を認め遺伝性球状赤血球症と考えられていたHb Koeln症の一例

    笠原 靖史, 細貝 亮介, 高地 貴行, 吉田 咲子, 今村 勝, 今井 千速

    日本小児血液・がん学会雑誌   49 ( 1-2 )   138 - 141   2012年5月

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    記述言語:日本語   出版者・発行元:(一社)日本小児血液・がん学会  

    先天性溶血性貧血の異常部位には赤血球膜、赤血球酵素、ヘモグロビンが知られている。遺伝性球状赤血球症(HS)は赤血球膜の異常に起因し、日本で最も高頻度の先天性溶血性貧血である。溶血性貧血を呈し、HSに矛盾しない背景を持つ場合では、他の稀な溶血性貧血が見逃される可能性も考えられる。Hb Koeln症はヘモグロビン異常症の一型で、稀な疾患である。今回、我々は複数の脾臓摘出者を認め、HSと考えられていた12歳男児のHb Koeln症を経験した。平均赤血球ヘモグロビン濃度(MCHC)は28.7%と低値、平時のSpO2は90%程と低値(高濃度酸素投与で92%)、HbA1cは2.0%と異常低値であった。これらの一般検査所見がHSとは矛盾したため、ヘモグロビン異常症を疑い精査を進めた。先天性溶血性貧血のような稀な疾患でも、日常的な検査の吟味が診断に重要と考えられた。(著者抄録)

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  • Lymphoblastic Lymphoma With Mature B-cell Immunophenotype and MLL-AF9 in a Child 査読

    Takayuki Takachi, Haruko Iwabuchi, Masaru Imamura, Chihaya Imai

    PEDIATRIC BLOOD & CANCER   57 ( 7 )   1251 - 1252   2011年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY PERIODICALS, INC  

    DOI: 10.1002/pbc.23228

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  • Disseminated BCG infection mimicking metastatic nasopharyngeal carcinoma in an immunodeficient child with a novel hypomorphic NEMO mutation. 査読 国際誌

    Masaru Imamura, Tomoki Kawai, Satoshi Okada, Kazushi Izawa, Takayuki Takachi, Haruko Iwabuchi, Sakiko Yoshida, Ryosuke Hosokai, Hirokazu Kanegane, Tatsuo Yamamoto, Hajime Umezu, Ryuta Nishikomori, Toshio Heike, Makoto Uchiyama, Chihaya Imai

    Journal of clinical immunology   31 ( 5 )   802 - 10   2011年10月

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    記述言語:英語  

    BACKGROUND: Nuclear factor-κB essential modulator (NEMO) deficiency is a developmental and immunological disorder. The genetic and phenotypic correlation has been described. METHODS: We report a unique clinical presentation and the identification of a novel missense mutation in the NEMO gene in a 3-year-old boy with bacillus Calmette-Guerin (BCG) infection. RESULTS: The patient presented with fever, cervical lymphadenopathy, and abnormal anti-Epstein-Barr virus (EBV) antibody titers, suggestive of EBV-related diseases including chronic active EBV infection, X-linked lymphoproliferative syndrome, or nasopharyngeal carcinoma. Although the biopsy specimen from a nasopharyngeal lesion was initially diagnosed as squamous cell carcinoma, this was changed to disseminated BCG infection involving the nasopharynx, multiple systemic lymph nodes, and brain. A novel mutation (designated D311E) in the NEMO gene, located in the NEMO ubiquitin-binding (NUB) domain, was identified as the underlying cause of the immunodeficiency. Impaired immune responses which are characteristic of patients with NEMO deficiency were demonstrated. The patient underwent successful unrelated bone marrow transplantation at 4.9 years of age. CONCLUSION: This study suggests the importance of the NUB domain in host defense against mycobacteria. The unique presenting features in our patient indicate that a hypomorphic NEMO mutation can be associated with atypical pathological findings of the epithelial tissues in patients with BCG infection.

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  • 急性リンパ性白血病治療中に発症し、アムホテリシンBリポソーム製剤が奏効した接合菌症の疑われる脳膿瘍の1例

    細貝 亮介, 高地 貴行, 吉田 咲子, 岩渕 晴子, 今村 勝, 今井 千速, 内山 聖

    日本小児血液学会雑誌   25 ( 2 )   97 - 101   2011年4月

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    記述言語:日本語   出版者・発行元:日本小児血液学会  

    3歳男児。B前駆細胞型小児急性リンパ性白血病(ALL)と診断し、超高危険群として寛解導入療法を開始した。治療開始42週目に2回目の再寛解導入療法に続く強化療法を開始した。一時解熱したが再度発熱し、発熱から10日後に全身強直性痙攣が出現した。頭部CTで右頭頂葉に輪状造影を伴う病変を認め、脳膿瘍が疑われた。接合菌症の可能性を考慮してliposomal amphotericin B(L-AMB)を開始したところ翌日には解熱し、発症2週後のDiffusion MRIでは右頭頂葉に膿瘍腔を示唆する高信号域を認めていたが、発症2ヵ月後には消失していた。しかし、CRPは0.3〜1.0mg/dl程度で著減していたため、L-AMB継続下にmercaptopurine(6MP)、methotrexate(MTX)内服による維持療法を開始した。発症4ヵ月後もDiffusion MRIの所見は変化を認めなかったが、血清クレアチニンは0.2mg/dlから0.5mg/dlへ上昇した。そのためL-AMBを5mg/kg/dayの隔日投与へ、さらに2週間後から週2回投与へ減量したが、CRPは増加傾向とはならなかった。Diffusion MRI所見の増悪もなく、週2回投与を2週間継続後にL-AMBを中止した。その後CRPは陰性化し、投与終了後約1年、脳膿瘍の再発は認めず、維持療法継続中である。

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2011&ichushi_jid=J02258&link_issn=&doc_id=20110511060006&doc_link_id=%2Fex9syoke%2F2011%2F002502%2F006%2F0097-0101%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fex9syoke%2F2011%2F002502%2F006%2F0097-0101%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • Reactive tonsillar enlargement with strong18F-FDG uptake after chemotherapy for tonsillar diffuse large B-cell lymphoma

    Ryosuke Hosokai, Chihaya Imai, Takayuki Takachi, Sakiko Yoshida, Haruko Iwabuchi, Masaru Imamura, Makoto Uchiyama

    Journal of Pediatric Hematology/Oncology   33 ( 2 )   e87 - e88   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We describe a 14-year-old boy who exhibited left palatine tonsillar enlargement after 6 cycles of aggressive chemotherapy for diffuse large B-cell lymphoma of the right palatine tonsil. The cervical computed tomography scan at 4 months after completion of chemotherapy revealed enlargement of the left palatine tonsil in addition to the thymus without any clinical symptoms. The18F-fluorodeoxyglucose positron emission tomography indicated focal areas of strong18F-fluorodeoxyglucose uptake in the left palatine tonsil. Histologic examination confirmed tonsillar hyperplasia with no evidence of recurrence. Reactive tonsillar hyperplasia after chemotherapy is rarely reported. Copyright © 2011 by Lippincott Williams &amp
    Wilkins.

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  • Reactive Tonsillar Enlargement With Strong F-18-FDG Uptake After Chemotherapy for Tonsillar Diffuse Large B-cell Lymphoma 査読

    Ryosuke Hosokai, Chihaya Imai, Takayuki Takachi, Sakiko Yoshida, Haruko Iwabuchi, Masaru Imamura, Makoto Uchiyama

    JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY   33 ( 2 )   E87 - E88   2011年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    We describe a 14-year-old boy who exhibited left palatine tonsillar enlargement after 6 cycles of aggressive chemotherapy for diffuse large B-cell lymphoma of the right palatine tonsil. The cervical computed tomography scan at 4 months after completion of chemotherapy revealed enlargement of the left palatine tonsil in addition to the thymus without any clinical symptoms. The F-18-fluorodeoxyglucose positron emission tomography indicated focal areas of strong F-18-fluorodeoxyglucose uptake in the left palatine tonsil. Histologic examination confirmed tonsillar hyperplasia with no evidence of recurrence. Reactive tonsillar hyperplasia after chemotherapy is rarely reported.

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  • Autonomously functioning thyroid nodule in a four-year-old boy with Sotos syndrome 査読

    Hiromi Nyuzuki, Keisuke Nagasaki, Hiroshi Matsuyama, Masahiko Tomita, Chihaya Imai, Yohei Ogawa, Toru Kikuchi, Makoto Uchiyama

    PEDIATRICS INTERNATIONAL   53 ( 1 )   137 - 138   2011年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

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  • Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma 査読

    Keichiro Mihara, Kazuyoshi Yanagihara, Misato Takigahira, Akira Kitanaka, Chihaya Imai, Joyeeta Bhattacharyya, Takanori Kubo, Yoshifumi Takei, Shin'ichiro Yasunaga, Yoshihiro Takihara, Akiro Kimura

    BRITISH JOURNAL OF HAEMATOLOGY   151 ( 1 )   37 - 46   2010年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    P>Using artificial receptors, it is possible to redirect the specificity of immune cells to tumour-associated antigens, which is expected to provide a useful strategy for cancer immunotherapy. Given that B-cell non-Hodgkin lymphoma (B-NHL) cells invariably express CD19 and CD38, these antigens may be suitable molecular candidates for such immunotherapy. We transduced human peripheral T cells or a T-cell line with either anti-CD19-chimeric receptor (CAR) or anti-CD38-CAR, which contained an anti-CD19 or anti-CD38 antibody-derived single-chain variable domain respectively. Retroviral transduction led to anti-CD19-CAR or anti-CD38-CAR expression in T cells with high efficiency (> 60%). The T cell line, Hut78, when transduced with anti-CD19-CAR or anti-CD38-CAR, exerted strong cytotoxicity against the B-NHL cell lines, HT and RL, and lymphoma cells isolated from patients. Interestingly, use of both CARs had an additive cytotoxic effect on HT cells in vitro. In conjunction with rituximab, human peripheral T cells expressing either anti-CD19-CAR or anti-CD38-CAR enhanced cytotoxicity against HT-luciferase cells in xenografted mice. Moreover, the synergistic tumour-suppressing activity was persistent in vivo for over 2 months. These results provide a powerful rationale for clinical testing of the combination of rituximab with autologous T cells carrying either CAR on aggressive or relapsed B-NHLs.

    DOI: 10.1111/j.1365-2141.2010.08297.x

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  • NK細胞療法の基礎と展望 招待 査読

    今井 千速

    小児がん   47 ( 2 )   268 - 274   2010年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • A 2-year-old boy with a stage III yolk sac tumor occurring in an intra-abdominal retained testis 査読

    Yutaka Hirayama, Masayuki Kubota, Masaru Imamura, Chihaya Imai, Naoki Okuyama, Mami Tsukada, Kumiko Kobayashi, Kanako Sato, Takayuki Takachi, Haruko Iwavuchi, Makoto Uchiyama

    JOURNAL OF PEDIATRIC SURGERY   44 ( 12 )   2395 - 2398   2009年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

    A major complication of retained testes is an occurrence of malignancy later in life. We, herein, report the case of a 2-year-old boy who presented with a huge yolk sac tumor with retroperitoneal lymph nodes metastasis that originated in a left intra-abdominal undescended testis. Computed tomography and magnetic resonance imaging showed a huge round tumor connecting to the left retroperitoneal lymph nodes with metastasis extending from the left pelvic region to the left renal hilum. The serum a-fetoprotein level was 36,528 ng/mL. The right abdominal tumor appeared to be a giant testis that had strangulated at the neck of the cord. The tumor had ruptured at the side of the left pelvic lymph node metastasis, and a yolk sac tumor was diagnosed from a histologic analysis of the resected specimens. Postoperative PEB chemotherapy was effective, and a complete surgical resection of the tumor was performed 3 months after the initial laparotomy. The pathologic findings showed fibrous tissue without any tumor cells. The patient has been doing well for 18 months after the radical operation. This case might be a coincidental association of a yolk sac tumor occurring in an undescended testis, which thus caused a delay in making an accurate diagnosis. (C) 2009 Elsevier Inc. All rights reserved.

    DOI: 10.1016/j.jpedsurg.2009.08.024

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  • A novel homozygous 8-base pair deletion mutation in the glycoprotein Ibalpha gene in a patient with Bernard-Soulier syndrome.

    Imai Chihaya, Kunishima Shinji, Takachi Takayuki, Iwabuchi Haruko, Nemoto Tae, Imamura Masaru, Uchiyama Makoto

    Blood Coagul Fibrinolysis   20 ( 6 )   470 - 474   2009年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We present a patient with Bernard-Soulier syndrome harboring a novel mutation. Flow cytometric analysis showed that the glycoprotein (GP) Ib/IX complex was absent from the platelet surface. By immunoblotting, GPIbalpha, GPIbbeta and GPIX were not detected in the platelet lysates. Glycocalicin, the soluble GPIbalpha fragment, was also absent in the plasma. Genetic analysis revealed a novel homozygous 8-base pair deletion in the GPIbalpha gene, 1136_1143delTTCACATG, which was predicted to cause a frame shift and the addition of 13 altered amino acids followed by premature termination. No mutation was found in the coding sequence of the GPIbbeta or GPIX genes. We demonstrated that the novel deletion mutation resulted in complete defectiveness of the GPIbalpha protein and null expression of the entire GPIb/IX complex, and was responsible for the Bernard-Soulier syndrome phenotype in this patient. Although the presence of a truncated GPIbalpha protein has been often documented, complete absence of the protein has been scarcely reported in Bernard-Soulier syndrome patients with a GPIbalpha mutation causing a premature stop codon. An underlying molecular mechanism to explain how the synth

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  • Activated T-cell-mediated Immunotherapy With a Chimeric Receptor Against CD38 in B-cell Non-Hodgkin Lymphoma 査読

    Keichiro Mihara, Kazuyoshi Yanagihara, Misato Takigahira, Chihaya Imai, Akira Kitanaka, Yoshihiro Takihara, Akiro Kimura

    JOURNAL OF IMMUNOTHERAPY   32 ( 7 )   737 - 743   2009年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    T-cell-mediated immunotherapy with a chimeric antigen receptor (CAR) is expected to become a powerful treatment for cancer. CD38, highly expressed in B-cell non-Hodgkin lymphoma (B-NHL) cells, is in attractive target in immunotherapy for B-NHL. We retrovirally transduced a T-cell line, Hut78, expressing little CD38, with an anti-CD38-CAR. Hut78 cells with the anti-CD38-CAR were cocultured with B-NHL cell lines hearing CD38 and also B-NHL cells from patients. Four days later most of the lymphoma cells were killed (the level of cytotoxicity was > 95%). By contrast, there was undetectable cytotoxicity against CD38-negative cell lines. Then, we introduced the anti-CD38-CAR into human peripheral T cells. However, the recovery of viable cells was very low, presumably because of all autolytic reaction caused by the association of the anti-CD38-CAR with CD38 on the cell surface. The addition of an anti-CD38 antibody increased the yield of viable transduced T cell probably by blocking the autolytic reaction. We cocultured human peripheral T cells hearing anti-CD38-CAR with B-NHL cells. The median specific cytotoxicity was greater than 90%. These cells were injected 4 times into NOD/SCID mice, which were inoculated with B-NHL cells luciferase. Luciferase activity was not detectable even 30 days after the inoculation in 5 of 6 mice injected. By contrast, it increased in all of the mice injected with the mock vector-transduced T cell. In conclusion, T cell with the anti-CD38-CAR showed powerful cytotoxicity against B-NHL cells in vitro and in vivo. These findings may provide all important Clue for improving the methodology of T-cell-mediated immunotherapy.

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  • A novel homozygous 8-base pair deletion mutation in the glycoprotein Ib alpha gene in a patient with Bernard-Soulier syndrome 査読

    Chihaya Imai, Shinji Kunishima, Takayuki Takachi, Haruko Iwabuchi, Tae Nemoto, Masaru Imamura, Makoto Uchiyama

    BLOOD COAGULATION & FIBRINOLYSIS   20 ( 6 )   470 - 474   2009年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

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  • Replicative potential of human natural killer cells 査読

    Hiroyuki Fujisaki, Harumi Kakuda, Chihaya Imai, Charles G. Mullighan, Dario Campana

    BRITISH JOURNAL OF HAEMATOLOGY   145 ( 5 )   606 - 613   2009年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    The replicative potential of human CD56(+) CD3(-) natural killer (NK) cells is unknown. We found that by exposing NK cells to the leukaemic cell line K562 genetically modified to express 4-1BB ligand and interleukin 15 (K562-mb15-41BBL), they expanded for up to 30 population doublings, achieving numbers that ranged from 1.6 x 10(5) to 1.2 x 10(11)% (median, 5.9 x 10(6)%; n = 7) of those originally seeded. However, NK cells eventually became unresponsive to stimulation and died. Their demise could be suppressed by enforcing the expression of the human telomerase reverse transcriptase gene (TERT). TERT-overexpressing NK cells continued to proliferate in response to K562-mb15-41BBL stimulation for more than 1 year of culture, while maintaining a normal karyotype and genotype. Long-lived NK cells had high cytotoxicity against myeloid and T-lineage leukaemic cells. They remained susceptible to genetic manipulation, becoming highly cytotoxic to B-lineage leukaemic cells after expression of anti-CD19 signaling receptors. Thus, human NK cells have a replicative potential similar to that of T lymphocytes and their lifespan can be significantly prolonged by an increase in TERT activity. We suggest that the methods described here should have many applications in studies of NK cell biology and NK cell-based therapies.

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  • Replicative potential of human natural killer cells.

    Fujisaki Hiroyuki, Kakuda Harumi, Imai Chihaya, Mullighan Charles G, Campana Dario

    Br J Haematol   145 ( 5 )   606 - 613   2009年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The replicative potential of human CD56(+) CD3(-) natural killer (NK) cells is unknown. We found that by exposing NK cells to the leukaemic cell line K562 genetically modified to express 4-1BB ligand and interleukin 15 (K562-mb15-41BBL), they expanded for up to 30 population doublings, achieving numbers that ranged from 1.6 x 10(5) to 1.2 x 10(11)% (median, 5.9 x 10(6)%; n = 7) of those originally seeded. However, NK cells eventually became unresponsive to stimulation and died. Their demise could be suppressed by enforcing the expression of the human telomerase reverse transcriptase gene (TERT). TERT-overexpressing NK cells continued to proliferate in response to K562-mb15-41BBL stimulation for more than 1 year of culture, while maintaining a normal karyotype and genotype. Long-lived NK cells had high cytotoxicity against myeloid and T-lineage leukaemic cells. They remained susceptible to genetic manipulation, becoming highly cytotoxic to B-lineage leukaemic cells after expression of anti-CD19 signaling receptors. Thus, human NK cells have a replicative potential similar to that of T lymphocytes and their lifespan can be significantly prolonged by an increase in TERT activity.

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  • Expansion of highly cytotoxic human natural killer cells for cancer cell therapy.

    Fujisaki Hiroyuki, Kakuda Harumi, Shimasaki Noriko, Imai Chihaya, Ma Jing, Lockey Timothy, Eldridge Paul, Leung Wing H, Campana Dario

    Cancer Res   69 ( 9 )   4010 - 4017   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Infusions of natural killer (NK) cells are an emerging tool for cancer immunotherapy. The development of clinically applicable methods to produce large numbers of fully functional NK cells is a critical step to maximize the potential of this approach. We determined the capacity of the leukemia cell line K562 modified to express a membrane-bound form of interleukin (IL)-15 and 41BB ligand (K562-mb15-41BBL) to generate human NK cells with enhanced cytotoxicity. Seven-day coculture with irradiated K562-mb15-41BBL induced a median 21.6-fold expansion of CD56(+)CD3(-) NK cells from peripheral blood (range, 5.1- to 86.6-fold; n = 50), which was considerably superior to that produced by stimulation with IL-2, IL-12, IL-15, and/or IL-21 and caused no proliferation of CD3(+) lymphocytes. Similar expansions could also be obtained from the peripheral blood of patients with acute leukemia undergoing therapy (n = 11). Comparisons of the gene expression profiles of the expanded NK cells and their unstimulated or IL-2-stimulated counterparts showed marked differences. The expanded NK cells were significantly more potent than unstimulated or IL-2-stimulated NK cells against acute myeloid leukem

    DOI: 10.1158/0008-5472.CAN-08-3712

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  • Expansion of Highly Cytotoxic Human Natural Killer Cells for Cancer Cell Therapy 査読

    Hiroyuki Fujisaki, Harumi Kakuda, Noriko Shimasaki, Chihaya Imai, Jing Ma, Timothy Lockey, Paul Eldridge, Wing H. Leung, Dario Campana

    CANCER RESEARCH   69 ( 9 )   4010 - 4017   2009年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER ASSOC CANCER RESEARCH  

    Infusions of natural killer (NK) cells are an emerging tool for cancer immunotherapy. The development of clinically applicable methods to produce large numbers of fully functional NK cells is a critical step to maximize the potential of this approach. We determined the capacity of the leukemia cc line K562 modified to express a membrane-bound form of interleukin (IL)-15 and 41BB ligand (K562-mb15-41BBL) to generate human NK cells with enhanced cytotoxicity. Seven-day coculture with irradiated K562-mb15-41BBL induced a median 21.6-fold expansion of CD56(+)CD3(-) NK cells from peripheral blood (range, 5.1- to 86.6-fold; n = 50), which was considerably superior to that produced by stimulation wit IL-2, IL-12, IL-15, and/or IL-21 and caused no proliferation of CD3(+) lymphocytes. Similar expansions could also be obtained from the peripheral blood of patients with acute leukemia undergoing therapy (n = 11). Comparisons of the gene expression profiles of the expanded NK cells and their unstimulated or IL-2-stimulated counterparts showed marked differences. The expanded NK cells were significantly more potent than unstimulated or IL-2-stimulated NK cells against acute myeloid leukemia cells in vitro. They could be detected for >1 month when injected into immunodeficient mice and could eradicate leukemia in murine models of acute myeloid leukemia. We therefore adapted the K562-mb15-41BBL, stimulation method to large-scale clinical-grade conditions, generating large numbers of highly cytotoxic NK cells. The results that we report here provide rationale and practical platform for clinical testing of expanded and activated NK cells for cell therapy of cancer. [Cancer Res 2009;69(9):4010-7]

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  • Sotos症候群に合併した機能性甲状腺結節の1例

    入月 浩美, 笠原 靖史, 高地 貴行, 今村 勝, 長崎 啓祐, 今井 千速, 内山 聖

    日本小児科学会雑誌   113 ( 4 )   754 - 755   2009年4月

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  • Effect of charcoal hemoperfusion for removal of plasma methotrexate in a patient with acute renal failure

    Tae Nemoto, Chihaya Imai, Utako Kaneko, Takayuki Takachi, Haruko Iwabuchi, Atsushi Tanaka, Gen Nakamura, Akira Ogose, Makoto Uchiyama

    Pediatric Hematology and Oncology   26 ( 7 )   520 - 525   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Strategies effective for accelerating methotrexate removal in delayed methotrexate excretion have not been universally accepted. The authors report a case of a 12-year-old girl with osteosarcoma who developed acute renal failure immediately after the first administration of high-dose methotrexate. Plasma methotrexate was effectively removed with repeated charcoal hemoperfusion in addition to plasma exchange and leucovorin rescue. Charcoal hemoperfusion was most effective for reducing plasma methotrexate with approximately 50% of methotrexate being reduced during each of the procedures. No rebound increase in MTX levels was observed. The patient received further therapy with other cancer drugs and has been well for 3.5 years. © 2009 Informa UK Ltd.

    DOI: 10.1080/08880010902976023

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  • NK細胞療法の基礎と展望~NK細胞の体外増幅と遺伝子改変を中心に. 招待

    今井 千速

    第51回日本小児血液学会・第25回日本小児がん学会 教育セッションテキスト   110 - 114   2009年

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    記述言語:日本語   掲載種別:研究論文(研究会,シンポジウム資料等)  

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  • EFFECT OF CHARCOAL HEMOPERFUSION FOR REMOVAL OF PLASMA METHOTREXATE IN A PATIENT WITH ACUTE RENAL FAILURE 査読

    Tae Nemoto, Chihaya Imai, Utako Kaneko, Takayuki Takachi, Haruko Iwabuchi, Atsushi Tanaka, Gen Nakamura, Akira Ogose, Makoto Uchiyama

    PEDIATRIC HEMATOLOGY AND ONCOLOGY   26 ( 7 )   520 - 525   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS INC  

    Strategies effective for accelerating methotrexate removal in delayed methotrexate excretion have not been universally accepted. The authors report a case of a 12-year-old girl with osteosarcoma who developed acute renal failure immediately after the first administration of high-dose methotrexate. Plasma methotrexate was effectively removed with repeated charcoal hemoperfusion in addition to plasma exchange and leucovorin rescue. Charcoal hemoperfusion was most effective for reducing plasma methotrexate with approximately 50% of methotrexate being reduced during each of the procedures. No rebound increase in MTX levels was observed. The patient received further therapy with other cancer drugs and has been well for 3.5 years.

    DOI: 10.1080/08880010902976023

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  • 特異的遺伝子転座を認めず胞巣状構造を呈した横紋筋肉腫の1例

    李 貴東, 生越 章, 堀田 哲夫, 川島 寛之, 遠藤 直人, 梅津 哉, 今井 千速, 窪田 正幸, 奥山 直樹, 平山 裕, 小川 淳, 浅見 恵子, 岩渕 晴子

    臨床整形外科   43 ( 8 )   833 - 837   2008年8月

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    記述言語:日本語   出版者・発行元:(株)医学書院  

    胞巣状構造を呈するが特異的遺伝子転座を認めない横紋筋肉腫1例を経験したので報告する.症例は1歳2ヵ月の女児で,針細胞診で横紋筋肉腫と診断し,広範切除を行った.術後組織病理学所見では,胎児型の部分と胞巣状構造が混じったパターンであった.典型的胞巣型と異なり,線維性間質に乏しく,大量の横紋筋芽細胞が混在するのが特徴であった.胞巣型に特異的なt(2;13)またはt(1;13)の転座を認めなかった.術後6年9ヵ月の現在,多発性転移を認め,再発と軽快を繰り返し,現在化学療法中である.(著者抄録)

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  • Enhancement of the anti-leukemic activity of cytokine induced killer cells with an anti-CD19 chimeric receptor delivering a 4-1BB-zeta activating signal

    Virna Marin, Harurni Kakuda, Erica Dander, Chihaya Imai, Dario Carnpana, Andrea Biondi, Giovanna D'Amico

    EXPERIMENTAL HEMATOLOGY   35 ( 9 )   1388 - 1397   2007年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    Objective. There is growing interest in the use of cytokine-induced killer (CIK) cells in cancer therapy. In this study, we sought to maximize the antileukemic activity of anti-CD19 receptor-modified CIK cells against B-lineage acute lymphoblastic leukemia (ALL).
    Materials and Methods. CIK cells were transduced with retroviral vectors carrying different types of anti-CD19 chimeric receptors: anti-CD19-xi, anti-CD19-DAP10, anti-CD19-4-1BB-xi, and anti-CD19-CD28-xi. A truncated form of the receptor was used as a control. Transduced CIK cells were then analyzed for their cytotoxic activity against ALL cells and for their capability to proliferate and to release cytokines after ALL encounter.
    Results. CIK cells were efficiently transduced with all the anti-CD19 retroviral vectors. Anti-CD19 receptor expression conferred powerful killing activity against ALL cells. However, there were clear advantages when receptors containing the co-stimulatory molecules 4-1BB or CD28 were transduced. Such cells had significantly more potent cytotoxicity than cells expressing the anti-CD19-xi or anti-CD19-DAP10. Moreover, the presence of 4-1BB or CD28 in the receptor increased the production of interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, TNF-beta, IL-5, IL-6, and IL-8 elicited by coculture with ALL cells. Notably, anti-CD19-4-1BB-xi CIK cells secreted particularly low levels of interleukin-10 and proliferated strongly after contact with ALL cells.
    Conclusions. Anti-CD19 chimeric receptors delivering primary and costimulatory signals render CIK cells powerfully cytotoxic against ALL cells and induce secretion of immunostimulatory cytokines and proliferation. These results support the testing of genetically modified CIK cells in clinical trials. (c) 2007 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

    DOI: 10.1016/j.exphem.2007.05.018

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  • Genetic Modification of Natural Killer Cells for Leukemia Therapies. 招待 査読

    Imai C, Kakuda H, Fujisaki H, Iwamoto S, Campana D

    Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry.   6 ( 2 )   101 - 108   2007年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Synthetic messenger RNA as a tool for gene therapy

    Peter M. Rabinovich, Marina E. Komarovskaya, Zhi-Jia Ye, Chihaya Imai, Dario Campana, Erkut Bahceci, Sherman M. Weissman

    HUMAN GENE THERAPY   17 ( 10 )   1027 - 1035   2006年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MARY ANN LIEBERT INC  

    Transfection of human cells with DNA in biomedical applications carries the risk of insertional mutagenesis. Transfection with mRNA avoids this problem; however, in vitro production of mRNA, based on preliminary DNA template cloning in special vectors, is a laborious and time-consuming procedure. We report an efficient vector-free method of mRNA production from polymerase chain reaction-generated DNA templates. For all cell types tested mRNA was transfected more readily than DNA, and its expression was highly uniform in cell populations. Even cell types relatively resistant to transfection with DNA could express transfected mRNA well. The level of mRNA expression could be controlled over a wide range by changing the amount of input RNA. Cells could be efficiently and simultaneously loaded with several different transcripts. To test a potential clinical application of this method, we transfected human T lymphocytes with mRNA encoding a chimeric immune receptor directed against CD19, a surface antigen widely expressed in leukemia and lymphoma. The transfected mRNA conferred powerful cytotoxicity to T cells against CD19(+) targets from the same donor. These results demonstrate that this method can be applied to generate autologous T lymphocytes directed toward malignant cells.

    DOI: 10.1089/hum.2006.17.1027

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  • 遺伝子操作により誘導される抗白血病NK細胞 招待

    今井 千速

    血液・腫瘍科   52 ( 4 )   414 - 423   2006年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • 抗CD19レセプターを導入したNK細胞による白血病・リンパ腫の治療 招待

    今井 千速

    臨床免疫   45 ( 5 )   503 - 510   2006年

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    記述言語:日本語   掲載種別:研究論文(学術雑誌)  

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  • Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells

    C Imai, S Iwamoto, D Campana

    BLOOD   106 ( 1 )   376 - 383   2005年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AMER SOC HEMATOLOGY  

    Natural killer (NK) cells hold promise for improving the therapeutic potential of allogeneic hematopoietic transplantation, but their effectiveness is limited by inhibitory HLA types. We sought to overcome this intrinsic resistance by transducing CD56(+)CD3(-) NK cells with chimeric receptors directed against CD19, a molecule widely expressed by malignant B cells. An abundance of NK cells for transduction was secured by culturing peripheral blood mononuclear cells with K562 cells expressing the NK-stimulatory molecules 4-1BB ligand and interleukin 15, which yielded a median greater than 1000-fold expansion of CD56(+)CD3(-) cells at 3 weeks of culture, without T-lymphocyte expansion. Expression of anti-CD19 receptors linked to CD3 xi overcame NK resistance and markedly enhanced NK-cell-mediated killing of leukemic cells. This result was significantly improved by adding the 4-1 BB costimulatory molecule to the chimeric anti-CD19-CD3 xi receptor; the cytotoxicity produced by NK cells expressing this construct uniformly exceeded that of NK cells whose signaling receptors lacked 4-1BB, even when natural cytotoxicity was apparent. Addition of 4-1 BB was also associated with increased cell activation and production of interferon gamma and granulocyte-macrophage colony-stimulating factor. Our findings indicate that enforced expression of signaling receptors by NK cells might circumvent inhibitory signals, providing a novel means to enhance the effectiveness of allogeneic stem cell transplantation.

    DOI: 10.1182/blood-2004-12-4797

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  • Primary tuberculous osteomyelitis of the mandible 査読

    M Imamura, T Kakihara, K Yamamoto, C Imat, A Tanaka, M Uchiyama

    PEDIATRICS INTERNATIONAL   46 ( 6 )   736 - 739   2004年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING ASIA  

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  • A gene homologous to human endogenous retrovirus overexpressed in childhood acute lymphoblastic leukemia

    H Iwabuchi, T Kakihara, T Kobayashi, C Imai, A Tanaka, M Uchiyama, T Fukuda

    LEUKEMIA & LYMPHOMA   45 ( 11 )   2303 - 2306   2004年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    To clarify the mechanism of progression and acquired drug resistance of leukemia, we searched for an overexpressed gene in drug-resistant leukemia cells and identified an approximately 5-kb transcript by using the subtraction method. The nucleotide sequence of the gene was highly homologous to those of human endogenous retrovirus (HERV) transcripts. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that the gene was overexpressed in cells from 6 childhood acute lymphoblastic leukemia patients (60%) but not in bone marrow cells at remission. Peripheral blood mononuclear cells from normal controls (n=11) and bone marrow cells from non-leukemia patients (n=13) did not express the gene. These findings indicate that the gene may play a role in leukemogenesis and may be a novel leukemia marker. Further studies on the functional role of the gene are needed.

    DOI: 10.1080/10428190412331272758

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  • Glomerular dysfunction, independent of tubular dysfunction, induced by antineoplastic chemotherapy in children 査読

    Y Ikarashi, T Kakihara, C Imai, A Tanaka, A Watanabe, M Uchiyama

    PEDIATRICS INTERNATIONAL   46 ( 5 )   570 - 575   2004年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING ASIA  

    Background: For the purpose of studying renal side-effects induced by antineoplastic agents, the authors examined glomerular injury as well as tubular injury of patients with chemotherapy.
    Methods: Thirteen patients underwent a combined total of 64 courses of chemotherapy. Urinary albumin, beta2-microglobulin (beta2-MG), N-acetyl-beta-glucosaminidase (NAG) and urinary protein were measured before and serially after chemotherapy.
    Results: The values of albumin/creatinine (albumin/cre) ratio and beta2-MG/creatinine (beta2-MG/cre) ratio after chemotherapy were higher than those before chemotherapy (P < 0.01). NAG/creatinine (NAG/cre) ratio and creatinine clearance (Ccr) were not different. These were also examined before the next course of chemotherapy and were compared with those of control children. Albumin/cre ratio was significantly different (P < 0.01). beta2-MG/cre ratio and NAG/cre were not different. Furthermore, in patients with normal beta2-MG/cre, the albumin/cre ratio was significantly higher than in control children.
    Conclusions: These results indicate that antineoplastic agents can not only induce tubular dysfunction but also glomerular dysfunction, which is persistent and independent of tubular dysfunction.

    DOI: 10.1111/j.1442-200x.2004.01958.x

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  • Expression of the adaptor protein BLNK/SLP-65 in childhood acute lymphoblastic leukemia

    C Imai, ME Ross, G Reid, E Coustan-Smith, KR Schultz, CH Pui, Downing, JR, D Campana

    LEUKEMIA   18 ( 5 )   922 - 925   2004年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Deficient expression of BLNK, an adaptor molecule crucial for normal B-cell development, is associated with increased pro-B/pre-B-cell expansion in mice. It has been proposed that BLNK deficiency is a primary cause of B-lineage acute lymphoblastic leukemia (ALL). We studied BLNK expression in the leukemic cells from 352 patients with childhood ALL (309 B-lineage; 43 T-lineage). By HG_U95Av2 Affymetrix GeneChip analysis, BLNK was expressed in 275 of 284 (96.8%) B-lineage ALL samples but in only one of 43 (2.3%) T-lineage ALL samples. Of 118 B-lineage ALL samples analyzed with the HG_U133A GeneChip, 117 (99.2%) expressed BLNK. All 30 primary B-lineage ALL samples studied by RT-PCR expressed BLNK transcripts; all 19 samples studied by Western blotting or flow cytometry expressed BLNK protein. Levels of BLNK in B-lineage ALL were as high as those of their normal counterparts; they were not related with genetic subgroups or differentiation stage. These results indicate that BLNK deficiency is a rare occurrence in childhood B-lineage ALL and is unlikely to be a common leukemogenic event as previously proposed.

    DOI: 10.1038/sj.leu.2403349

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  • Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia

    C Imai, K Mihara, M Andreansky, IC Nicholson, CH Pui, TL Geiger, D Campana

    LEUKEMIA   18 ( 4 )   676 - 684   2004年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    To develop a therapy for drug-resistant B-lineage acute lymphoblastic leukemia (ALL), we transduced T lymphocytes with anti-CD19 chimeric receptors, consisting of an anti-CD19 single-chain variable domain (reactive with most ALL cases), the hinge and transmembrane domains of CD8alpha, and the signaling domain of CD3zeta. We compared the antileukemic activity mediated by a novel receptor ('anti-CD19-BB-zeta') containing the signaling domain of 4-1BB (CD137; a crucial molecule for T-cell antitumor activity) to that of a receptor lacking costimulatory molecules. Retroviral transduction produced efficient and durable receptor expression in human T cells. Lymphocytes expressing anti-CD19-BB-zeta receptors exerted powerful and specific cytotoxicity against ALL cells, which was superior to that of lymphocytes with receptors lacking 4-1BB. Anti-CD19-BB-zeta lymphocytes were remarkably effective in cocultures with bone marrow mesenchymal cells, and against leukemic cells from patients with drug-resistant ALL: as few as 1% anti-CD19-BB-zeta-transduced T cells eliminated most ALL cells within 5 days. These cells also expanded and produced interleukin-2 in response to ALL cells at much higher rates than those of lymphocytes expressing equivalent receptors lacking 4-1BB. We conclude that anti-CD19 chimeric receptors containing 4-1BB are a powerful new tool for T-cell therapy of B-lineage ALL and other CD19(+) B-lymphoid malignancies.

    DOI: 10.1038/sj.leu.2403302

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  • Double leukemias simultaneously showing lymphoblastic leukemia of the bone marrow and monocytic leukemia of the central nervous system 査読

    Y Ikarashi, T Kakihara, C Imai, A Tanaka, A Watanabe, M Uchiyama

    AMERICAN JOURNAL OF HEMATOLOGY   75 ( 3 )   164 - 167   2004年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    A rare case of different leukemias simultaneously occurring in the bone marrow (BM) and the central nervous system (CNS) was encountered. A 4-year-old girl was diagnosed with acute lymphoblastic leukemia and achieved a complete remission with chemotherapy. Two years after diagnosis, she was found to have acute monocytic leukemia at first relapse in the BM. One month after the second course of induction therapy, lymphoblastic leukemia in the BM and monocytic leukemia in the CNS were found simultaneously. Chromosomal analysis of leukemia cells in the BM and CNS showed distinct results. The mechanism of double leukemias occurring was obscure, although a lineage switch, therapy-related, or de novo leukemia could be considered as possibilities. Double leukemias should be kept in mind when leukemias relapse in several sites. Am. J. Hematol. 75:164-167, 2004. (C) 2004 Wiley-Liss, Inc.

    DOI: 10.1002/ajh.10478

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  • Genetic modification of T cells for cancer therapy

    C Imai, D Campana

    JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS   18 ( 1 )   62 - 71   2004年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOLIFE SAS  

    The use of immune cells with restricted specificities for the treatment of cancer is a rapidly emerging area of clinical research. Chimeric receptors composed of the single-chain variable domain of murine antibodies and human signaling molecules are a promising tool to redirect the specificity of autologous or allogeneic immune cells. The success of this approach depends on the identification of target molecules expressed preferentially on cancer cells. Moreover, appropriate primary and secondary stimuli must be delivered to generate vigorous and durable immune responses. Since cancer cells often lack ligands for key co-stimulatory molecules, the addition of molecules such as CD28 or 4-1BB to the chimeric receptors can significantly improve their function. Studies in vitro and in animal models indicate that immune cells expressing chimeric receptors can have remarkable anti-cancer activity, while experimental and clinical data indicate that long-term persistence of adoptively transferred cells is feasible. Therefore, testing of this approach in clinical trials is warranted. We here review the principles and methodologies for designing chimeric receptors and delivering them into immune cells, as well as some of the potential complications associated with this form of cell therapy.

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  • Anticancer Drugs Overexpress Fas-associated Phosphatase-1 in Some Leukemic Cells. 査読

    Imamura M, Kakihara T, Kobayashi T, Imai C, Tanaka A, Uchiyama M

    Acta Medica et Biologica   52 ( 3 )   81 - 89   2004年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Psychosomatic reaction exhibiting hemorrhagic erythema and motorsensory disturbance 査読

    T Kakihara, A Tanaka, C Imai, Y Ikarashi, M Uchiyama, Emura, I

    PEDIATRICS INTERNATIONAL   45 ( 4 )   472 - 474   2003年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING ASIA  

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  • Atypical hemophagocytic lymphohistiocytosis following bacterial tonsillitis in acute lymphoblastic leukemia 査読

    T Kakihara, C Imai, T Kaneko, A Tanaka, M Uchiyama

    LEUKEMIA & LYMPHOMA   44 ( 7 )   1247 - 1248   2003年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    We report a rare case of acute lymphoblastic leukemia (ALL) who developed dyspnea, neurological disturbance with illusions, pancytopenia, phagocytosis and coagulation disturbances following bacterial tonsillitis. The values of soluble interleukin-2 receptor (slL-2R), IL-6 and IL-8 were also elevated. Her clinicolaboratory findings were similar to hemophagocytic lymphohistiocytosis (HLH), which is a cytokine disease induced by activated T cells and macrophages. Atypical HLH following bacterial tonsillitis should be kept in mind in leukemia patients.

    DOI: 10.1080/1042819031000079078

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  • Glomerular vasculopathy after unrelated cord blood transplantation

    C Imai, T Kakihara, H Iwabuchi, A Tanaka, T Furukawa, M Uchiyama

    PEDIATRIC NEPHROLOGY   18 ( 4 )   399 - 402   2003年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SPRINGER-VERLAG  

    A 1-year-old boy with hemophagocytic lymphohistiocytosis exhibited proteinuria I month after unrelated cord blood cell transplantation, which persisted without hematuria. Laboratory study showed an increase of factor VIII-related antigen and total plasminogen activator inhibitor, suggesting endothelial injury. Histological examination of autopsy materials showed increased mesangial matrices and double-contoured basement membranes, and ultrastructurally, swelling of the endothelial cells and widening of the subendothelial space with mesangial interposition. Thrombosis was not observed at any of the sites. This case may be vasculopathy distinct from thrombotic microangiopathy (TMA) or a variant form of TMA following blood stem cell transplantation (BSCT). This vasculopathy should be considered in the differential diagnosis of proteinuria in the early stages after BSCT.

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  • Development and functional characterization of human bone marrow mesenchymal cells immortalized by enforced expression of telomerase

    K Mihara, C Imai, E Coustan-Smith, JS Dome, M Dominici, E Vanin, D Campana

    BRITISH JOURNAL OF HAEMATOLOGY   120 ( 5 )   846 - 849   2003年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    To create immortal mesenchymal cell lines, we transduced primary human bone marrow mesenchymal cells with telomerase reverse transcriptase (TERT). TERT+ mesenchymal cells continued to grow for > 2 years; parallel TERT- cultures underwent senescence after 15 weeks. TERT+ mesenchymal cells did not form foci in soft agar, had a normal karyotype and could differentiate into osteoblasts and chondrocytes. Their capacity to support leukaemic lymphoblasts and normal CD34(+) haematopoietic cells was equal to or greater than that of primary cells; 42 TERT+ mesenchymal cell clones varied in their supporting capacity. Immortalized mesenchymal cells offer a promising tool for identifying molecules that regulate human haematopoiesis.

    DOI: 10.1046/j.1365-2141.2003.04217.x

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  • Impaired tubular excretory function as a late renal side effect of chemotherapy in children

    T Kakihara, C Imai, H Hotta, Y Ikarashi, A Tanaka, M Uchiyama

    JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY   25 ( 3 )   209 - 214   2003年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    Purpose: Renal drug excretion is variously influenced by nephrotoxic drugs. This study was designed to evaluate renal function as a late renal side effects in children receiving combination chemotherapy for malignancy.
    Patients and Methods: Follow-up studies of 30 newly diagnosed patients were performed a median of 12 months after completion of chemotherapy. The glomerular filtration rate (GFR) was measured using sodium thiosulfate. The following were also assessed: urinary high-molecular-weight fraction (urinary albumin/urinary creatinine ratio); para-aminohippurate (PAH) clearance; urinary low-molecular-weight fraction (urinary beta2-microglobulin/urinary creatinine ratio); and routine serum and urinary parameters.
    Results: Serum and urinary electrolytes were normal in most patients. GFR was low in four patients (13%). Urinary high-molecular-weight fraction was elevated in two patients. Urinary low-molecular-weight fraction was elevated in one patient. PAH clearance was below the referenced normal value in 73% of the patients.
    Conclusions: This report demonstrates decreased PAH clearance as a late renal side effect of chemotherapy and suggests disturbed function of the organic anion transport system. The unexpected high serum concentration of drugs excreted through the organic anion transport system may induce severe side effects. Elucidation of the mechanism and clinical relevance of decreased PAH clearance is warranted.

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  • Centrofacial malignant T-cell lymphoma exhibiting recurrent fever and skin ulcer in a 3-year-old girl

    T Kakihara, C Imai, H Hotta, Y Ikarashi, A Tanaka, M Uchiyama

    PEDIATRIC HEMATOLOGY AND ONCOLOGY   19 ( 8 )   575 - 580   2002年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS INC  

    A rare case of undetermined fever and skin ulcers is reported. The patient had an 8-month history of recurrent fever destructive ulceration of the midline facial tissue, and symmetrical skin ulcer in the cheeks and the back of the hand. Pathological examination revealed that the patient had lethal midline granuloma (centrofacial malignant T-cell lymphoma), which is very rare in childhood. Centrofacial malignant T-cell lymphoma should be considered as a differential diagnosis Of unexplained fever and skin ulcer in children.

    DOI: 10.1080/08880010290097422

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  • Chemotherapy-induced multiple vertebral compression fractures in a boy with acute lymphoblastic leukemia

    T Kakihara, A Watanabe, C Imai, H Hotta, A Tanaka, M Uchiyama

    PEDIATRICS INTERNATIONAL   44 ( 6 )   683 - 685   2002年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING ASIA  

    DOI: 10.1046/j.1442-200X.2002.01619.x

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  • Acute suppurative thyroiditis as a rare complication of aggressive chemotherapy in children with acute myelogeneous leukemia

    C Imai, T Kakihara, A Watanabe, Y Ikarashi, H Hotta, A Tanaka, M Uchiyama

    PEDIATRIC HEMATOLOGY AND ONCOLOGY   19 ( 4 )   247 - 253   2002年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS INC  

    Acute suppurative thyroiditis (AST) is quite rare, even in immunocompromised patients. The authors describe 2 cases of AST during aggressive chemotherapy for acute myelogeneous leukemia (AML). They were treated with aggressive combination chemotherapy and achieved complete remission. After several courses of chemotherapy, they developed fiver and pain in the region of the thyroid gland. Laboratory tests showed hyperthyroidism and elevated levels of thyroglobulin and C-reactive protein. Ultrasonography revealed hypoechoic areas in the thyroid gland. A diagnosis of AST was made. Bacterial infections were suspected because they were success fully treated with antibiotics. After a month, the patients' thyroid function and thyroglobulin levels returned to normal without a period of transient hypothyroidism. A pyriform sinus fistula was not demonstrated. The results suggest that neutropenia and preceding cellulitis around the thyroid gland, which might be subsequent to oral mucosal damage induced by anticancer drugs, may play a role in the development of AST. AST should be considered a potential complication of aggressive chemotherapy for leukemia.

    DOI: 10.1080/08880010252899415

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  • Morphological differences between glomerular epithelial cells (GEC) excreted during chemotherapy with antineoplastic drugs and GEC excreted in renal diseases 査読

    A Watanabe, T Kakihara, M Hara, A Tanaka, K Kanno, C Imai, Y Ikarashi, S Okubo, T Yanagihara, M Uchiyama

    PEDIATRICS INTERNATIONAL   43 ( 6 )   587 - 591   2001年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING ASIA  

    Background: To better understand the mechanisms of glomerular epithelial cell (GEC) injuries in various diseases. we compared GEC excreted during chemotherapy (antineoplastic drugs) and GEC excreted in renal diseases.
    Methods: For 19 patients undergoing chemotherapy (85 courses), 69 patients with IgA nephropathy and 16 patients with Henoch-Scholein purpura nephritis. the number of excreted GEC and GEC casts were counted by an immunofluorescent study. The morphological features of GEC were also studied in an immunofluorescent study combined with Hoechst stain.
    Results: Glomerular epithelial cells were detected in 78% of the chemotherapy courses and in 94% of the patients with renal diseases. The GEC casts were observed in 2% of chemotherapy courses, while in renal diseases GEC casts were observed in 60% of the patients. Proteinuria ( > 30 mg/dL) and hematuria were not identified in any of the chemotherapy courses. The morphology and size of GEC were more variable than that in patient,, with nephropathy. Furthermore, GEC in patients undergoing chemotherapy often showed small nuclei and fragmented nuclei, which were rarely observed in patients with nephropathy.
    Conclusions: These result,, showed that the detachment of podocytes was not directly associated with proteinuria or hematuria, The findings also suggest that GEC are damaged via an apoptotic process by chemotherapy. On the contrary, GEC may be detached through a non-apoptotic process in renal diseases.

    DOI: 10.1046/j.1442-200X.2001.01473.x

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  • Vincristine-induced fever in a child with rhabdomyosarcoma: Cellular hypersensitivity to vincristine demonstrated by leukocyte migration test 査読

    C Imai, K Uno, T Kakihara, A Tanaka, M Uchiyama

    JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY   23 ( 1 )   73 - 74   2001年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    DOI: 10.1097/00043426-200101000-00020

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  • Infantile exanthematous disease with elevated anti-toxic shock syndrome toxin-1 antibody: Related to toxic shock syndrome toxin-1?

    C Imai, M Uchiyama

    PEDIATRICS INTERNATIONAL   42 ( 2 )   178 - 180   2000年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL SCIENCE ASIA  

    DOI: 10.1046/j.1442-200x.2000.01188.x

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  • Contingent negative variation in children with anorexia nervosa 査読

    K Torigoe, O Numata, T Sato, C Imai, K Takeuchi, H Yamazaki, H Hotta, N Boku, S Yazaki, S Sudo, A Kuwabara, S Hasegawa, M Hiura, H Ino

    PEDIATRICS INTERNATIONAL   41 ( 3 )   285 - 291   1999年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Background: Central catecholamines: particularly dopaminergic and noradrenergic systems, have affected the appetitive behavior in patients with anorexia nervosa (AN). The purpose of this study is to distinguish the characteristics of contingent negative variation (CNV) and postimperative negative variation (PINV), which may reflect the level of catecholamine in children with AN.
    Methods: Eight children with AN aged 10 to 15 years and 23 age-matched healthy children were recruited. Contingent negative variation was recorded from the frontal midline (Fz), central midline (Cz) and parietal midline (Pz) referenced to linked earlobes during 30 trials consisting of a warning stimulus and an imperative stimulus with an interstimulus interval of 2 s and an intertrial interval of 10 s. The imperative stimulus of each trial required a button press.
    Results: Children with AN had a diminished amplitude of the CNV. They had a significantly more attenuated early CNV and late CNV amplitude at Ct than normal children. No significant differences were observed between AN children and normal children in the amplitude of PINV at all three electrode sites. No difference could be found between the two groups in the frequencies of normal and abnormal duration of PINV.
    Conclusion: These findings suggest that early CNV may be diminished by norepinephrine deficiency and late CNV may be attenuated by dopaminergic deficiency in children with AN. Reduced CNV may represent impaired cognitive processes which reflect impaired appetitive behavior in AN children.

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  • Ratio of eosinophil cationic protein/eosinophil count as a new marker in children with acute asthma

    C Imai, H Yamazaki, Y Tanaka, M Matsunaga, O Numata, K Torigoe

    PEDIATRICS INTERNATIONAL   41 ( 2 )   142 - 146   1999年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL SCIENCE ASIA  

    Background: It is a matter of concern whether serum eosinophil cationic protein (ECP) can be considered as a disease marker in children with acute asthma being treated without corticosteroids.
    Methods: Fourteen children (nine male, five female, aged 6-12 years) with acute asthmatic exacerbation, administered the appropriate drugs, with the exception of systemic or inhaled corticosteroids, were examined. They were all free from apparent asthmatic attacks during a follow-up period of 1 month. Serum ECP, eosinophil count and forced expiratory volume in 1 s (FEV1) were measured at referral, on the day of discharge, I week and 4 weeks after discharge, respectively.
    Results: The ratio of ECP/eosinophil count (ECP:Eo ratio), expressed as micrograms of ECP (mu g/L)/the number of eosinophil (/mu L)x 1000, was also evaluated as a marker of eosinophil activation. Compared with the value at referral, FEV1 (% predicted) significantly increased on the day of discharge (P < 0.05), 1 week after (P < 0.05) and 4 weeks after discharge (P < 0.05). However, serum ECP concentrations showed no significant changes during the follow-up period. Eosinophil count showed no significant changes on the day of discharge or I week after discharge, but significantly increased 4 weeks after discharge (P < 0.05). In contrast, the ECP:Eo ratio significantly decreased on the day of discharge (P < 0.05), 1 week after (P < 0.05) and 4 weeks after discharge (P < 0.05).
    Conclusion: These data suggest that serum ECP is a poor disease marker in asthmatic children with acute exacerbation who receive no corticosteroid therapy, probably due to marked changes in the eosinophil count. However, the ECP:Eo ratio might be a better marker than serum ECP in such patients.

    DOI: 10.1046/j.1442-200X.1999.4121045.x

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  • Effect of weight loss on body fat distribution in obese children 査読

    K Torigoe, O Numata, M Matsunaga, Y Tanaka, C Imai, H Yamazaki

    ACTA PAEDIATRICA JAPONICA   39 ( 1 )   28 - 33   1997年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL SCIENCE  

    The intra-abdominal visceral fat to subcutaneous fat ratio (V/S ratio) has been reported to be strongly related to disorders of glucose and lipid metabolism, and hypertension. It is a matter of concern as to whether weight loss causes an improvement of the V/S ratio or not in obese children. Changes in body fat distribution during weight loss in 23 obese children were quantified by weight, bioelectrical impedance analysis (BIA) and computed tomography (CT scan of the abdomen). Twenty-three patients were divided into two groups; six were in the inpatient group and 17 were in the outpatient group. Bodyweight, body fat percentage, subcutaneous fat and visceral fat were significantly higher in the inpatient group than in the outpatient group before weight loss. Whereas the V/S ratio was almost equal between the two groups before weight loss. Bodyweight, body fat percentage, subcutaneous fat and visceral fat were found to decrease significantly during weight loss in the two groups. The V/S ratio of the outpatient group did not change after weight loss. In contrast, the V/S ratio of the inpatient group decreased significantly during weight loss. These preliminary findings suggest that a large amount of body fat and a high obesity rate are not always accompanied by a high V/S ratio in obese children. The fat pattern changes during weight loss with strict dietary therapy and therapeutic exercise. A larger sample of obese children should be studied to test this conjecture.

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MISC

  • 初発髄芽腫に対する術後2週間以内の全脳脊髄照射及びSJMB‐96式自家末梢血幹細胞救援併用反復大量化学療法:単一施設での治療経験

    今村勝, 石井孝規, 久保暢大, 笠原靖史, 岩渕晴子, 棗田学, 大石誠, 今井千速, 吉村淳一, 青山英史, 藤井幸彦

    小児の脳神経   44 ( 2 )   125   2019年4月

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    記述言語:日本語  

    J-GLOBAL

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  • Characteristics and Outcomes of Childhood Acute Lymphoblastic Leukemia with ETV6-RUNX1 Fusion Gene: The CCLSG ALL 2004 Study

    Chihaya Imai, Toshinori Hori, Yasuto Shimomura, Nobuyuki Hyakuna, Junko Yamanaka, Tomomi Yamada, Kenichiro Watanabe, Yasuo Horikoshi, Takashi Taga, Atsushi Kikuta, Arata Watanabe

    PEDIATRIC BLOOD & CANCER   64   S15 - S15   2017年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY  

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  • Adoptive T Cell Immunotherapy Against a Wide Range of Malignancies by Using Chimeric Antigen Receptors with NK cell-like Specificity (NKp44-CAR)

    Yasushi Kasahara, Changsu Shin, Takayuki Takachi, Nobuhiro Kubo, Haruko Iwabuchi, Masaru Imamura, Akihiko Saitoh, Chihaya Imai

    PEDIATRIC BLOOD & CANCER   64   S22 - S22   2017年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:WILEY  

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  • A Novel NKp44-Based Chimeric Antigen Receptor That Targets Multiple Types of Cancer

    Yasushi Kasahara, Changsu Shin, Sakiko Yoshida, Takayuki Takachi, Nobuhiro Kubo, Haruko Iwabuchi, Masaru Imamura, Akihiko Saitoh, Chihaya Imai

    BLOOD   128 ( 22 )   2016年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC HEMATOLOGY  

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  • DONOR KIR HAPLOTYPE B EXACERBATES ACUTE GVHD IN HLA-MISMATCHED HEMATOPOIETIC CELL TRANSPLANTATION: A SINGLE-CENTER RETROSPECTIVE ANALYSIS

    R. Hosokai, M. Masuko, Y. Shibazaki, A. Saitoh, T. Furukawa, C. Imai

    HAEMATOLOGICA   101   625 - 625   2016年6月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:FERRATA STORTI FOUNDATION  

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  • Interleukin-21 Gene Transduction in Human Natural Killer Cells Enhances Their Anti-Leukemic Capacity

    Yasushi Kasahara, Changsu Shin, Takayuki Takachi, Haruko Iwabuchi, Masaru Imamura, Akihiko Saitoh, Chihaya Imai

    BLOOD   126 ( 23 )   2015年12月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC HEMATOLOGY  

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  • 4-1BB Chimeric Antigen Receptors

    Dario Campana, Herbert Schwarz, Chihaya Imai

    CANCER JOURNAL   20 ( 2 )   134 - 140   2014年3月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:LIPPINCOTT WILLIAMS & WILKINS  

    In addition to T-cell receptor signals, T lymphocytes require costimulatory signals for robust activation. Among these, those mediated by 4-1BB (CD137, TNFRSF9) are critical for tumor immunity. 4-1BB is expressed in T-cell receptor-activated lymphocytes as well as natural killer cells and other hematopoietic and nonhematopoietic cells. 4-1BB ligation induces a signaling cascade that results in cytokine production, expression of antiapoptotic molecules, and enhanced immune responses. In line with the described function of 4-1BB, its addition to CD3 zeta chimeric antigen receptors (CARs) increases their capacity to provoke T-cell expansion and antitumor activity. The results of preclinical studies with 4-1BB CARs have been corroborated by encouraging results from clinical trials. Advantages and disadvantages of 4-1BB CARs versus CARs bearing other costimulatory components remain to be fully elucidated. In this review, we discuss the properties of 4-1BB, the design of 4-1BB CARs, and the function of T lymphocytes and natural killer cells expressing them.

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  • 小児がん治療におけるIntensive Oral Managementの粘膜炎・発熱病悩期間短縮効果

    勝良 剛詞, 斎藤 美紀子, 林 孝文, 高木 律男, 今井 千速, 吉田 吹子, 細貝 亮介, 後藤 早苗, 三富 智子

    日本口腔ケア学会雑誌   7 ( 1 )   109 - 109   2013年3月

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    記述言語:日本語   出版者・発行元:(一社)日本口腔ケア学会  

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  • Patients' Peripheral Blood as a Possible Source of Donor-Derived NK Cells for Ex Vivo Expansion and Genetic Modification for Post-Transplant Cellular Immunotherapy In Cord Blood Recipients

    Chihaya Imai, Sakiko Yoshida, Takayuki Takachi, Masaru Imamura, Ryosuke Hosokai, Haruko Iwabuchi, Makoto Uchiyama, Keiko Asami, Atsushi Ogawa, Akihiro Watanabe

    BLOOD   116 ( 21 )   868 - 869   2010年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC HEMATOLOGY  

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  • Juvenile myelomonocytic leukemia with less aggressive clinical course and KRAS mutation

    Masaru Imamura, Chihaya Imai, Takayuki Takachi, Tac Nemoto, Atsushi Tanaka, Makoto Uchiyama

    PEDIATRIC BLOOD & CANCER   51 ( 4 )   569 - 569   2008年10月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)   出版者・発行元:WILEY-LISS  

    DOI: 10.1002/pbc.21626

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  • The outcome for medulloblastoma treated with craniospinal irradiation in the ultra-early postoperative phase-our institutional experience 査読

    Junichi Yoshimura, Manabu Natsumeda, Kenichi Nishiyama, Takayuki Takachi, Chihaya Imai, Yukihiko Fujii

    NEURO-ONCOLOGY   10 ( 3 )   499 - 500   2008年6月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:DUKE UNIV PRESS  

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  • The management of fetal brain tumors: Challenges and controversies 査読

    Manabu Natsumeda, Junichi Yoshimura, Kenichi Nishiyama, Takayuki Takachi, Chihaya Imai, Yukihiko Fujii

    NEURO-ONCOLOGY   10 ( 3 )   437 - 437   2008年6月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:DUKE UNIV PRESS  

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  • Activated T cell-mediated immunotherapy with a chimeric receptor against CD38 in B-cell malignancies

    Keichiro Mihara, Kazuyoshi Yanagihara, Misato Takigahira, Takahiro Ochiya, Chihaya Imai, Akira Kitanaka, Yoshihiro Takihara, Akiro Kimuna

    BLOOD   110 ( 11 )   696A - 696A   2007年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC HEMATOLOGY  

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  • Sustained expansion of human natural killer cells for leukemia therapy.

    Hiroyuki Fujisaki, Harumi Kakuda, Chihaya Imai, Dario Campana

    BLOOD   108 ( 11 )   1062A - 1062A   2006年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC HEMATOLOGY  

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  • L-serine produced by mesenchymal cells in the bone marrow microenvironment is a trophic factor for hematopoietic progenitor cells.

    S Iwamoto, K Mihara, C Imai, D Campana

    BLOOD   106 ( 11 )   175A - 175A   2005年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC HEMATOLOGY  

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  • A novel method for propagating primary natural killer (NK) cells allows highly efficient expression of anti-CD19 chimeric receptors and generation of powerful cytotoxicity against NK-resistant acute lymphoblastic leukemia cells.

    C Imai, S Iwamoto, D Campana

    BLOOD   104 ( 11 )   91A - 91A   2004年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC HEMATOLOGY  

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  • Development of effective immunotherapy for B-cell non-Hodgkin's lymphoma with CD19-specific cytotoxic T cells

    K Mihara, K Yanagihara, C Imai, A Kimura, D Campana

    BLOOD   104 ( 11 )   895A - 896A   2004年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC HEMATOLOGY  

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  • T-Cell immunotherapy for B-lineage acute lymphoblastic leukemia using chimeric antigen receptors that deliver 4-1BB-mediated costimulatory signals.

    C Imai, K Mihara, M Andreansky, TL Geiger, D Campana

    BLOOD   102 ( 11 )   66A - 67A   2003年11月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:AMER SOC HEMATOLOGY  

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  • Vincristine-induced fever in a child with rhabdomyosarcoma: Cellular hypersensitivity to vincristine demonstrated by leukocyte migration test

    Chihaya Imai, Katsuji Uno, Toshio Kakihara, Atsushi Tanaka, Makoto Uchiyama

    American Journal of Pediatric Hematology/Oncology   23 ( 1 )   73 - 74   2001年

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)  

    DOI: 10.1097/00043426-200101000-00020

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  • Ratio of eosinophil cationic protein/eosinophil count as a new marker in children with acute asthma. (vol 41, pg 142, 1999)

    C Imai, H Yamazaki, Y Tanaka, M Matsunaga, O Numata, K Torigoe

    PEDIATRICS INTERNATIONAL   41 ( 4 )   457 - 457   1999年8月

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    記述言語:英語   出版者・発行元:BLACKWELL SCIENCE ASIA  

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受賞

  • 令和2年度公益信託日本白血病研究基金 臨床医学特別賞

    2020年11月   公益信託日本白血病研究基金   初発の高リスクB前駆細胞性急性リンパ性白血病に対する二重特異性抗体ブリナツモマブの効果に関わる免疫分子の探索的検討

    今井千速

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  • 平成22年度公益信託日本白血病研究基金 一般研究賞

    2010年11月   公益信託日本白血病研究基金   臍帯血移植生着早期の患者末梢血を用いた、ドナー由来NK細胞の体外増幅と遺伝子改変技術の創生:臍帯血移植におけるドナーNK細胞輸注療法の開発に向けて

    今井 千速

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    受賞区分:出版社・新聞社・財団等の賞 

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  • 第12回有壬記念学術奨励賞(基礎医学分野)

    2008年6月  

    今井 千速

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    受賞区分:出版社・新聞社・財団等の賞 

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  • 平成19年度財団法人新潟大学学術奨励会

    2008年3月   財団法人新潟大学学術奨励会  

    今井 千速

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    受賞区分:出版社・新聞社・財団等の賞 

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共同研究・競争的資金等の研究

  • NK細胞様の応答性を持つCAR-T細胞による難治がん治療の実用化研究

    研究課題/領域番号:19K08317  2019年4月 - 2022年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    今井 千速

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    配分額:4420000円 ( 直接経費:3400000円 、 間接経費:1020000円 )

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  • 難治がん克服を目指したNKp44-キメラ型受容体と新規NK細胞増幅法の開発

    2016年4月 - 2019年3月

    日本学術振興会  科学研究費助成事業 

    今井 千速

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    担当区分:研究代表者  資金種別:競争的資金

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  • 同種NK細胞療法におけるドナー選択の最適化とキメラ型人工受容体発現の新手法の開発

    2013年4月 - 2016年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    今井千速

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    担当区分:研究代表者  資金種別:競争的資金

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  • 遺伝子改変NK細胞の難治性白血病への臨床応用に向けた研究

    2009年4月 - 2013年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    今井千速

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    担当区分:研究代表者  資金種別:競争的資金

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  • ヒストン脱アセチル化酵素阻害剤バルプロ酸による白血病細胞のimmunogenecityの変化と、体外増幅・活性化Natural Killer細胞による細胞障害活性増強に関する研究

    2007年4月 - 2008年3月

    新潟大学  新潟大学プロジェクト推進経費若手研究者奨励研究 

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    資金種別:競争的資金

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  • 遺伝子改変NK細胞を用いた、白血病・リンパ腫に対する新たな治療戦略の開発

    2006年4月 - 2009年3月

    日本学術振興会  科学研究費助成事業  若手研究(B)

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    資金種別:競争的資金

    配分額:1400000円 ( 直接経費:1400000円 )

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  • 遺伝子改変Ex Vivo-activated Natural Killer細胞を用いた、T細胞性白血病・リンパ腫に対する新たな細胞療法の開発

    2006年4月 - 2007年3月

    新潟大学  新潟大学プロジェクト推進経費若手研究者奨励研究 

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    資金種別:競争的資金

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  • キメラ受容体遺伝子導入Natural Killer細胞を用いた白血病・リンパ腫

    2006年4月 - 2007年3月

    民間財団等  2006年度乳酸菌研究会研究費 

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    資金種別:競争的資金

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  • 抗原特異的人工受容体遺伝子導入Natural Killer細胞を用いた移植後再発白血病・リンパ腫の治療:新たな遺伝子改変細胞療法の開発

    2005年4月 - 2006年3月

    新潟大学  新潟大学プロジェクト推進経費若手研究者奨励研究 

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    資金種別:競争的資金

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▶ 全件表示

 

担当経験のある授業科目

  • 疾病の成因と治療Ⅱ

    2017年
    -
    現在
    機関名:新潟大学