Development of a novel therapy targeting intracellular cholesterol for leukemia
Project/Area Number |
16K09851
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Saga University |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | シクロデキストリン / コレステロール / 白血病 / アポトーシス / 葉酸受容体 / 葉酸修飾シクロデキストリン / 慢性骨髄性白血病 / 急性骨髄性白血病 / 細胞増殖抑制 / 細胞周期停止 / 葉酸修飾 / 白血病細胞 / 脂質ラフト / 抗腫瘍作用 |
Outline of Final Research Achievements |
2-Hydroxypropyl-β-cyclodextrin (HP-β-CyD) extracts cholesterol from chronic myelogenous leukemia (CML) cells and may have antitumor effects not only on CML cells but also on CML stem cells. In the present study, we investigated the effects of HP-β-CyD on acute myeloid leukemia (AML). Anti-leukemic effect of folate-appended HP-β-CyD was also examined. AML cell line showed similar effect. In addition, folate-appended HP-β-CyD showed 10 to 20 times the antitumor activity of HP-β-CyD. Moreover, these actions are specific to folate receptor-expressing cells, and are considered to be promising as leukemia cell-targeted therapeutic agents.
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Academic Significance and Societal Importance of the Research Achievements |
白血病は医療の進歩により予後は改善されてきたものの依然難治である。そこで、腫瘍細胞の生存や治療抵抗性に関わるとされている細胞内コレステロールを標的とする治療法は、従来の薬剤と作用機序も異なり、新規治療として期待できる。さらに、正常細胞と比較して腫瘍細胞でより高発現している葉酸受容体を標的とする葉酸修飾シクロデキストリンは、無修飾のシクロデキストリンの10-20倍の抗腫瘍活性を示すことがわかり、より有効な白血病治療の開発につながる成果と考えられる。
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Report
(5 results)
Research Products
(63 results)
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[Journal Article] Reconstitution of NK Cells Expressing KIR3DL1 Is Associated With Reduced NK Cell Activity and Relapse of CML After Allogeneic Hematopoietic Stem Cell Transplantation2020
Author(s)
Ureshino H, Shindo T, Sano H, Kubota Y, Ando T, Kidoguchi K, Kusaba K, Itamura H, Kojima H, Kusunoki Y, Miyazaki Y, Kojima K, Tanaka H, Saji H, Oshima K, Kimura S
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Journal Title
International Journal of Hematology
Volume: 111
Issue: 5
Pages: 733-738
DOI
Related Report
Peer Reviewed
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[Journal Article] Epstein-Barr virus-positive diffuse large B cell lymphoma, not otherwise specified, carrying a t(19;22)(q13;q11) translocation.2020
Author(s)
Yamaguchi K, Kubota Y, Kishimori C, Ohno H, Kidoguchi K, Kizuka-Sano H, Nishioka A, Katsuya H, Ando T, Kimura S.
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Journal Title
Ann Hematol
Volume: 99
Issue: 2
Pages: 389-390
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical impact of the CONUT score in patients with multiple myeloma2020
Author(s)
Okamoto S, Ureshino H*, Kidoguchi K, Kusaba K, Kizuka-Sano H, Sano H, Nishioka A, Yamaguchi K, Kamachi K, Itamura H, Yoshimura M, Yokoo M, Shindo T, Kubota Y, Ando T, Kojima K, Kawaguchi A, Sueoka E, Kimura S.
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Journal Title
Ann Hematol
Volume: 99
Issue: 1
Pages: 113-119
DOI
Related Report
Peer Reviewed
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[Journal Article] Severe infusion reaction, anti-rituximab antibodies and lymphoma.2020
Author(s)
Kidoguchi K, Kubota Y, Kusaba K, Kizuka-Sano H, Yamaguchi K, Nishioka A, Yokoo M, Ando T, Kojima K, Kimura S.
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Journal Title
QJM
Volume: 113
Issue: 4
Pages: 273-274
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Primary Chest Wall MYC/BCL6 Double-hit Lymphoma with t (3;7) (q27;p12) and t (8;14) (q24;q32) Translocations2019
Author(s)
Kamachi K, Kubota Y, Nagaie T, Yamaguchi K, Ogusu S, Kidoguchi K, Kusaba K, Kizuka-Sano H, Nishioka A, Yoshimura M, Yokoo M, Ando T, Kai K, Kojima K, Ohshima K, Sueoka E, Kimura S.
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Journal Title
Internal Medicine
Volume: 58
Issue: 14
Pages: 2073-2077
DOI
NAID
ISSN
0918-2918, 1349-7235
Year and Date
2019-07-15
Related Report
Peer Reviewed / Open Access
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[Journal Article] Significance of FLT3-tyrosine kinase domain mutation as a prognostic factor for acute myeloid leukemia.2019
Author(s)
Sakaguchi M, Yamaguchi H, Kuboyama M, Najima Y, Usuki K, Ueki T, Oh I, Mori S, Kawata E, Uoshima N, Kobayashi Y, Kako S, Tajika K, Shono K, Kayamori K, Hagihara M, Kanda J, Uchiyama H, Kuroda J, Uchida N, Kubota Y, Kimura S, Kurosawa S, et al
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Journal Title
Int J Hematol
Volume: 110
Issue: 5
Pages: 566-574
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical impact of the CONUT score and mogamulizumab in adult T cell leukemia/lymphoma.2019
Author(s)
Ureshino H, Kusaba K, Kidoguchi K, Sano H, Nishioka A, Itamura H, Yoshimura M, Yokoo M, Shindo T, Kubota Y, Ando T, Kojima K, Sueoka E, Kimura S.
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Journal Title
Annals of Hematology
Volume: 98
Issue: 2
Pages: 465-471
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prognostic impact of low allelic ratio FLT3-ITD and NPM1 mutation in acute myeloid leukemia.2018
Author(s)
Sakaguchi M, Yamaguchi H, Najima Y, Usuki K, Ueki T, Oh I, Mori S, Kawata E, Uoshima N, Kobayashi Y, Kako S, Tajika K, Gomi S, Shono K, Kayamori K, Hagihara M, Kanda J, Uchiyama H, Kuroda J, Uchida N, Kubota Y, Kimura S, et al.
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Journal Title
Blood Advances
Volume: 2
Issue: 20
Pages: 2744-2754
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Successful Autologous Hematopoietic Stem Cell Transplantation Followed by Bortezomib Maintenance in a Patient with Relapsed CD138-low Multiple Solitary Plasmacytomas Harboring a 17p Deletion2018
Author(s)
Kitamura H, Kubota Y, Yamaguchi K, Kamachi K, Nishioka A, Yokoo M, Shindo T, Ando T, Kojima K, Kimura S.
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Journal Title
Internal Medicine
Volume: 57
Issue: 6
Pages: 855-860
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
Peer Reviewed / Open Access
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[Journal Article] The novel BMI-1 inhibitor PTC596 downregulates MCL-1 and induces p53-independent mitochondrial apoptosis in acute myeloid leukemia progenitor cells.2017
Author(s)
Nishida Y, Maeda A, Kim MJ, Cao L, Kubota Y, Ishizawa J, AlRawi A, Kato Y, Iwama A, Fujisawa M, Matsue K, Weetall M, Dumble M, Andreeff M, Davis TW, Branstrom A, Kimura S, Kojima K.
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Journal Title
Blood Cancer J
Volume: 17
Issue: 2
Pages: e527-e527
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Famotidine-induced reactive plasmacytosis and generalized lymphadenopathy: a case report and review of the literature.2016
Author(s)
Hiroaki Kitamura, Yasushi Kubota, Noriyasu Fukushima, Tatsuo Ichinohe, Daisuke Hayasaka, Kazuharu Kamachi, Mari Yoshihara, Hidekazu Itamura, Takashi Hisatomi, Kazuo Wakayama, Eisaburo Sueoka, Shinya Kimura
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Journal Title
Int J Clin Exp Pathol
Volume: 9
Pages: 7680-7685
Related Report
Peer Reviewed / Open Access
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[Journal Article] Rituximab-induced Acute Thrombocytopenia in High Tumor Burden Follicular Lymphoma2016
Author(s)
Ureshino H, Nishioka A, Kojima K, Suzuki M, Kizuka H, Sano H, Shindo T, Kubota Y, Ando T, Kimura S
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Journal Title
Internal Medicine
Volume: 55
Issue: 15
Pages: 2061-2064
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
Peer Reviewed / Open Access
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[Presentation] 2つの異なる免疫表現型を有した初期前駆T細胞性急性リンパ芽球性白血病と考えられた1例2019
Author(s)
海野 晃久, 城戸口 啓介, 本田 美穂, 岡崎 智満, 吉原 由利重, 若山 一夫, 川崎 誠司, 横尾 眞子, 久保田 寧, 木村 晋也, 末岡 榮三朗
Organizer
第81回日本血液学会学術集会
Related Report
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[Presentation] t(19;22)(q13.1;q11.2)を認めたEBV陽性DLBCLの一例2019
Author(s)
山口 享祐, 久保田 寧, 横尾 眞子, 岸森 千幸, 大野 仁嗣, 城戸口 啓介, 草場 香那, 佐野 遥菜, 西岡 敦二郎, 安藤 寿彦, 小島 研介, 木村 晋也
Organizer
第81回日本血液学会学術集会
Related Report
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[Presentation] 超高齢DLBCL患者における臨床学的特徴についての後方視的研究2019
Author(s)
西岡 敦二郎, 久保田 寧, 草場 香那, 城戸口 啓介, 佐野 遥菜, 山口 享祐, 蒲池 和晴, 嬉野 博志, 横尾 眞子, 安藤 寿彦, 末岡 榮三朗, 小島 研介, 木村 晋也
Organizer
第81回日本血液学会学術集会
Related Report
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[Presentation] FLT3-ITD陽性急性骨髄性白血病を対象とした13番染色体長腕ヘテロ接合性消失の解析2019
Author(s)
神田 真志, 脇田 知志, 新井 悠, 名島 悠峰, 臼杵 憲祐, 植木 俊充, 翁 家国, 森 慎一郎, 魚嶋 伸彦, 小林 裕, 賀古 真一, 田近 賢二, 鐘野 勝洋, 栢森 健介, 萩原 政夫, 諫田 淳也, 内山 人二, 黒田 純也, 内田 直之, 久保田 寧ら
Organizer
第81回日本血液学会学術集会
Related Report
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[Presentation] 大量化療前導入治療R-CHOP-14とR-CHOP-14/CHASERの比較試験:JCOG09082018
Author(s)
Dai Maruyama, Yoshitoyo Kagami, Taro Shibata, Kensei Tobinai, Kazuhito Yamamoto, Yoshitaka Imaizumi, Toshiki Uchida, Kazuyuki Shimada, Koichiro Minauchi, Noriko Fukuhara, Hirofumi Kobayashi, Nobuhiko Yamauchi, Hedeki Tsujimura, Akira Hangaishi, Ryo Tominaga, Yasushi Kubota, et al.
Organizer
第80回日本血液学会学術集会
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[Presentation] 急性骨髄性白血病におけるFLT3-ITD低アレル比とNPM1の予後因子としての重要性2018
Author(s)
Nana Nakajima, Masahiro Sakaguchi, Yuho Najima, Kensuke Usuki, Toshimitsu Ueki, Iekuni Oh, Sinichiro Mori, Eri Kawata, Nobuhiko Uoshima, Yutaka Kobayashi, Shinichi Kako, Kenji Tajika, Katsuhiro Shono, Kensuke Kayamori, Masao Hagihara, Junya Kanda, Hitoji Uchiyama, Junya Kuroda, Naoyuki Uchida, Yasushi Kubota, et al.
Organizer
第80回日本血液学会学術集会
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[Presentation] Ponatinib for relapsed Ph+ leukemia with T315I mutation after allogeneic stem cell transplantation2017
Author(s)
Kana Kusaba, Yasushi Kubota, Haruhiko Sano, Haruna Kizuka, Hidekazu Itamura, Toshihiko Ando, Kensuke Kojima, Masatomo Miura, Naoto Takahashi, Koichi Ohshima, Shinya Kimura
Organizer
第79回日本血液学会学術集会
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[Presentation] 広範な皮下血腫と高度の貧血を呈した真性多血症と第XIII/13因子(F13)欠乏症の合併症例2016
Author(s)
嬉野 博志, 木塚 遥菜, 佐野 晴彦, 西岡 敦二郎, 進藤 岳郎, 久保田 寧, 安藤 寿彦, 尾崎 司, 惣宇利 正善, 片山 義雄, 小島 研介, 一瀬 白帝, 木村 晋也
Organizer
第78回日本血液学会学術集会
Place of Presentation
パシフィコ横浜
Year and Date
2016-10-13
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[Presentation] 輸血とHLA検査について2016
Author(s)
山田 尚友, 山田 麻里江, 中尾 真実, 久保田 寧, 末岡 榮三朗
Organizer
第17回日本検査血液学会学術集会
Place of Presentation
福岡国際会議場
Year and Date
2016-08-06
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