Measurement of trace elements with micro-PIXE method in myeloma cells and development of novel drugs

• Project/Area Number: 26460720
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical Physics and Radiological Technology
• Research Institution: Gunma University
• Principal Investigator: Murakami Hirokazu 群馬大学, 大学院保健学研究科, 教授 (40166260)
• Co-Investigator(Kenkyū-buntansha): 神谷 富裕 群馬大学, 大学院理工学府, 教授 (70370385) ; 齋藤 貴之 群馬大学, 大学院保健学研究科, 教授 (80375542) ; 長嶺 竹明 群馬大学, その他部局等, 名誉教授 (90180520)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 多発性骨髄腫 / マイクロPIXE / 微量元素 / ボルテゾミブ / bortezomib

Outline of Final Research Achievements

We introduced an in-air micro-PIXE (micro-PIXE) method in the measurement of trace elements in cultured myeloma cells and analyzed the change of trace elements before and after the treatment with bortezomib (proteasome inhibitor) and melphalan (alkylating agent). The cells were gathered on polycarbonate film with cytocentrifuge and measured with micro-PIXE. We established the micro-PIXE method to analyze trace elements in free cultured cells. Phosphate and Calcium changed by high-dose bortezomib treatment, but not by melphalan.

Research Products

• [Journal Article] Primary leptomeningeal B-cell lymphoma with normal pressure hydrocephalus at diagnosis (2015)
  • Author(s): Chiaki Suto, Hirokazu Murakami, Yoshino Kobayashi, Takeaki Nagamine, Takayuki Saitoh, Tetsuhiro Kasamatsu, Hatsue Ogawara, Masami Murakami.
  • Journal Title: Rinsho Ketsueki Volume: 56 Issue: 12 Pages: 2441-2446
  • DOI: 10.11406/rinketsu.56.2441
  • NAID: 130005116919
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] XRCC1 Arg194Trp and XRCC1 Arg399Gln polymorphisms affect clinical features and prognosis of meylodysplastic syndrome. (2015)
  • Author(s): Batchimeg Norjimaa, Takayuki Saitoh, Titsuhiro Kasamatsu, Yusuke Minato, Hirokazu Murakami.
  • Journal Title: Kitakanto Medical Journal Volume: 65 Pages: 11-19
  • Peer Reviewed
• [Journal Article] Post-marketing surveillance of the treatment with THALEDR CAPSULE in patients with relapsed/refractory multiple myeloma. (2015)
  • Author(s): Hirokazu Murakami, Kazuyuki Shimizu and Toshiyuki Takagi.
  • Journal Title: International Journal of Myeloma Volume: 5 Pages: 8-14
  • Peer Reviewed
• [Journal Article] Trends of survival in patients with multiple myeloma in Japan: a multicenter retrospective collaborative study of the Japanese Society of Myeloma. (2015)
  • Author(s): Ozaki S, Handa H, Saitoh T, Murakami H, Itagaki M, Asaoku H, Suzuki K, Isoda A, Matsumoto M, Sawamura M, Konishi J, Sunami K, Takezako N, Hagiwara S, Kuroda Y, Chou T, Nagura E, Shimizu K.
  • Journal Title: Blood Cancer J Volume: 5 Issue: 9 Pages: e349-e349
  • DOI: 10.1038/bcj.2015.79
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] High Percentage of Regulatory T Cells before and after Vitamin B12 Treatment in Patients with Pernicious Anemia. (2014)
  • Author(s): Watanabe S, Ide N, Ogawara H, Yokohama A, Mitsui T, Handa H, Koiso H, Tsukamoto N, Saitoh T, Murakami H.
  • Journal Title: Acta Haematol. Volume: 133 Issue: 1 Pages: 83-88
  • DOI: 10.1159/000362356
  • Peer Reviewed
• [Journal Article] A new staging system to predict prognosis of patients with multiple myeloma in an era of novel therapeutic agents. (2014)
  • Author(s): Iriuchishima H, Saitoh T, Handa H, Isoda A, Matsumoto M, Sawamura M, Iwasaki A, Ushie C, Hattori H, Sasaki Y, Mitsui T, Yokohama A, Tsukamoto N, Murakami H, Nojima Y.
  • Journal Title: Eur J Haematol. Volume: 94 Issue: 2 Pages: 145-151
  • DOI: 10.1111/ejh.12407
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Survival of Multiple Myeloma Patients Aged 65-70 Years in the Era of Novel Agents and Autologous Stem Cell Transplantation. A Multicenter Retrospective Collaborative Study of the Japanese Society of Myeloma and the European Myeloma Network. (2014)
  • Author(s): Ozaki S, Harada T, Saitoh T, Shimazaki C, Itagaki M, Asaoku H, Kuroda Y, Chou T, Yoshiki Y, Suzuki K, Murakami H, Hayashi K, Mina R, Palumbo A, Shimizu K.
  • Journal Title: Acta Haematol. Volume: 132 Pages: 211-219
  • Peer Reviewed
• [Presentation] 気Micro-PIXE法を用いた多発性骨髄腫細胞内微量元素の動態解析 (2017)
  • Author(s): 笠松哲光、長嶋友海、長嶺竹明、村上博和、山田尚人、喜多村茜、佐藤隆博、江夏昌志、神谷富裕
  • Organizer: 第1回QST高崎研シンポジウム
  • Place of Presentation: 高崎
  • Year and Date: 2017-01-26
• [Presentation] 気Micro-PIXE法を用いた多発性骨髄腫細胞内微量元素の動態解析 (2016)
  • Author(s): 長嶋友海、笠松哲光、長嶋友海、長嶺竹明、村上博和、山田尚人、喜多村茜、佐藤隆博、江夏昌志、神谷富裕
  • Organizer: 第63回 北関東医学会総会
  • Place of Presentation: 前橋
  • Year and Date: 2016-09-29
• [Presentation] Loop Regulation Between microRNAs and Epigenetics Underlie microRNA Dysregulation in Multiple Myeloma and Is Associated with the Disease Progression (2015)
  • Author(s): Kei Kimura, et al.
  • Organizer: 第57回 アメリカ血液学会
  • Place of Presentation: オーランド、アメリカ合衆国
  • Year and Date: 2015-12-04
  • Int'l Joint Research
• [Presentation] Long Non-Coding RNA MALAT1 Is Associated with the Progression of Multiple Myeloma and Induced By Cellular Stress (2015)
  • Author(s): Yuko Kuroda, et al.
  • Organizer: 第57回 アメリカ血液学会
  • Place of Presentation: オーランド、アメリカ合衆国
  • Year and Date: 2015-12-04
  • Int'l Joint Research
• [Presentation] Th1 Polarization of Cytokine and Cytokine Receptor Polymorphisms Affect the Susceptibility and Severity of ITP (2015)
  • Author(s): Noriyuki Takahashi, et al.
  • Organizer: 第57回 アメリカ血液学会
  • Place of Presentation: オーランド、アメリカ合衆国
  • Year and Date: 2015-12-04
  • Int'l Joint Research
• [Presentation] Prognostic Impact of Cytogenetic Abnormalities in Adult Patients with Philadelphia-Chromosome(Ph)-Negative Acute Lymphoblastic Leulemia(ALL) Who Underwent Allogeneic Stem Cell Transplant(allo-SCT) (2015)
  • Author(s): Hiroaki Shimizu, et al.
  • Organizer: 第57回 アメリカ血液学会
  • Place of Presentation: オーランド、アメリカ合衆国
  • Year and Date: 2015-12-04
  • Int'l Joint Research
• [Presentation] LncRNA MALAT1 is induced by cellular stress and associated with multiple myeloma progression. (2015)
  • Author(s): Yuko Kuroda, et al.
  • Organizer: 第77回日本血液学会
  • Place of Presentation: 金沢市、石川県
  • Year and Date: 2015-10-16
• [Presentation] Global micro RNA dysregulation caused by various mechanisms is a hallmark of myeloma progression (2015)
  • Author(s): Kei Kimura, et al.
  • Organizer: 第77回日本血液学会
  • Place of Presentation: 金沢市、石川県
  • Year and Date: 2015-10-16
• [Presentation] High expression level and D148E polymorphism of APE1 are associated with acute myeloid leukemia (2015)
  • Author(s): Nanami Gotoh, et al.
  • Organizer: 第77回日本血液学会
  • Place of Presentation: 金沢市、石川県
  • Year and Date: 2015-10-16
• [Presentation] Th1 polarization of cytokine polymorphisms affect the susceptibility and severity of ITP (2015)
  • Author(s): Noriyuki Takahashi, et al.
  • Organizer: 第77回日本血液学会
  • Place of Presentation: 金沢市、石川県
  • Year and Date: 2015-10-16
• [Presentation] Effect of rHuEPO on peripheral blood WBC (2015)
  • Author(s): Tomomi Nagashima, et al.
  • Organizer: 第77回日本血液学会
  • Place of Presentation: 金沢市、石川県
  • Year and Date: 2015-10-16
• [Presentation] Methylation and hydroxymethylation of common fragile site gene in acute myeloid leukemia (2015)
  • Author(s): Itsumi Suda,
  • Organizer: 第77回日本血液学会
  • Place of Presentation: 金沢市、石川県
  • Year and Date: 2015-10-16
• [Presentation] Recent management of stage I follicular lymphoma in Gunma (2015)
  • Author(s): Akihiko Yokohama, et al.
  • Organizer: 第77回日本血液学会
  • Place of Presentation: 金沢市、石川県
  • Year and Date: 2015-10-16
• [Presentation] Revised International Staging System: a multicenter study of the Japanese Society of Myeloma (2015)
  • Author(s): Shuji Ozaki, et al.
  • Organizer: 第77回日本血液学会
  • Place of Presentation: 金沢市、石川県
  • Year and Date: 2015-10-16
• [Presentation] Four cases of classical Hodgkin lymphoma with leukocytosis and serum G-CSF elevation (2015)
  • Author(s): Syuuhei Kanaya, et al.
  • Organizer: 第77回日本血液学会
  • Place of Presentation: 金沢市、石川県
  • Year and Date: 2015-10-16
• [Presentation] Efficacy and safety of VTD-PACE in relapse and refractory multiple myeloma patients (2015)
  • Author(s): Hiroyuki Noguchi, et al.
  • Organizer: 第77回日本血液学会
  • Place of Presentation: 金沢市、石川県
  • Year and Date: 2015-10-16
• [Presentation] Methylation and Hydroxymethylation Status of Tumor Suppressor Genes and Common Fragile Sites Genes in Acute Myeloid Leukemia (2014)
  • Author(s): Suda Y, Murakami H et al.
  • Organizer: Annual Meeting of American Society of Hematology
  • Place of Presentation: ニューオーリンズ
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] BCL6 Does Not Negatively Regulate DNA Damage Response Genes in Multiple Myeloma Cells (2014)
  • Author(s): Tahara K, Murakami H et al.
  • Organizer: Annual Meeting of American Society of Hematology
  • Place of Presentation: ニューオーリンズ
  • Year and Date: 2014-12-06 – 2014-12-09
• [Presentation] The Polymorphism of IL-10-592 C/A is associated with high risk of myelodysplastic syndromes(MDS) (2014)
  • Author(s): KasamatsuT, Saitoh T, Gotoh N, NittaY, Kaneko A, Suda I, Masuda Y, Norjimaa B, Takahashi N, Inoue M, Alkebsi L, Minato Y, HoshinoT, Hatsumi H, Takada S, Sakura T, Shimizu H, Ishizaki T, Takizawa M, Koiso H, Mitsui T, Yokohama A, Tsukamoto N, Handa H, Nojima Y, Murakami H.
  • Organizer: 日本血液学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] High expression level of PARP-1 in multiple myeloma (2014)
  • Author(s): Minato Y, Murakami H, et al.
  • Organizer: 日本血液学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Attempts of differential diagnosis for cytopenia based on XE-5000 and FACS analysis (2014)
  • Author(s): Inoue M, Murakami H, et al.
  • Organizer: 日本血液学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Soluble-form IL-2 receptor predicts survival of follicular lymphoma as well as beta2 microglobulin (2014)
  • Author(s): Yokohama A, Murakami H, et al.
  • Organizer: 日本血液学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] FGFR1 and histone methyltransferase WHSC1L1 at chromosome 8p11 region in multiple myeloma (2014)
  • Author(s): Masuda Y, Murakami H, et al.
  • Organizer: 日本血液学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Network Analysis of microRNA and Epigenetics in Acute Myeloid Leukemia (2014)
  • Author(s): 金子文香、村上博和等
  • Organizer: 日本血液学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Methylation of Common Fragile Site gene PARK2,WWOX in myeloid malignancies. (2014)
  • Author(s): 須田いつみ、村上博和ら
  • Organizer: 日本血液学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] Polymorphism of PARP1 Val762Ala is not associated with chronic immune thrombocytopenia(ITP) (2014)
  • Author(s): Nitta Y, Murakami H, et al.
  • Organizer: 日本血液学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] The polymorphisms of base excision repair genes affect the clinical feature in acute myeloid leukemia (2014)
  • Author(s): 後藤七海、村上博和等
  • Organizer: 日本血液学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] マントル細胞リンパ腫由来の細胞株GUNHL2の樹立 (2014)
  • Author(s): 永井清絵、村上博和等
  • Organizer: 日本血液学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-10-31 – 2014-11-02
• [Presentation] 多発性骨髄腫におけるFGFRおよびヒストンメチル化酵素（HMT）発現 (2014)
  • Author(s): 増田裕太、半田寛、金子文香、須田いつみ、木村恵、黒田裕子、新田恭浩、笠松哲光、齋藤貴之、村上博和
  • Organizer: 日本臨床検査学教育学会
  • Place of Presentation: 蒲田
  • Year and Date: 2014-08-01
• [Presentation] 多発性骨髄腫（MM）患者におけるIL-10，IL-17，IL-18サイトカイン遺伝子多型解析 (2014)
  • Author(s): 新田恭浩、齋藤貴之、後藤七海、ノルジマーバトチメグ、金子文香、須田いつみ、増田裕太、笠松哲光、湊雄介、村上博和
  • Organizer: 日本臨床検査学教育学会
  • Place of Presentation: 蒲田
  • Year and Date: 2014-08-01
• [Presentation] 急性骨髄性白血病におけるp15，WWOX，PARK2のメチル化 (2014)
  • Author(s): 須田いつみ、半田寛、金子文香、増田裕太、黒田裕子、木村恵、新田恭浩、笠松哲光、齋藤貴之、村上博和
  • Organizer: 日本臨床検査学教育学会
  • Place of Presentation: 蒲田
  • Year and Date: 2014-08-01
• [Presentation] 悪性リンパ腫におけるR-CHOP療法によるＴ細胞サブセットの変動 (2014)
  • Author(s): 永井清絵、木村恵、黒田裕子、後藤七海、笠松哲光、湊雄介、小磯博美、半田寛、齋藤貴之、村上博和
  • Organizer: 日本臨床検査学教育学会
  • Place of Presentation: 蒲田
  • Year and Date: 2014-08-01
• [Presentation] レナリドミド治療による多発性骨髄腫患者の免疫細胞サブセットの変化 (2014)
  • Author(s): 神谷明、大宮千春、永井清絵、成塚靖浩、金子文香、須田いつみ、増田裕太、齋藤貴之、村上博和、半田寛
  • Organizer: 日本検査血液学会
  • Place of Presentation: 仙台
  • Year and Date: 2014-07-20 – 2014-07-21
• [Presentation] 急性骨髄性白血病における塩基除去修復遺伝子APE1、XRCC1遺伝子多型の解析 (2014)
  • Author(s): 後藤七海、齋藤貴之、岩崎篤史、新田恭浩、ノルジマー バトチメグ、湊雄介、笠松哲光、佐倉徹、半田寛、村上博和
  • Organizer: 日本検査血液学会
  • Place of Presentation: 仙台
  • Year and Date: 2014-07-20 – 2014-07-21
• [Presentation] Network of micro RNA and epigenetics are associated with the progression of MGUS and multiple myeloma. (2014)
  • Author(s): Masuda Y, Handa H, Hattori H, Kaneko A, Suda I, Lobna Alkebsi, Saitoh T, Iriuchishima H, Takizawa M, Koiso H, Isoda A, Matsumoto M, Sawamura M, Tahara K, Ishizaki T, Mitsui T, Shimizu H, Yokohama A, Tsukamoto N, Nojima Y, Murakami H.
  • Organizer: Annual Meeting of European Hematology Association
  • Place of Presentation: ミラノ
  • Year and Date: 2014-06-12 – 2014-06-15
• [Book] スタンダード検査血液学第3版第２刷 (2015)
  • Author(s): 村上博和、齋藤貴之、笠松哲光
  • Total Pages: 461
  • Publisher: 医歯薬出版
• [Book] 医歯薬出版 (2014)
  • Author(s): 村上博和、齋藤貴之、笠松哲光
  • Total Pages: 496
  • Publisher: スタンダード検査血液学第3版
• [Book] 多発性骨髄腫Updationg 6 (2014)
  • Author(s): 齋藤貴之、笠松哲光、村上博和
  • Total Pages: 295
  • Publisher: 医薬ジャーナル
• [Book] 白血病と言われたら (2014)
  • Author(s): 齋藤貴之、村上博和
  • Total Pages: 217
  • Publisher: 全国骨髄バンク推進連絡協議会
• [Book] 多発性骨髄腫Updationg 5 (2014)
  • Author(s): 齋藤貴之、村上博和、半田寛
  • Total Pages: 207
  • Publisher: 医薬ジャーナル