Establishment of basic molecular mechanism of carcinogenesis by ROS in malignant leukemia in aim of molecular targeting therapy

• Project/Area Number: 21591357
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Shinshu University
• Principal Investigator: SHIOHARA Masaaki 信州大学, 医学部・附属病院, 特任研究員 (00293514)
• Co-Investigator(Kenkyū-buntansha): HIGUCHI Tsukasa 信州大学, 医学部, 助教 (80397306) ; SAKASHITA Kazuo 信州大学, 医学部附属病院, 助教 (10345746)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 小児血液学 / 活性酸素種 / リンパ性白血病 / 活性酸素産生酵素

Research Abstract

We analyzed the mechanism of carcinogenesis mediated by Nox-generating ROS in acute lymphoblastic leukemia. ROS generated by Nox5 expressed in part of ALL cells were related to the growth and inhibition of apoptosis of tumor cells. It was shown that Nox5 can be a molecular target of the therapy.

Research Products

• [Journal Article] Critical illness polyneuropathy and myopathy caused by Bacillus Cereus sepsis in acute lymphoblastic leukemia (2012)
  • Author(s): Hirabayashi K, Shiohara M, Suzuki T, Saito S, Tanaka M, Yanagisawa R, Tsuruta G, Fukuyama T, Hidaka Y, Nakazawa Y, Shimizu T, Sakashita K, Koike K
  • Journal Title: J Pediatr Hematol Oncol Volume: 34 Issue: 3 Pages: 110-113
  • DOI: 10.1097/mph.0b013e318234620b
  • Peer Reviewed
• [Journal Article] Hyperacute graft-versus-host disease : histological assessment of skin biopsy specimens from 19 cases (2012)
  • Author(s): Shiohara J, Takata M, Shiohara M, Ito T, Ishida F
  • Journal Title: Clin Exp Dermatol Volume: (in press) Issue: 4 Pages: 335-340
  • DOI: 10.1111/j.1365-2230.2011.04261.x
  • Peer Reviewed
• [Journal Article] 好中球二次顆粒欠損症 (2012)
  • Author(s): 塩原正明
  • Journal Title: 標本に学ぶ血液疾患症例医薬ジャーナル Pages: 148-153
  • URL: http://www.iyaku-j.com/
• [Journal Article] 小児慢性特定疾患治療研究事業における「血小板の異常をきたす疾患」の登録状況 (2011)
  • Author(s): 草刈麻衣、塩原正明、齋藤章治、田中美幸、柳沢龍、坂下一夫、加藤忠明、藤本純一郎、小池健一
  • Journal Title: 日小血会誌 Volume: 25 Pages: 74-80
  • NAID: 10029312127
  • Peer Reviewed
• [Journal Article] 先天性線状黄色腫の一例 (2011)
  • Author(s): 新倉冬子、徳田安孝、小金平容子、中澤功、塩原正明、奥山隆平
  • Journal Title: 皮膚病診療 Volume: 33 Pages: 945-948
  • Peer Reviewed
• [Journal Article] Genetic analysis of TP53 in childhood myelodysplastic syndrome and juvenile myelomonocytic leukemia (2011)
  • Author(s): Saito S, Matsuda K, Taira C, Sano K, Tanaka-Yanagisawa M, Yanagisawa R, Nakazawa Y, Sakashita K, Shiohara M, Koike K
  • Journal Title: Leuk Res Volume: 35 Pages: 1578-84
  • NAID: 120007108235
  • URL: http://dx.doi.org/10.1016/j.leukres.2011.06.027
  • Peer Reviewed
• [Journal Article] Engraftment syndrome, but not acute GVHD, younger age, CYP3A5 or MDR1 polymorphisms, increases tacrolimus clearance in pediatric hematopoietic SCT (2011)
  • Author(s): Yanagisawa R, Katsuyama Y, Shigemura T, Saito S, Tanaka M, Nakazawa Y, Sakashita K, Shiohara M, Koike K
  • Journal Title: Bone Marrow Transplant Volume: 46 Issue: 1 Pages: 90-97
  • DOI: 10.1038/bmt.2010.64
  • Peer Reviewed
• [Journal Article] Myelodysplastic syndrome in a child with 15q24 deletion syndrome (2011)
  • Author(s): Narumi Y, Shiohara M, Wakui K, Hama A, Kojima S, Yoshikawa K, Amano Y, Kosho T, Fukushima Y
  • Journal Title: Am J Med Genet Volume: 158(A) Issue: 2 Pages: 412-416
  • DOI: 10.1002/ajmg.a.34395
  • Peer Reviewed
• [Journal Article] Retrospective analysis of risk factors for development of liver dysfunction transient leukemia of Down syndrome (2011)
  • Author(s): Hirabayashi K, Shiohara M, Takahashi D, Saito S, Tanaka M, Yanagisawa R, Sakashita K, Nakamura T, Ishii E, Koike K
  • Journal Title: Luek Lymphoma Volume: 52 Issue: 8 Pages: 1523-1527
  • DOI: 10.3109/10428194.2011.573888
  • Peer Reviewed
• [Journal Article] Disappearance of minimal residual disease after the early withdrawal of immnunosuppressants in a patient with juvenile myelomonocytic leukemia (2011)
  • Author(s): Yanagisawa R, Matsuda K, Sakashita K, Nakazawa Y, Tanaka M, Saito S, Yoshikawa K, Kamijo T, Shiohara M, Koike K
  • Journal Title: Pediatr Blood Cancer Volume: 56 Issue: 3 Pages: 166-71
  • DOI: 10.1002/pbc.22849
  • Peer Reviewed
• [Journal Article] Genetic analysis of TP53 in childhood myelodysplastic syndrome and juvenile myelomonocytic leukemia (2011)
  • Author(s): Saito S, Shiohara M, 他8名
  • Journal Title: Leuk Res Volume: 35 Pages: 1578-1584
  • NAID: 120007108235
  • Peer Reviewed
• [Journal Article] Defective membrane expression of the Na+-HCO3-cotransporter NBCe1 is associated with familial migrane (2010)
  • Author(s): Suzuki M, Paesschen WV, Stalmans I, Horita S, Yamada H, Bergmans BA, Legius E, Riant F, Jonghe PD, Li Yuehong, Sekine T, Igarashi T, Fujimoto I, Mikoshiba K, Shimadzu M, Shiohara M, Braverman N, Al-Gazal L, Fujita T, Seki G
  • Journal Title: Proc Natl Acad Sci USA Volume: 107 Issue: 36 Pages: 15963-15968
  • DOI: 10.1073/pnas.1008705107
  • Peer Reviewed
• [Journal Article] Increased pretransplant QT dispersion as a risk factor for the development of cardiac complications during and after preparative conditioning for pediatric hematopoietic stem cell transplantation (2010)
  • Author(s): Motoki N, Shimizu T, Akazawa Y, Saito S, Tanaka M, Yanagisawa R, Motoki H, Nakazawa Y, Sakashita K, Iwasaki Y, Shiohara M, Koike K
  • Journal Title: Pediatr Transplant Volume: 14 Issue: 8 Pages: 986-992
  • DOI: 10.1111/j.1399-3046.2010.01389.x
  • Peer Reviewed
• [Journal Article] Exercise effects on methylation of ASC gene (2010)
  • Author(s): Nakajima K ; Takeoka, M ; Mori M ; Sakurai A ; Nose H ; Higuchi K ; Itano N ; Shiohara M ; Taniguchi S
  • Journal Title: Int J Sports Med Volume: 31 Issue: 09 Pages: 1-5
  • DOI: 10.1055/s-0029-1246140
  • Peer Reviewed
• [Journal Article] Effect of the mutant microphthalmia-associated transcription factor found in Tietz syndrome on the in vitro development of mast cells (2010)
  • Author(s): Shigemura T, Shiohara M, Tanaka M., Takeuchi K., Koike K
  • Journal Title: J Pediatr Hematol Oncol Volume: 32 Issue: 6 Pages: 442-447
  • DOI: 10.1097/mph.0b013e3181d9da5d
  • Peer Reviewed
• [Journal Article] Polymyxin-directed hemoperfusion for sepsis-induced multiple organ failure (2010)
  • Author(s): Hirabayashi K, Shiohara M, Saito S, Tanaka M, Yanagisawa R, Tsuruta G, Fukuyama T, Hidaka Y, Nakazawa Y, Shimizu T, Sakashita K, Koike K
  • Journal Title: Pediatr Blood Cancer Volume: 55 Issue: 1 Pages: 202-205
  • DOI: 10.1002/pbc.22447
  • Peer Reviewed
• [Journal Article] Long-term survival after non-intensive chemotherapy in some juvenile myelomonocytic leukemia patients with CBL mutations, and the possible presence of healthy persons with the mutations (2010)
  • Author(s): Matsuda K, Taira C, Sakashita K, Saito S, Tanaka M, Yanagisawa R, Nakazawa Y, Shiohara M, Fukushima K, Oda M, Honda T, Nakahata T, Koike K
  • Journal Title: Blood Volume: 115 Pages: 5429-5431
  • URL: http://intl.bloodjournal.org
  • Peer Reviewed
• [Journal Article] Tokyo Children's Cancer Study Group. Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia (2010)
  • Author(s): Tsuchida M, Ohara A, Manabe A, Kumagai M, Shimada H, Kikuchi A, Mori T, Saito M, Akiyama M, Fukushima T, Koike K, Shiobara M, Ogawa C, Kanazawa T, Noguchi Y, Oota S, Okimoto Y, Yabe H, Kajiwara M, Tomizawa D, Ko K, Sugita K, Kaneko T, Maeda M, Inukai T, Goto H, Takahashi H, Isoyama K, Hayashi Y, Hosoya R, Hanada R
  • Journal Title: Leukemia Volume: 24 Issue: 2 Pages: 383-396
  • DOI: 10.1038/leu.2009.260
  • Peer Reviewed
• [Journal Article] Genital abnormalities in Pallistar-Hall syndrome : Report of two patients and review of the literature (2010)
  • Author(s): Narumi Y, Kosho T, Tsuruta G, Shiohara M, Shimazaki E, Mori T, Shimizu A, Igawa Y, Nishizawa S, Takagi K, Kawamura R, Wakui K, Fukushima Y
  • Journal Title: Am J Med Genet Volume: 152A Issue: 12 Pages: 3143-3147
  • DOI: 10.1002/ajmg.a.33720
  • Peer Reviewed
• [Journal Article] Long-term survival after non-intensive chemotherapy in some juvenile myelomonocytic leukemia patients with CBL mutations, and the possible presence of healthy persons with the mutations. (2010)
  • Author(s): Matsuda Kazuyuki
  • Journal Title: Blood Volume: 115 Pages: 5429-5431
  • Peer Reviewed
• [Journal Article] Long-term results of Tokyo Children's Cancer Study Group trials for childhood acute lymphoblastic leukemia 1984-1999. (2010)
  • Author(s): Tsuchida Masahiro
  • Volume: 24
  • Pages: 383-396
  • Peer Reviewed
• [Journal Article] Disappearance of minimal residual disease after the early withdrawal of immunos uppressants in a patient with juvenile myelomonocytic leukemia. (2010)
  • Author(s): Yanagisawa Ryu
  • Journal Title: Pediatr Blood Cancer Volume: 56 Pages: 501-502
  • Peer Reviewed
• [Journal Article] Quantitative assessment of PTPN11 or RAS mutations at the neonatal period and during the clinical course in patients with juvenile myelomonocytic leukaemia. (2009)
  • Author(s): Matsuda K, Sakashita K, Taira C, Tanaka-Yanagisawa M, Yanagisawa R, Shiohara M, Kanegane H, Hasegawa DKawasaki K, Endo M, Yajima S, Sasaki S, Kato K, Koike K, Kikuchi A, Ogawa A, Watanabe A, Sotomatsu M, Nonoyama S, Koike K
  • Journal Title: Br J Haematol Volume: 141 Issue: 4 Pages: 567-575
  • DOI: 10.1111/j.1365-2141.2009.07968.x
  • Peer Reviewed
• [Journal Article] MITF-CM, a newly identified isoform of microphthalmia-associated transcription factor, is expressed in cultured mast cells. (2009)
  • Author(s): Shiohara Masaaki
  • Journal Title: Int J Lab Hematol 31 Pages: 215-226
  • Peer Reviewed
• [Journal Article] Urinary excretion of ganciclovir contributes to improvement of adenovirus-associated hemorrhagic cystitis after allogeneic bone marrow transplantation. (2009)
  • Author(s): Nakazawa Yozo
  • Journal Title: Pediatr Transplant 13 Pages: 632-635
  • Peer Reviewed
• [Journal Article] Low toxicity of a conditioning with 8-Gy total body irradiation, fludarabine and cyclophosphamide as preparative regimen for allogeneic hemato poietic stem cell transplantation in pediatric hematological malignancies (2009)
  • Author(s): Yanagisawa Ryu
  • Journal Title: Pediatr Transplant 13 Pages: 737-745
  • Peer Reviewed
• [Presentation] A critical mediating role of the superoxide-generating oxidase Nox5 in maintenance of HTLV-1 transformation phenotype (2011)
  • Author(s): Shigemura T, Shiohara M, Fujii M, Tanaka Y, Furuta S, Kamata T
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] A novel mediating role of ROS-generating Nox5 in growth and survival of HTLV-1-infected cells (2010)
  • Author(s): Shiohara M, Fujii M, Nakamura M, Mori N, Furuta S, Kamata T
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] 造血幹細胞移植におけるタクロリムスのクリアランスに影響する因子の検討 (2010)
  • Author(s): 柳沢龍
  • Organizer: 第32回日本造血細胞移植学会総会
  • Place of Presentation: 浜松
  • Year and Date: 2010-02-19
• [Presentation] A novel mediating role of ROS-generating Nox5 in growth and survival of HTLV-1-infected T-cells (2009)
  • Author(s): Shigemura T, Shiohara M, Zhang Y, Kato M, Mori N, Fujii M, Tanaka Y, Kike K, Kamata T
  • Organizer: 第71回日本血液学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2009-10-23