Establishment and Verification of MIC Diagnostic Paradigm in Cancers

2008 Fiscal Year Final Research Report

• Project/Area Number: 17390165
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Nagasaki University
• Principal Investigator: KAMIHIRA Shimeru Nagasaki University, 大学院・医歯薬学総合研究科, 教授 (80108290)
• Co-Investigator(Kenkyū-buntansha): YAMADA Yashuaki 長崎大学, 医歯薬学, 准教授 (60145232)
• Research Collaborator: 菅原 和行 長崎大学, 付属病院, 技師 ; 佐々木 大介 長崎大学, 付属病院, 技師 ; 鶴田 一人 長崎大学, 付属病院, 技師 ; 石崎 明希子 長崎大学, 付属病院, 技師 ; 森 沙耶香 長崎大学, 付属病院, 技師
• Project Period (FY): 2005 – 2008
• Keywords: 発癌 / 遺伝子検査 / 遺伝子検査分子標的療法

Research Abstract

研究の促進に不可欠なCell and Gene Bankの充実をはかり、それを活用して, ATL細胞を腫瘍細胞のモデルとしてHDL inhibitorやTRAIL+BB1及びTRAIL+JCBの抗癌作用に伴うがんシグナルを明らかにした。将来のサイトカイン+small chemicalの併用分子標的療法に繋がるものと期待される。造血器腫瘍の治療指向型診断、thernostics,を目指したMIC検査については、形質検査の長所と欠点を整理し、弱点を相補する実践的遺伝子検査の技術開発導入に一部成功した。例えば、サザンブロット検査の短縮化と品質保証、特に検出感度の方法論的確立、Long InversePCR法の迅速化・精度の向上を樹立した。 また、Imatinibなどの分子標的療法の導入にてtumor burdenの評価、治療効果の至適判断に不可欠なMRDの代理検査としての絶対的real-time RT PCR法の正確性の向上、至適cDNA化、至適な内部control、Data normalizationについて成果を得、BCR-ABL, PML-RARa、WT1, Tax Cyclin D1 mRNAの定量系を確立し、患者中心の科学的医療支援体制を検査室の立場から構築し、一部Clinical Settingし、その有用性や将来の新たな視点での検査パラダイムの一部を確立した。

Research Products

• [Journal Article] Relationsship between MGUS and radiation exposure in Nagasaki atomic bomb survivors (2008)
  • Author(s): Iwanaga M, Kamihira S, et.al.
  • Journal Title: Blood
  • Peer Reviewed
• [Journal Article] A novel role of serum cyto-c as a tumor marker in patients with operable cancer (2008)
  • Author(s): Osaka a, Kamihira S. et.al.
  • Journal Title: J Cancer Clin Oncol
  • Peer Reviewed
• [Journal Article] Autocrine and/or paracrine growth of aggressive ATL cells caused by HGF and c-Met (2008)
  • Author(s): Onimaru Y, Kamihira S. et.al.
  • Journal Title: Int J Onccol 33 Pages: 697-703
  • Peer Reviewed
• [Journal Article] Foxp3 expression on normal and leukemic CD4+CD25+ T-cells implicated in HTLV-1 is inconsistent with Treg cells (2008)
  • Author(s): Abe M, Kamihira S. et.al.
  • Journal Title: Eur J Haematol 81 Pages: 209-17
  • Peer Reviewed
• [Journal Article] Characteristic Expression of HBZ transcripts in HTLV-1 provirus-positive cells (2008)
  • Author(s): Usui T, Kamihira S. et.al.
  • Journal Title: Retrovirology 5 Pages: 34
  • Peer Reviewed
• [Journal Article] Usefulness of long-distance inverse polymerase chain reaction for molecular detection of 14q32 translocation in a clinical setting (2008)
  • Author(s): Ishizaki A, Sugahara K, Tsuruda K, Hasegawa H, Yanagihara K, Tsukasaki K, Yamada Y, Kamihira S
  • Journal Title: Scand J Clin Lab Invest (Epub ahead of print) Pages: 1-7
  • Peer Reviewed
• [Journal Article] Serum cytochrome c to indicate the extent of ongoing tumor cell death (2008)
  • Author(s): Osaka A, Hasegawa H, Tsuruda K, Inokuchi N, Yanagihara K, Yamada Y. Aoyama M, Sawada T, Kamihira S.
  • Journal Title: Int J Lab Hematol (Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Inactivation of p14ARF as a key event for the progression of adult T cell leukemia/lymphoma (2007)
  • Author(s): Kohno T, Yamada Y, Tawara M, Takasaki Y, Kamihira S, Tomonaga M. Matsuyama T.
  • Journal Title: Leuk Res 31(12) Pages: 1625-32
  • Peer Reviewed
• [Journal Article] High IL-21 receptor expression and apoptosis induction by IL-21 in follicular lymphoma (2007)
  • Author(s): Akamatsu N, Yamada Y, Hasegawa H, Makabe K, Asano R, Kumagai I, Murata K, Imaizumi Y, Tsukasaki K, Tsuruda K, Sugahara K, Atogami S, Yanagihara K, Kamihira S.
  • Journal Title: Cancer Lett 256(2) Pages: 196-206
  • Peer Reviewed
• [Journal Article] A novel natural compound, a cycloanthranilylproline derivative (Fuligocandin B) (2007)
  • Author(s): Hasegawa H, Yamada Y, Komiyama K, Hayashi M, Ishibashi M, Sunazuka T, Izuhara T, Sugahara K, Tsuruda K, Masuda M, Takasu N, Tsukasaki K, Tomonaga M, Kamihira S.
  • Journal Title: sensitizes leukemia cells to apoptosis induced by tumor necrosis factor related apoptosis-inducing ligand (TRAIL) through 15-deoxy-Delta 12, 14 prostaglandin J2 production. Blood 110(5) Pages: 1664-74
  • Peer Reviewed
• [Journal Article] Rapid and high-resolution detection of IgH gene rearrangements using PCR and melting curve analysis (2007)
  • Author(s): Uemura A, Mori S, Sugahara K, Akamatsu N, Tsuruda K, Tsukasaki K, Hirakata Y, Atogami S, Hasegawa H, Yamada Y, Kamihira S.
  • Journal Title: Int J Lab Hematol 29(3) Pages: 200-7
  • Peer Reviewed
• [Journal Article] Primary T-cell lymphoma of the thyroid gland with chemokine receptors of Th1 phenotype complicating autoimmune thyroiditis (2007)
  • Author(s): Koida S, Tsukasaki K, Tsuchiya T, Harasawa H, Fukushima T, Yamada Y, Ohshima K, Kamihira S, Kikuchi M, Tomonaga M.
  • Journal Title: Haematologica 92(3) Pages: e37-40
  • Peer Reviewed
• [Journal Article] The possibility of a valuable resource of circulating DNA for single nucleotide polymorphisms genotyping: the application of a rapid and simple polymerase chain reaction with melting curve analysis for methyltetrahydrofolate reductase polymorphisms (2007)
  • Author(s): Mori S, Sugahara K, Uemura A, Yamada Y, Uzihara K, Hayashida H, Ideguchi T, Ishibashi K, Nakazato M, Maeda T, Takamura N, Kamihira S.
  • Journal Title: Lab Hematol 13(1) Pages: 1-5
  • Peer Reviewed
• [Journal Article] Impact of visceral involvements and blood cell count abnormalities on survival in adult T-cell leukemia/lymphoma (ATLL) (2007)
  • Author(s): Takasaki Y, Iwanaga M, Tsukasaki K, Kusano M, Sugahara K, Yamada Y, Kamihira S, Ikeda S, Tomonaga M.
  • Journal Title: Leuk Res 31(6) Pages: 751-7
  • Peer Reviewed
• [Journal Article] A genomic analysis of adult T-cell leukemia (2007)
  • Author(s): Choi YL, Tsukasaki K, O'Neill MC, Yamada Y, Onimaru Y, Matsumoto K, Ohashi J, Yamashita Y, Tsutsumi S, Kaneda R, Takada S, Aburatani H, Kamihira S, Nakamura T, Tomonaga M, Mano H.
  • Journal Title: Oncogene 26(8) Pages: 1245-55
  • Peer Reviewed
• [Journal Article] Survey of chemokine receptor expression reveals frequent co-expression of skin-homing CCR4 and CCR10 in adult T-cell leukemia/lymphoma (2006)
  • Author(s): Harasawa H, Yamada Y, Hieshima K, Jin Z, Nakayama T, Yoshie O, Shimizu K, Hasegawa H, Hayashi T, Imaizumi Y, Ikeda S, Soda H, Soda H, Atogami S, Takasaki Y, Tsukasaki K, Tomonaga M, Murata K, Sugahara K, Tsuruda K, Kamihira S.
  • Journal Title: Leuk Lymphoma 47(10) Pages: 2163-73
  • Peer Reviewed
• [Journal Article] A subtype of aggressive B-cell lymphoma with an unusual presentation of effusion without masses (2006)
  • Author(s): Kamihira S, Jiann C, Uemura A, Tsuruda K, Hasegawa H, Sugahara K, Yamada Y.
  • Journal Title: Leuk Lymphoma 47(9) Pages: 1991-3
  • Peer Reviewed
• [Journal Article] Endoscope disinfection using chlorine dioxide in an automated washer-disinfector (2006)
  • Author(s): Isomoto H, Urata M, Kawazoe K, Matsuda J, Nishi Y, Wada A, Ohnita K, Hirakata Y, Matsuo N, Inoue K, Hirayama T, Kamihira S, Kohno S.
  • Journal Title: J Hosp Infect 63(3) Pages: 298-305
  • Peer Reviewed
• [Journal Article] A novel alternative splicing isoform of human T-cell leukemia virus type 1 bZIP factor (HBZ-SI) targets distinct subnuclear localization (2006)
  • Author(s): Murata K, Hayashibara T, Sugahara K, Uemura A, Yamaguchi T, Harasawa H, Hasegawa H, Tsuruda K, Okazaki T, Koji T, Miyanishi T, Yamada Y, Kamihira S.
  • Journal Title: J Virol 80(5) Pages: 2495-505
  • Peer Reviewed
• [Journal Article] Comparative genomic hybridization analysis of Japanese B-cell chronic lymphocytic leukemia: correlation with clinical course (2006)
  • Author(s): Tsukasaki K, Lohr D, Sugahara K, Kamihira S, Tomonaga M, Bartram CR, Jauch A.
  • Journal Title: Leuk Lymphoma 47(2) Pages: 261-6
  • Peer Reviewed
• [Journal Article] Dihydroflavonol BB-1, an extract of natural plant Blumea balsamifera, abrogates TRAIL resistance in leukemia cells (2006)
  • Author(s): Hasegawa H, Yamada Y, Komiyama K, Hayashi M, Ishibashi M, Yoshida T, Sakai T, Koyano T, Kam TS, Murata K, Sugahara K, Tsuruda K, Akamatsu N, Tsukasaki K, Masuda M, Takasu N, Kamihira S.
  • Journal Title: Blood 107(2) Pages: 679-88
  • Peer Reviewed
• [Journal Article] Impact of p53 aberration on the progression of Adult T-cell Leukemia/Lymphoma (2006)
  • Author(s): Tawara M, Hogerzeil SJ, Yamada Y, Takasaki Y, Soda H, Hasegawa H, Murata K, Ikeda S, Imaizumi Y, Sugahara K, Tsuruda K, Tsukasaki K, Tomonaga M, Hirakata Y, Kamihira S.
  • Journal Title: Cancer Lett 234(2) Pages: 249-55
  • Peer Reviewed
• [Journal Article] Inactivation of tumor suppressor genes and the progression of adult T-cell leukemia-lymphoma (2005)
  • Author(s): Yamada Y, Kamihira S.
  • Journal Title: Leuk Lymphoma 46(11) Pages: 1553-9
  • Peer Reviewed
• [Journal Article] Usefulness of a comprehensive PCR-based assay for human herpes viral DNA in blood mononuclear cell samples (2005)
  • Author(s): Mori S, Sugahara K, Uemura A, Akamatsu N, Hirakata Y, Murata K, Hasegawa H, Yamada Y, Kamihira S.
  • Journal Title: Lab Hematol 11(3) Pages: 163-70
  • Peer Reviewed
• [Journal Article] Possible origin of adult T-cell leukemia/lymphoma cells from human T lymphotropic virus type-1-infected regulatory T cells (2005)
  • Author(s): Kohno T, Yamada Y, Akamatsu N, Kamihira S, Imaizumi Y, Tomonaga M, Matsuyama T.
  • Journal Title: Cancer Sci. 96(8) Pages: 527-33
  • Peer Reviewed
• [Journal Article] Proviral status of HTLV-1 integrated into the host genomic DNA of adult T-cell leukemia cells (2005)
  • Author(s): Kamihira S, Sugahara K, Tsuruda K, Minami S, Uemura A, Akamatsu N, Nagai H, Murata K, Hasegawa H, Hirakata Y, Takasaki Y, Tsukasaki K, Yamada Y.
  • Journal Title: Clin Lab Haematol 27(4) Pages: 235-41
  • Peer Reviewed
• [Journal Article] Dual targeting of transformed and untransformed HTLV-1-infected T cells by DHMEQ, a potent and selective inhibitor of NF-kappaB, as a strategy for chemoprevention and therapy of adult T-cell leukemia (2005)
  • Author(s): Watanabe M, Ohsugi T, Shoda M, Ishida T, Aizawa S, Maruyama-Nagai M, Utsunomiya A, Koga S, Yamada Y, Kamihira S, Okayama A, Kikuchi H, Uozumi K, Yamaguchi K, Higashihara M, Umezawa K, Watanabe T, Horie R.
  • Journal Title: Blood 106(7) Pages: 2462-71
  • Peer Reviewed
• [Journal Article] An ATL cell line with an IgH pseudo-rearranged band pattern by southern blotting: a pitfall of genetic diagnosis (2005)
  • Author(s): Uemura A, Sugahara K, Nagai H, Murata K, Hasegawa H, Hirakata Y, Tsukasaki K, Yamada Y, Kamihira S.
  • Journal Title: Lab Hematol 11(1) Pages: 8-13
  • Peer Reviewed
• [Journal Article] A novel plasmacytoid dendritic cell line, CAL-1, established from a patient with blastic natural killer cell lymphoma (2005)
  • Author(s): Maeda T, Murata K, Fukushima T, Sugahara K, Tsuruda K, Anami M, Onimaru Y, Tsukasaki K, Tomonaga M, Moriuchi R, Hasegawa H, Yamada Y, Kamihira S.
  • Journal Title: Int J Hematol 81(2) Pages: 148-54
  • Peer Reviewed
• [Journal Article] Kusunoki M, Nobori T. Methylthioadenosine phosphorylase gene is silenced by promoter hypermethylation in human lymphoma cell line DHL-9 : another mechanism of enzyme deficiency (2005)
  • Author(s): Ishii M, Nakazawa K, Wada H, Nishioka J, Nakatani K, Yamada Y, Kamihira S.
  • Journal Title: Int J Oncol 26(4) Pages: 985-91
  • Peer Reviewed
• [Journal Article] Sensitivity of adult T-cell leukaemia lymphoma cells to tumour necrosis factor-related apoptosis-inducing ligand (2005)
  • Author(s): Hasegawa H, Yamada Y, Harasawa H, Tsuji T, Murata K, Sugahara K, Tsuruda K, Ikeda S, Imaizumi Y, Tomonaga M, Masuda M, Takasu N, Kamihira S
  • Journal Title: Br J Haematol 128(2) Pages: 253-65
  • Peer Reviewed
• [Journal Article] Restricted expression of tumor necrosis factor-related apoptosis-inducing ligand receptor 4 in human peripheral blood lymphocytes (2004)
  • Author(s): Hasegawa H, Yamada Y, Harasawa H, Tsuji T, Murata K, Sugahara K, Tsuruda K, Masuda M, Takasu N, Kamihira S.
  • Journal Title: Cell Immunol 231(1-2) Pages: 1-7
  • Peer Reviewed
• [Presentation] ATL cell biology (2007)
  • Author(s): Kamihira S.
  • Organizer: 3th International Coferance on Human retrovirology -HTLV-1 and Related Viruses
  • Place of Presentation: Hakone
  • Year and Date: 20070522-27
• [Presentation] Nutlin-3a an MDM2 antagonist (2006)
  • Author(s): Hasegawa H, Kamihira S. et.al.
  • Organizer: induces cellular senescence in ATL cells : Blood 2006 : 108 Supple)
  • Place of Presentation: Orland, Florida, USA
  • Year and Date: 20061009-12
• [Presentation] Molecularallelo-karyotyping of ATL usng high SNP genotyping misroarrays (2006)
  • Author(s): Muto s, Kamihira S, et.al.
  • Organizer: ASH
  • Place of Presentation: Orland, Florida, USA
  • Year and Date: 20061009-12
• [Presentation] Trend in Prevalence of HTLV-1 in Japanese blood donors, Nagasaki 1999 to 2006 (2006)
  • Author(s): Iwanaga M, Kamihira S. et.al.
  • Organizer: ASH
  • Place of Presentation: Orland, Florida, USA
  • Year and Date: 20061009-12
• [Presentation] A long-term study on indolent ATL (2006)
  • Author(s): Takasaki U, Kamihira S. et.al.
  • Organizer: ASH
  • Place of Presentation: Orland, Florida, USA
  • Year and Date: 20061009-12
• [Book] HTLV-1と疾患 (2007)
  • Author(s): 上平憲, 渡邊俊樹、山口一成
  • Publisher: 文光堂
• [Book] スタンダ-ド検査血液学(B.白血球検査 ) (2007)
  • Author(s): 上平憲
  • Publisher: 医歯薬出版
• [Patent(Industrial Property Rights)] 癌の浸潤と転移の検査方法および検査用試薬 (2008)
  • Inventor(s): 尾坂明美, 上平憲, 沢田高志
  • Industrial Property Rights Holder: 長崎大学
  • Industrial Property Number: 技術分野, 2008-60050
  • Filing Date: 2008-03-10
• [Patent(Industrial Property Rights)] 新規ヒト形質細胞様樹状細胞株 (2005)
  • Inventor(s): 前田隆浩・上平憲
  • Industrial Property Rights Holder: 長崎大学
  • Industrial Property Number: 2007-44008(P2007-44008A)
  • Filing Date: 2005-08-12