Elucidation of molecular mechanism of hematological malignancies associated with persistent viral infection

• Project/Area Number: 26461423
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kochi University
• Principal Investigator: DAIBATA Masanori 高知大学, 教育研究部医療学系基礎医学部門, 教授 (50263976)
• Co-Investigator(Kenkyū-buntansha): 村上 雅尚 高知学園短期大学, その他部局等, 准教授(移行) (80571017)
• Co-Investigator(Renkei-kenkyūsha): TAKEUCHI Hiroaki 高知大学, 教育研究部医療学系臨床医学部門, 講師 (90346560)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: リンパ腫 / ウイルス / 感染 / 炎症 / 癌 / 造血器腫瘍 / 感染症 / 微生物

Outline of Final Research Achievements

We aimed to find candidate genes associated with pathogenesis of malignant lymphomas in the context of chronic inflammation and viral infection. Pyothorax-associated lymphoma (PAL) develops in patients with a long-standing pyothorax caused by an artificial pneumothorax created for previous treatment of pulmonary tuberculosis. The most striking feature of this lymphoma is that the Epstein-Barr virus (EBV) genome is present in the lymphoma cells of all cases. Thus, PAL is representative of lymphoma associated with viral infection and chronic inflammation. Our PCR array analysis identified several upregulated genes in PAL cells compared with other EBV-negative lymphoma cells. The upregulated genes included genes encoding cytokines and chemokines/chemokine receptors, such as IL12a and CCL4/CCR5, and genes involved in signaling pathways that are associated with cell proliferation. These genes may be potential therapeutic targets for lymphomas associated with chronic inflammation.

Research Products

• [Journal Article] Monitoring of Epstein-Barr virus load and killer T cells in patients with juvenile idiopathic arthritis treated with methotrexate or tocilizumab. (2017)
  • Author(s): Mikiya Fujieda, Kazushi Tsuruga, Tetsuya Sato, Hiroaki Kikuchi, Wataru Tamaki, Masayuki Ishihara, Masaki Yamamoto, Taku Oishi, Hiroshi Tanaka, Masanori Daibata.
  • Journal Title: Modern Rheumatology Volume: 27 Issue: 1 Pages: 66-71
  • DOI: 10.1080/14397595.2016.1177247
  • Peer Reviewed
• [Journal Article] Establishment and characterization of a novel Hodgkin lymphoma cell line, AM-HLH, carrying the Epstein-Barr virus genome integrated into the host chromosome. (2017)
  • Author(s): Masahiko Hayashida, Masanori Daibata, Erika Tagami, Takahiro Taguchi, Fumiyo Maekawa, Katsuhiro Fukutsuka, Takamasa Hayashi, Yoshinori Iwatani, Hitoshi Ohno.
  • Journal Title: Hematological Oncology Volume: 印刷中 Issue: 4 Pages: 567-575
  • DOI: 10.1002/hon.2369
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] High load of Merkel cell polyomavirus DNA detected in the normal skin of Japanese patients with Merkel cell carcinoma. (2016)
  • Author(s): Yumiko Hashida, Kimiko Nakajima, Hideki Nakajima, Takeo Shiga, Moe Tanaka, Masanao Murakami, Shigenobu Matsuzaki, Seiji Naganuma, Naoki Kuroda, Yasutaka Seki, Harutaka Katano, Shigetoshi Sano, Masanori Daibata.
  • Journal Title: Journal of Clinical Virology Volume: 82 Pages: 101-107
  • DOI: 10.1016/j.jcv.2016.07.011
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ecology of Merkel Cell Polyomavirus in Healthy Skin Among Individuals in an Asian Cohort (2016)
  • Author(s): Hashida Y, Kamioka M, Tanaka M, Hosokawa S, Murakami M, Nakajima K, Kikuchi H, Fujieda M, Sano S, Daibata M
  • Journal Title: J Infect Dis Volume: 213(11) Issue: 11 Pages: 1708-1716
  • DOI: 10.1093/infdis/jiw040
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Characterization of Pseudomonas aeruginosa phage KPP21 belonging to family Podoviridae genus N4-like viruses isolated in Japan (2016)
  • Author(s): Shigehisa, R., Uchiyama, J., Kato S, Takemura-Uchiyama, I, Yamaguchi, K., Miyata, R., Ujihara, T., Sakaguchi, Y., Okamoto, N., Shimakura, H., Daibata, M., Sakaguchi, M., and Matsuzaki, S.
  • Journal Title: Microbiology and Immunology Volume: 60 Issue: 1 Pages: 64-67
  • DOI: 10.1111/1348-0421.12347
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epstein-Barr virus-positive pyothorax-associated lymphoma arising from a posttraumatic empyema. (2015)
  • Author(s): Ayuko Taniguchi, Yumiko Hashida, Yuiko Nemoto, Hisanori Machida, SungGi Chi, Takayuki Ikezoe, Akihito Yokoyama, Masanori Daibata
  • Journal Title: Acta Haematologica Volume: 134 Issue: 3 Pages: 155-160
  • DOI: 10.1159/000380809
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Concurrent Merkel cell carcinoma and squamous cell carcinoma in a chest nodule. (2015)
  • Author(s): Misaki Takahashi, Hidetsugu Fukuda, Yuki Yokouchi, Yumiko Hashida, Masanori Daibata, Hideki Mukai.
  • Journal Title: European Journal of Dermatology Volume: 25 Issue: 5 Pages: 492-494
  • DOI: 10.1684/ejd.2015.2607
  • Peer Reviewed
• [Journal Article] Prevalence of human cytomegalovirus, polyomaviruses, and oncogenic viruses in glioblastoma among Japanese subjects. (2015)
  • Author(s): Yumiko Hashida, Ayuko Taniguchi, Toshio Yawata, Sena Hosokawa, Masanao Murakami, Makoto Hiroi, Tetsuya Ueba, Masanori Daibata.
  • Journal Title: Infectious Agents and Cancer. Volume: 10 Issue: 1 Pages: 3-3
  • DOI: 10.1186/1750-9378-10-3
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] PCR array analysis of gene expressi on profiles in chronic active Epste in-Barr virus infection (2014)
  • Author(s): Murakami M, Hashida Y, Imajoh M, Ma eda A, Kamioka M, Senda Y, Sato T, Fujieda M, Wakiguchi H, Daibata M
  • Journal Title: Microbes a nd Infection Volume: (掲載決定) Issue: 7 Pages: 581-586
  • DOI: 10.1016/j.micinf.2014.04.004
  • Peer Reviewed
• [Journal Article] Considerations on the link between Merkel cell polyomavirus and lung cancer. (2014)
  • Author(s): Yumiko Hashida, Masanori Daibata.
  • Journal Title: Lung Cancer Management. Volume: 3 Pages: 297-299
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Epidemiological study of Merkel cell polyomavirus in healthy skin among healthy individuals in Japan. (2016)
  • Author(s): Yumiko Hashida, Moe Tanaka, Masanao Murakami, Shigenobu Matsuzaki, Masanori Daibata.
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2016-10-23
• [Presentation] Phylogenetic analysis of Merkel cell polyomavirus based on full-length LT and VP1 sequences derived from normal skin of healthy individuals. (2016)
  • Author(s): Moe Tanaka, Yumiko Hashida, Masanao Murakami, Shigenobu Matsuzaki, Masanori Daibata.
  • Organizer: 第64回日本ウイルス学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2016-10-23
• [Presentation] Ecology of Merkel cell polyomavirus in healthy skin among individuals in an Asian cohort shows close agreement with IL-1 loop model in langerhans cell histiocytosis. (2016)
  • Author(s): Ichiro Murakami, Junko Nakashima, Yumiko Hashida, Masanori Daibata, Michiko Matsushita,Takeshi Iwasaki, Satoshi Kuwamoto, Masako Kato, Keiko Nagata, Kazuhiko Hayashi, Takashi Oka, Tadashi Yoshino, Toshihiko Imamura, Akira Morimoto, Shinsaku Imashuku, Jean Gogusev, Francis Jaubert.
  • Organizer: 32nd Annual Meeting of the Histiocyte Society
  • Place of Presentation: Dublin (Ireland)
  • Year and Date: 2016-10-17
  • Int'l Joint Research
• [Presentation] High burden of Merkel cell polyomavirus DNA in the nonlesional, sun-exposed skin of patients with Merkel cell carcinoma. (2016)
  • Author(s): Kimiko Nakajima, Yumiko Hashida, Hideki Nakajima, Takeo Shiga, Masanori Daibata, Shigetoshi Sano.
  • Organizer: 46th Annual European Society of Dermatological Research (ESDR) meeting
  • Place of Presentation: Munich (Germany)
  • Year and Date: 2016-09-07
  • Int'l Joint Research
• [Presentation] 膠芽腫におけるウイルス感染 (2016)
  • Author(s): 上岡樹生、橋田裕美子、大畑雅典、松村敬久
  • Organizer: 第32回世界医学検査学会、第65回日本医学検査学会
  • Place of Presentation: 神戸国際会議場（兵庫県・神戸市）
  • Year and Date: 2016-09-01
• [Presentation] EBウイルスゲノムが染色体にインテグレイトされたホジキンリンパ腫細胞株AM-HLHの樹立 (2016)
  • Author(s): 林田雅彦、竹岡加陽、福塚勝弘、大野仁、林孝昌、田上恵里香、田口尚弘、大畑雅典
  • Organizer: 第56回日本リンパ網内系学会総会
  • Place of Presentation: ホテル日航熊本・くまもと県民交流館パレア（熊本県・熊本市）
  • Year and Date: 2016-09-01
• [Presentation] High burden of Merkel cell polyomavirus DNA in the sun-exposed skin of elder adults. (2016)
  • Author(s): Kimiko Nakajima, Yumiko Hashida, Yuka Shibata, Takeo Shiga, Hideki Nakajima, Masanori Daibata, Shigetoshi Sano.
  • Organizer: Asia-Pacific Combined Dermatology Research Conference
  • Place of Presentation: Noosa (Australia)
  • Year and Date: 2016-08-25
  • Int'l Joint Research
• [Presentation] Mycobacterium smegmatisに感染するバクテリオファージの形態学的解析(Morphological characterization of Mycobacterium smegmatis bacteriophages) (2016)
  • Author(s): 氏原隆子、大原直也、谷口初美、山崎利雄、大畑雅典、松崎茂展
  • Organizer: 第89回日本細菌学会総会
  • Place of Presentation: 大阪国際交流センター（大阪府・大阪市）
  • Year and Date: 2016-03-23
• [Presentation] Virus infection in glioblastoma multiforme (GBM): Possible association of human papillomavirus with pathogenesis of GBM. (2015)
  • Author(s): Yumiko Hashida, Ayuko Taniguchi, Toshio Yawata, Sena Hosokawa, Moe Tanaka, Masanao Murakami, Mikio Kamioka, Makoto Hiroi, Tetsuya Ueba, and Masanori Daibata.
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場(福岡県・福岡市）
  • Year and Date: 2015-11-22
• [Presentation] 非小細胞肺癌発症におけるメルケル細胞ポリオーマウイルスの関与 (2015)
  • Author(s): 上岡樹生、橋田裕美子、松村敬久、大畑雅典、杉浦哲朗
  • Organizer: 第62回日本臨床検査医学会学術集会
  • Place of Presentation: 長良川国際会議場・岐阜都ホテル(岐阜県・岐阜市）
  • Year and Date: 2015-11-19
• [Presentation] 若年性特発性関節炎（JIA）における治療とEBウイルス（EBV）動態について (2015)
  • Author(s): 佐藤哲也、石原正行、藤枝幹也、敦賀和志、大畑雅典
  • Organizer: 第47回日本小児感染症学会総会・学術集会
  • Place of Presentation: ザ・セレクトン福島、ホテル福島グリーンパレス、コラッセふくしま(福島県・福島市）
  • Year and Date: 2015-10-31
• [Presentation] 若年性特発性関節炎（JIA）におけるEpstein- Barr virus (EBV) 動態について (2015)
  • Author(s): 石原正行、佐藤哲也、敦賀和志、田中 完、大畑雅典、藤枝幹也
  • Organizer: 第25回日本小児リウマチ学会総会・学術集会
  • Place of Presentation: 金沢歌劇座（石川県・金沢市）
  • Year and Date: 2015-10-09
• [Presentation] Nm23-H1 regulates cell migration via interaction with Asef1 and Asef2. (2015)
  • Author(s): Masanao Murakami, Yumiko Hashida, Mikio Kamioka, Yoshihiro Kawasaki, Kazuyosi Yanagihara, Shigetoshi Matsuzasi, Tetsu Akiyama, and Masanori Daibata.
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（愛知県・名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] Mycobacterium smegmatisバクテリオファージの長期保存状態における生存率 (2015)
  • Author(s): 松崎茂展、大原直也、谷口初美、山崎利雄、氏原隆子、村上雅尚、大畑雅典
  • Organizer: 第68回日本細菌学会中国・四国支部総会
  • Place of Presentation: 岡山大学（岡山県・岡山市）
  • Year and Date: 2015-10-03
• [Presentation] 膠芽腫におけるウイルス感染の調査 (2014)
  • Author(s): 橋田裕美子、八幡俊男、村上雅尚、谷口亜裕子、上岡樹生、上羽哲也、大畑雅典
  • Organizer: 日本ウイルス学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県・横浜市）
  • Year and Date: 2014-11-10 – 2014-11-12
• [Presentation] Adult T-cell Leukemia/Lymphoma cells identified by flow cytometry and HTLV-1 proviral load. (2014)
  • Author(s): Mika Teraishi, Sayo Kataoka, Masanao Murakami, Masanori Daibata, Shigetoshi Sano.
  • Organizer: Eastern Asia Dermatology Congress
  • Place of Presentation: Jeju International Convention Center, Jeju (Korea)
  • Year and Date: 2014-09-24 – 2014-09-26
• [Presentation] PCR array analysis of gene expression profiles in chronic active Epstein-Barr virus infection. (2014)
  • Author(s): Masanao Murakami, Yumiko Hashida, Masayuki Imajoh, Akihiko Maeda, Mikio Kamioka, Yasutaka Senda, Tetsuya Sato, Mikiya Fujieda, Hiroshi Wakiguchi, Masanori Daibata.
  • Organizer: International Herpesvirus Workshop
  • Place of Presentation: Kobe Convention Center, Kobe (Japan)
  • Year and Date: 2014-07-19 – 2014-07-23
• [Book] ＥＢウイルスが関与するホジキンリンパ腫（血液フロンティア ホジキンリンパ腫） (2016)
  • Author(s): 谷口亜裕子、大畑雅典
  • Total Pages: 148
  • Publisher: 医薬ジャーナル社
• [Book] マイクロバイオームとウイローム：バクテリオファージ療法（臨床と微生物） (2015)
  • Author(s): 松崎茂展、氏原隆子、村上雅尚、大畑雅典
  • Total Pages: 96
  • Publisher: 近代出版
• [Remarks] http://www.kochi-ms.ac.jp/~ff_mcrbi/index.html