The role of HIF-1a in the development of lymphoproliferative diseases in transgenic mouse model

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591393
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Saga University
• Principal Investigator: SUEOKA Eizaburo 佐賀大学, 医学部, 教授 (00270603)
• Co-Investigator(Kenkyū-buntansha): ARAGANE Naoko 佐賀大学, 医学部, 講師 (20321846)
• Co-Investigator(Renkei-kenkyūsha): IDE Masaru 佐賀大学, 医学部, 助教 (00398124)
• Project Period (FY): 2011 – 2013
• Keywords: 低酸素応答 / HIF-1 / リンパ腫 / 造血幹細胞 / がん幹細胞 / 薬剤耐性

Research Abstract

Hypoxia-inducible factor-1alfa (HIF-1 alfa) plays an important role in the induction of various genes under hypoxic condition. We investigate the role of HIF-1 alfa in tumor development and metastasis, and established transgenic mice constitutively expressing HIF-1A gene under regulation of the cytomegalovirus gene promoter. HIF-1 alfa protein levels varied among organs, but the expression of HIF-1 alfa mRNA gradually increased in an age-dependent manner. The transgenic mice developed tumors in the lymphoid, lung, and breast; the most prominent tumor was lymphoma appearing in the intestinal mucosa and intra-mesenchymal tissues. The lymphocytes of the transgenic mice revealed prolonged survival under long-term culture conditions and revealed increased resistance to cytotoxic drugs. These results suggest that HIF-1 alfa play an important role in lymphomagenesis mediated through the prolonged survival of lymphocytes in this transgenic mouse model.

Research Products

• [Journal Article] Therapeutic management in cardiac lymphoma (2014)
  • Author(s): Yoshihara M, Itamura H, Fukushima N, Itoh M, Furukawa K, Nagatomo D, Kamachi K, Kitamura H, Shindo T, Kubota Y, Sueoka E, Morita S, Ichinohe T, Kimura S
  • Journal Title: Leuk Lymphoma Volume: 55 Pages: 1215-7
  • Peer Reviewed
• [Journal Article] 電子カルテと輸血管理システムの連携による輸血後鉄過剰症モニタリングプログラムの運用とその課題 (2014)
  • Author(s): 末岡榮三朗、山田尚友、山田麻里江、久保田寧、吉村麻里子、板村英和、出勝、横尾眞子、吉原麻里、蒲池和晴、北村浩晃、進藤岳郎、安藤寿彦、小島研介、東谷孝徳、木村晋也
  • Journal Title: 日本輸血細胞治療学会誌 Volume: 60 Pages: 12-17
  • Peer Reviewed
• [Journal Article] 抗M(IgM+IgG)において抗体価測定時に反応増強剤無添加間接抗グロブリン試験で一部陰性を示した妊婦の1例 (2014)
  • Author(s): 山田麻里江、山田尚友、久保田寧、木村晋也、東谷孝徳、末岡榮三朗
  • Journal Title: 日本輸血細胞治療学会誌 Volume: 60 Pages: 32-37
  • Peer Reviewed
• [Journal Article] Direct identification method for bacteria in positive blood culture bottles using MALDI biotyper (2013)
  • Author(s): Uki N, Oho M, Nagasawa Z, Higashitani T, Ohta S, Sueoka E, Miyamoto H
  • Journal Title: Rinsho Byori Volume: 61(3) Pages: 224-30
  • Peer Reviewed
• [Journal Article] Tumor promoters : from chemicals to inflammatory proteins (2013)
  • Author(s): Fujiki H, Sueoka E, Suganuma M
  • Journal Title: J Cancer Res Clin Oncol Volume: 139(10) Pages: 1603-14
  • Peer Reviewed
• [Journal Article] Development of lymphoproliferative diseases by hypoxia inducible factor-1alpha is associated with prolonged lymphocyte survival (2013)
  • Author(s): Sueoka E , Sueoka-Aragane N, Sato A, Ide M, Nakamura H, Sotomaru Y, Taya C, Yonekawa H, Kitagawa T, Kubota Y, Kimura S, Nakachi K, Tanimoto K
  • Journal Title: PLoS One Volume: 8(4) Pages: e57833
  • Peer Reviewed
• [Journal Article] 輸血後鉄過剰症の現状と問題点 (2013)
  • Author(s): 末岡榮三朗、山田尚友、山田麻里江、久保田寧、浦田千紗子、吉村麻里子、板村英和、久富崇、福島伯泰、出勝、横尾眞子、吉原麻里、蒲池和晴、北村浩晃、進藤岳郎、一戸辰夫、東谷孝徳、木村晋也
  • Journal Title: 日本輸血細胞治療学会誌 Volume: 59 Pages: 73-78
  • Peer Reviewed
• [Journal Article] Platelets with a W127X mutation in GPIX express sufficient residual amounts of GPIbαto support adhesion to von Willebrand factor and collagen (2012)
  • Author(s): Takata Y, Kanaji T, Moroi M, Seki R, Sano M, Nakazato S, Sueoka E, Imamura Y, Okamura T
  • Journal Title: Int J Hematol Volume: 96 Pages: 733-42
  • Peer Reviewed
• [Journal Article] Prognostic index for acute- and lymphoma-type adult T-cell leukemia/lymphoma (2012)
  • Author(s): Katsuya H, Yamanaka T, Ishitsuka K, Utsunomiya A, Sasaki H, Hanada S, Eto T, Moriuchi Y, Saburi Y, Miyahara M, Sueoka E, Uike N, Yoshida S, Yamashita K, Tsukasaki K, Suzushima H, Ohno Y, Matsuoka H, Jo T, Suzumiya J, Tamura K
  • Journal Title: J Clin Oncol Volume: 30 Pages: 1635-40
  • Peer Reviewed
• [Journal Article] Successful reduced-intensity umbilical cord blood transplant for fulminant hemophagocytic syndrome in an adult with pre-existing rheumatoid arthritis and autoimmune hemolytic anemia (2012)
  • Author(s): Itamura H, Fukushima N, Kondo S, Urata C, Tanaka-Yoshimura M, Yokoo M, Ide M, Hisatomi T, Kubota Y, Sueoka E, Ichinohe T, Kimura S
  • Journal Title: Leuk Lymphoma Volume: 53 Pages: 2307-9
  • Peer Reviewed
• [Journal Article] Co-existence of positive MET FISH status with EGFR mutations signifies poor prognosis in lung adenocarcinoma patients (2012)
  • Author(s): Tanaka A, Sueoka-Aragane N, Nakamura T, Takeda Y, Mitsuoka M, Yamasaki F, Hayashi S, Sueoka E, Kimura S
  • Journal Title: Lung Cancer Volume: 75 Pages: 89-94
  • Peer Reviewed
• [Journal Article] Phase II study of SMILE chemotherapy for newly-diagnosed stage IV, relapsed or refractory extranodal NK/T-cell lymphoma, nasal type : the NK-cell Tumor Study Group (NKTSG) study (2011)
  • Author(s): Yamaguchi M, Kwong Y, Kim K, Maeda Y, Hashimoto C, Suh C, Izutsu K, Ishida F, Isobe Y, Sueoka E, Suzumiya J, Kodama T, Kimura H, Hyo R, Nakamura S, Oshimi K, Suzuki R
  • Journal Title: J Clin Oncol Volume: 29 Pages: 4410-6
  • Peer Reviewed
• [Journal Article] Influences of %T>MIC achievement probability due to the difference of the MIC measurement concentration range-analysis of meropenem for Pseudomonas aeruginosa (2011)
  • Author(s): Nagasawa Z, Nakashima Y, Fukutomi Y, Uki N, Kusaba K, Nagumo F, Ohta S, Sueoka E, Miyamoto H
  • Journal Title: Rinsho Biseibutshu Jinsoku Shindan Kenkyukai Shi Volume: 22 Pages: 11-22
  • Peer Reviewed
• [Journal Article] Clinical presentation and outcome in patients of over 75 years old with malignant lymphoma (2011)
  • Author(s): Fukushima N, Itamura H, Urata C, Tanaka M, Hisatomi T, Kunota Y, Sueoka E, Kimura S
  • Journal Title: Int J Clin Med Volume: 2 Pages: 246-253
  • Peer Reviewed
• [Journal Article] Lenalidomide in combination with dexamethasone induced rhabdomyolysis in a multiple myeloma patient treated with pravastatin (2011)
  • Author(s): Urata C, Yoshimura M, Itamura H, Hisatomi T, Kubota Y, Fukushima N, Sueoka E, Kimura S
  • Journal Title: Int J Hematol Volume: 94 Pages: 216-7
• [Journal Article] A non-invasive system for monitoring resistance to EGFR tyrosine kinase inhibitors with plasma DNA (2011)
  • Author(s): Nakamura T, Sueoka-Aragane N, Iwanaga K, Sato A, Komiya K, Abe T, Ureshino U, Hayashi S, Hosomi, Hirai M, Sueoka E, Kimura S
  • Journal Title: J Thorac Oncol Volume: 6 Pages: 1639-48
  • Peer Reviewed
• [Journal Article] A fully integrated, automated and rapid detection system for KRAS mutations (2011)
  • Author(s): Ureshino N, Sueoka-Aragane N, Nakamura T, Sato A, Komiya K, Iwanaga K, Mitsuoka M, Takeda Y, Hayashi S, Sueoka E, Kimura S
  • Journal Title: Oncol Rep Volume: 26 Pages: 609-13
  • Peer Reviewed
• [Journal Article] A fully integrated and automated detection system for single nucleotide polymorphisms of UGT1A1 and CYP2C19 (2011)
  • Author(s): Ureshino N, Aragane N, Nakamura T, Ide M, Mochinaga S, Fukushima N, Hayashi S, Sueoka E, Kimura S
  • Journal Title: Oncol Res Volume: 19 Pages: 111-4
  • Peer Reviewed
• [Journal Article] NK314 potentiates anti-tumor activity with adult T-cell leukemia-lymphoma cells by inhibition of dual targets on topoisomerase IIa and DNA-dependent protein kinase (2011)
  • Author(s): Hisatomi T, Sueoka-Aragane N, Sato A, Tomimasu R, Ide M, Kurimasa A, Okamoto K, Kimura S, Sueoka E
  • Journal Title: Blood Volume: 117 Pages: 3575-84
  • Peer Reviewed
• [Presentation] 低酸素応答遺伝子HIF-1αによる腫瘍原性と造血幹細胞への作用 (2013)
  • Author(s): 末岡榮三朗、出勝、荒金尚子、佐藤明美、久保田寧、木村晋也、谷本圭司
  • Organizer: がんとハイポキシア研究会
  • Year and Date: 20131211-13
• [Presentation] HTLV-1ウイルス関連疾患診療ネットワーク構築のための佐賀県における総合的な取り組み (2013)
  • Author(s): 末岡榮三朗、柘植薫、福島伯泰、久保田寧、吉原麻里、蒲池和晴、北村浩晃、板村英和、吉村麻里子、進藤岳郎、安藤寿彦、出勝、横尾眞子、一戸辰夫、木村晋也
  • Organizer: 第75回日本血液学会総会
  • Year and Date: 20130911-13
• [Presentation] Deferasirox in iron-overloaded patients with hematologic disease at Saga University Hospital (2013)
  • Author(s): Abe O, Yoshihara M, Kubota Y, Sueoak E, Kamachi K, Kitamura H, Itamura H, Nishi M, Shindo T, Fukushima N, Hamasaki Y, Kimura S
  • Organizer: 第75回日本血液学会総会
  • Year and Date: 20130911-13
• [Presentation] 10 cases of Mogamulizumab treatment for Adult T cell Leukemia in Saga prefecture (2013)
  • Author(s): Ureshino H, Miyahara M, Kamachi K, Yoshihara M, Kitamura H, Itamura H, Yoshimura M, Yokoo M, Ide M, Kubota Y, Shindo T, Fukushima N, Sueoka E, Kimura S
  • Organizer: 第75回日本血液学会総会
  • Year and Date: 20130911-13
• [Presentation] Quenching probe法を用いたBRAF遺伝子変異検出システムの確立と本邦悪性黒色腫におけるBRAF変異の臨床的特徴 (2013)
  • Author(s): 出勝、荒金尚子、佐藤明美、木村晋也、末岡榮三朗
  • Organizer: 第17回日本がん分子標的治療学会学術集会
  • Year and Date: 20130612-14
• [Presentation] NOJ/SCIDマウスを用いたヒト肺がん転移モデルの確立 (2013)
  • Author(s): 佐藤明美、荒金尚子、小林直美、出勝、横尾眞子、末岡榮三朗、岡田誠治、木村晋也
  • Organizer: 第17回日本がん分子標的治療学会学術集会
  • Year and Date: 20130612-14
• [Presentation] Establishment of automated monitoring program for transfusional iron overload using electronic medical recording system (2013)
  • Author(s): Eisaburo, Sueoka.; Naotomo, Yamada.; Marie, Yamada.; Yasushi, Kubota.; Shinya, Kimura
  • Organizer: EUROMEDLAB Milano 2013
  • Year and Date: 20130519-22
• [Presentation] Establishment of a rapid and automated detection system for BRAF mutations in malignant melanoma (2013)
  • Author(s): Masaru Ide, Shinichi Koba, Yumi Nagano, Naoko Aragane-Sueoka, Akemi Sato, Takuya Inoue, Naomi Kobayashi, Noriyuki Misago, Yutaka Narisawa,Shinya Kimura, Eisaburo Sueoka
  • Organizer: AACR Annual Meeting 2013
  • Year and Date: 20130406-10
• [Presentation] Development of animal model mimicking metastasis of human lung cancers using NOJ/SCID mice (2013)
  • Author(s): Naoko Sueoka-Aragane, Akemi Sato, Naomi Kobayashi, Masaru Ide, Eisaburo Sueoka, Seiji Okada, Shinya Kimura
  • Organizer: AACR Annual Meeting 2013
  • Year and Date: 20130406-10
• [Presentation] 医療現場の隙間をうめる部門システムと電子カルテの連携‐佐賀大方式輸血後鉄過剰症モニタリングプログラムの開発‐ (2013)
  • Author(s): 末岡榮三朗、山田尚友、山田麻里江、東谷孝則、木村晋也
  • Organizer: 平成24年度大学病院情報マネージメント部門連絡会議
  • Year and Date: 20130207-08
• [Presentation] 迅速診断法によるメラノーマにおけるBRAF変異の解析 (2012)
  • Author(s): 出勝、古場慎一、長野由美、荒金尚子、佐藤明美、三砂範幸、成澤寛、木村晋也、末岡榮三朗
  • Organizer: 第44回日本臨床検査自動化学会
  • Year and Date: 20121012-13
• [Presentation] レクチンアレイを用いたATL細胞に発現するグリカンのプロファイリング (2012)
  • Author(s): 伊波英克、池辺詠美、手塚健太、藤澤順一、田中勇悦、末岡榮三朗、森下和弘、堀光雄
  • Organizer: 第71回日本癌学会総会
  • Year and Date: 20120919-21
• [Presentation] 耐性原因マーカーのモニタリングによるテーラーメイド治療 (2012)
  • Author(s): 荒金尚子、中村朝美、岩永健太郎、小宮一利、末岡榮三朗、木村晋也
  • Organizer: 日本分子標的治療学会
  • Year and Date: 2012-06-27
• [Presentation] 血漿DNAを用いた非侵襲的EGFR遺伝子変異モニタリングシステムの確立 (2012)
  • Author(s): 中村朝美、荒金尚子、岩永健太郎、末岡榮三朗、木村晋也
  • Organizer: 日本分子標的治療学会
  • Year and Date: 2012-06-27
• [Presentation] Overexpression of hnRNP B1 inhibits DNA repair by interaction with DNA-dependent protein kinase complex in adult T-cell leukemia (2011)
  • Author(s): Sueoka E, Hisatomi T, Sueoka-Aragane N, Sato A, Tomimasu R, Ide M, Kimura S
  • Organizer: 25th International Symposium of the International Association for Comparative Research on Leukemia and Related Diseases
  • Year and Date: 20110915-17
• [Presentation] DNA-dependent protein kinase as a promising molecular target for the treatment of adult T-cell leukemia-lymphoma (2011)
  • Author(s): Hisatomi T, Sueoka-Aragane N, Sato A, Tomimasu R, Ide M, Kunimasa A, Okamoto K, Kimura S, Sueoka E
  • Organizer: The 16th European Hematology Association Congress
  • Year and Date: 20110609-12
• [Presentation] Development of New Methods for Detecting Circular Nucleic Acids as Cancer Biomarkers in Lung Cancer Patients (2011)
  • Author(s): Sueoka E, Sueoka-Aragane N, Sato A, Nakamura T, Iwanaga K and Kimura S
  • Organizer: IIFCC WorrlldLab EurroMedLab Berrlliin 2011
  • Year and Date: 20110516-19
• [Presentation] Gene regulation induced by constitutive expression of HIF-1αin transgenic mice (2011)
  • Author(s): Ide M, Sueoka-Aragane N, Sato A, Nakamura T, Yokoo M, Kimura S, Tanimoto K, Sueoka E
  • Organizer: AACR 102nd Annual Meeting
  • Year and Date: 20110402-06
• [Presentation] A non-invasive system for monitoring resistance to EGFR tyrosine kinase inhibitors with plasma DNA in lung cancer patients (2011)
  • Author(s): Sueoka-Aragane N, Nakamura T, Iwanaga K, Sato A, Komiya K, Abe T, Ureshino N, Hayashi S, Hosomi T, Hirai M, Sueoka E, Kimura S
  • Organizer: AACR 102nd Annual Meeting
  • Year and Date: 20110402-06
• [Remarks]
  • URL: http://www.intmed.med.saga-u.ac.jp/kenkyuugroup/group/blood-hp/index.html