Analysis of microenvironment and exploration of new biomarker for pulmonary arterial hypertention

• Project/Area Number: 15K08359
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Hokkaido University
• Principal Investigator: Tanino Mishie 北海道大学, 医学研究院, 講師 (90360908)
• Co-Investigator(Kenkyū-buntansha): 辻野 一三 北海道大学, 医学研究院, 特任教授 (00344507) ; 仙葉 愼吾 北海道大学, 医学研究院, 学術研究員 (40466496) ; 谷野 功典 福島県立医科大学, 医学部, 准教授 (10443863)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 肺高血圧 / ニース分類 / 免疫組織化学染色 / 遺伝子解析 / 肺線維症 / 膠原病 / 血管拡張薬 / 炎症細胞 / サイトカイン / 成長因子 / 病理 / 免疫染色

Outline of Final Research Achievements

(1)Immunohistochemisty for FGFR1, VEGFR2, EGFR in the lungs of pulmonary venous obstructive hypertension(PVOD) showed higher expression of FGFR compared to VEGFR and EGFR in PVOD lungs. FGF-FGFR may pathway contribute the pathogenesis of PVOD. (2)Therapy related proteins such as PDE5、ER-A/B、PGI2、sGCα/βexpressed higher in pulmonary hypertension(PH) compared to controls, however there were no difference between Group 1-PH and Group 3-PH. These drugs contribute to dilate vessel wall in both types of PH. (3) Systemic sclerosis (Ssc) related PH showed denser fibrosis compared to SLE related PH and replacement myocardial fibrosis was demonstrated at the site of late gadolinium enchancement of MRI in Ssc patient.(4) FoxF1 mutation was detected in Alveolar capillary dysplasia related PH children and Heterozygous mutations in OAS1 were detected in infantile-onset pulmonary alveolar proteinosis with hypogammaglobulinemia. These genetic background relate to secondary PH.

Research Products

• [Journal Article] A Clinicopathological Analysis of Six Autopsy Cases of Sudden Unexpected Death due to Infectious Aortitis in Patients with Aortic Tears (2018)
  • Author(s): Kato MI, Tanino MA, Miyazaki M, Kimura T, Ishida Y, Wang L, Tsuda M, Nishihara H, Nagashima K, Tanaka S
  • Journal Title: Internal Medicine Volume: 57 Issue: 10 Pages: 1375-1380
  • DOI: 10.2169/internalmedicine.8976-17
  • NAID: 130006734384
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2018-05-15
  • Peer Reviewed / Open Access
• [Journal Article] Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia. (2018)
  • Author(s): Cho K, Yamada M, Agematsu K, Kanegane H, Miyake N, Ueki M, Akimoto T, Kobayashi N, Ikemoto S, Tanino M, Fujita A, Hayasaka I, Miyamoto S, Tanaka-Kubota M, Nakata K, Shiina M, Ogata K, Minakami H, Matsumoto N, Ariga T.
  • Journal Title: Am J Hum Genet Volume: 102 Issue: 3 Pages: 480-486
  • DOI: 10.1016/j.ajhg.2018.01.019
  • NAID: 120006502505
  • Peer Reviewed / Open Access
• [Journal Article] Chorionic Gonadotropin-β Modulates Epithelial-Mesenchymal Transition in Colorectal Carcinoma Metastasis (2018)
  • Author(s): Kawamata Futoshi、Nishihara Hiroshi、Homma Shigenori、Kato Yasutaka、Tsuda Masumi、Konishi Yuji、Wang Lei、Kohsaka Shinji、Liu Cheng、Yoshida Tadashi、Tanino Mishie、Tanaka Shinya、Kawamura Hideki、Kamiyama Toshiya、Taketomi Akinobu
  • Journal Title: Am J Pathol Volume: 188 Issue: 1 Pages: 204-215
  • DOI: 10.1016/j.ajpath.2017.08.034
  • Peer Reviewed / Open Access
• [Journal Article] Involvement of midkine in the development of pulmonary fibrosis (2017)
  • Author(s): Misa Kenichi、Tanino Yoshinori、Wang Xintao、Nikaido Takefumi、Kikuchi Masami、Sato Yuki、Togawa Ryuichi、Tanino Mishie、Tanaka Shinya、Kadomatsu Kenji、Munakata Mitsuru
  • Journal Title: Physiol Rep Volume: 5 Issue: 16 Pages: e13383-e13383
  • DOI: 10.14814/phy2.13383
  • Peer Reviewed / Open Access
• [Journal Article] Notch1 regulates invasion and metastasis of head and neck squamous cell carcinoma by inducing EMT through c-Myc. (2017)
  • Author(s): Inamura N, Kimura T, Wang L, Yanagi H, Tsuda M, Tanino M, Nishihara H, Fukuda S, Tanaka S.
  • Journal Title: Auris Nasus Larynx Volume: 44 Issue: 4 Pages: 447-457
  • DOI: 10.1016/j.anl.2016.08.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel signaling collaboration between TGF-beta and adaptor protein Crk facilitates EMT in human lung cancer (2016)
  • Author(s): Elmansuri AZ, Tanino MA, Mahabir R, Wang L, Kimura T, Nishihara H, Kinoshita I, Dosaka-Akita H, Tsuda M and Tanaka S
  • Journal Title: Oncotarget Volume: （in press） Issue: 19 Pages: 27094-107
  • DOI: 10.18632/oncotarget.8314
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genetic interaction of hnRNPA2B1 and DNAJB6 in a Drosophila model of multisystem proteinopathy. (2016)
  • Author(s): Li S, Zhang P, Freibaum BD, Kim NC, Kolaitis RM, Molliex A, Kanagaraj AP, Yabe I, Tanino M, Tanaka S, Sasaki H, Ross ED, Taylor JP, Kim HJ.
  • Journal Title: Hum Mol Genet. Volume: 25 Issue: 5 Pages: 936-50
  • DOI: 10.1093/hmg/ddv627
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Analysis of NAB2-STAT6 Gene Fusion in 17 Cases of Meningeal Solitary Fibrous Tumor/Hemangiopericytoma: Review of the Literature. (2016)
  • Author(s): Yuzawa S, Nishihara H, Wang L, Tsuda M, Kimura T, Tanino M, Tanaka S
  • Journal Title: Am J Surg Pathol Volume: 40 Issue: 8 Pages: 1031-40
  • DOI: 10.1097/pas.0000000000000625
  • Peer Reviewed / Open Access
• [Journal Article] Clinical impact of targeted amplicon sequencing for meningioma as a practical clinical-sequencing system. (2016)
  • Author(s): Yuzawa S, Nishihara H, Yamaguchi S, Mohri H, Wang L, Kimura T, Tsuda M, Tanino M, Kobayashi H, Terasaka S, Houkin K, Sato N, Tanaka S.
  • Journal Title: Mod Pathol. Volume: 29 Issue: 7 Pages: 708-16
  • DOI: 10.1038/modpathol.2016.81
  • NAID: 120005905622
  • Peer Reviewed / Open Access
• [Journal Article] Aldo-keto reductase 1C1 induced by interleukin-1beta mediates the invasive potential and drug resistance of metastatic bladder cancer cells. (2016)
  • Author(s): Matsumoto R, Tsuda M, Yoshida K, Tanino M, Kimura T, Nishihara H, Abe T, Shinohara N, Nonomura K, Tanaka S
  • Journal Title: Scientific reports Volume: 4 Issue: 1 Pages: 34625-34625
  • DOI: 10.1038/srep34625
  • Peer Reviewed / Open Access
• [Journal Article] Colon Involvement in Blastic Plasmacytoid Dendritic Cell Neoplasm (2015)
  • Author(s): Saito M, Irie T, Miyashita K, Tanino M
  • Journal Title: Intern Med. Volume: 54 Issue: 1 Pages: 1677-1677
  • DOI: 10.1007/s10014-015-0241-5
  • NAID: 130005086449
  • Peer Reviewed / Open Access
• [Journal Article] Rapid immunohistochemistry based on alternating current electric field for intraoperative diagnosis of brain tumors. (2015)
  • Author(s): Tanino M, Sasajima T, Nanjo H, Akesaka S, Kagaya M, Kimura T, Ishida Y, Oda M, Takahashi M, Sugawara T, Yoshioka T, Nishihara H, Akagami Y, Goto A, Minamiya Y, Tanaka S; R-IHC Study Group.
  • Journal Title: Brain Tumor Pathol. Volume: 32 Issue: 1 Pages: 12-19
  • DOI: 10.1007/s10014-014-0188-y
  • NAID: 120005682120
  • Peer Reviewed / Open Access
• [Journal Article] Serum syndecan-4 as a possible biomarker in patients with acute pneumonia (2015)
  • Author(s): Nikaido T, Tanino Y, Wang X, Sato S, Misa K, Fukuhara N, Sato Y, Fukuhara A, Uematsu M, Suzuki Y, Kojima T, Tanino M, Endo Y, Tsuchiya K, Kawamura I, Frevert C, Munakata M
  • Journal Title: J Infect Dis Volume: 212 Issue: 9 Pages: 1500-1508
  • DOI: 10.1093/infdis/jiv234
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neuropeptide signaling through neurokinin-1 and 2 receptors augments antigen presentation by human dendritic cells. (2015)
  • Author(s): Junya Ohtake, Shun Kaneumi, Mishie Tanino, Takuto Kishikawa, Satoshi Terada, Kentaro Sumida, Kazutaka Masuko, Yosuke Ohno, Toshiyuki Kita, Sadahiro Iwabuchi, Toshiya Shinohara, Yoshinori Tanino, Tamiko Takemura, Shinya Tanaka, Hiroya Kobayashi, and Hidemitsu Kitamura.
  • Journal Title: Journal of Allergy and Clinical Immunology. Volume: 136 Issue: 6 Pages: 1690-1694
  • DOI: 10.1016/j.jaci.2015.06.050
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Multicentric Castleman's disease with impaired lymphocytic apoptosis (2015)
  • Author(s): Minemura H, Ikeda K, Tanino Y, Hashimoto Y, Nikaido T, Fukuhara A, Yokouchi H, Sato S, Tanino M, Oka T, Hebisawa A, Suzuki H, Ogawa K, Takeishi Y, Munakata M.
  • Journal Title: Allergology International Volume: 64 Issue: 1 Pages: 112-114
  • DOI: 10.1016/j.alit.2014.08.009
  • NAID: 130004873132
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed
• [Journal Article] A late presenter and long-term survivor of alveolar capillary dysplasia with misalignment of the pulmonary veins. (2015)
  • Author(s): Ito Y, Akimoto T, Cho K, Yamada M, Tanino M, Dobata T, Kitaichi M, Kumaki S, Kinugawa Y
  • Journal Title: Eur J Pediatr Volume: 174 Issue: 8 Pages: 1123-6
  • DOI: 10.1007/s00431-015-2543-3
  • Peer Reviewed
• [Presentation] グリオーマの日常診断におけるintegrated diagnosisの現状 (2017)
  • Author(s): 谷野美智枝、谷川聖、石田雄介、木村太一、岡田佳奈子、佐藤真美、津田真寿美、西原広史、長嶋和郎、田中伸哉
  • Organizer: 第58回日本神経病理学会総会学術研究会
• [Presentation] 59歳男性、視床下部から側脳室前角に進展した腫瘍 (2017)
  • Author(s): 谷野美智枝
  • Organizer: 第122回東京脳腫瘍研究会
• [Presentation] 右背部痛を主訴とした右肺下葉均等影の一例 (2017)
  • Author(s): 谷野美智枝
  • Organizer: 第51回呼吸器病理研究会
• [Presentation] Analysis of relationship between BRAFV600E mutation and expression for p16 in pleomorphic xanthoastrocytoma (2017)
  • Author(s): 谷野美智枝、南條博、津田真寿美、杉野弘和、王磊、石田雄介、田中伸哉
  • Organizer: 第76回日本癌学会学術総会
• [Presentation] 症例検討会：右背部痛を主訴とした右肺下葉均等影の一例 (2017)
  • Author(s): 谷野美智枝
  • Organizer: 第57回日本呼吸器学会学術講演会
• [Presentation] シンポジウム「膠原病関連肺高血圧症の病理―基礎疾患別の特徴」 (2017)
  • Author(s): 谷野美智枝
  • Organizer: 第2回日本肺高血圧・肺循環学会学術集会
  • Invited
• [Presentation] 子宮頸癌細胞への放射線照射後の悪性転化におけるYAP1の役割の解析 (2016)
  • Author(s): 岡森優唯、谷野美智枝、津田真寿美、鈴鹿淳、王磊、森谷純、木村太一、石田雄介、西原広史、田中伸哉
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（横浜市）
  • Year and Date: 2016-11-30
• [Presentation] 多形黄色星細胞腫におけるBRAF遺伝子変異（BRAFV600E）とリン酸化ERK及びp16の発現の検討 (2016)
  • Author(s): 谷野美智枝、津田真寿美、石田雄介、木村太一、西原広史、田中伸哉
  • Organizer: 第62回 日本病理学会秋季特別総会
  • Place of Presentation: 金沢市文化ホール（金沢市）
  • Year and Date: 2016-11-10
• [Presentation] 脳腫瘍迅速病理診断における迅速免疫染色装置（ラピート）の有用性の検討 (2016)
  • Author(s): 森谷純、谷野美智枝、田中伸哉
  • Organizer: 第62回 日本病理学会秋季特別総会
  • Place of Presentation: 金沢市文化ホール（金沢市）
  • Year and Date: 2016-11-10
• [Presentation] 脳腫瘍術中迅速病理診断における迅速免疫染色装置（ラピート）の有用性の検討 (2016)
  • Author(s): 森谷 純、谷野美智枝、竹浪智子、漆戸万紗那、鈴鹿 淳、石田雄介、王磊、木村太一、津田真寿美、西原広史、田中伸哉
  • Organizer: 第８回迅速免疫染色研究会
  • Place of Presentation: 仙台厚生病院（仙台市）
  • Year and Date: 2016-10-15
• [Presentation] 右後頭部傍矢状洞髄膜腫を疑われた29歳女性 (2015)
  • Author(s): 谷野美智枝、進藤孝一郎, 木村太一、津田真寿美、西原広史、長嶋和郎、田中伸哉
  • Organizer: 第117回東京脳腫瘍研究会
  • Place of Presentation: 東京医科大学（東京都）
  • Year and Date: 2015-11-14
• [Presentation] B型肝硬変・肝細胞癌に対して生体肝移植後10年に胸膜中皮腫を発症した症例 (2015)
  • Author(s): 谷野美智枝、石田雄介、山下健一郎、嶋村剛、朝比奈肇、岡本賢三、田中伸哉
  • Organizer: 第22回 石綿・中皮腫研究会
  • Place of Presentation: ソリッドスクエア（神奈川県、川崎市）
  • Year and Date: 2015-10-31
• [Presentation] 脳腫瘍迅速診断におけるラピートを用いた迅速免疫化学染色の有用性 (2015)
  • Author(s): 谷野美智枝、森谷純、竹浪智子、漆戸万紗那、鈴鹿淳、木村太一、津田真寿美、西原広史、田中伸哉
  • Organizer: 第48回北海道病理談話会
  • Place of Presentation: 札幌医科大学（北海道、札幌市）
  • Year and Date: 2015-10-17
• [Presentation] 電界撹拌迅速免疫染色機を使用した脳腫瘍術中迅速細胞免疫染色の有用性 (2015)
  • Author(s): 谷野美智枝、森谷純、竹浪智子、瀧山晃弘、木村太一、西原広史、田中伸哉
  • Organizer: 第33回日本脳腫瘍病理学会
  • Place of Presentation: JRホテルクレメント高松（香川県、高松市）
  • Year and Date: 2015-05-29
• [Presentation] 肺高血圧症における血管病変の形態学的・免疫組織学的変化 (2015)
  • Author(s): 谷野美智枝、辻野一三、石田雄介、加藤容崇、王磊、木村太一、西原広史、田中伸哉
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋国際会議場（愛知県、名古屋市）
  • Year and Date: 2015-04-30
• [Book] 鑑別診断アトラス 脳腫瘍 (2017)
  • Author(s): 谷野美智枝、田中伸哉（分担）
  • Total Pages: 240
  • Publisher: 文光堂
• [Book] 脳腫瘍臨床病理カラーアトラス (2017)
  • Author(s): 谷野美智枝、田中伸哉（分担）
  • Total Pages: 218
  • Publisher: 医学書院
• [Book] 医療系学生のための病理学 第4版 (2016)
  • Author(s): 中村仁志夫、佐藤達資、石津明洋、田中伸哉、池田仁、渋谷みよ、成松英明、西原広史、野島孝之、柳輝希、渡邊純
  • Total Pages: 208
  • Publisher: 講談社
• [Remarks] 北海道大学医学研究院 腫瘍病理学教室
  • URL: http://patho2.med.hokudai.ac.jp/
• [Remarks] 北海道大学医学研究科 腫瘍病理学分野
  • URL: http://patho2.med.hokudai.ac.jp/
• [Patent(Industrial Property Rights)] ホルマリン固定生体組織内での活性型低分子量GTP結合蛋白質検出方法 (2016)
  • Inventor(s): 田中伸哉、津田真寿美、谷野美智枝
  • Industrial Property Rights Holder: 田中伸哉、津田真寿美、谷野美智枝
  • Industrial Property Rights Type: 特許
  • Filing Date: 2016-03-15
  • Overseas