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2013 Fiscal Year Final Research Report

Basic research for early diagnosis of lung carcinomas by the application of DNA methylation analysis

Research Project

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Project/Area Number 24701008
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor diagnosis
Research InstitutionKagoshima University

Principal Investigator

YOKOYAMA Seiya  鹿児島大学, 医歯(薬)学総合研究科, 助教 (20569941)

Project Period (FY) 2012-04-01 – 2014-03-31
Keywordslung adenocarcinomas / mucin / DNA methylation / demethylation / ten eleven translocation
Research Abstract

Lung cancer is still a disease of high mortality, despite advanced diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in lung neoplasms. We have developed a novel 'methylation-specific electrophoresis (MSE)' method to analyze the DNA methylation status of MUC1 and MUC4 by high sensitivity and resolution.
By using the MSE method, we evaluated lung tissue samples from 33 patients with various lung lesions. Our results showed that the TET1 was important factor for DNA demethylation to regulate the expression of MUC1 and MUC4 in lung cancer. The analysis of the epigenetic changes of MUC1 and MUC4 may be useful for diagnosing the carcinogenic risk and predicting outcome of patients.

  • Research Products

    (25 results)

All 2014 2013 2012 2011 Other

All Journal Article (14 results) (of which Peer Reviewed: 10 results) Presentation (8 results) Remarks (1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] Diagnosis of pancreatic neoplasms using a novel method of DNA methylation analysis of mucin expression in pancreatic juice2014

    • Author(s)
      Yokoyama S, Kitamoto S, Higashi M, Goto Y, Hara T, Ikebe D, Yamaguchi T, Arisaka Y, Niihara, Nishimata H, Tanaka S, Takaori K, Batra S K, Yonezawa S
    • Journal Title

      PLoS ONE

      Volume: 9(4) Pages: e93760

    • DOI

      10.1371/journal.pone.0093760

    • Peer Reviewed
  • [Journal Article] Pathobiological implications of mucin (MUC) expression in the outcome of small bowel cancer2014

    • Author(s)
      Shibahara H, Higashi M, Koriyama C, Yokoyama S, Kitazono I, Yasuhiro K, Narita M, Kuze S, Takanori K, Mita S, Arai T, Kato T, Yuasa N, Yamaguchi R, Kubota H, Suzuki H, Baba S, Rousseau K, Batra S K, Yonezawa S
    • Journal Title

      PLoS ONE

      Volume: 9(4) Pages: e86111

    • DOI

      10.1371/journal.pone.0086111

    • Peer Reviewed
  • [Journal Article] Expression of MUC4 mucin is observed mainly in the intestinal-type of intraductal papillary mucinous neoplasm of the pancreas2013

    • Author(s)
      Kitazono I, Higashi M, Kitamoto S, Yokoyama S, Horinouchi M, Osako M, Shimizu T, Tabata M, Batra S K, Goto M, Yonezawa S
    • Journal Title

      Pancreas

      Volume: 42(7) Pages: 1120-1128

    • DOI

      10.1097/MPA.0b013e3182965915

    • Peer Reviewed
  • [Journal Article] MUC1 enhances hypoxia-driven angiogenesis through the regulation of multiple proangiogenic factors2013

    • Author(s)
      Kitamoto S, Yokoyama S, Higashi M, Yamada N, Takao S, Yonezawa S
    • Journal Title

      Oncogene

      Volume: 32(39) Pages: 4614-4621

    • DOI

      10.1038/onc.2012.478

    • Peer Reviewed
  • [Journal Article] Identification of mucins by using a method involving a combination of on-membrane chemical deglycosylation and immunostaining2013

    • Author(s)
      Matsuno YK, Dong W, Yokoyama S, Yonezawa S, Narimatsu H, Kameyama A
    • Journal Title

      Journal of Immunological Methods

      Volume: 394(1-2) Pages: 125-30

    • DOI

      10.1016/j.jim.2013.06.002

    • Peer Reviewed
  • [Journal Article] 特集 : 粘液産生性胆道系腫瘍の再出発-エビデンスとしての画像と病理「胆道系腫瘍における粘液産生の組織学的側面」2013

    • Author(s)
      東美智代、柴原弘明、後藤優子、平木翼、横山勢也、米澤傑
    • Journal Title

      胆と膵

      Volume: 34(5) Pages: 353-358

  • [Journal Article] 特集胆膵病理II : 胆膵共通のトピックス【胆膵共通疾患とトピックス】膵胆道腫瘍におけるMUC発現2013

    • Author(s)
      米澤傑、東美智代、横山勢也、後藤優子、北島信一
    • Journal Title

      病理と臨床

      Volume: 31(4) Pages: 399-408

  • [Journal Article] MUC4 and MUC1 expression in adenocarcinoma of the stomach correlates with vessel invasion and lymph node metastasis : an immunohistochemical study of early gastric cancer2012

    • Author(s)
      Tamura Y, Higashi M, Kitamoto S, Yokoyama S, Osako M, Horinouchi M, Shimizu T, Tabata M, Batra SK, Goto M, Yonezawa S
    • Journal Title

      PLoS ONE

      Volume: 7(11) Pages: e49251

    • DOI

      10.1371/journal.pone.0049251

    • Peer Reviewed
  • [Journal Article] Expression of MUC17 is regulated by HIF1α-mediated hypoxic responses and requires a methylation-free hypoxia responsible element in pancreatic cancer2012

    • Author(s)
      Kitamoto S, Yokoyama S, Higashi M, Yamada N, Matsubara S, Takao S, Batra S K, Yonezawa S
    • Journal Title

      PLoS ONE

      Volume: 7(9) Pages: e44108

    • DOI

      10.1371/journal.pone.0044108

    • Peer Reviewed
  • [Journal Article] A novel anti-MUC1 antibody against the MUC1 cytoplasmic tail domain : use in sensitive identification of poorly differentiated cells in adenocarcinoma of the stomach2012

    • Author(s)
      Yonezawa S, Kitajima S, Higashi M, Osako M, Horinouchi M, Yokoyama S, Kitamoto S, Yamada N, Tamura Y, Shimizu T, Tabata M, Goto M
    • Journal Title

      Gastric Cancer

      Volume: 15(4) Pages: 370-381

    • DOI

      10.1007/s10120-011-0125-2

    • Peer Reviewed
  • [Journal Article] The application of methylation specific electrophoresis (MSE) to DNA methylation analysis of the 5' CpG island of mucin in cancer cells2012

    • Author(s)
      Yokoyama S, Kitamoto S, Yamada N, Houjyo I, Sugai T, Nakamura S, Arisaka Y, Takaori K, Higashi M, Yonezawa S
    • Journal Title

      BMC Cancer

      Volume: 12 (published online) Pages: 67

    • DOI

      10.1186/1471-2407-12-67

    • Peer Reviewed
  • [Journal Article] Pathobiological implications of expression of MUC16/CA125 in intrahepatic cholangiocarcinoma-mass forming type2012

    • Author(s)
      Higashi M, Yamada N, Yokoyama S, Kitamoto S, Tabata K, Koriyama C, Batra SK, Yonezawa S
    • Journal Title

      Pathobiology

      Volume: 79(2) Pages: 101-106

    • DOI

      10.1159/000335164

    • Peer Reviewed
  • [Journal Article] 胆管内乳頭状腫瘍(IPNB) : 粘液,MUC発現からのアプローチ2012

    • Author(s)
      東美智代、横山勢也、北本祥、米澤傑
    • Journal Title

      肝胆膵

      Volume: 65(3) Pages: 487-494

  • [Journal Article] 癌におけるムチンの臨床病理学的意義および診断への応用-難治性膵胆管癌の早期診断に向けて-2012

    • Author(s)
      米澤傑、東美智代、横山勢也、北本祥、山田宗茂
    • Journal Title

      MEDICAL TECNOLOGY

      Volume: 40(4) Pages: 419-425

  • [Presentation] Application of a novel DNA methylation analysis method (MSE) for mucin expression in pancreatic, biliary and pulmonary neoplasms2013

    • Author(s)
      Yonezawa S, Yokoyama S, Kitamoto S, Higashi M
    • Organizer
      MUCINS IN HEALTH AND DISEASE (12th International Workshop on Carcinoma-associated Mucins)
    • Place of Presentation
      Robinson College (Cambridge, UK)
    • Year and Date
      20130727-31
  • [Presentation] Diagnosis of pancreatic neoplasms by application of a novel DNA methylation analysis method (MSE) for mucin expression in pancreatic juices2013

    • Author(s)
      Yonezawa S, Yokoyama S, Higashi M, Goto Y, Kitajima S
    • Organizer
      Worldwide Innovative Networking in personalized cancer medicine
    • Place of Presentation
      Le Palais des Congres (Paris, France)
    • Year and Date
      20130710-12
  • [Presentation] Examination of mucin expression including a novel DNA methylation analysis method (MSE) : Its application for diagnosis of human pancreatic neoplasms2013

    • Author(s)
      Yonezawa S, Yokoyama S, Goto Y, Higashi M
    • Organizer
      19th International Charles Heidelberger Symposium on Cancer Research
    • Place of Presentation
      William Willis Hall (Kagoshima, Japan)
    • Year and Date
      20130214-16
  • [Presentation] DNA promoter methylation status and mRNA expression of MUC1 in human lung cancer2013

    • Author(s)
      Yokoyama S, Kitamoto S, Tsutsumida H, Wakimoto J, Higashi M, Yonezawa S
    • Organizer
      19th International Charles Heidelberger Symposium on Cancer Research
    • Place of Presentation
      William Willis Hall (Kagoshima, Japan)
    • Year and Date
      20130214-16
  • [Presentation] MUC1 Enhances Hypoxia-Driven Angiogenesis Through the Regulation of Multiple Proangiogenic Factors2012

    • Author(s)
      Kitamoto S, Yokoyama S, Higashi M, Yamada N, Takao S, Yonezawa S
    • Place of Presentation
      京都国際コンベンションセンター(京都)
    • Year and Date
      20121004-06
  • [Presentation] The Application of New DNA Methylation Analysis, Designated Methylation Specific Electrophoresis (MSE) for Pancreatic Juice Analysis2012

    • Author(s)
      Yokoyama S, kitamoto S, Hara T, Arisaka Y, Takaori K, Yamamoto T, Niihara T, Nishimata H, Tanaka S, Higashi M, Yonezawa S
    • Place of Presentation
      京都国際コンベンションセンター(京都)
    • Year and Date
      20121004-06
  • [Presentation] CTGF is enhanced by hypoxia through nuclear recruitment of MUC1 in pancreatic cancer2012

    • Author(s)
      Kitamoto S, Higashi M, Yokoyama S, Takao S, Yonezawa S
    • Organizer
      22nd Biennial Congress of the European Association for Cancer Research
    • Place of Presentation
      バルセロナ国際会議場(Barcelona, Spain)
    • Year and Date
      20120707-10
  • [Presentation] TET1 was important factor for DNA demethylation to regulate the expression of MUC1 and MUC4 in lung cancer2012

    • Author(s)
      Yokoyama S, Kitamoto S, Tsutsumida H, Wakimoto J, Higashi M, Yonezawa S
    • Organizer
      23^<rd> Biennial Ccongress of the European Association for Cancer Research
    • Place of Presentation
      International Congress Center Munich (Munchen, Germany) (発表確定)
    • Year and Date
      20120705-08
  • [Remarks] 鹿児島大学医歯学総合絵研究科先進治療科学専攻腫瘍学講座人体がん病理学

    • URL

      http://www.kufm.kagoshima-u.ac.jp/~byouri2/

  • [Patent(Industrial Property Rights)] METHOD FOR DIAGNOSING TYPE OF PANCREATIC TUMOR2012

    • Inventor(s)
      横山勢也、米澤 傑、北本 祥
    • Industrial Property Rights Holder
      鹿児島大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      国際出願番号2012JP067262
    • Filing Date
      2012-06-29
    • Overseas
  • [Patent(Industrial Property Rights)] NOVEL DNA METHYLATION ANALYSIS METHOD2011

    • Inventor(s)
      横山勢也、米澤 傑
    • Industrial Property Rights Holder
      鹿児島大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      国際出願番号2011JP060339
    • Filing Date
      2011-04-21
    • Overseas

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Published: 2015-06-25  

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