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Increased circulating cell signaling phosphoproteins in sera are useful for early detection and the tailor-made therapy for pancreatic and biliary duct cancer patients.

Research Project

Project/Area Number 21390372
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionChiba University

Principal Investigator

MIYAZAKI Masaru  千葉大学, 大学院・医学研究院, 教授 (70166156)

Co-Investigator(Kenkyū-buntansha) KIMURA Fumio  千葉大学, 大学院・医学研究院, 准教授 (70334208)
SHIMIZU Hiroaki  千葉大学, 大学院・医学研究院, 講師 (80272318)
YOSHIDOME Hiroyuki  千葉大学, 大学院・医学研究院, 講師 (10312935)
KATO Atushi  千葉大学, 大学院・医学研究院, 助教 (70344984)
高野 重紹  千葉大学, 大学院・医学研究院, 助教 (20436380)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2011: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2010: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2009: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
Keywordsproteomics / 膵癌 / 胆道癌 / 腫瘍マーカー / リン酸化蛋白 / ERK / Proteomics / シグナル伝達物質 / 自己抗体複合体
Research Abstract

Intracellular phosphoprotein activation significantly regulatescancer progression. We investigated the serum phosphoprotein profile involved in pancreatic cancer by a novel approach that comprehensively measured serum phosphoproteins levels, and clinically applied this method to the detection of pancreatic cancer. We analyzed the serum phosphoproteins that comprised cancer cellular signal pathways by comparing sera from pancreatic cancer patients and benign controls including healthy volunteers and pancreatitis patients. Hierarchical clustering analysis between pancreatic cancer patients and healthy volunteers revealed differential pathway-specific profiles. In particular, the components of the extracellular signal-regulated kinase (ERK) signaling pathway were significantly increased in the sera from pancreatic cancer patients compared with healthy volunteers. The positive rate of p-ERKI/2 (82%) was found to be superior to that of CA19-9 (53%) for early stage pancreatic cancer. For the combination of these serum levels, the area under the receiver-operator-characteristics curves were showing significant ability to distinguish between the two populations in independent validation set, and between cancer and non-cancer populations in another validation set. The comprehensive measurement of serum cell signal phosphoproteins is useful for, the detection of pancreatic cancer. Further investigations will lead to the implementation of tailor-made molecular-targeted therapeutics.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (31 results)

All 2011 2010 2009 2008 Other

All Journal Article (25 results) (of which Peer Reviewed: 24 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Usefulness of Preoperative Partial Splenic Embolization in Hepatocellular carcinoma and Hypersplenic2011

    • Author(s)
      Yoshidome H, Kimura F, Shimizu H, Ohtsuka M, Kato A, Yoshitomi H, Furukawa K, Takeuchi D, Takayashiki T, Suda K, Takano S, Miyazaki M.
    • Journal Title

      Thrombocyto penia Hapato-Gastroenterology

      Volume: 58 Pages: 2062-2066

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Similarties and Differences Between Intra ducal Papillary Tumors of the Bile Duct Wi th and Without Macroscopically Visible Mu cin Secretion2011

    • Author(s)
      Ohtsuka M, Kimura M, Shimizu H, Yoshidame H, Kato A, Yoshitomi. H, Furukawa K, Takeuchi D, Takayashiki T, Suda K, Takino S, Kondo Y, Miyazaki M
    • Journal Title

      Am J Surg Pathol

      Volume: 35(4) Pages: 512-521

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Treatment Strategy for Hepatocellular Car rcinoma with Major Portal Vein or Inferior Vona Cava Invasion : A Single Institution. Experience2011

    • Author(s)
      Yoshidome H, Takeuchi D, Kimura F, Shimizu H, Ohtsuka M, Kate A, Furukawa K, Yoshitomi H, Miyazaki M
    • Journal Title

      J Am Coll Surg

      Volume: 212(5) Pages: 796-803

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatocyte apoptosis is enhanced after isc hernia/ reperfusion in the steatotic liver2011

    • Author(s)
      Suzuki T, Yoshidome H, Kimura F, Shimizu H, Ohtsua M Takeuchi D, Kate A, Furukawa K, Yoshitomi H, Iida A, Dochi T, Miyazaki M
    • Journal Title

      J. Clin

      Volume: 48(2) Pages: 142-148

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] CXCR4/CXCL12 expression profile is associated with tumor microenvironment and clinical outcome of liver metastases of colorectal cancer2011

    • Author(s)
      Sakai N, et al.
    • Journal Title

      Clin Exp metastasis

      Volume: 29 Issue: 2 Pages: 101

    • DOI

      10.1007/s10585-011-9433-5

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 膵発生における血管内皮細胞の役割2011

    • Author(s)
      吉富秀幸, ら
    • Journal Title

      胆と膵

      Volume: 32 Pages: 1213-1218

    • Related Report
      2011 Annual Research Report
  • [Journal Article] One hundred seven consective surgical resections for hilar cholangiocarcinoma of Bismuth types II, III, IV between 2001 and 2008 J Hepatobiliary Pancreat2010

    • Author(s)
      Miyazaki M, Kimura F, Shimizu H, Yoshidome H, Ohtuka M, Kate A, Yoshitomi H, Furukawa K, Takeuchi D, Takayashiki T, Suda K, Takano S
    • Journal Title

      Sci

      Volume: 17 Pages: 470-475

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatocyte nuclear factor-kappa (NF-kB) activation is protective but is decreased in the cholestatic liver with endotoxemia2010

    • Author(s)
      Iida A, Yoshidome H, Shida T, Takano S, Takeuchi D, Kimura F, Shimizu H, Ohtsuka, Miyazaki M
    • Journal Title

      Surgery

      Volume: 148(3) Pages: 477-489

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Partial Hepatic Venous Congesti on on Hepatic2010

    • Author(s)
      Okuno A, Kimura F, Nakagawa K, Shimizu H, Yoshidome H, Ohtsuka M, Kate A, Fukuda T, Miyazaki M
    • Journal Title

      Hepato-Gastroenterology

      Volume: 57 Pages: 127-133

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased circulating cell signalling phosphoproteins in sera are useful for the detection of pancreatic cancer2010

    • Author(s)
      Takano S, Sogawa K, Yoshitomi H, Shida T, Mogushi K, Shimizu H, Yoshidome H, Ohtsuka M, Kate A, Ishihara T, Tanaka H, Yokosuka O, Nomura F, Miyazaki M
    • Journal Title

      British Journal of Cancer

      Volume: 103 Pages: 223-231

    • Related Report
      2011 Final Research Report 2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of perioperative immunonutrition on cell-mediated immunity, T helper type 1(Th1)/Th2 differentiation, and Th17 rasp onse after pancreaticoduodenectomy2010

    • Author(s)
      Suzuki D, Furukawa K, Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Kate A, Yoshitomi H, Miyazaki M
    • Journal Title

      Surgery

      Volume: 148(3) Pages: 573-581

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Partial Hepatic Venous Congesti on on Hepatic Hemodynamics and Historo ogy2010

    • Author(s)
      Okuno A, Kimura F, Nakamura K, Shimizu H, Yoshidome H, Ohtsuka M, Kate A, Fukada T, Miyazaki M
    • Journal Title

      hepato-Gastroenterology

      Volume: 57 Pages: 127-133

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Multicentric evaluation of a clnical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas2010

    • Author(s)
      Georgios C. Sotiropoulous, Miyazaki M, Mancusos M. Konstadoulakis, Andreas Paul, Ernest P. Molmenti, Ilias P. Gomatos, Arnold Raadtke, Hideo A. Baba, Susanne Beckebaum, Erini I. Brokalaki, Ohtsuka M, Myron E. Schwartz, Christoph E. Broelsh George Sgourakis
    • Journal Title

      Liver International

      Volume: 30 Pages: 966-1002

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of an activated mammalian targetof rapamycin (mTOR) in gastoroente ropancreatic neuroendocrine tumors2010

    • Author(s)
      Shida T, Kishimoto T, Furuya M, Nikaido T, Koda K, Takano S, Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Tanizawa T, Nakatani Y, Miyazaki M
    • Journal Title

      Cancer Chemother Pharmacol

      Volume: 65 Pages: 889-893

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aggressive Surgical Resection for Hilar Cholangiocarcinoma of the Left-side Predo minance2010

    • Author(s)
      Shimizu H, Kimura F, Yoshidome H, Ohtsuka M, Kato A, Yoshitomi H, Furukawa K, Miyazaki M
    • Journal Title

      Ann Surg

      Volume: 251 Pages: 281-286

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of an activated mammalian target of rapamycin (mTOR)in gastoroenteropancreatic neuroendocrine tumors.2010

    • Author(s)
      Miyazaki M
    • Journal Title

      Cancer Chemother Pharmacol

      Volume: 65 Pages: 889-893

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] One hundred seven consective surgical resections for hilar cholangiocarcinoma of Bismuth types II, III, IV between 2001 and 20082010

    • Author(s)
      Miyazaki M
    • Journal Title

      Japan Hepatobihary Pancreat Science

      Volume: 17 Pages: 470-475

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of Antitumor Response by In Vivo Allogeneic Major Histocompatibility Complex Gene Transfer Using Electropora Tion2009

    • Author(s)
      Shimizu H, Nukui Y, Mitsuhashi N, Kimura F, Yoshidome H, Ohtsuka M, Kato A, Miyazaki M
    • Journal Title

      J Surg Res

      Volume: 154 Pages: 60-67

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Risk Factors of liver dysfunction after extended hepatic resection in biliary tract malignancies2009

    • Author(s)
      Suda K, Ohtsuka M, Ambiru S, Kimura F, Shimizu H, Yoshidome H, Miyazaki M.
    • Journal Title

      J Am Coll Surg

      Pages: 752-758

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Excessive Acute-phase Response on Liver Regeneration after Partial Hepate ctomy in Rats2009

    • Author(s)
      Kusashio K, Shimizu H, Kimura F, Yoshidome H, Ohtsuka M, Kato A, Yoshitomi H, Furukawa K, Fukada T, Miyazaki M
    • Journal Title

      Hepato-Gastroenterol

      Volume: 56 Pages: 824-828

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of Kupffer Cells in Tolerance Indac tion after Portal Venous Administration of Alloantigen2009

    • Author(s)
      Shimizu H, Kataoka M, Kimura F, Yoshi dome H, Ohtsuka M, Kato A, Miyazaki M
    • Journal Title

      Hepato-Gastroenterol

      Volume: 56 Pages: 783-787

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Randomized, Controlled Study of Continu ous 5-FU Infusion Starting Immediately after Curative Surgery for Advanced Cal orectal Cancer2009

    • Author(s)
      Koda K, Saito N, Ochiai T, Miyazaki M, Sarashina H, Nakajima N
    • Journal Title

      Hepato-Gastroenterol

      Volume: 56 Pages: 116-119

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Risk factor of liver dysfunction after extended hepatic resection in biliary tract malignancies2009

    • Author(s)
      Masaru Miyazaki
    • Journal Title

      The American Journal of Surgery 197

      Pages: 752-758

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical Significance of Biliary Vascular Anatomy of the Right Liver For Hilar Cholangiocarcinoma Applied to Left Hemihepatectomy2009

    • Author(s)
      Masaru Miyazaki
    • Journal Title

      Ann Srug 249

      Pages: 435-439

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interval Period Tumor Progression : Delaye d Hepatectomy Detect Occult Metastases in Synchronous Colorectal Liver Metasta ses2008

    • Author(s)
      Yoshidome H, Fumio Kimura, Shimizu H, Ohtsuka M, Kato A, Yoshitomi H, Furukaw a K, Mitsuhashi. N, Takeuchi D, Iida A, Mi yazaki M
    • Journal Title

      J Gastrointest Surg

      Volume: 12 Pages: 1391-1398

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] 網羅的蛋白質解析による新規膵癌血中マーカー開発への試み2011

    • Author(s)
      吉富秀幸, ら
    • Organizer
      JDDW 2011
    • Place of Presentation
      福岡
    • Year and Date
      2011-10-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] 膵癌術後補助療法の個別化を目指したGemcitabine耐性因子の同定とAkt/mTORシグナル制御の意義2011

    • Author(s)
      吉富秀幸, ら
    • Organizer
      第66回日本消化器外科学会総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-07-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] 胆道・膵臓悪性腫瘍の病態と治療の進歩2010

    • Author(s)
      宮崎勝
    • Organizer
      日本消化器病学会東海支部第112回例会
    • Place of Presentation
      三島東レ総合研修センター
    • Year and Date
      2010-06-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] 教育セッション7 講師 がん治療update2009

    • Author(s)
      宮崎勝
    • Organizer
      第47回 日本癌治療学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2009-10-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] 膵癌における癌幹細胞マーカー発現形式の検討と臨床病理学因子との関係

    • Author(s)
      高原義博, ら
    • Organizer
      第111回日本外科学会定期学術集会
    • Place of Presentation
      (紙上発表)
    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.ho.chiba-u.ac.jp/5/

    • Related Report
      2011 Final Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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