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2013 Fiscal Year Final Research Report

Molecular mechanisms responsible for the development of scirrhous gastric cancer: analysis of cancer stem cells.

Research Project

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Project/Area Number 22390262
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

HIRAKAWA Kosei  大阪市立大学, 医学(系)研究科(研究院), 教授 (40188652)

Co-Investigator(Kenkyū-buntansha) YASHIRO Masakazu  大阪市立大学, 大学院・医学研究科, 准教授 (60305638)
Project Period (FY) 2010-04-01 – 2014-03-31
Keywordsスキルス胃癌 / 癌幹細胞 / 胃癌由来線維芽細胞 / TGFβ / integrin / 腹膜転移
Research Abstract

Scirrrhous gastric cancer frequently develops into peritoneal metastasis, resulting in a poor prognosis. Cancer stem cells (CSCs) are considered to be responsible for cancer metastasis. The side population (SP), as evaluated by a flowcytometic analysis has been known as CSCs rich population. The aim of this study is to clarify the characterization of the SP cells in peritoneal metastasis of gastric carcinoma and to determine an effective signal inhibitor with effects on the proliferation of CSC. We used three gastric cancer cell lines and three SP-enriched CSC cell lines. CSCs-like SP cells expressing integrin, and CD44 may play an important role for peritoneal metastasis in gastric carcinoma. CSCs have chemoresistance to irinotecan. c-Met inhibitor may be a promising target molecule for irinotecan-based chemotherapy of gastric cancer. CAFs might regulate the stemness of CSCs in scirrhous gastric cancer by TGF-beta signaling.

  • Research Products

    (48 results)

All 2014 2013 2012 2011 Other

All Journal Article (43 results) (of which Peer Reviewed: 43 results) Presentation (2 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Cancer-associated fibroblasts might sustain the stemness of scirrhous gastric cancer cells via transforming growth factor-β signaling2014

    • Author(s)
      Hasegawa T Yashiro M, Nishii T, Matsuoka J, Morisaki T, Fukuoka T, Shimizu K, Shimizu T, Miwa A, Hirakawa K
    • Journal Title

      Int J Cancer

      Volume: 134 Pages: 1785-1795

    • Peer Reviewed
  • [Journal Article] A cMet inhibitor increases the chemosensitivity of cancer stem cells to the irinotecan in gastric carcinoma2013

    • Author(s)
      Yashiro M, Nishii T, Matsuzaki T, Hasegawa T, Morisaki T, Fukuoka T, Hirakawa K
    • Journal Title

      Br J Cancer

      Volume: 109 Pages: 2619-28

    • Peer Reviewed
  • [Journal Article] Association of MHC class I expression and lymph node metastasis of gastric carcinoma2013

    • Author(s)
      Yoshii M, Tanaka H, Ohira M, Muguruma K, Sakurai K, Kubo N, Yashiro M, Sawada T, Hirakawa K
    • Journal Title

      Hepatogastroenterology

      Volume: 60 Pages: 611-5

    • Peer Reviewed
  • [Journal Article] Design and synthesis of a series of alpha-benzyl phenylpropanoic acid-type peroxisome proliferator-activated receptor (PPAR) gamma partial agonists with improved aqueous solubility2013

    • Author(s)
      Ohashi M, Oyama T, Putranto EW, Waku T, Nobusada H, Kataoka K, Matsuno K, Yashiro M, Morikawa K, Huh NH, Miyachi H
    • Journal Title

      BioorgMed Chem

      Volume: 21 Pages: 2319-32

    • Peer Reviewed
  • [Journal Article] SPan-1 is a useful prognostic marker for patients with stage IV gastric cancer who underwent palliative gastrectomy : a retrospective multivariate study2013

    • Author(s)
      Kubo N, Ohira M, Sakurai K, Toyokawa T, Tanaka H, Muguruma K, Nagahara H, Kimura K, Noda E, Amano R, Yamada N, Yashiro M, Maeda K, Sawada T, Hirakawa K
    • Journal Title

      World J Surg

      Volume: 37 Pages: 1681-7

    • Peer Reviewed
  • [Journal Article] Expression of E-cadherin and KRAS mutation may serve as biomarkers of cetuximab-based therapy in metastatic colorectal cancer2013

    • Author(s)
      Nakamoto K, Nagahara H, Maeda K, Noda E, Inoue T, Yashiro M, Nishiguchi Y, Ohira M, Hirakawa K
    • Journal Title

      Oncol Lett

      Volume: 5 Pages: 1295-300

    • Peer Reviewed
  • [Journal Article] MUC1 and HER2 might be associated with invasive phenotype of intraductal papillary mucinous neoplasm (IPMN)2013

    • Author(s)
      Ohira G, Kimura K, Ymada N, Amano R, Nakata B, Doi Y, Murata A, Yashiro M, Tanaka S, Ohsawa M, Wakasa K, Hirakawa K
    • Journal Title

      Hepatogastroenterology

      Volume: 60

    • Peer Reviewed
  • [Journal Article] Hypoxia stimulates the EMT of gastric cancer cells through autocrine TGFbeta signaling2013

    • Author(s)
      Matsuoka J, Yashiro M, Doi Y, Fuyuhiro Y, Kato Y, Shinto O, Aomatsu N, Hirakawa T, Hasegawa T, Shimizu K, Shimizu T, Miwa A, Yamada N, Sawada T, Hirakawa K
    • Journal Title

      PLoS One

      Volume: 8 Pages: e62310

    • Peer Reviewed
  • [Journal Article] Prognostic predictive values of gemcitabine sensitivity-related gene products for unresectable or recurrent biliary tract cancer treated with gemcitabine alone2013

    • Author(s)
      Murata A, Amano R, Yamada N, Kimura K, Yashiro M, Nakata B, Hirakawa K
    • Journal Title

      World J Surg Oncol

      Volume: 11 Pages: 117

    • Peer Reviewed
  • [Journal Article] IGF-1 receptor and IGF binding protein-3 might predict prognosis of patients with resectable pancreatic cancer2013

    • Author(s)
      Hirakawa T, Yashiro M, Murata A, Hirata K, Kimura K, Amano R, Yamada N, Nakata B, Hirakawa K
    • Journal Title

      BMC Cancer

      Volume: 13 Pages: 392

    • Peer Reviewed
  • [Journal Article] A prognostic indicator for the resection of liver metastasis of colorectal cancer2013

    • Author(s)
      Amano R, Yamada N, Nakata B, Kimura K, Yashiro M, Ohira M, Hirakawa K
    • Journal Title

      Surg Today

    • Peer Reviewed
  • [Journal Article] Glyoxalase 1 as a candidate for indicating the metastatic potential of SN12C human renal cell carcinoma cell clones2013

    • Author(s)
      Tanaka T, Kuramitsu Y, Wang Y, Baron B, Kitagawa T, Tokuda K, Hirakawa K, Yashiro M, Naito S, Nakamura K
    • Journal Title

      Oncol Rep

    • Peer Reviewed
  • [Journal Article] Successful resection of esophageal cancer with right aortic arch by video-assisted thoracoscopic surgery : a case report2013

    • Author(s)
      Kubo N, Ohira M, Lee T, Sakurai K, Toyokawa T, Tanaka H, Muguruma K, Kimura K, Nagahara H, Noda E, Amano R, Ohtani H, Yamashita Y, Yashiro M, Maeda K, Hirakawa K
    • Journal Title

      Anticancer Res

      Volume: 33 Pages: 1635-40

    • Peer Reviewed
  • [Journal Article] c-Kit expression as a prognostic molecular marker in patients with basal-like breast cancer2013

    • Author(s)
      Kashiwagi S, Yashiro M, Takashima T, Aomatsu N, Kawajiri H, Ogawa Y, Onoda N, Ishikawa T, Wakasa K, Hirakawa K
    • Journal Title

      Br J Surg

      Volume: 100 Pages: 490-6

    • Peer Reviewed
  • [Journal Article] Predictive value of expression of ERCC 1 and GST-p for 5-fluorouracil/oxaliplatin chemotherapy in advanced colorectal cancer2013

    • Author(s)
      Noda E, Maeda K, Inoue T, Fukunaga S, Nagahara H, Shibutani M, Amano R, Nakata B, Tanaka H, Muguruma K, Yamada N, Yashiro M, Ohira M, Ishikawa T, Hirakawa K
    • Journal Title

      Hepatogastroenterology

      Volume: 59 Pages: 130-3

    • Peer Reviewed
  • [Journal Article] VEGF-A/VEGFR-2 Signaling Plays an Important Role for the Motility of Pancreas Cancer Cells2012

    • Author(s)
      DoiY,YashiroM,YamadaN,AmanoR,NodaS,HirakawaK
    • Journal Title

      Ann Surg Oncol

      Volume: 19 Pages: 2733-43

    • Peer Reviewed
  • [Journal Article] CD133 is a useful surrogate marker for predicting chemosensitivity to neoadjuvant chemotherapy in breast cancer2012

    • Author(s)
      Aomatsu N, Yashiro M, Kashiwagi S, Takashima T, Ishikawa T, Ohsawa M, Wakasa K, Hirakawa K
    • Journal Title

      PLoS One

      Volume: 7 Pages: e45865

    • Peer Reviewed
  • [Journal Article] Multipeptide immune response to cancer vaccine IMA901 after single dose cyclophosphamide associates with longer patient survival2012

    • Author(s)
      Hirakawa K (他38名)
    • Journal Title

      Nat Med

      Volume: 18 Pages: 1254-61

    • Peer Reviewed
  • [Journal Article] Foretinib (GSK1363089), a multi-kinase inhibitor of MET and VEGFRs, inhibits growth of gastric cancer cell lines by blocking inter-receptor tyrosine kinase networks2012

    • Author(s)
      Kataoka Y, Mukohara T, Tomioka H, Funakoshi Y, Kiyota N, Fujiwara Y, Yashiro M, Hirakawa K, Hirai M, Minami H
    • Journal Title

      Invest New Drugs

      Volume: 30 Pages: 1352-60

    • Peer Reviewed
  • [Journal Article] Concurrent biological targeting therapy of squamous cell carcinoma of the esophagus with cetuximab and trastuzumab2012

    • Author(s)
      Yamazaki M, Yamashita Y, Kubo N, Yashiro M, Ohira M, Ako E, Tanaka H, Muguruma K, Sawada T, Hirakawa K
    • Journal Title

      Oncol Rep

      Volume: 28 Pages: 49-54

    • Peer Reviewed
  • [Journal Article] Role of the stemness factors sox2, oct3/4, and nanog in gastric carcinoma2012

    • Author(s)
      Matsuoka J, Yashiro M, Sakurai K, Kubo N, Ohira M, Hirakawa K
    • Journal Title

      J Surg Res

      Volume: 174 Pages: 130-5

    • Peer Reviewed
  • [Journal Article] Expression of Forkhead box P3 in tumour cells causes immunoregulatory function of signet ring cell carcinoma of the stomach2012

    • Author(s)
      Yoshii M, Tanaka H, Ohira M, Muguruma K, Yashiro M, Sawada T, Hirakawa K
    • Journal Title

      Br J Cancer

      Volume: 106 Pages: 1668-74

    • Peer Reviewed
  • [Journal Article] NC-6301, a polymeric micelle rationally optimized for effective release of docetaxel, is potent but is less toxic than native docetaxel in vivo2012

    • Author(s)
      Harada M, Iwata C, Saito H, Yashiro M, Hirakawa K, Miyazono K, Kato Y, Kano MR
    • Journal Title

      Int J Nanomedicine

      Volume: 7 Pages: 2713-27

    • Peer Reviewed
  • [Journal Article] Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for gastric cancer and expression of MHC class I2012

    • Author(s)
      Ito G, Tanaka H, Ohira M, Yoshii M, Yashiro M, Yamada N, Maeda K, Sawada T, Hirakawa K
    • Journal Title

      Exp Ther Med

      Volume: 3 Pages: 925-30

    • Peer Reviewed
  • [Journal Article] Successful resection of esophageal carcinoma associated with double aortic arch : a case report2012

    • Author(s)
      Kubo N, Ohira M, Yamashita Y, Sakurai K, Kimura K, Nagahara H, Noda E, Amano R, Yashiro M, Maeda K, Hirakawa K
    • Journal Title

      Anticancer Res

      Volume: 32 Pages: 3351-5

    • Peer Reviewed
  • [Journal Article] Plasminogen activator inhibitor 1 RNAi suppresses gastric cancer metastasis in vivo2012

    • Author(s)
      Nishioka N, Matsuoka T, Yashiro M, Hirakawa K, Roberts JD
    • Journal Title

      Cancer Sci

      Volume: 103 Pages: 228-32

    • Peer Reviewed
  • [Journal Article] Polymeric micelles incorporating (1,2-diaminocyclohexane)platinum (II) suppress the growth of orthotopic scirrhous gastric tumors and their lymph node metastasis2012

    • Author(s)
      Rafi M, Cabral H, Kano MR, Mi P, Iwata C, Yashiro M, Hirakawa K, Miyazono K, Nishiyama N, Kataoka K
    • Journal Title

      J Control Release

      Volume: 159 Pages: 189-96

    • Peer Reviewed
  • [Journal Article] PI3K/Akt signalling is required for the attachment and spreading, and growth in vivo of metastatic scirrhous gastric carcinoma2012

    • Author(s)
      Matsuoka T, Yashiro M, Nishioka N, Hirakawa K, Olden K, Roberts JD
    • Journal Title

      Br J Cancer

      Volume: 106 Pages: 1535-42

    • Peer Reviewed
  • [Journal Article] Coordinated expression of REG4 and aldehyde dehydrogenase 1 regulating tumorigenic capacity of diffuse-type gastric carcinoma-initiating cells is inhibited by TGF-beta2012

    • Author(s)
      Katsuno Y, Ehata S, Yashiro M, Yanagihara K, Hirakawa K, Miyazono K
    • Journal Title

      J Pathol

      Volume: 228(3) Pages: 391-404

    • Peer Reviewed
  • [Journal Article] Cancer-associated orthotopic myofibroblasts stimulates the motility of gastric carcinoma cells2012

    • Author(s)
      Fuyuhiro Y, Yashiro M, Noda S, Matsuoka J, Hasegawa T, Kato Y, Sawada T, Hirakawa K
    • Journal Title

      Cancer Sci

      Volume: 103 Pages: 797-805

    • Peer Reviewed
  • [Journal Article] An EGFR inhibitor enhances the efficacy of SN38, an active metabolite of irinotecan, in SN38-refractory gastric carcinoma cells2011

    • Author(s)
      Yashiro M, Qiu H, Hasegawa T, Zhang X, Matsuzaki T, Hirakawa K
    • Journal Title

      Br J Cancer

      Volume: 105 Pages: 1522-32

    • Peer Reviewed
  • [Journal Article] Intraperitoneal administration of an adenovirus vector carrying REIC/Dkk-3 suppresses peritoneal dissemination of scirrhous gastric carcinoma2011

    • Author(s)
      Than SS, Kataoka K, Sakaguchi M, Murata H, Du G, Yashiro M, Yanagihara K, Nasu Y, Kumon H, Huh NH
    • Journal Title

      Oncol Rep

      Volume: 25 Pages: 989-95

    • Peer Reviewed
  • [Journal Article] Bone morphogenetic protein-2 and -4 play tumor suppressive roles in human diffuse-type gastric carcinoma2011

    • Author(s)
      Shirai YT, Ehata S, Yashiro M, Yanagihara K, Hirakawa K, Miyazono K
    • Journal Title

      Am J Pathol

      Volume: 179 Pages: 2920-30

    • Peer Reviewed
  • [Journal Article] A FGFR2 inhibitor, Ki23057, enhances the chemosensitivity of drug-resistant gastric cancer cells2011

    • Author(s)
      Qiu H, Yashiro M, Zhang X, Miwa A, Hirakawa K
    • Journal Title

      Cancer Lett

      Volume: 307 Pages: 47-52

    • Peer Reviewed
  • [Journal Article] Borrmann's macroscopic criteria and p-Smad2 expression are useful predictive prognostic markers for cytology-positive gastric cancer patients without overt peritoneal metastasis2011

    • Author(s)
      Noda S, Yashiro M, Toyokawa T, Sawada T, Hirakawa K
    • Journal Title

      Ann Surg Oncol

      Volume: 18 Pages: 3718-25

    • Peer Reviewed
  • [Journal Article] Linoleic acid enhances angiogenesis through suppression of angiostatin induced by plasminogen activator inhibitor 12011

    • Author(s)
      Nishioka N, Matsuoka T, Yashiro M, Hirakawa K, Olden K, Roberts JD
    • Journal Title

      Br J Cancer

      Volume: 105 Pages: 1750-8

    • Peer Reviewed
  • [Journal Article] RhoA/ROCK signaling mediates plasticity of scirrhous gastric carcinoma motility2011

    • Author(s)
      Matsuoka T, Yashiro M, Shinto O, Hirakawa K
    • Journal Title

      Clin Exp Metastasis

      Volume: 28 Pages: 627-36

    • Peer Reviewed
  • [Journal Article] Effects of acute and chronic hypoxia on the radiosensitivity of gastric and esophageal cancer cells2011

    • Author(s)
      Kato Y, Yashiro M, Fuyuhiro Y, Kashiwagi S, Matsuoka J, Hirakawa T, Noda S, Aomatsu N, Ohira M, Hirakawa K
    • Journal Title

      Anticancer Res

      Volume: 31 Pages: 3369-75

    • Peer Reviewed
  • [Journal Article] Advantages of adjuvant chemotherapy for patients with triple-negative breast cancer at Stage II : usefulness of prognostic markers E-cadherin and Ki672011

    • Author(s)
      Kashiwagi S, Yashiro M, Takashima T, Aomatsu N, Ishikawa T, Hirakawa K
    • Journal Title

      Breast Cancer Res

      Volume: 13 Pages: R122

    • Peer Reviewed
  • [Journal Article] Identification of HLA-A*2402-restricted epitope peptide derived from ERas oncogene expressed in human scirrhous gastric cancer2011

    • Author(s)
      Iwauchi T, Tanaka H, Yamazoe S, Yashiro M, Kubo N, Muguruma K, Sawada T, Ohira M, Hirakawa K
    • Journal Title

      Cancer Sci

      Volume: 102 Pages: 683-9

    • Peer Reviewed
  • [Journal Article] Upregulation of cancer-associated myofibroblasts by TGF-beta from scirrhous gastric carcinoma cells2011

    • Author(s)
      Fuyuhiro Y, Yashiro M, Noda S, Kashiwagi S, Matsuoka J, Doi Y, Kato Y, Hasegawa T, Sawada T, Hirakawa K
    • Journal Title

      Br J Cancer

      Volume: 105 Pages: 996-1001

    • Peer Reviewed
  • [Journal Article] THBS4, a novel stromal molecule of diffuse-type gastric adenocarcinomas, identified by transcriptome-wide expression profiling2011

    • Author(s)
      Forster S, Gretschel S, Jons T, Yashiro M, Kemmner W
    • Journal Title

      Mod Pathol

      Volume: 24 Pages: 1390-403

    • Peer Reviewed
  • [Journal Article] Transforming growth factor-beta decreases the cancer-initiating cell population within diffuse-type gastric carcinoma cells2011

    • Author(s)
      Ehata S, Johansson E, Katayama R, Koike S, Watanabe A, Hoshino Y, Katsuno Y, Komuro A, Koinuma D, Kano MR, Yashiro M, Hirakawa K, Aburatani H, Fujita N, Miyazono K
    • Journal Title

      Oncogene.

      Volume: 30 Pages: 1693-705

    • Peer Reviewed
  • [Presentation] A c-Met inhibitor increases the chemosensitivity of cancer stem cells to the irinotecan active metabolite SN38 in gastric carcinoma2013

    • Author(s)
      Yashiro M, Fukuoka T, Kinoshita H, Nishii T, Hasegawa T, Matsuzaki T, Morisaki T, Hirakawa K
    • Organizer
      American Association for Cancer Research 104rd Annual Meeting
    • Place of Presentation
      Washington
    • Year and Date
      2013-04-07
  • [Presentation] An EGFR inhibitor enhances the efficacy of SN38, an active metabolite of irinotecan, in SN38-refractory gastric carcinoma cells2012

    • Author(s)
      Yashiro M, Fukuoka T, Kinoshita H, Nishii T, Hasegawa T, Matsuzaki T, Morisaki T, Hirakawa K
    • Organizer
      American Association for Cancer Research 103rd Annual Meeting.
    • Place of Presentation
      Convention Center, Chicago
    • Year and Date
      2012-04-04
  • [Book] 最新胃癌学2014

    • Author(s)
      八代正和
    • Total Pages
      751
    • Publisher
      日本臨床
  • [Remarks]

    • URL

      http://www.med.osaka-cu.ac.jp/surgical-oncology

  • [Patent(Industrial Property Rights)] プロスタグランジンD2合成酵素を利用した消化器癌治療剤2013

    • Inventor(s)
      公立大学法人大阪市立大学
    • Industrial Property Rights Holder
      平川弘聖, 八代正和, 福岡達成
    • Industrial Property Number
      特願2013-268465
    • Filing Date
      2013-12-26

URL: 

Published: 2015-06-25  

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