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Development of diagnostic and therapeutic strategies for gastrointestinalcancer : focus on tumor-associated ribosomal proteins

Research Project

Project/Area Number 20590746
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionSapporo Medical University

Principal Investigator

SASAKI Yasushi  Sapporo Medical University, 医学部, 准教授 (70322328)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsリボゾーム蛋白質 / 消化器癌 / p53 / 抗癌剤感受性 / アポトーシス / リボソーム蛋白質
Research Abstract

We report here that L13 is activated in human gastrointestinal cancers. By using qRT-PCR, we analyzed expression of L13 in freshly resected cancer tissue of the stomach, colorectum, and liver. Upregulation of L13 mRNA expression was observed in 10 (28%) of 36 stomach, 19 (41%) of 46 colorectal, and 5 (20%) of 25 liver cancer tissue samples compared to adjacent normal tissue samples. We also found that increased expression of the L13 gene was correlated with clinical staging in stomach cancers. Importantly, we discovered that L13 expression was inversely related to p53 mutational status in primary gastric cancer, and siRNA-mediated L13 suppression resulted in robust induction of p53 protein. These findings suggest that L13 plays an essential role in the progression of some gastrointestinal malignancies by numbing the p53 pathway, thus allowing tumorigenic growth in the presence of wild-type p53.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (52 results)

All 2011 2010 2009 2008 Other

All Journal Article (34 results) (of which Peer Reviewed: 34 results) Presentation (13 results) Remarks (2 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [Journal Article] Myogenic lineage differentiated mesenchymal stem cells enhance recovery from dextran sulfate sodium-induced colitis in the rat.2011

    • Author(s)
      Tanaka H, Arimura Y, Yabana T, Goto A, Hosokawa M, Nagaishi K, Yamashita K, Yamamoto H, Sasaki Y, Fujimiya M, Imai K, Shinomura Y.
    • Journal Title

      J Gastroenterol. 46

      Pages: 143-152

    • NAID

      10029027000

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of early growth response 2, a zinc-finger transcription factor, as a p53-regulated proapoptotic gene(Corresponding author)2010

    • Author(s)
      Yokota I, Sasaki Y, Kashima L, Idogawa M, Tokino T.
    • Journal Title

      Int J Oncol. 37

      Pages: 1407-1416

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] IGFBP7 is a p53 responsive gene specifically silenced in colorectal cancer with CpG island methylator phenotype.2010

    • Author(s)
      Suzuki H, Igarashi S, Nojima M, Maruyama R, Yamamoto E, Kai M, Akashi H, Watanabe Y, Yamamoto H, Sasaki Y, Itoh F, Imai K, Sugai T, Shen L, Issa JP, Shinomura Y, Tokino T, Toyota M.
    • Journal Title

      Carcinogenesis 31

      Pages: 342-349

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA methylation of interferon regulatory factors in gastric cancer and noncancerous gastric mucosae.2010

    • Author(s)
      Yamashita M, Toyota M, Suzuki H, Nojima M, Yamamoto E, Kamimae S, Watanabe Y, Kai M, Akashi H, Maruyama R, Sasaki Y, Yamano H, Sugai T, Shinomura Y, Imai K, Tokino T, Itoh F.
    • Journal Title

      Cancer Sci. 101

      Pages: 1708-1716

    • NAID

      10026594987

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genomic screening for genes upregulated by demethylation revealed novel targets of epigenetic silencing in breast cancer.2010

    • Author(s)
      Fujikane T, Sasaki Y, Ohmura T, Hirata K, Tokino T(計14名,11番目)
    • Journal Title

      Breast Cancer Res Treat. 122

      Pages: 699-710

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification and characterization of early growth response 2, a zinc-finger transcription factor, as a p53-regulated proapoptotic gene2010

    • Author(s)
      Yokota I, et al
    • Journal Title

      Int J Oncol.

      Volume: 37 Pages: 1407-16

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA methylation of interferon regulatory factors in gastric cancer and noncancerous gastric mucosae2010

    • Author(s)
      Yamashita M, et al
    • Journal Title

      Cancer Sci.

      Volume: 101 Pages: 1708-16

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genomic screening for genes upregulated by demethylation revealed novel targets of epigenetic silencing in breast cancer2010

    • Author(s)
      Fujikane T, et al
    • Journal Title

      Breast Cancer Res Treat

      Volume: 122 Pages: 699-710

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IGFBP7 is a p53-responsive gene specifically silenced in colorectal cancer with CpG island methylator phenotype.2010

    • Author(s)
      Suzuki H, et al
    • Journal Title

      Carcinogenesis

      Volume: 31 Pages: 342-9

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Myogenic lineage differentiated mesenchymal stem cells enhance recovery from dextran sulfate sodium-induced colitis in the rat2010

    • Author(s)
      Tanaka H, et al
    • Journal Title

      J Gastroenterol

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic alteration of DNA in mucosal wash fluid predicts invasiveness of colorectal tumors2010

    • Author(s)
      Kamimae S, et al
    • Journal Title

      Cancer Prev.Res.

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IGFBP7 is a p53 Responsive Gene Specifically Silenced in Colorectal Cancer with CpG Island Methylator Phenotype2010

    • Author(s)
      Suzuki H, et al
    • Journal Title

      Carcinogenesis 31

      Pages: 342-49

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genomic screening for genes upregulated by demethylation revealed novel targets of epigenetic silencing in breast cancer2010

    • Author(s)
      Fujikane T, et al
    • Journal Title

      Breast Cancer Res Treat (In press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p53 Family Members Regulate the Expression of the Apolipoprotein D Gene.2009

    • Author(s)
      Sasaki Y, Negishi H, Koyama R, Anbo N, Ohori K, Idogawa M, Mita H, Toyota M, Imai K, Shinomura Y, Tokino T.
    • Journal Title

      J Biol Chem. 284

      Pages: 872-883

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A single recombinant adenovirus expressing p53 and p21-targeting artificial microRNAs efficiently induces apoptosis in human cancer cells.2009

    • Author(s)
      Idogawa M, Sasaki Y, Suzuki H, Mita H, Imai K, Shinomura Y, Tokino T.
    • Journal Title

      Clin Cancer Res. 15

      Pages: 3725-3732

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] CHFR, a potential tumor suppressor, downregulates interleukin-8 through the inhibition of NF-kappaB.2009

    • Author(s)
      Kashima L, Toyota M, Mita H, Suzuki H, Idogawa M, Ogi K, Sasaki Y, Tokino T.
    • Journal Title

      Oncogene 28

      Pages: 2643-2653

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhancing epithelial engraftment of rat mesenchymal stem cells restores epithelial barrier integrity.2009

    • Author(s)
      Yabana T, Arimura Y, Sasaki Y, Isobe M, Fujimiya M, Imai K, Shinomura Y(計14名,10番目)
    • Journal Title

      J Pathol. 218

      Pages: 350-359

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genomic screening for genes silenced by DNA methylation revealed an association between RASD1 inactivation and dexamethasone resistance in multiple myeloma.2009

    • Author(s)
      Nojima M, Sasaki Y, Imai K, Tokino T, Ishida T, Toyota M, Shinomura Y(計16名,7番目)
    • Journal Title

      Clin Cancer Res. 15

      Pages: 4356-4364

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers : involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth.2009

    • Author(s)
      Mita H, Toyota M, Aoki F, Akashi H, Maruyama R, Sasaki Y, Suzuki H, Idogawa M, Kashima L, Yanagihara K, Fujita M, Hosokawa M, Kusano M, Tatsumi H, Imai K, Shinomura Y, Tokino T.
    • Journal Title

      BMC Cancer. 9

      Pages: 198-198

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] P53 Family Members Regulate the Expression of the Apolipoprotein D Gene2009

    • Author(s)
      Sasaki Y, et al
    • Journal Title

      J Biol Chem 284

      Pages: 872-83

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] N-propionyl-cysteaminylphenol-magnetite conjugate(NPrCAP/M)is a novel nanoparticle for the targeted growth suppression of melanoma cells2009

    • Author(s)
      Sato M, et al
    • Journal Title

      J Invest Dermatol 129

      Pages: 2233-41

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A single recombinant adenovirus expressing p53 and p21-targeting artificial microRNAs efficiently induces apoptosis in human cancer cells2009

    • Author(s)
      Idogawa M, et al
    • Journal Title

      Clin Cancer Res 15

      Pages: 3725-32

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CHFR, a potential tumor suppressor, downregulates interleukin-8 through the inhibition of NF-kappaB2009

    • Author(s)
      Kashima L, et al
    • Journal Title

      Oncogene 28

      Pages: 2643-53

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhancing epithelial engraftment of rat mesenchymal stem cells restores epithelial barrier integrity2009

    • Author(s)
      Yabana T, et al
    • Journal Title

      J Pathol 218

      Pages: 350-59

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers : involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth2009

    • Author(s)
      Mita H, et al
    • Journal Title

      BMC Cancer 9

      Pages: 198-198

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genomic screening for genes silenced by DNA methylation revealed an association between RASD1 inactivation and dexamethasone resistance in multiple myeloma2009

    • Author(s)
      Nojima M, et al
    • Journal Title

      Clin Cancer Res 15

      Pages: 4356-64

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] p53 family members regulate the expression of the apolipoprotein D gene2009

    • Author(s)
      Sasaki Y, et al
    • Journal Title

      J Biol Chem. 284

      Pages: 872-883

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of flotillin-2, a major protein on lipid rafts, as a novel target of the p53 family members.2008

    • Author(s)
      Sasaki Y, Oshima Y, Koyama R, Maruyama R, Akashi H, Mita H, Toyota M, Shinomura Y, Imai K, Tokino T.
    • Journal Title

      Mol Cancer Res. 6

      Pages: 395-406

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histone deacetylase inhibitor FK228 enhances adenovirus-mediated p53 family gene therapy in cancer models.2008

    • Author(s)
      Sasaki Y, Negishi H, Idogawa M, Suzuki H, Mita H, Toyota M, Shinomura Y, Imai K, Tokino T.
    • Journal Title

      Mol Cancer Ther. 7

      Pages: 779-787

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cytoplasmic RASSF2A is a pro-apoptotic mediator whose expression is epigenetically silenced in gastric cancer.2008

    • Author(s)
      Maruyama R, Toyota M, Sasaki Y, Imai K, Shinomura Y (計18名,10番目)
    • Journal Title

      Carcinogenesis 29

      Pages: 1312-1318

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] LINE-1 hypomethylation is associated with increased CpG island methylation in Helicobacter pylori-related enlarged-fold gastritis.2008

    • Author(s)
      Yamamoto E, Toyota M, Suzuki H, Sasaki Y, Hayashi N, Mori M, Imai K, Tokino T, Shinomura Y(計17名,12番目)
    • Journal Title

      Cancer Epidemiol Biomarkers Prev. 17

      Pages: 2555-2564

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer.2008

    • Author(s)
      Toyota M, Suzuki H, Sasaki Y, Maruyama R, Imai K, Shinomura Y, Tokino T.
    • Journal Title

      Cancer Res. 68

      Pages: 4123-4132

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of flotillin-2, a major protein on lipid rafts, as a novel target of the p53 family mem2008

    • Author(s)
      Sasaki Y, et al
    • Journal Title

      Mol Cancer Res. 6

      Pages: 395-406

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The histone deacetylase inhibitor FK228 enhances adenovirus-mediated p53 family gene therapy in cancer m〓2008

    • Author(s)
      Sasaki Y, et al
    • Journal Title

      Mol Cancer Ther. 7

      Pages: 779-787

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] p53ファミリーの新規標的ICAM2の同定:がん細胞の接着・遊走能への関与2010

    • Author(s)
      平野雄大, ら
    • Organizer
      第33回日本分子生物学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] p53により発現抑制される分泌性増殖因子HDGFの同定2010

    • Author(s)
      佐々木泰史, 根岸秀明, 横田育子, 鹿島理沙, 井戸川雅史, 鈴木拓, 豊田実, 今井浩三, 篠村恭久, 時野隆至
    • Organizer
      第69回日本癌学会学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Negative regulation of hepatoma-derived growth factor by p53.2010

    • Author(s)
      Sasaki Y, Negishi H, Koyama R, Kusano M, Suzuki H, Fujita M, Toyota M, Tokino T
    • Organizer
      38th Congress of the International Society of Oncology and BioMarkers.
    • Place of Presentation
      Munchen, Germany
    • Year and Date
      2010-09-04
    • Related Report
      2010 Final Research Report
  • [Presentation] Negative regulation of hepatoma-derived growth factor by p532010

    • Author(s)
      Sasaki Y, et al
    • Organizer
      38th Congress of the International Society of Oncology and BioMarkers
    • Place of Presentation
      Munchen, Germany
    • Year and Date
      2010-09-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] hCLCA2, a p53 inducible transmembrane protein regulates cancer cell migration and adhesion.2010

    • Author(s)
      佐々木泰史, 横田育子, 鹿島理沙, 井戸川雅史, 鈴木拓, 豊田実, 今井浩三, 篠村恭久, 時野隆至
    • Organizer
      8th AACR-JCA Joint International Conference.
    • Place of Presentation
      Waikoloa, Hawaii
    • Year and Date
      2010-02-08
    • Related Report
      2010 Final Research Report
  • [Presentation] p53ファミリーの標的遺伝子CLCA2の同定と機能解析2009

    • Author(s)
      佐々木泰史, 安保直樹, 鹿島理沙, 井戸川雅史, 鈴木拓, 豊田実, 今井浩三, 篠村恭久, 時野隆至
    • Organizer
      第68回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2009-10-02
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] ヒストン脱アセチル化酵素阻害剤の併用によるp53遺伝子治療の作用増強2009

    • Author(s)
      佐々木泰史, ら
    • Organizer
      第25回日本DDS学会総会
    • Place of Presentation
      東京
    • Year and Date
      2009-07-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] p53により発現抑制される分泌性増殖因子HDGFの同定-胃癌組織における発現解析2009

    • Author(s)
      佐々木泰史, 井戸川雅史, 鈴木拓, 豊田実, 今井浩三, 篠村恭久
    • Organizer
      第95回日本消化器病学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2009-05-08
    • Related Report
      2010 Final Research Report
  • [Presentation] p53により発現抑制される分泌性増殖因子HDGFの同定2009

    • Author(s)
      佐々木泰史, ら
    • Organizer
      第95回日本消化器病学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2009-05-08
    • Related Report
      2009 Annual Research Report
  • [Presentation] p53 family members regulate the expression of the apolipoprotein D gene2009

    • Author(s)
      佐々木泰史, et al
    • Organizer
      American Association of Cancer Research Annual meeting
    • Place of Presentation
      米国 デンバー
    • Year and Date
      2009-04-21
    • Related Report
      2009 Annual Research Report
  • [Presentation] p53 family members regulate the expression of the apolipoprotein D gene.2009

    • Author(s)
      Sasaki Y, Negishi H, Koyama R, Anbo N, Yokota I, Ohori K, Idogawa M, Mita H, Toyota M, Imai K, Shinomura Y, Tokino T
    • Organizer
      American Association of Cancer Research (AACR) Annual meeting.
    • Place of Presentation
      Denver, USA
    • Year and Date
      2009-04-20
    • Related Report
      2010 Final Research Report
  • [Presentation] p53ファミリー(p73,p63)の標的遺伝子apolipoprotein Dの同定2008

    • Author(s)
      佐々木泰史, 安保直樹, 根岸秀明, 井戸川雅史, 見田裕章, 豊田実, 今井浩三, 篠村恭久, 時野隆至
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-29
    • Related Report
      2010 Final Research Report
  • [Presentation] p53ファミリー(p73, p63)の標的遺伝子apolipoprotein Dの同定2008

    • Author(s)
      佐々木泰史, 他
    • Organizer
      第67回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-10-28
    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://web.sapmed.ac.jp/canmol/index.html

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://web.sapmed.ac.jp/canmol/index.html

    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] Apoptosis inducer2009

    • Inventor(s)
      井戸川雅史, 佐々木泰史, 時野隆至
    • Industrial Property Rights Holder
      井戸川雅史, 佐々木泰史, 時野隆至
    • Filing Date
      2009-04-13
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] Apoptosis inducer2009

    • Inventor(s)
      井戸川雅史, 佐々木泰史, 時野隆至
    • Industrial Property Rights Holder
      井戸川雅史, 佐々木泰史, 時野隆至
    • Filing Date
      2009-04-13
    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] p53とmiRNAによる治療剤2008

    • Inventor(s)
      井戸川雅史
    • Industrial Property Rights Holder
      井戸川雅史, 佐々木泰史, 他
    • Filing Date
      2008-04-10
    • Related Report
      2008 Annual Research Report
    • Overseas

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Published: 2008-04-01   Modified: 2016-04-21  

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