Development of individualized diagnosis for cancer of digestive organ

• Project/Area Number: 17015042
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Keio University
• Principal Investigator: SAKAMOTO Michiie Keio University, 医学部, 教授 (40221270)
• Project Period (FY): 2005 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥66,700,000 (Direct Cost: ¥66,700,000); Fiscal Year 2009: ¥13,300,000 (Direct Cost: ¥13,300,000); Fiscal Year 2008: ¥13,400,000 (Direct Cost: ¥13,400,000); Fiscal Year 2007: ¥13,400,000 (Direct Cost: ¥13,400,000); Fiscal Year 2006: ¥13,400,000 (Direct Cost: ¥13,400,000); Fiscal Year 2005: ¥13,200,000 (Direct Cost: ¥13,200,000)
• Keywords: 多段階発がん / 早期肝細胞がん / 浸潤性膵管がん / 神経浸潤 / 移植モデル / 遺伝子発現プロファイル / プロテオーム / 浸潤 / synuclein-Y / Schwann細胞 / 予後因子 / 悪性度 / CD74

Research Abstract

We found that cyclase-associated protein 2 (CAP2) is up-regulated in early HCC and is further up-regulated in progressed HCC. Another homologue CAP1 was overexpressed in pancreatic cancer and was involved in cancer cell motility and poor prognosis. We established a novel perineural invasion model and distinguished high- and low- perineural invasion group in pancreatic cancer. Gene expression analysis revealed CD74 as a possible molecule involved in perineural invasion. Proteomic analysis revealed synuclein-γ is closely involved in perineural invasion and distant metastasis and is a prognostic factor in pancreatic cancer.

Research Products

• [Journal Article] Bmi-1 gene is upregulated in early-stage hepatocellular carcinoma and correlates with ATP-binding cassette transporter B1 (ABCB1) expression. (2010)
  • Author(s): Effendi K, Mori T, Komuta M, Masugi Y, Du W, Sakamoto M
  • Journal Title: Cancer Sci (in press)
  • Peer Reviewed
• [Journal Article] Endothelin-2 is upregulated in basal cell carcinoma under control of Hedgehog signaling pathway. (2010)
  • Author(s): Tanese K, Fukuma M, Ishiko A, Sakamoto M
  • Journal Title: Biochem Biophys Res Commun 391 Pages: 486-491
  • Peer Reviewed
• [Journal Article] Bmi-1 gene is upregulated in early-stage hepatocellular carcinoma and correlates with ATP-binding cassette transporter B1 (ABCB1) expression. (2010)
  • Author(s): Effendi K, Mori T, Komuta M, Masugi Y, Du W, Sakamoto M.
  • Journal Title: Cancer Sci (in press)
  • Peer Reviewed
• [Journal Article] Endothelin-2 is upregulated in basal cell carcinoma under control of Hedgehog signaling pathway. (2010)
  • Author(s): Tanese K, Fukuma M, Ishiko A, Sakamoto M.
  • Journal Title: Biochem Biophys Res Commun. 391 Pages: 486-491
  • Peer Reviewed
• [Journal Article] Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility. (2009)
  • Author(s): Yamazaki K, Takamura M, Masugi Y, Mori T, Du W, Hibi T, Hiraoka N, Ohta T, Ohki M, Hirohashi S, Sakamoto M
  • Journal Title: Lab Invest 89(4) Pages: 425-432
  • Peer Reviewed
• [Journal Article] Construction of human monoclonal single-chain Fv antibodies against small-cell lung cancer by phage display libraries derived from cell-immunized SCID mice engrafted with human peripheral blood lymphocytes. (2009)
  • Author(s): Douguchi J, Hashiguchi A, Sakamoto M
  • Journal Title: Proteomics Clin Appl 3 Pages: 1265-1272
  • Peer Reviewed
• [Journal Article] Synuclein-gamma is closely involved in perineural invasion and distant metastasis in mouse models and is a novel prognostic factor in pancreatic cancer. (2009)
  • Author(s): Hibi T, Mori T, Fukuma M, Yamazaki K, Hashiguchi A, Yamada T, Tanabe M, Aiura K, Kawakami T, Ogiwara A, Kosuge T, Kitajima M, Kitagawa Y, Sakamoto M
  • Journal Title: Clin Cancer Res 15(8) Pages: 2864-2871
  • Peer Reviewed
• [Journal Article] Early HCC : diagnosis and molecular markers. (2009)
  • Author(s): Sakamoto M.
  • Journal Title: J Gastroenterol. 44Suppl19 Pages: 108-111
  • NAID: 10024364289
  • Peer Reviewed
• [Journal Article] Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility. (2009)
  • Author(s): Yamazaki K, Takamura M, Masugi Y, Mori T, Du W, Hibi T, Hiraoka N, Ohta T, Ohki M, Hirohashi S, Sakamoto M.
  • Journal Title: Lab Invest. 89(4) Pages: 425-432
  • Peer Reviewed
• [Journal Article] Pathologic diagnosis of early hepatocellular carcinoma : a report of the international consensus group for hepatocellular neoplasia. (2009)
  • Author(s): International Consensus Group for Hepatocellular Neoplasia.
  • Journal Title: Hepatology. 49(2) Pages: 658-664
  • Peer Reviewed
• [Journal Article] Intraductal carcinoma component as a favorable prognostic factor in biliary tract carcinoma. (2009)
  • Author(s): Ojima H, Kanai Y, Iwasaki M, Hiraoka N, Shimada K, Sano T, Sakamoto Y, Esaki M, Kosuge T, Sakamoto M, Hirohashi S.
  • Journal Title: Cancer Sci. 100(1) Pages: 62-70
  • NAID: 10025141316
  • Peer Reviewed
• [Journal Article] Construction of human monoclonal single-chain Fvantibodies against small-cell lung cancer by phagedisplay libraries derived from cell-immunized SCID mice engrafted with human peripheral blood lymphocytes. (2009)
  • Author(s): Douguchi J, Hashiguchi A, Sakamoto M.
  • Journal Title: Proteomics Clin Appl 3 Pages: 1265-1272
  • Peer Reviewed
• [Journal Article] Synuclein-gamma is closely involved in perineural invasion and distant metastasis in mouse models and is a novel prognostic factor in pancreatic cancer. (2009)
  • Author(s): Hibi T, Mori T, Fukuma M, Yamazaki K, Hashiguchi A, Yamada T, Tanabe M, Aiura K, Kawakami T, Ogiwara A, Kosuge T, Kitajima M, Kitagawa Y, Sakamoto M.
  • Journal Title: Clin Cancer Res 15(8) Pages: 2864-2871
  • Peer Reviewed
• [Journal Article] Adenylate cyclase-associated protein 1 overexpressed in pancreatic cancers is involved in cancer cell motility (2009)
  • Author(s): Yamazaki K, Takamura M, Masugi Y, Mori T, Du W, Hibi T, Hiraoka N, Ohta T, Ohki M, Hirohashi S, Sakamoto M
  • Journal Title: Lab Invest (in press)
  • Peer Reviewed
• [Journal Article] Synuclein-y is closely involved in perineural invasion and distant metastasis in mouse models and is a novel prognostic factor in pancreatic cancer (2009)
  • Author(s): Hibi T, Mori T, Fukuma M, Yamazaki K, Hashiguchi A, Yamada T, Tanabe M, Aiura K, Kawakami T, Ogiwara A, Kosuge T, Kitajima M, Kitagawa Y. Sakamoto M
  • Journal Title: Clin Cancer Res (in press)
  • Peer Reviewed
• [Journal Article] G-Protein-Coupled Receptor GPR49 is Up-regulated in Basal Cell Caricinoma and Promotes Cell Proliferation and Tumor Formation. (2008)
  • Author(s): Tanese K, Fukuma M, Yamada T, Mori T, Yoshikawa T, Watanabe W, Ishiko A, Amagai M, Nihsikawa T, Sakamoto M
  • Journal Title: Am J Pathol 173 Pages: 835-843
  • Peer Reviewed
• [Journal Article] Histopathological features and prognostic significance of the micropapillary pattern in lung adenocarcinoma. (2008)
  • Author(s): Kamiya K, Hayashi Y, Douguchi J, Hashiguchi A, Yamada T, Izumi Y, Watanabe M, Kawamura M, Horinouchi H, Shimada N, Kobayashi K, Sakamoto M
  • Journal Title: Mod Pathol 21 Pages: 992-1001
  • Peer Reviewed
• [Journal Article] Expression Profile of Early Lung Adenocarcinoma: Identification of MRP3 as a Molecular Marker for Early Progression. (2008)
  • Author(s): Hanada S, Maeshima A, Matsuno Y, Ohta T, Ohki M, Yoshida T, Hayashi Y, Yoshizawa Y, Hirohashi S, Sakamoto M
  • Journal Title: J Pathol 216 Pages: 75-82
  • Peer Reviewed
• [Journal Article] Establishment of an ovarian metastasis model and possible involvement of E-cadherin down-regulation in the metastasis. (2008)
  • Author(s): Kuwabara Y, Yamada T, Yamazaki K, Du W, Banno K, Aoki D, Sakamoto M
  • Journal Title: Cancer Sci 99 Pages: 1933-1939
  • NAID: 10024011784
  • Peer Reviewed
• [Journal Article] G-Protein-Coupled Receptor GPR49 is Up-regulated inBasal Cell Caricinoma and Promotes Cell Proliferation and Tumor Formation (2008)
  • Author(s): Tanese K, Fukuma M, Yamada T, Mori T, Yoshikawa T, Watanabe W, Ishiko A, Amagai M, Nihsikawa T, Sakamoto M
  • Journal Title: Am J Pathol 173 Pages: 835-843
  • Peer Reviewed
• [Journal Article] Histopathological features and prognostic significance of the micropapillary pattern in lung adenocarcinoma (2008)
  • Author(s): Kamiya K, Hayashi Y, Douguchi J, Hashiguchi A, Yamada T, Izumi Y, Watanabe M, Kawamura M, Horinouchi H, Shimada N, Kobayashi K, Sakamoto M
  • Journal Title: Mod Pathol 21 Pages: 992-1001
  • Peer Reviewed
• [Journal Article] Expression Profile of Early Lung Adenocarcinoma : Identification of MRP3 as a Molecular Marker for Early Progression (2008)
  • Author(s): Hanada S, Maeshima A, Matsuno Y, Ohta T, Ohki M, Yoshida T, Hayashi Y, Yoshizawa Y, Hirohashi S, Sakarnnin M
  • Journal Title: J Pathol 216 Pages: 75-82
  • Peer Reviewed
• [Journal Article] Establishment of an ovarian metastasis model and possible involvement of E-cadherin down-regulation in the metastasis (2008)
  • Author(s): Kuwabara Y, Yamada T, Yamazaki K, Du W, Banno K, Aoki D, Sakamoto M
  • Journal Title: Cancer Sci 99 Pages: 1933-1939
  • NAID: 10024011784
  • Peer Reviewed
• [Journal Article] Reconstitution of Schwannian Stroma in Neuroblastomas Using Human Bone Marrow Stromal Cells (2008)
  • Author(s): Du W, Hozumi N, Sakamoto M, Hata J, Yamada T
  • Journal Title: AmJ Pathol 173 Pages: 1153-1164
  • Peer Reviewed
• [Journal Article] Specific Expression of Hepatocyte Nuclear Factor-1βin the Ovarian Clear Cell Adenocarcinoma and its Application to Cytological Diagnosis. (2007)
  • Author(s): Higashiguchi A, Yamada T, Susumu N, Mori T, Suzuki A, Aoki D, Sakamoto M
  • Journal Title: Cancer Sci 98 Pages: 387-391
  • Peer Reviewed
• [Journal Article] Gene therapy of liver timors with human liver-specific nanoparticles. (2007)
  • Author(s): Iwasaki Y, Ueda M, Yamada T, Kondo A, Seno M, Tanizawa K, Kuroda S, Sakamoto M. Kitaiima M
  • Journal Title: Cancer Gene Therapy 14 Pages: 74-81
  • Peer Reviewed
• [Journal Article] Specific Expression of Hepatocyte Nuclear Factor。1Bin theOvarian Clear Cell Adenocarcinoma and its Application to Cytological Diagnosis. (2007)
  • Author(s): Higashiguchi A, Yamada T, Susumu N, Mori T, SuzukiA, Aoki D, Sakamoto M
  • Journal Title: Cancer Sci 98 Pages: 387-391
  • Peer Reviewed
• [Journal Article] Genome-wide array-based comparative genomic hybridizationanalysis of pancreatic adenocarcinoma: Identification of genti indicators that predict patient outcome. (2007)
  • Author(s): Loukopoulos P, Shibata T, Katoh H, Kokubu A, Saka moto M, Yamazaki K, Kosuge T, Kanai Y, Hosoda F, Imoto I, Ohki M, Inazawa J, Hirohashi S
  • Journal Title: Cancer Sci 98 Pages: 392-400
  • Peer Reviewed
• [Journal Article] Efficient immortalization of primary human cells by p16INK4a-specific short hairpin RNA or Bmi-1, combined with introduction of hTERT. (2007)
  • Author(s): Haga K, Ohno S, Yugawa T, Narisawa-Saito M, FujitaM, Sakamoto M, GallowayDA, Kiyono T
  • Journal Title: Cancer Sci 98 Pages: 147-154
  • Peer Reviewed
• [Journal Article] Establishment of a novel childhood acute myeloid leukemia cell line, KOPM-88, containing partial tandem duplication of theMLL gene and an in vivo model for childhood acute myeloid leukemia using NOD/SCID mice. (2007)
  • Author(s): Hayashi M, Kondoh K, Nakata Y; Kinoshita A, ]Mori T, Takahashi T, Sakamoto M, Yamada T:
  • Journal Title: Br J Haematol 137 Pages: 221-232
  • Peer Reviewed
• [Journal Article] Gene therapy of liver timors with human liver-specific nanoparticles (2007)
  • Author(s): Iwasaki Y, Ueda M, Yamada T, Kondo A, Seno M, Tanizawa K, Kuroda S, Sakamoto M, Kitajima M
  • Journal Title: Cancer Gene Therapy 14 Pages: 74-81
• [Journal Article] Efficient immortalization of primary human cells by p16INK4a-specific short hairpin RNA or Bmi-1, combined with introduction of hTERT (2007)
  • Author(s): Haga K, Ohno S, Yugawa T, Narisawa-Saito M, Fujita M, Sakamoto M, Galloway DA, Kiyono T
  • Journal Title: Cancer Sci 98 Pages: 147-154
• [Journal Article] Specific Expression of Hepatocyte Nuclear Factor-1 β in the Ovarian Clear Cell Adenocarcinoma and its Application to Cytological Diagnosis (2007)
  • Author(s): Higashiguchi A, Yamada T, Susumu N, Mori T, Suzuki A, Aoki D, Sakamoto M
  • Journal Title: Cancer Sci 98 Pages: 387-391
  • NAID: 10019481758
• [Journal Article] Establishment of Perineural Invasion Models and Analysis of Gene Expression Revealed an Invariant Chain (CD74) as a Possible Molecule involved in Perineural Invasion in Pancreatic Cancer. (2006)
  • Author(s): Koide N, Yamada T, Shibata R, Mori T, Fukuma M, Yamazaki K, Aiura K, Shimazu M, Hirohashi S, Nimura Y, Sakamoto M
  • Journal Title: Clin Cancer Res 12(8) Pages: 2419-2426
  • Peer Reviewed
• [Journal Article] Overexpression of cyclase-associated protein 2 in multistage hepatocarcinogenesis. (2006)
  • Author(s): Shibata R, Mori T, Du W, Chuma M, Gotoh M, Shimazu M, Ueda M, Hirohashi S, Sakamoto M
  • Journal Title: Clin Cancer Res 12(18) Pages: 5363-5368
  • Peer Reviewed
• [Journal Article] Establishment of Perineural Invasion Models and Analysis of Gene Expression Revealed an Invariant Chain (CD74) as a Possible Molecule involved in Perineural Invasion in Pancreatic Cancer (2006)
  • Author(s): Koide N, Yamada T, Shibata R, Mori T, Fukuma M, Yamazaki K, Aiura K, Shimazu M, Hirohashi S, Nimura Y, Sakamoto M
  • Journal Title: Clin Cancer Res 12(8) Pages: 2419-2426
• [Journal Article] CT Evalution of the Progression of Hypoattenuating Nodular Lesions in Virus-Related Chronic liver Disease (2006)
  • Author(s): Takaysu K, Muramatsu Y, Mizuguchi Y, Okusaka T, Shimada K, Tkayama T, Sakamoto M
  • Journal Title: AJR 187 Pages: 454-463
• [Journal Article] Overexpression of cyclase-associated protein 2 in multistage hepatocarcinogenesis (2006)
  • Author(s): Shibata H, Mori T, Du W, Chuma M, Gotoh M, Shimazu M, Ueda M, Hirohashi S, Sakamoto M
  • Journal Title: Ciln Cancer Res 12(18) Pages: 5363-5368
• [Journal Article] Akt Phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular caricinoma. (2005)
  • Author(s): Nakanishi K, Sakamoto M, Yamasaki S, Todo S, Hirohashi S
  • Journal Title: Cancer 103 Pages: 307-312
  • Peer Reviewed
• [Journal Article] Multistep and multicentric development of hepatocellular carcinoma: histological analysis of 980 resected nodules. (2005)
  • Author(s): Oikawa T, Ojima H, Yamasaki S, Takayama T, Hirohashi S, Sakamoto M
  • Journal Title: J Hepatol 42 Pages: 225-229
  • Peer Reviewed
• [Journal Article] Multistep and multicentric development of hepatocellular carcinoma : histological analysis of 980 resected nodules. (2005)
  • Author(s): Oikawa T, Ojima H, Yamasaki S, Takayama T, Hirohashi S, Sakamoto M.
  • Journal Title: J Hepatol 42 Pages: 225-229
• [Journal Article] Proposal of histological criteria for intraepithelial atypical/ proliferative biliary epithelial lesions of the bile duct in hepatolithiasis with respect to cholangiocarcinoma : Preliminary report based on interobserver agreement. (2005)
  • Author(s): Yoh Z, Aishima S, Ajioka Y, Haratake J, Kage M, Kondo F, Nimura Y, Sakamoto M, Sasaki M, Shimamatsu K, Wakasa K, Young N.P, Ming F.C, Atomi Y, Nakanuma Y
  • Journal Title: Pathol Int 55 Pages: 180-188
  • NAID: 10016474999
• [Journal Article] Clinical and pathological significance of activation of signal trnansducer and activator of transcription 3 in prostate cancer. (2005)
  • Author(s): Horinaga M, Okita H, Nakashima J, Kanao K, Sakamoto M, Murai M
  • Journal Title: Urology 66 Pages: 671-675
• [Journal Article] Domain-specific function of ShcC docking protein in neuroblastoma cells. (2005)
  • Author(s): Miyake I, Hakomori Y, Misu Y, Nakadate H, Matsuura N, Sakamoto M, Sakai R
  • Journal Title: Oncogene 24 Pages: 3206-3215
• [Journal Article] Establishment of Perineural Invasion Models and Analysis of Gene Expression Revealed an Invariant Chain (CD74) as a Possible Molecule involved in Perineural Invasion in Pancreatic Cancer
  • Author(s): Koide N, Yamada T, Shibata R, Mori T, Fukuma M, Yamazaki K, Aiura K, Shimazu M, Hirohashi S, Nimura Y, Sakamoto M.
  • Journal Title: Clin Cancer Res (in press)(印刷中)
• [Patent(Industrial Property Rights)] 血中のCAP2の測定方法、肝臓疾患の検出方法及び血中CAP2測定用検出キット (2009)
  • Inventor(s): 坂元亨宇, 他2名
  • Industrial Property Rights Holder: 坂元亨宇, 他2名
  • Industrial Property Number: 2009-060966
  • Filing Date: 2009-03-13
• [Patent(Industrial Property Rights)] Hedgehogシグナル活性調節剤、細胞増殖調節剤及びその使用方法 (2006)
  • Inventor(s): 坂元亨宇, 他2名
  • Industrial Property Rights Holder: 坂元亨宇, 他2名
  • Industrial Property Number: 2006-317576
  • Filing Date: 2006-11-24