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1999 Fiscal Year Final Research Report Summary

Basic Research on the Development and Progression of Pancreatic Duct Adenocarcinoma

Research Project

Project/Area Number 08407009
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionNara Medical University

Principal Investigator

KONISHI Yoichi  Nara Medical Univeresity Oncological Pathology, Professor, 医学部, 教授 (00075061)

Co-Investigator(Kenkyū-buntansha) TSUTSUMI Masahiro  Nara Medical University Oncological Pathology, Assistant Prof., 医学部, 講師 (00207416)
DENDA Ayumi  Nara Medical University Oncological Pathology, Assistant Prof., 医学部, 講師 (90110858)
NAKAE Dai  Nara Medical University Oncological Pathology, Associate Prof., 医学部, 助教授 (90207712)
TSUJIUCHI Toshifume  Nara Medical University Oncological Pathology, Assistant Prof., 医学部, 助手 (10254492)
Project Period (FY) 1996 – 1999
Keywordspancreatic carcinoma / hamster / heterocyclicamine / carcinogen / chemoprevention
Research Abstract

The importance of basic research related to pancreatic cancer should be focused on ductal adenocarcinoma since the incidence of * cancer is the highest, showing poor prognosis among various histological types of human pancreatic malignant neoplasms. However, experimental pancreatic duct adenocarcinoma (PDA) resembled histologically, biologically and genetically to human PDA can be induced by nitrosamines only in hamsters and dogs but not in other animal spieces. In this projects, we performed the research related to control the development and progression of PDA using a rapid production model of PDC in hamsters which was developed by us (Mizumoto, K. et al.,J.Natl.Cancer Inst.1998 ; 80 : 1564-1567) and PDA cell lines which were also established by us (Mori, T.et al.Int.J.Pancreao.1994 ; 16 : 171-177).
Genetic alterations related to the development and progression of PDA
1. The shortened telomeas and increased telomerase activities were detected in hamster PDA and also increased telomeras … More e activities were detected in 32 out of 38 cases (84%) of human PDA tissues. Among those cases, Ki-ras mutations were also detected in 20 cases (53%).
2. Midkine, one of growth factors, was overexpressed at mRNA level and also expressed at protein level in PDAs.
3. MMP-2, one of MMP families, was importantly involved in the development and progression of PDAs.
4. Bax, one of apoptosis related genes, was overexpressed in PDAs.
5.β-catenine was not involved in the development and progression of PDAs.
Possible control of PDA
1. Possible involvement of heterocyclic amines of Trp-p-1 and DiMeIQx in the development of PDA was suggested.
2. OPB-3206, a inhibition of MMPs, inhibited pancreatic duct carcinogenesis.
3.β-carotin at a dose of 0.0025%, palm carotin at 0.004%, greentea polyphynol at 0.05 and 0.5%, 4-hydoxyphenyl retinamide (4-HPR) at 0.0015% and tranexamic acid at 0.1% in the diets inhibited pancreatic duct carcinogenesis.
4. 4-HPR at the concentration of 10μ M and auraptene at 50μ M introduced apoptosis in culture PDA cells. Less

  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] T. Shimizu: "Absence of a mutation of the p21/WAF1 gene in human lung and pancreatic cancers"Jpn. J. Cancer Res.. 87. 275-278 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 堤 雅弘: "外科診断"膵癌の診断と治療. 38. 397-402 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 堤 雅弘: "膵癌と癌遺伝子 消化器病と癌遺伝子"消化器病セミナー. 63. 135-150 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 堤 雅弘: "膵癌"病理と臨床. 14. 161-164 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Kamano: "Mutagenic activation of N-Nitrosobis(2-Oxopropyl)amine by pancrcatic juice and assessment of its ductal tumorigenicity following intraductal administration in dogs"Int. J Pancreatol. 20(10). 51-57 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Kobitsu: "Shortend telomere length and increased telomerase activity in hamster pancreatic duct adenocarcinomas and cell lines"Molecular Medicine. 18. 153-159 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Maruyama: "Anaplastic Ki-1-positive large cell lymphoma of the pancreas : a case report and review of the literature"Jpn. J. Clin. Oncl.. 27. 51-57 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 堤 雅弘: "膵癌発生の機構とその修飾"消化器癌. 7(2). 217-221 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Majima: "Mutations of K-ras but not p53 genes in biliary duct and panereatic duct carcinomas induced in hamsters by cholecystoduodenostomy with dissection of the common duct followed by N-nitrosobis(2-oxopropyl)amine"消化器病セミナー. 63. 47-53 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M. Tsutsumi: "Increased telomerase activities in human pancreatic duct adenocarcinoms"Jpn. J. Cancer Res. 88. 971-976 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 堤 雅弘: "膵癌の膵管内発生部位と発育・進展様式"担と膵. 19(1). 11-17 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Majima: "Inhibitory effects of b-carotene Palm carotene, and Green Tea polyphenols on pancreatic carcinogenesis initiated by N-Nitirosobis(2-oxopropyl)amine in Syrian golden hamsters"Pancreas. 16(1). 13-18 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Y. Konishi: "Mechanistic analysis of pancreatic ductal carcinogenesis in hamsters"Pancreas. 16(3). 334-340 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Tsujiuchi: "Telomerase activity in experimental animal tumors"Exp. Toxic. Pathol. 50. 371-374 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M・Mori: "A Case-Control Study OnRisk Ractors for Panceratic Diseases in Kerala"Hepato-Gastroenterology. 46. 25-30 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akirara Kido: "Overexpression of materix inetalloproteinase(MMP)-9 correlates with metastatic Potency of spontaneous and 4-hydroxyaminoquinoline 1-oxide(4HAQO)-induced transplantable osteosarcomas in rats"Cancer Lett,. 137. 209-216 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ayimi Denda: "Geneteic properties for the suppression of development of putative preneplastic glutathione S-transferanse placental form-positive foci in the liver of carcinogen-resistant DRH stain rats"Cancer Lett.. 140. 59-67 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tomokazu Fukuda: "Cloning of differentially expressed genes in highly and low metastatic rat osteosarcomas by a modified DNA-AFLP method"Biochemical and Biophysical Research Communications. 261. 30-40 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toru Morishita: "Delay in administration of CDDP until completion of AGM-1470treatment nhances antimetastatic and antitumor effects"Clinical & Experimental Metastasis. 17. 15-18 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masahiro Tsutsumi: "Inhibitory effects of combined administration of antibiotics and anti-inflammatory drugs on lung tu, or development initiated by N-nitrosobis(2-hydroxypropyl)amine in rats"Carcinogenesis. 21. 251-256 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Makoto Takahama: "Enhanced expression of tie2, Its ligand angiopoterim-1, vascurar endothelial growth factor, and CD31 in human non-small cell lung carcinomas"Clinical Cancer Research. 5. 1606-1510 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Katsumichi Iki: "Expression of matrix metalloproteinase 2(MMP-2), membranetype * MMP andtissue inhibitor ofmetall oproteinase 2 and activation of proMMP-2 in pancreatic duct adenocarcinomas in hamsters treated with N-nitrosobis(2-oxopropyl)amine, Carcinogenesis"Carcinogenesis. 20. 1323-1329 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toshifumi Tsujiuchi: "Hypomethyalation of CpG sties and c-myc gene overexpression in Hepatocclular carcinoms, but not Hyperplastic nodules, Induced by a Chloline-dericient L-amino acid defined diet in rats"Jpn. j. Cancer. Res. 90. 909-913 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masatoshi Yoshimoto: "Carcinogenicity of heterocyclic amines for the pancreatic duct epinelium in hamsters"Cancer Lett. 143. 235-239 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 堤 雅弘: "切除膵臓癌における遺伝子異常"胆と膵. 20. 741-746 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 堤 雅弘: "膵臓発生の分子機構"消化器科. 30. 64-69 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wakshi Kitayama: "Increased expression of cycloosygenase-2 protein in rat urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine"Carcinogenesis. 20. 2305-2310 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masahiro Tsutsumi: "Gastric and intestinal phenotypic expression of human signet ring cell carcinomas revealed by their biochemistry, mucin histochemistry. and ultrastruture"Cancer Res. 46. 4866-4872 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Dai Nakae: "Endogenous liver carsinogenesis in the rat"Pathology Interbational. 49. 1028-1239 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toshifumi Tsujiuchi: "Defferent trequencies and patterns of b-Carenin mutations in heparocellular carcinomas onduced by N-Nitorosodienthylamine and choline-dificient L-amino acid-defined diet rats"Cancer Research. 59. 3904-3907 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Dai Nakae: "Age and organ department spontaneous generation of nuclear 8-hydroxydeoxyguanosine in male fischer 344 rats"Labolatory Investigetion. 80. 249-261 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Shimizu, W.Miwa, S.Nakamori, O.Ishikawa, Y.Konishi and T.Sekiya: "Absence of a mutation of the p21/WAF1 gene in human lung and pancreatic cancers."Jpn. J. Clin. Oncl. 27. 51-57 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Kamano, Y.Mori, K.Suda, M.Takahashi, T.Uchida, T.Takada, M.Tsutsumi, Y.Konishi: "Mutagenic activation of N-Nitrosobis(2-Oxopropyl)amine by pancreatic juice and assessment of its ductal tumorigenicity following intraductal administration in dogs."Int. J. Pancreatol. 20, 1. 51-57 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Kobitsu, M.Tsutsumi, T.Tsujiuchi, F.Suzuki, A.Kido, E.Okajima, T.Fukuda, T.Sakai and Y.Konishi: "Shortened telomere length and increased telomerase activity in hamster pancreatic duct adenocarcinomas and cell lines."Mol. Carcinogenesis. 18. 153-159 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Maruyama, N.Nakatsuji, S.Sugihara, M.Atsumi, K.Shimamoto, K.Hayashi, M.Tsutsumi, Y.Konishi: "Anaplastic Ki-1-positive large cell lymphoma of the pancreas : a case report and review of the literature."Jpn. J. Clin. Oncl. 27. 51-57 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Majima, T.Tsujiuchi, M.Tsutsumi, T.Tsunoda, Y.Konishi: "Mutations of K-ras but not p53 genes in biliary duct and pancreatic duct carcinomas induced in hamsters by cholecystoduodenostomy with dissection of the common duct followed by N-nitrosobis(2-oxopropyl)amine."Cancer Letters. 118. 47-53 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Tsutsumi, T.Tsujiuchi, O.Ishikawa, T.Majima, M.Yoshimoto, Y.Sasaki, T.Fukuda, H.Oohigashi and Y.Konishi: "Increased telomerase activities in human pancreatic duct adenocarcinomas."Jpn. J. Cancer Res. 88. 971-976 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Majima, M.Tsutsumi, H.Nishino, T.Tsunoda and Y.Konishi: "Inhibitory effects of β-carotene, Palm carotene, and Green Tea polyphenols on pancreatic carcinogenesis initiated by N-Nitrosobis(2-oxopropyl)amine in Syrian golden hamsters."Pancreas. 16 : 1. 13-18 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Konishi, M.Tsutsumi and T.Tsujiuchi: "Mechanistic analysis of pancreatic ductal carcinogenesis in hamsters."Pancreas. 16 : 3. 300-306 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Konishi, M.Tsutsumi and D.S.Longnecker: "Mechanistic Analysis and Chemoprevention of Pancreatic Carcinogenesis."Pancreas. 17 : 4. 334-340 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Tsujiuchi, M.Tsutsumi and Y.Konishi: "Telomerase activity in experimental animal tumors."Exp. Toxic. Pathol. 50. 371-374 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Mori, M.Hariharan, M.Anandakumar M.Tsutsumi, O.Ishikawa, Y.Konishi, VG.Chellam, M.John, I.Praseeda, R.Priya, M.Narendranathan: "A Case-control study on risk factors for pancreatic diseases in Kerala."Hepato-Gastroenterology. 46. 25-30 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Iki, M.Tsutsumi, A.Kido, H.Sakitani, K.Tatsumi, T.Tsunoda, Y.Konishi: "Expression of matrix metalloproteinase 2(MMP-2), membranetype 1 MMP and tissue inhibitor of metalloproteinase 2 and activation of proMMP-2 in pancreatic duct adenocarcinomas in hamsters treated with N-nitrosobis(2-oxopropyl)amine."Carcinogenesis. 20 : 7. 1323-1329 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Yoshimoto, M.Tsutsumi, K.Iki, Y.Sasaki, T.Tsujiuchi, T.Sugimura, K.Wakabayashi, Y.Konishi: "Carcinogenicity of heterocyclic amines for the pancreatic duct epithelium in hamsters"Cancer Letter. 143. 235-239 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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