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Towards establishment of gene therapy for human pancreatic and endometrial cancers

Research Project

Project/Area Number 10557026
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Experimental pathology
Research InstitutionTohoku University

Principal Investigator

HORII Akira  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40249983)

Co-Investigator(Kenkyū-buntansha) YAJIMA Akira  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80004993)
FURUKAWA Toru  Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (30282122)
SAKATA Tsuneaki  Shionogi Pharmaceuticals, Chief Scientist, 主任研究員
SUNAMURA Makoto  Tohoku University, Graduate School of Medicine, Lecturer, 医学部附属病院, 講師 (10201584)
小針 雅男  東北大学, 医学部, 助教授 (30170369)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 1999: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1998: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsAdenovirus vector / SMAD4 / PTEN / pancreatic cancer / endometrial cancer / アデノウィルスベクター / 癌抑制遺伝子 / 遺伝子導入 / DNAミスマッチ修復異常 / DUSP6遺伝子
Research Abstract

1.Among regions of frequent chromosomal aberrations, loss of three chromosomal regions, 12q, 17p, and 18q, associated with poor prognosis in human pancreatic cancer. Adenoviral mediated delivery of the SMAD4 gene in pancreatic cancer cell lines with homozygous deletion of SMAD4 did not show any suppression of cell growth. We previously reported that, loss of 18q is an early event in pancreatic carcinogenesis. There is a possibility that mutation of the SMAD4 gene is responsible for the initial step of pancreatic carcinogenesis as well as prognosis defining factor. However, there is a possibility of unknown tumor suppressor gene on 18q that is distinct from SMAD4.
2.We and others previously reported frequent somatic mutation of the PTEN gene in endometrial cancer. We attempted a trial of gene therapy by adenovirus mediated introduction of this gene in endometrial cancer cell lines with two-hit mutation of this gene. The trial was successful in vitro, and apoptosis was induced in tumor cells after introduction of normal copy of PTEN. However, the attempt was not successful in vivo. These results suggested that the PTEN gene is a good candidate for gene therapy in human endometrial cancer after appropriate improvement.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (57 results)

All 2000 1999 1998 Other

All Journal Article (36 results) Publications (21 results)

  • [Journal Article] Mutational analysis of the CTNNB1 (β-catenin) gene in human endometrial cancer : Frequent mutations at codon 34 that cause nuclear accumulation.2000

    • Author(s)
      Ikeda, T.
    • Journal Title

      Oncol.Rep. 7

      Pages: 323-326

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] p24/ING1-ALT1 and p47/ING1-ALT2,distinct alternative transcripts of p33/ING12000

    • Author(s)
      Saito, A.
    • Journal Title

      J.Hum.Genet. 45

      Pages: 177-181

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Anticorresponding mutations of the KRAS and PTEN genes in human endometrial cancer.2000

    • Author(s)
      Ikeda, T.
    • Journal Title

      Oncol.Rep. 7

      Pages: 567-570

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Analysis of the candidate target genes for mutation in microsatellite instability-positive cancers of the colorectum, stomach, and endometrium.2000

    • Author(s)
      Semba, S.
    • Journal Title

      Int.J.Oncol. 16

      Pages: 731-737

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Asscciation of poor prognosis with loss of 12q,17p, and 18q, and concordant loss of 6q/17p and 12q/18q in human pancreatic ductal adenocarcinoma.2000

    • Author(s)
      Yatsuoka, T.
    • Journal Title

      Am.J.Gastroent. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Mutational analysis of the CTNNB1(β-catenin) gene in human endometrial cancer : Frequent mutations at codon 34 that cause nuclear accumulation.2000

    • Author(s)
      Ikeda, T,.Yoshinaga, K., Semba, S., Kondo, E., Ohmori, H., Horii, A.
    • Journal Title

      Oncol.Rep. 7

      Pages: 323-326

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1.2000

    • Author(s)
      Saito, A., Furukawa, T., Fukushige, S., Koyama, S., Hoshi, M., Hayashi, Y., Horii, A.
    • Journal Title

      J.Hum.Genet. 45

      Pages: 177-181

    • NAID

      10011570238

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Anticorresponding mutations of the KRAS and PTEN genes in human endometrial cancer.2000

    • Author(s)
      Ikeda, T., Yoshinaga, K., Suzuki, A., Sakurada, A., Ohmori, H., Horii, A.
    • Journal Title

      Oncol.Rep. 7

      Pages: 567-570

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Analysis of the candidate target genes for mutation in microsatellite instability-positive cancers of the colorectum, stomach, and endometrium.2000

    • Author(s)
      Semba, S., Ouyang, H., Han, S.-Y., Kato, Y., Horii, A.
    • Journal Title

      Int.J.Oncol. 16

      Pages: 731-737

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Association of poor prognosis with loss of 12q, 17p, and 18q, and concordant loss of 6q/17p and 12q/18q in human pancreatic ductal adenocarcinoma.2000

    • Author(s)
      Yatsuoka, T., Sunamura, M., Furukawa, T., Fukushige, S., Yokoyama, T., Inoue, H., Shibuya, K., Takeda, K., Matsuno, S., Horii, A.
    • Journal Title

      Am.J.Gastroent. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer.1999

    • Author(s)
      Abe, T.
    • Journal Title

      Genes Chromosomes Cancer 25

      Pages: 60-64

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Infrequent somatic mutations of the p73 gene in various human cancers.1999

    • Author(s)
      Han, S.
    • Journal Title

      Eur.J.Surg.Oncol. 25

      Pages: 194-198

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Genomic analysis of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 in human pancreatic ductal adenocarcinoma.1999

    • Author(s)
      Yatsuoka, T.
    • Journal Title

      Int.J.Panc. 25

      Pages: 97-102

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Controlling tumor angiogenesis and metastasis of C26 murin colon adenocarcinoma by a new matrix metalloproteinase inhibitor, KB-R7785,in two tumor models.1999

    • Author(s)
      Lozonschi L.
    • Journal Title

      Cancer Res. 59

      Pages: 1252-1258

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Cloning and characterization of the human UDP-N-acetylglucosamine : α-1,3-D-mannoside β-1,4-N-acetylglucosaminyltransferase IV-homologue (hGnT-IV-H) gene1999

    • Author(s)
      Furukawa, T.
    • Journal Title

      J.Hum.Genet. 44

      Pages: 397-401

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated transfer or p33^<ING> with p53 drastically augments apoptosis in gliomas.1999

    • Author(s)
      Shinoura, N.
    • Journal Title

      Cancer Res. 59

      Pages: 5521-5528

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated delivery of the PTEN gene inhibits cell growth by induction of apoptosis in endometrial cancer.1999

    • Author(s)
      Sakurada, A.
    • Journal Title

      Int.J.Oncol. 15

      Pages: 1069-1074

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer.1999

    • Author(s)
      Abe, T., Makino, N., Furukawa.T., Ouyang, H., Kimura, M., Yatsuoka T., Yokoyama, T., Inoue, H., Fukushige, S., Hoshi, M., Hayashi, Y., Sunamura, M., Kobari, M., Matsuno, S., Horii, A.
    • Journal Title

      Genes Chromosomes Cancer 25

      Pages: 60-64

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Infrequent somatic mutations of the p73 gene in various human cancers.1999

    • Author(s)
      Han, S., Semba, S., Abe, T., Makino, N., Furukawa, T., Fukushige, S., Takahashi, H., Sakurada, A., Sato, M., Shiiba, K., Matsuno, S., Nimura, Y., Nakagawara, A., Horii, A.
    • Journal Title

      Eur.J.Surg.Oncol. 25

      Pages: 194-198

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Genomic analysis of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 in human pancreatic ductal adenocarcinoma.1999

    • Author(s)
      Yatsuoka, T., Furukawa, T., Abe, T., Yokoyama, T., Sunamura, M., Kobari, M., Matsuno, S., Horii, A.
    • Journal Title

      Int.J.Panc. 25

      Pages: 97-102

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Controlling tumor angiogenesis and metastasis of C26 murin colon adenocarcinoma by a new matrix metalloproteinase inhibitor, KB-R7785, in two tumor models.1999

    • Author(s)
      Lozonschi L., Sunamura M., Kobari M., Egawa S., Ding L., Matsuno S.
    • Journal Title

      Cancer Res. 59

      Pages: 1252-1258

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Cloning and characterization of the human UDP-N-acetylglucosamine:a-1,3-D-mannosideb-1,4-N-acetylglucosaminyltransferase IV-homologue (hGnT-IV-H) gene.1999

    • Author(s)
      Furukawa.T., Youssef, E.M., Yatsuoka, T., Yokoyama, T., Makino, N., Inoue, H., Fukushige, S., Hoshi, M., Hayashi, Y., Sunamura, M., Horii, A.
    • Journal Title

      J.Hum.Genet. 44

      Pages: 397-401

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated transfer of p33ING with p53 drastically augments apoptosis in gliomas.1999

    • Author(s)
      Shinoura, N., Muramatsu, Y., Nishimura, M., Yoshida, Y., Saito, A., Yokoyama, T., Furukawa, T., Horii, A., Hashimoto, M., Asai, A., Kirino, T., Hamada, H.
    • Journal Title

      Cancer Res. 59

      Pages: 5521-5528

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Adenovirus-mediated delivery of the PTEN gene inhibits cell growth by induction of apoptosis in endometrial cancer.1999

    • Author(s)
      Sakurada, A., Hamada, H., Fukushige, S., Yokoyama, T., Yoshinaga, K., Furukawa, T., Sato, S., Yajima, A., Sato, M., Fujimura, S., Horii, A.
    • Journal Title

      Int.J.Oncol. 15

      Pages: 1069-1074

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Genomic analysis of DUSP6,a dual specificity MAP kinase phosphatase, in pancreatic cancer.1998

    • Author(s)
      Furukawa, T.
    • Journal Title

      Cytogenetics and Cell Genetics 82

      Pages: 156-159

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Loss of chromosome 18q is an early event in pancreatic ductal tumorigenesis.1998

    • Author(s)
      Fukushige, S.
    • Journal Title

      Cancer Research 58

      Pages: 4222-4226

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] The PTEN, BAX, and 1GF11R genes are mutatead in endometrial atypical hyperplasia.1998

    • Author(s)
      Yoshinaga, K.
    • Journal Title

      Japanese Journal of Cancer Research 89

      Pages: 985-990

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Identification of a 100-kb region of common allelic loss on chromosome bands 10q25-q26 in human endometrial cancer.1998

    • Author(s)
      Yamakawa, H.
    • Journal Title

      Genes, Chromosomes & Cancer 23

      Pages: 74-77

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] The BAX gene, the promoter of apoptosis, is mutated in genetically unstable cancers of the colorectum, stomach, and endometrium.1998

    • Author(s)
      Ouyang, H.
    • Journal Title

      Clinical Cancer Research 4

      Pages: 1071-1074

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Identification of two common regions of allelic loss in chromosome arm 12q in human pancreatic cancer.1998

    • Author(s)
      Kimura, M.
    • Journal Title

      Cancer Research 58

      Pages: 2456-2460

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Genomic analysis of DUSP6, a dual specificity MAP kinase phosphatase, in pancreatic cancer.1998

    • Author(s)
      Furukawa, T., Yatsuoka, T., Youssef, E.M., Abe, T., Yokoyama, T., Fukushige, S., Soeda, E., Hoshi, M., Hayashi, Y., Sunamura, M., Kobari, M., Horii, A.
    • Journal Title

      Cytogenet.Cell Genet. 82

      Pages: 156-159

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Loss of chromosome 18q is an early event in pancreatic ductal tumorigenesis.1998

    • Author(s)
      Fukushige, S., Furukawa, T., Satoh, K., Sunamura, M., Kobari.M., Koizumi, M., Horii, A.
    • Journal Title

      Cancer Res. 58

      Pages: 4222-4226

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] The PTEN, BAX, and IGFIIR genes are mutated in endometrial atypical hyperplasia.1998

    • Author(s)
      Yoshinaga, K., Sasano, H., Furukawa, T., Yamakawa, H., Yuki, M., Sato, S., Yajima, A., Horii, A.
    • Journal Title

      Jpn.J.Cancer Res. 89

      Pages: 985-990

    • NAID

      10008086671

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Identification of a 100-kb region of common allelic loss on chromosome bands 10q25-q26 in human endometrial cancer.1998

    • Author(s)
      Yamakawa, H., Nagase, S., Yuki, M., Shiwaku, H.O., Furukawa, T., Yoshinaga, K., Soeda, E., Hoshi, M., Hayashi, Y., Sato, S., Yajima, A., Horii, A.
    • Journal Title

      Genes Chromosomes Cancer 23

      Pages: 74-77

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] The BAX gene, the promoter of apoptosis, is mutated in genetically unstable cancers of the colorectum, stomach, and endometrium.1998

    • Author(s)
      Ouyang, H., Furukawa, T., Abe, T., Kato, Y., Horii, A.
    • Journal Title

      Clin.Cancer Res. 4

      Pages: 1071-1074

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Journal Article] Identification of two common regions of allelic loss in chromosome arm 12q in human pancreatic cancer.1998

    • Author(s)
      Kimura, M., Furukawa, T., Abe, T., Yatsuoka, T., Youssef, E.M., Yokoyama, T., Ouyang, H., Ohnishi, Y., Sunamura, M., Kobari, M., Matsuno, S., Horii, A.
    • Journal Title

      Cancer Res. 58

      Pages: 2456-2460

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yatsuoka T.: "Association of poor prognosis with loss of 12q, 17p, and 18q, and concordant loss of 6q/17p and 12q/18q in human pancreatic ductal adenocarcinoma"Am.J. Gastroent.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Semba S.: "Analysis of the candidate target genes for mutation in microsatellite instability-positive cancers of the colorectum, stomach, and endometrium"Int.J. Oncol.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikeda T.: "Anticorresponding mutations of the KRAS and PTEN genes in human endometrial cancer"Oncol. Rep.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Saito A.: "p24/ING1-ALT1 and p47/ING1-ALT2, distinct alternative transcripts of p33/ING1"J.Hum. Genet.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikeda T.: "Mutational analysis of the CTNNB1 (β-catenin) gene in human endometrial cancer: Frequent mutations at codon 34 that cause nuclear accumulation"Oncol. Rep.. 7. 323-326 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sakurada A.: "Adenovirus-mediated delivery of the PTEN gene inhibits cell growth by induction of apoptosis in endometrial cancer"Int.J. Oncol. 15. 1069-1074 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shinoura N.: "Adenovirus-mediated transfer of p33^<ING> with p53 drastically augments apoptosis in gliomas"Cancer Res.. 59. 5521-5528 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Furukawa T.: "Cloning and characterization of the human UDP-N-acetylglucosamine: α-1,3-D-mannoside β-1,4-N-acetylglucosaminyltransferase IV-homologue (hGnT-IV-H) gene"J.Hum. Genet.. 44. 397-401 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yatsuoka T.: "Genomic analysis of the thymine-DNA glycosylase (TDG) gene on 12q22-q24.1 in human pancreatic ductal adenocarcinoma"Int.J. Panc.. 25. 97-102 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Han S.: "Infrequent somatic mutations of the p73 gene in various human cancers"Eur.J. Surg. Oncol.. 25. 194-198 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Abe T.: "Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer"Genes Chromosomes Cancer. 25. 60-64 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Lozonschi L.: "Controlling tumor angiogenesis and metastasis of C26 murin colon adenocarcinoma by a new matrix metalloproteinase inhibitor, KB-R7785, in two tumor models"Cancer Res.. 59. 1252-1258 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Furukawa,T.: "Genomic analysis of DUSP6,a dual specificity MAP kinase phosphatase,in pancreatic cancer." Cytogenetics and Cell Genetics. 82. 156-159 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fukushige,S.: "Loss of chromosome 18q is an early event in pancreatic duc-tal tumorigenesis." Cancer Research. 58. 4222-4226 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshinaga,K.: "The PTEN,BAX,and IGFIIR genes are mutated in endometrial atypical hyperplasia." Japanese Journal of Cancer Research. 89. 985-990 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamakawa,H.: "Identification of a 100-kb region of common allelic loss on chromosome bands 10q25-q26 in human endometrial cancer." Genes,Chromosomes & Cancer. 23. 74-77 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ouyang,H.: "The BAX gene,the promoter of apoptosis,is mutated in genetically unstable cancers of the colorectum,stomach,and endometrium." Clinical Cancer Research. 4. 1071-1074 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kimura,M.: "Identification of two common regions of allelic loss in chro-mosome arm 12q in human pancreatic cancer." Cancer Research. 58. 2456-2460 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Abe,T.: "Identification of three commonly deleted regions on chromosome arm 6q in human pancreatic cancer." Genes,Chromosomes & Cancer. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Han,S.: "Infrequent somatic mutations of the p73 gene in various human cancers." European Journal of Surgical Oncology. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Yatsuoka,T.: "Genomic analysis of the thymine-DNA glycosylase(TDG)gene on 12q22-q24.1 in human pancreatic ductal adenocarcinoma." International Journal of Pancreatology. (in press).

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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