1999 Fiscal Year Final Research Report Summary
Establishment of novel efficient methods for pancreatic cancer patients based on genetic abnormality.
| Project/Area Number |
10307032
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Tohoku Uniersity |
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Principal Investigator |
MATSUNO Seiki Tohoku University, School of Medicine, First Department of Surgery, Professor, 大学院・医学系研究科, 教授 (80004737)
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| Co-Investigator(Kenkyū-buntansha) |
HORII Akira Tohoku University, School of Medicine, Department of Molecular Pathology, Professor, 大学院・医学系研究科, 教授 (40249983)
SUNAMURA Makoto Tohoku University, Hospital, First Department of Surgery, Lecturer, 医学部附属病院, 講師 (10201584)
FUKUSHIGE Shinichi Tohoku University, School of Medicine, Department of Molecular Pathology, Lecturer, 大学院・医学系研究科, 講師 (90192723)
FURUKAWA Toru Tohoku University, School of Medicine, Department of Molecular Pathology, Research Associate, 大学院・医学系研究科, 助手 (30282122)
SHIBUYA Kazuhiko Tohoku University, Hospital, First Department of Surgery, Research Associate, 医学部附属病院, 助手 (70260429)
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| Project Period (FY) |
1998 – 1999
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| Keywords | tumor suppressor gene / pancreatic cancer / 6q / 12q / 17p / 18q / gene therapy / angiogenesis |
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| 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.
2.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. If this is the case, then the SMAD4 gene associate with poor prognosis that disrupt at the late stage, and disruption of the unknown putative tumor suppressor gene plays at the early stage tumors.
3.In 6q and 12q, we identified three and two commonly deleted region. We further narrowed down the regions, and constructed BAC contigs in three regions; one on 6q and two on 12q. We isolated and characterized the DUSP6 and TDG genes on 12q and found that expressions of both genes were significantly reduced. We are now further characterizing the gene to investigate their roles in pancreatic carcinogenesis.
4.We demonstrated inhibition of angiogenesis by MMP inhibitors and IL-12. These results will lead to establishment of clinical application through regulation of tumor angiogenesis. We also established mutant adenovirus that only can survive in cells with disrupted p53.
This virus is a good candidate for gene therapy of pancreatic cancer.
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Research Products
(18 results)
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[Journal Article] Effective gene therapy for pancreatic cancer by cytokines mediated by restricted replication-competent adenovirus.2000
Author(s)
Motoi, F., Sunamura, M., Ding, L., Yoshida, Y., Matsuno, S., Hamada, H.
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Journal Title
Hum.Gene Ther. 11
Pages: 223-235
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Effect of intraportal adoptive immunotherapy on liver metastases after resection of pancreatic cancer.2000
Author(s)
Kobari, M., Egawa, S., Shibuya, K., Sunamura, M., Saitoh, K., Matsuno, S.
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Journal Title
Br.J.Surg. 87
Pages: 43-48
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Direct in vitro evidence and in vivo analysis of the anti-angiogenesis effects of interleukin 12.2000
Author(s)
Duda, D.G., Sunamura, M., Lozonschi, L., Kodama, T., Egawa, S., Matsumoto, G., Shimamura, H., Shibuya, K., Takeda, K., Matsuno, S.
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Journal Title
Cancer Res. 60
Pages: 1111-1116
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Eur.J.Surg.Oncol. 25
Pages: 194-198
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Int.J.Panc. 25
Pages: 97-102
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Genes Chromosomes Cancer 25
Pages: 60-64
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
J.Hum.Genet. 44
Pages: 397-401
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Intraductal papillary mucinous tumors of the pancreas comprise 2 clinical subtypes.1999
Author(s)
Kobari, M., Egawa, S., Shibuya K., Shimamura, H., Sunamura, M., Takeda, K., Matsuno, S.
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Journal Title
Arch.Surg. 134
Pages: 1131-1136
Description
「研究成果報告書概要(欧文)」より
