Establishment of melecular-based diagnositics for esophageal cancer

• Project/Area Number: 15390398
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: KYUSHU UNIVERSITY
• Principal Investigator: MORI Masaki Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (70190999)
• Co-Investigator(Kenkyū-buntansha): INOUE Hiroshi Kyushu University, Medical institute of Bioregulation, Associate Professor, 生体防御医学研究所, 助教授 (90203249) ; UTSUNOMIYA Tohru Kyushu University, Kyushu Univ. Hospital, Assistant Professor, 大学病院, 講師 (30304801) ; MIMORI Koshi Kyushu University, Medical institute of Bioregulation, Research Associate, 生体防御医学研究所, 助手 (50322748)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥14,800,000 (Direct Cost: ¥14,800,000); Fiscal Year 2004: ¥7,100,000 (Direct Cost: ¥7,100,000); Fiscal Year 2003: ¥7,700,000 (Direct Cost: ¥7,700,000)
• Keywords: micrometastasis / esohageal cancer / chemical carcinogenesis / radiation sensitivity / MAL / MMP2 / FHIT / CKS2 / CEA / cytokeratin7 / Lyn B tyrosine kinase

Research Abstract

Esophageal cancer is considered to be one of the most aggressive malignacy in the Eastern countries, including Japan. Early detection of the tumor development as well as tumor recurences has been a key subject of the disease. The purpose of our current study is to establish molecular-based diagnositics for esophageal cancer and we have conveyed 4 major researches for this purpose : 1) the detection of the tumor cells (micrometastasis) in either blood or bone marrow of the patient for the postoperative disease surveillance, 2) the establishment of rat esophageal chemical-induced carcinoma model for the elucidation of the genes associated with esophageal carcinogenesis, 3) the detection of the genes responsible for radiation sensitivities, 4) the detection of tumor associated genes using DNA microarray methodology applied for the human esophageal tumor specimens. Results : 1) The blood and bone marrow samples were obtained from 150 patients with esophageal cancer. No significant differences were currently observed between the cases with early recurrence or metastasis of the tumor. More detailed-studies are needed for longer period of the postoperative observation. 2) Genes such as rat gelatinase A (MMP2), keratin 6a, Lyn B tyrosine kinase were found to be highly expressed in development of carcinoma. Genes such as ALDH. SLP were repressed along the tumor development. 3) Genes such as SPP1, CKS2 were found to be associated with tumor radio sensitivity. 4) Transfection of MAL and FHIT genes induce dramatic changes in tumor cell biology. For the gene FHIT, the mechanism of apoptotic activity by Ad-FHIT is to identify the candidate cancer associated targets affected by Ad-FHIT treatment. Those molecules may consider to be both tumor markers for the early detection of tumor development, and also a fine molecular target for the treatments of esophagel cancer.

Research Products

• [Journal Article] Global Analysis of Altered Gene Expressions during the Process of Esophageal Squamous Cell Carcinogenesis in the Rat : A Study Combined with a Laser Microdi ssection and a cDNA Microarray. Cancer (2005)
  • Author(s): Nishida K. et al.
  • Journal Title: Cancer Res 65 Pages: 401-409
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Familial cancer associated with a polymorphism in ARLTS1 (2005)
  • Author(s): Calim, G.A., et al.
  • Journal Title: N Engl J Med 26 Pages: 41-47
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Somatic mutations of epidermal growth factor receptor in colorectal carcinoma. (2005)
  • Author(s): Nagahara H et al.
  • Journal Title: Clin Cancer Res 11 Pages: 1368-1371
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Detection of occult cancer cells in peripheral blood and bone marrow by quantitative RT-PCR assay for cytokeratin-7 in breast cancer patients. (2005)
  • Author(s): Masuda, T.A., et al.
  • Journal Title: Int J Oncol 26 Pages: 721-730
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Global analysis of altered gene expressions during the process of esophageal squamous cell carcinogenesis in the rat : a study combined with a laser microdissection and a cDNA microarray. (2005)
  • Author(s): Nishida, K., Mine, S., Utsunomiya, T., Inoue, H., Okamoto, M., Udagawa, H., Hanai, T., Mori M.
  • Journal Title: Cancer Res 65 Pages: 401-409
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Familial cancer associated with a polymorphism in ARLTS1. (2005)
  • Author(s): Calin, G.A., Trapasso, F., Shimizu, M., Dumitru, C.D., Yendamuri, S., Godwin, A.K., Ferracin, M., Bernardi, G., Chatterjee, D., Baldassarre, G., Rattan, S., Alder, H., Mabuchi, H., Shiraishi, T., Hansen, L.L., Overgaard, J., Herlea, V., Mauro, F.R., Dighiero, G., Movsas, B., Rassenti, L., Kipps, T., Baffa, R., Fusco, A., Mori, M., Russo, G., Liu, C.G., Neuberg, D., Bullrich, F., Negrini, M., Croce, C.M.
  • Journal Title: N Eng1 J Med 26 Pages: 41-47
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Somatic mutations of epidermal growth factor receptor in colorectal carcinoma. (2005)
  • Author(s): Nagahara, H., Mimori, K., Ohta, M., Utsunomiya, T., Inoue, H., BARNARD, G.F., Ohira, M., Hirakawa K., Mori, M.
  • Journal Title: Clin Cancer Res 11 Pages: 1368-1371
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Detection of occult cancer cells in peripheral blood and bone marrow by quantitative RT-PCR assay for cytokeratin-7 in breast cancer patients. (2005)
  • Author(s): Masuda, T.A., Kataoka, A., Ohno, S., Murakami, S., Mimori, K., Utsunomiya, T., Inoue, H., Tsutsui, S., Kinoshita, J., Masuda, N., Moriyama, N., Mori, M.
  • Journal Title: Int J Oncol 26 Pages: 721-730
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Global Analysis of Altered Gene Expressions during the Process of Esophageal Squamous Cell Carcinogenesis in the Rat : A Study Combined with a Laser Microdissection and a cDNA Microarray. Cancer (2005)
  • Author(s): Nishida K. et al.
  • Journal Title: Cancer Res 65 Pages: 401-409
• [Journal Article] The high expression of Fractalkine results in a better prognosis for colorectal cancer patients. (2005)
  • Author(s): Ohta M et al.
  • Journal Title: Int J Oncol 26 Pages: 41-47
• [Journal Article] N-cadherin is regulated by activin A and associated with tumor aggressiveness in esophageal carcinoma. (2004)
  • Author(s): Yoshinaga, K., et al.
  • Journal Title: Clin Cancer Res 10 Pages: 5702-5707
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Clinical significance of elongation factor-1 delta mRNA expression in oesophageal carcinoma. (2004)
  • Author(s): Ogawa, K et al.
  • Journal Title: Br J Cancer 91 Pages: 282-286
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] N-cadherin is regulated by activin A and associated with tumor aggressiveness in esophageal carcinoma. (2004)
  • Author(s): Yoshinaga, K., Inoue, H., Utsunomiya, T., Sonoda, H., Masuda, T., Mimori, K., Tanaka, Y., Mori, M.
  • Journal Title: Clin Cancer Res 10 Pages: 5702-5707
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Clinical significance of elongation factor-1 delta mRNA expression in oesophageal carcinoma. (2004)
  • Author(s): Ogawa, K., Utsunomiya, T., Mimori, K., Tanaka, Y., Tanaka, F., Inoue, H., Murayama, S., Mori, M.
  • Journal Title: Br J Cancer 91 Pages: 282-286
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Clinical significance of the overexpression of the candidate oncogene CYP24 in esophageal cancer (2004)
  • Author(s): Mimori K et al.
  • Journal Title: Ann Oncol 15 Pages: 236-241
• [Journal Article] A gene-expression signiture can quantify the degree of hepatic fibrosis in the rat (2004)
  • Author(s): Utusunomiya T et al.
  • Journal Title: J Hepatol 41 Pages: 399-406
• [Journal Article] Differential expression of MMP and uPA systems and prognostic relevance of thier expression in esophageal squamous cell carcinoma (2004)
  • Author(s): Ymashita K et al.
  • Journal Title: Int J Cancer 110 Pages: 201-207
• [Journal Article] N-cadherin is regulated by activin A and associated with tumor aggressiveness in esophageal carcinoma (2004)
  • Author(s): Inoue H. et al.
  • Journal Title: Clin Cancer Res 10 Pages: 5702-5707
• [Publications] Masuda TA, Inoue H, et al.: "Cyclin-dependent kinase 1 gene expression is associated with poor prognosis in gastric carcinoma."Clin Cancer Res. 15. 5693-5698 (2003)
• [Publications] Matsuyama A, Shiraishi T, et al.: "Fragile site orthologs FHIT/FRA3B and Fhit/Fra14A2:Evolutionarily conserved but highly recombinogenic"Proc Natl Acad Sci U S A. 100. 14988-14993 (2003)
• [Publications] Yamashita K, Mimori K, et al.: "A tumor-suppressive role for trypsin in human cancer progression."Cancer Res. 63. 6575-6578 (2003)
• [Publications] Yamashita K, Sunil, et al.: "MAL gene expression in esophageal cancer suppresses motility, invasion and tumoril genicity and enhances apoptosis through the Fas pathway"Oncogene. 22. 3463-3471 (2003)
• [Publications] Mimori K, Inoue H, et al.: "INI-1,a partner gene of ALL-1,is highly conserved in human acute leukemia"Oncology Rep. 10. 551-553 (2003)
• [Publications] 黒木 保, 井上 裕, 森 正樹: "消化器外科 レビュー:発癌機構(分担執筆)"総合医学社. 268 (2003)