Research Project
Grant-in-Aid for Scientific Research (C)
We have been studied molecular mechanisms of gastrointestinal carcinogenesis and cancer progression. One of our research focuses is colorectal cancer, and we have found the cancer specific mutation in E2F4, one of the important transcription factors, as a new gene strongly related to the colorectal cancer progression characterized as microsatellite instability phenotype (published 2 articles in Cancer Res.). We also found ING-1 as a new important target gene in esophageal squamouse cell cancer (published in Cancer Res.). We also studied the molecular events occur in early stages (just invaded into submucosa) of colorectal cancer, and we found high prevalence of microsatellite in low frequency (MSI-L) in this group of cancers (published in Cancer Res. ). Frequency of MSI-L in advanced colorectal cancer is really low around 10%, however, we found MSI-L phenotype in 50% of the early stage colorectal cancers. Now more and more researchers are involved in the new MSI-L carcinogenesis pathwa … More y, which was thought to be an artifact an thus not a meaningful phenomenon.Recently not only genetic, including mutations and deletions, but also epigenetic phenomenon are involved in many types of carcinogenesis. The most typical epigenetic alteration is the promoter hypermethylation, which causes the silencing of the gene. DNA methylation occurs preferentially within dense clusters of CpG sites know as CpG islands. Therefore reference is made to a CpG island methlator phenotype (CIMP). Most of our recent work was focused on this promoter methylation of multiple genes in gastrointestinal cancers, and we made tremendous progress in this field. We found that the important DNA repair gene MGMT (O6-methylguanine DNA methyltransferase) is controlled of its expression by promoter methylation, by analyzing precise map of methylation in its promoter. We also found that the level of methylation is strongly related to the prognosis and chemoresistance of colorectal cancers (Clinical Cancer Research). Furthermore, we classified colorectal cancer by mutational status of KRAS and BRAF, and showed close correlation to the methylation status of the multiple promoter methylation in colorectal cancer (Journal of Clinical Oncology). Less
All 2005 2004 2003 2002 Other
All Journal Article (30 results) Book (1 results) Publications (5 results)
Nucleic Acids Res. 33
Cancer Chemoth.Pharm.
Nucleic Acids Res. 33(5)
Int J.Oncol 25
Pages: 1273-1278
J.Clin.Oncol. 22
Pages: 4584-4594
Disease Markers 20
Pages: 277-282
BioTchniques 36
Pages: 846-855
Gut 53
Pages: 1137-1144
Oncol.Rep. 12
Pages: 339-345
Oral Oncol. 40
Pages: 597-603
Gene Chromosome Canc. 40
Pages: 1-9
Clinical Cancer Res. 10
Pages: 1758-1763
Clinical Cancer Res. 9
Pages: 5306-5312
Cancer Res. 62
Pages: 5988-5990
Pages: 3641-3645
Int J.Oncol 21
Pages: 949-956
Cancer Chemoth. Pharm.
120002314067
Int. J. Oncol. 25
J. Clip. Oncol. 22(22)
Disease Markers 20(4-5)
Bio Tchniques 36
Oncol. Rep. 12
Pages: 339-45
120002312161
Int. J. Oncol. 21