Establishment of melecular-based diagnositics for esophageal cancer

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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.