Establishment of melecular-based diagnositics for esophageal cancer

食管癌在包括日本在内的东方国家被认为是最具侵略性的癌症之一。早期发现肿瘤的发展以及肿瘤的复发一直是该病研究的关键课题。我们目前研究的目的是建立食管癌的分子诊断学，为此我们进行了4项主要研究：1）肿瘤细胞的检测（微转移）用于术后疾病监测，2）建立大鼠食管化学致癌模型，研究食管癌发生的相关基因，3）放射敏感性相关基因的检测; 4）食管癌组织中肿瘤相关基因的检测。结果：1）收集了150例食管癌患者的血液和骨髓标本。目前未观察到肿瘤早期复发或转移病例之间的显著差异。需要更详细的研究进行更长时间的术后观察。2)明胶酶A（MMP 2）、角蛋白6 a、林恩B酪氨酸激酶等基因在肿瘤发生发展过程中呈高表达。基因如ALDH。SLP在肿瘤发展过程中沿着受到抑制。3)SPP 1、CKS 2等基因与肿瘤放射敏感性相关。4)MAL和FHIT基因的转染诱导肿瘤细胞生物学的显著变化。对于基因FHIT，Ad-FHIT的凋亡活性的机制是鉴定受Ad-FHIT治疗影响的候选癌症相关靶标。这些分子既可作为早期发现肿瘤发展的肿瘤标志物，也可作为治疗食管癌的良好分子靶点。

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.