Influences of multidisciplinary treatment for ovarian cancer on the cytobilogical polyclonality

卵巢表面细胞在发育过程中模拟苗勒管形态的观点已逐渐得到发展，并已被广泛接受，但动物实验的证据很少。卵巢内插入7，12-二甲基苯并[a]蒽（DMBA）涂层缝线成功地在Wistar品系大鼠中产生卵巢癌。由此产生的肿瘤已被证明发展成巨大的卵巢肿瘤，偶尔表现出腹膜内扩散，伴有血性腹水，模仿人类肿瘤的生长模式。这些诱导的肿瘤中的大多数表现出上皮肿瘤的组织学，包括浆液性腺癌、类浆液性腺癌和鳞状细胞癌，尽管它们中的大多数被归类为混合上皮肿瘤。此外，DMBA诱导的卵巢癌在致瘤过程中表现出突变型p53的表达，这表明该动物癌是一种适合于人类卵巢癌的模型。法师基因最初是从黑色素瘤组织中获得的，法师-4蛋白在卵巢癌患者中被发现。由于在晚期疾病患者中观察到较高水平的蛋白，因此MAGE蛋白测定有望作为新的肿瘤标志物。而限制CTL识别法师蛋白的HLA-A1在日本人中发病率相当低。在这些结果的基础上，我们现在使用HLA-A24或HLA-A2限制性抗原肽进行一种新的癌症疫苗治疗，该抗原肽在约60%的日本人口中表达。

The concept that the ovarian surface cells simulate the mulerian form in tum or formation has developed by degrees, and is now widely accepted, but with little evidence supported by animal study. Intraovarian insertion of 7,12-dimethylbenz [a] anthracene (DMBA)-coated suture successfully produces ovarian cancer in Wistar strain rats. The resulting neoplasms have been shown to develop into massive ovarian tumors, and occasionally show intraperitoneal spread with bloody ascites mimicking the growth pattern of human tumors. A majority of these induced tumors exhibit the histology of epithelial tumors, including serous adenocarcinoma, endometrioid adenocarcinoma and squamous cell carcinoma although most of them are categorized in mixed epithelial tumor. Furthermore the DMBA-induced canecr exhibits the expression of mutant p53 during the tumorigenic process, suggesting that the animal cancer is a suitable model for human ovarian cancer. MAGE gene was originally obatained from melanoma tissue, and MAGE-4 protein is found in patients with ovarian cancer. Since the higher level of the protein is observed in patients with the advanced stage disease, the usefulness of the MAGE-protein determineation is expected as a new tumor marker. However, HLA-A1, which restricts CTL recognizing MAGE protein, is rather rared type in Japanese in incidence. On the base of these results, we now conduct a novel cancer vaccine therapy using HLA-A24 or HLA-A2 ristricted antigen-peptide, which is expressed in about 60% of Japanese population.