Influences of multidisciplinary treatment for ovarian cancer on the cytobilogical polyclonality

卵巢表面细胞模拟卵母细胞形态的概念已逐渐发展，现已被广泛接受，但很少有动物研究支持的证据。将7，12-二甲基苯并[a]菲(DMBA)包被的缝线植入卵巢内，成功地在Wistar系大鼠体内制造了卵巢癌。由此产生的肿瘤已被证明发展为巨大的卵巢肿瘤，偶尔会出现腹膜内扩散，伴血性腹水，类似于人类肿瘤的生长模式。这些诱导性肿瘤大多具有上皮性肿瘤的组织学特征，包括浆液性腺癌、子宫内膜样腺癌和鳞癌，但大多数属于混合性上皮性肿瘤。此外，DMBA诱导的卵巢癌在致癌过程中有突变型P53的表达，提示该动物癌是一种适合于人卵巢癌的动物模型。MAGE基因最初从黑色素瘤组织中获得，在卵巢癌患者中发现MAGE-4蛋白。由于晚期疾病患者的MAGE蛋白水平较高，因此MAGE蛋白检测有望成为一种新的肿瘤标志物。然而，限制CTL识别MAGE蛋白的人类白细胞抗原A1在日本人中的发病率较低。在这些结果的基础上，我们现在进行了一种新的癌症疫苗治疗，使用的是人类白细胞抗原A24或人类白细胞抗原A2限制性抗原肽，它在大约60%的日本人中表达。

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.