Influences of multidisciplinary treatment for ovarian cancer on the cytobilogical polyclonality

卵巢癌多学科治疗对细胞生物学多克隆性的影响

基本信息

批准号：
09671724
负责人：
NISHIDA Takashi
金额：
$ 2.05万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671724/
关键词：
ovarian cancer MAGE-4 SART-1 ART-4 DMBA rat p53 Cytotoxic T lymphocyte immunotherapy experimental model mullerian form 卵巣癌抑制癌遺伝子 p53 MAGE遺伝子化学発癌腫瘍マーカー

项目摘要

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.

卵巢表面细胞在肿瘤或形成过程中模拟苗勒管形态的概念已逐渐发展，现已被广泛接受，但动物研究支持的证据很少。卵巢内插入 7,12-二甲基苯并[a]蒽 (DMBA) 涂层缝合线成功在 Wistar 品系大鼠中产生卵巢癌。由此产生的肿瘤已被证明会发展成巨大的卵巢肿瘤，并且偶尔会出现腹膜内扩散，并伴有血性腹水，模仿人类肿瘤的生长模式。大多数这些诱导肿瘤表现出上皮肿瘤的组织学特征，包括浆液性腺癌、子宫内膜样腺癌和鳞状细胞癌，尽管其中大多数被归类为混合上皮肿瘤。此外，DMBA诱导的癌症在致瘤过程中表现出突变型p53的表达，表明动物癌症是人类卵巢癌的合适模型。 MAGE基因最初是从黑色素瘤组织中获得的，MAGE-4蛋白是在卵巢癌患者中发现的。由于在晚期疾病患者中观察到该蛋白水平较高，因此 MAGE 蛋白测定有望作为新的肿瘤标志物。然而，限制CTL识别MAGE蛋白的HLA-A1在日本人中发病率相当罕见。基于这些结果，我们现在使用 HLA-A24 或 HLA-A2 限制性抗原肽进行新型癌症疫苗疗法，这种抗原肽在约 60% 的日本人口中表达。