Expression of MAGE gene in esophageal carcinomas and its clinical application

MAGE基因在食管癌中的表达及其临床应用

• 批准号: 07671439
• 负责人: TOH Yuji
• 金额: $ 1.41万
• 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: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671439/
• 关键词: MAGE gene family; MAGE-1 protein; MAGE-4 protein; monoclonal antibody; polyclonal antibody; lymphocytes; killer T cell; 食道癌; MAGE蛋白抗原; HLA class I抗原; killer T細胞; 腫瘍マーカー; MAGE-1遺伝子; 特異的免疫療法

MAGE gene family was expressed in some esophageal squamous cell lines with an incidence of 67% to 22% (MAGE-1.67% ; MAGE-2.22% ; MAGE-3.33% : MAGE-3/6.78% ; and MAGE-4/41.44%), while in 65 patients with esophageal squamous cell cancer the incidence was 19%, 26%, 2%, 5%, and 8%, respectively. In the lymph nodes with positive metastasis, gene expression was recognized in MAGE-1 and -2 with an incidence rate was 46% and 18%, respectively. A comparative study was also done between MAGE gene expression and clinicopathologic findings. By this study, a significant difference was found between the tumor invasion low and high, and staging 0-II and III-IV.There was no statistical significant difference between the expression of MAGE gene and postoperative survivals. Immunohistochemistry using anti-MAGE-1 and anti-MAGE-4 monoclonal antibody which were made by our institution, was performed to some cell lines and frozen specimens of the esophageal cancer. Both antibodies showed a good reaction in Western blotting analysis, but anti-MAGE-1 monoclonal antibody poorly reacted to the flesh specimens. Therefore, ELISA kit was made using ant-mage-4 monoclonal and polyclonal antibodies. In the analyzes of MAGE-4 protein concentration using normal cases, most cases showed the MAGE-4 values of less than 1.0 ng/ml. By this result, the cut-off line was set at 1.15ng/ml with a 2S.D.level. In patients with squamous cell carcinoma of the esophagus, MAGE-4 positive was found in 8 of 38 cases, with an incidence of 21%. Clear reductions in serum MAGE-4 protein was found in cases with good prognosis before and after curative esophagectyomy. Although we attempted to induce tumor specific cytotoxic T lymphocytes using recombinant MAGE proteins, this study was failed because tumor specific T lymphocytes were not induced.

MAGE基因家族在一些食管鳞状细胞系中表达，发生率为67%至22%（MAGE-1.67%；MAGE-2.22%；MAGE-3.33%：MAGE-3/6.78%；和MAGE-4/41.44%） ），而在 65 名食管鳞状细胞癌患者中，发生率分别为 19%、26%，分别为 2%、5% 和 8%。在转移阳性的淋巴结中，MAGE-1和-2基因表达，发生率分别为46%和18%。还对 MAGE 基因表达和临床病理结果进行了比较研究。本研究发现肿瘤侵袭性低、高、分期0-II、III-IV期之间存在显着性差异。MAGE基因表达与术后生存率无统计学差异。采用我所生产的抗MAGE-1和抗MAGE-4单克隆抗体对部分食管癌细胞系和冰冻标本进行免疫组化分析。两种抗体在蛋白质印迹分析中均表现出良好的反应，但抗MAGE-1单克隆抗体对肉标本的反应较差。因此，使用ant-mage-4单克隆和多克隆抗体制作了ELISA试剂盒。在使用正常病例对MAGE-4蛋白浓度进行分析时，大多数病例显示MAGE-4值低于1.0ng/ml。根据该结果，截止线设定为 1.15ng/ml，2S.D.水平。食管鳞癌患者38例中，MAGE-4阳性8例，发生率为21%。在食管切除术前后预后良好的病例中，血清 MAGE-4 蛋白明显降低。尽管我们尝试使用重组MAGE蛋白诱导肿瘤特异性细胞毒性T淋巴细胞，但该研究失败了，因为没有诱导肿瘤特异性T淋巴细胞。

项目成果

Toh Y: "Expression of MAGE-1 gene by esophageal carcinomas" Jpn J Cancer Res. 86. 714-717 (1995)

Toh Y：“食管癌中 MAGE-1 基因的表达”Jpn J Cancer Res。

Toh Y: "Expression of MAGE-1 gene by esophageal carcinomas." Jpn J Cancer Res. 86. 714-717 (1995)

Toh Y：“食管癌中 MAGE-1 基因的表达。”