An analysis of the role of survivin in tumorigenesis of Epstein-Barr virus (+) gastric cancer

生存素在Epstein-Barr病毒胃癌发生中的作用分析

• 批准号: 11670190
• 负责人: TAKANO Yasuo
• 金额: $ 2.3万
• 依托单位: TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670190/
• 关键词: Survivin; Y-49; malognantlymphoma; Gastric cancer; malignant lymphoma; survivin; gastric cancer; survivin associated antigen

We have performed these subjects as below during the term of Grant-in-Aid for Scientific Research (C).1) We have produced a monoclonal antibody, named as Y-49, against synthesized polypeptides selected from survivin amino-acid sequence. This antibody did not react survivin but recognized some antigen reacting to proliferating cells and malignant cells in the immunohistochemical study. Three bands were noticed at 22, 60 and 85 kds on the basis of Western blotting of cultured lymphoma cells.2) After twice of subcloning, 22 kd band became dense and clear, and cell fractionation revealed that only 22 kd protein existed in the nuclei of lymphoma cells and those three proteins were present in the cytoplasm.3) Flow cytometric analysis using PHA stimulated normal lymphocytes disclosed that Y-49 was strongly labeled in the cell cycle of S and G2/M.4) An immunohistochemical study for malignant lymphoma cases employing Y-49 resulted : (1) Y-49 was highly labeled in extranodal and diffuse large cell lymphomas.(2) High labeling indices of Y-49 represented worse prognosis of lymphoma patients with statistics.(3) By multivariate analysis, high labeling indices of Y-49 was an independent prognostic factor.

我们在科学研究资助(C)期间进行了以下实验。1)我们生产了一种单克隆抗体，命名为Y-49，针对从survivin氨基酸序列中选择的合成多肽。在免疫组化研究中，该抗体不与survivin反应，但能识别一些与增殖细胞和恶性细胞反应的抗原。体外培养淋巴瘤细胞在22、60和85 kds时出现3条条带。2)经过2次亚克隆后，22 kd条带变得致密清晰，细胞分离结果显示，在淋巴瘤细胞的细胞核中只存在22 kd蛋白，这3种蛋白均存在于细胞质中。3)利用PHA刺激的正常淋巴细胞进行流式细胞分析，发现Y-49在S和G2/M细胞周期中被强烈标记。4)利用Y-49对恶性淋巴瘤病例进行免疫组化研究，结果表明：(1)Y-49在结外和弥漫性大细胞淋巴瘤中高度标记。(2) Y-49标记指数高，有统计学意义表明淋巴瘤患者预后较差。(3)多因素分析表明，Y-49高标记指数是独立的预后因素。

项目成果

Yasuo Takano et.al.: "CYCLON D2, BUT NOT CYCLIN D1,OVEREXPRESSION CLOSELY CORRELATES WITH GASTRIC CANCER PROGRESSION AND PROGNOSIS"Journal of Pathology. 189. 194-200 (1999)

Yasuo Takano 等人：“CYCLON D2，但不是 CYCLIN D1，过度表达与胃癌进展和预后密切相关”病理学杂志。

Yasuo Takano et. al.: "Cyclin D2 Overexpression and Lack of p27 Correlate Positively and Cyclin E Inversely with a Poor Prognosis in Gastric Cancer Casses"American Journal of Pathology. 156. 585-594 (2000)

高野康夫等.

Yoshihiro Murai et. al.: "Study on the role of G1 cyclins in Epstein-Barr virus associated human lymphomas maintained in severe combined immune deficiency (SCID) mice."International Journal of Cancer. (in press).

村井义宏等。

Yasuo Takano et.al.: "Cyclin D2 Overexpression and Lack of p27 Correlate Positively and Cyclin E Inversely with a Poor Prognosis in Gastric Cancer Casses"American Journal of Pathology. 156. 585-594 (2000)

Yasuo Takano 等人：“胃癌病例中细胞周期蛋白 D2 过度表达和 p27 缺乏与不良预后呈正相关，而细胞周期蛋白 E 则与不良预后呈负相关”《美国病理学杂志》。

Eikichi Okada et.al.: "Survivin expression in tumor cell nuclei is predictive of a favorableprognosis in gastric cancer patients."Cancer Let. 163. 109-116 (2000)

Eikichi Okada 等人：“肿瘤细胞核中的生存素表达预示着胃癌患者的良好预后。”Cancer Let。