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Clinicopathological study in the relationship among sensitivity, clonality, and growth potential after treatment in human gliomas

人胶质瘤敏感性、克隆性和治疗后生长潜力之间关系的临床病理学研究

基本信息

批准号：
09671407
负责人：
YOSHII Yoshihiko
金额：
$ 2.11万
依托单位：
UNIVERSITY OF THE RYUKYUS
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 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671407/
关键词：
gliomas clonality resistant factor immunohistochemical study Vitamin K2 apoptsis oxidative stress 防御因子 DNA Ploidy 治療予後 clonality

项目摘要

In 30 well-studied patients with gliomas, immunoreactivity for Cu/Zn SOD, GST-pi, metallothionein, bcl-2, p53 and cytometric evidence of DNA ploidy in the G2M cell cycle phase were evaluated from routinely prepared tissue blocks. Hypertetraploid gliomas with high SOD immunoreactivity showed a significantly short time to progression (p<0.05) (1 to 5 months after radiotherapy and chemotherapy) compared with hypertetraploid, low-SOD immunoreactivity gliomas or tetraploid, low-SOD immunoreactivity gliomas. The tumor cells with high SOD activity also tended to be resistant for radiotherapy and anticancer drugs.On the other hand, in 12 well-studied pairs who had the malignant brain tumors and received the first removal of the tumor at onset and the second operation at recurrence after the initial operation combined with radiotherapy and chemotherapy, those immunoreactivity was also evaluated. On conclusion, it suggests that the oncogene of bcl-2 in the malignant brain tumors may show more important factor for the resistance to adjuvant therapy than an antioxidant enzyme such as GST-pi and that the intrinsic factors like Cu/Zn SOD, GST-pi, and bcl-2 is also induced by radiation and anti-cancer drugs.The antitumor effects of vitamin K2 were studied using three glioma cell lines. As the results, vitamin K2 showed growth inhibition in a dose-dependent manner and resulted in oligonucleosomal DNA fragmentation. Furthermore, the vitamin K2 significantly accumulated in the G0G1 phase of the cell cycle. Those results suggested that the vitamin K2 can inhibit the proliferation of the cells through the induction of cell cycle arrest and apoptosis for the tumor cells.The combined treatment of vitamin K2 with ACNU, 5-FU and INF-b enhanced the growth inhibition significantly.

在30例研究充分的胶质瘤患者中，从常规制备的组织块中评价了Cu/Zn SOD、GST-π、金属硫蛋白、bcl-2、p53的免疫反应性和G2 M细胞周期期DNA倍体的细胞计数证据。与超四倍体、低SOD免疫反应性胶质瘤或四倍体、低SOD免疫反应性胶质瘤相比，超四倍体、高SOD免疫反应性胶质瘤的进展时间显著缩短（p<0.05）（放疗和化疗后1 - 5个月）。另一方面，在12对研究充分的恶性脑肿瘤患者中，在初次手术联合放疗和化疗后，首次接受肿瘤切除术和复发后再次手术，也评估了这些免疫反应性。结果提示，bcl-2癌基因可能是恶性脑肿瘤对辅助治疗抵抗的重要因素，而抗氧化酶如GST-π可能是恶性脑肿瘤对辅助治疗抵抗的重要因素，而Cu/Zn SOD、GST-π和bcl-2等内源性因子也可能是放射和抗癌药物诱导的。结果表明，维生素K2以剂量依赖性方式显示生长抑制，并导致寡核小体DNA片段化。此外，维生素K2在细胞周期的G 0 G1期显著积累。提示维生素K_2可通过诱导肿瘤细胞周期阻滞和凋亡抑制肿瘤细胞的增殖，维生素K_2与ACNU、5-FU、INF-b联合应用可明显增强其抑制作用。