Effects of anti-cancer chemotherapy, anabolic hormone, cytokine an apoptosis

抗癌化疗、合成代谢激素、细胞因子和细胞凋亡的影响

• 批准号: 09671343
• 负责人: SUGANUMA Masashi
• 金额: $ 1.79万
• 依托单位: Fujita Health 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 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671343/
• 关键词: apoptosis; 5-fluorouracil; cisplatin; nude mouse; thymidylate synthese; gastrointestinal cancer; 消化器癌; 癌化学療法

In vitro study recently showed that induction of apoptosis is an important mechanism responsible for the anti-cancer effects of chemotherapeutic agents. In vivo long-term and short-term effects of 5-fluorouracil (5-FU) and cisplatin and their combination on papooses, thymidylate synthase and its inhibition were examined using human gastrointestinal cancer xenografts transplanted in nude mice. Previously established xenografts of human stomach carcinoma (SC-1-NU) and colon carcinoma (Co-4) subcutaneously transplanted in male BALB/c nude mice were used for the experimental anti-cancer chemotherapy regimen. The combination of 5-FU and cisplatin increased apoptosis only after the short-term treatment performed on SC-1-NU tumor. While administration of 5-FU markedly increased percent thymidylate inhibition rate, additional dose of cisplatin did not further increase the percent thymidylate synthase inhibition rate regardless of the tumor xenograft and the duration of the treatment. These results suggests that apoptosis play an important role in potentiating effect of cisplatin with 5-FU. No further increase in thymidylate synthase inhibition after the combination of 5-FU and cisplatin indicates that thymidylate synthase inhibition is not a major mechanism responsible for potentiating the anti0cancer effects.

最近的体外研究表明，诱导细胞凋亡是化疗药物抗癌作用的重要机制。以人胃肠道癌裸鼠移植瘤为模型，观察了5-氟尿嘧啶(5-FU)、顺铂及其联合用药对乳头瘤、胸苷合成酶及其抑制作用的长期和短期影响。以已建立的人胃癌(SC-1-Nu)和结肠癌(Co-4)裸鼠皮下移植瘤为实验抗癌化疗方案。5-FU联合顺铂仅在SC-1-NU肿瘤短期治疗后增加细胞凋亡率。5-FU能显著提高胸苷合成酶的抑制率，而顺铂的增加剂量不会进一步增加胸苷合成酶的抑制率，与移植瘤和治疗时间无关。这些结果提示，细胞凋亡在顺铂与5-FU协同作用中起重要作用。联合应用5-FU和顺铂后胸苷合成酶抑制没有进一步增加，说明胸苷合成酶抑制不是增强抗癌作用的主要机制。

项目成果

浦口 貴: "ヌードマウス可移植性ヒト消化器癌株に対する5-FU、シスプラチン併用low dose FP療法の効果"藤田学園医会誌. (印刷中). (2000)

Takashi Uraguchi：“5-FU 和顺铂低剂量 FP 治疗对裸鼠可移植人胃肠道癌细胞系的影响”Fujita Gakuen Medical Association Journal（2000 年出版）。

浦口 貴: "ヌードマウス可移植性ヒト消化器癌株における5-Fluorouracil,cisplatin 単独および併用療法の効果と効果増強の機序に関する研究"藤田学園医会誌. (印刷中). (2000)

Takashi Uraguchi：“5-氟尿嘧啶、顺铂单独和联合治疗的作用以及在裸鼠移植性人胃肠道癌细胞系中的作用增强机制的研究”Fujita Gakuen Medical Society Journal（2000 年出版）。

浦口 貴: "フッ化ピリミジン系の薬剤、とくにFP療法施行後の腫瘍におけるチミジル酸合成酵素およびdihydropyrimidine dehydrogenase に対する効果"藤田学園医会誌. (印刷中). (2000)

Takashi Uraguchi：“氟嘧啶药物的影响，尤其是 FP 治疗后对肿瘤中胸苷酸合成酶和二氢嘧啶脱氢酶的影响”Fujita Gakuen Medical Association Journal（2000 年出版）。