New Chemotherapy using induction of apoptotic cell death in gastric cancer cells.

1、化疗诱导永生化癌细胞凋亡细胞死亡（体外）对两种不同细胞系人胃癌细胞（HSC-39和MKN-28） DNA片段化作为细胞凋亡的指标进行了分析。用阿霉素和顺铂孵育HSC-39细胞1小时后，检测到细胞DNA的断裂。然而，在MKN-28细胞中，与这两种药物孵育6小时后，未检测到DNA的断裂。结果提示HSC-39对阿霉素和顺铂更敏感。2、术前轻度化疗诱导凋亡细胞死亡（体内）我们观察胃癌或结直肠癌患者术前给予5-氟尿嘧啶（5-FU） （500mg/体/天，连用7天）是否能增加诱导癌细胞凋亡。此外，我们还研究了细胞凋亡诱导与Ki-67、p53或c-myc的表达之间的关系，这些基因被报道与细胞凋亡有关。5- fu治疗组胃癌和结直肠癌细胞凋亡明显增加。Ki-67的表达与细胞凋亡程度呈负相关。凋亡的表达与p53或c-myc的表达没有明显的相关性。3、轻度化疗的临床效果5-FU术前轻度化疗（500 mg/天/天，疗程3 ~ 14天）已在胃癌或结直肠癌患者中进行，并检测细胞凋亡程度。目前正在研究术前5-FU化疗对患者生存和无病期的影响。此外，在复发或不能切除的胃癌患者中，采用5-FU轻度化疗和低剂量顺铂，明显不同于传统的强化化疗。结果，即抗肿瘤作用和生存期也在研究中。

1, Induction og apoptotic cell death in immortalized cancer cells by chemotherapy (in vitro)The fragmentation of DNA,an indicator of apotosis, was analyzed in two different lines of human gastric cancer cells (HSC-39 and MKN-28). The fragmentation of DNA was detected in HSC-39 cells after a 1-h incubation wtih adriamycin and cisplatin. However, in MKN-28 cells, the fragmentation of DNA was not detected after a 6-h incubation with both agents. The results suggest that HSC-39 is more sensitive to adriamycin and to cisplatin.2, Induction of apoptotic cell death by preoperative mild chemotherapy (in vivo)We examined whether 5-fluorouracil (5-FU), administered preoperatively (500mg/body/day for 7 days) to patients with gastric cancer or colorectal cancer could increase the induction of apoptosis of cancer cells. Furthermore, we examined the relation between induction of apoptosis and expression of Ki-67, p53 or c-myc, which are reported to be relevant to apoptosis. Apoptosis of cancer cells increased significantly in 5-FU-treated group in both gastric and colorectal carcinomas. Expression of Ki-67 was inversely correlated with the extent of apoptosis. There were no clear correlation between expression of apoptosis and the expression of p53 or c-myc.3, Clinical effects of mild chemotherapyPreoperative mild chemotherapy with 5-FU (500 mg/dody/day for 3 to 14 days) has been performed in patients with gastric cancer or colorectal cancer and the extent of apoptosis was examined. Effects of apoptosis by preoperative 5-FU chemotherapy on survival and didease free period of patients are now studying. Furthermore, mild chemotherapy with 5-FU and low dose of cisplatin, clearly different from conventional intensive chemotherapy, has been performed in patients with recurrent or unresectable patients with gastric cancer. Results, namely, anti-tumor effects and survival period also now studying.