Apoptosis induced by preoperative oral 5′-DFUR administration in gastric adenocarcinoma and its mechanism of action

AIM： To study the apoptosis induced by preoperative oral 5＇-DFUR administration in gastric adenocarcinorna and its mechanism of action. METHODS： Sixty gastric cancer patients were divided randomly into three groups （20 each group） before operation： group one： 5＇-DFUR oral administration at the dose of 800-1200mg/d for 3 - 5 d, group two： 500mg 5-FU ± 200 mg/d CF by venous drip for 3 - 5 d, group three （control group）. One or two days after chemotherapy, the patients were operated. Fas/FasL, PD-ECGF and PCNA were examined by immunohistochemistry and apoptotic tumor cells were detected by in situ TUNEL method. Fifty-four patients received gastrectomy, including 12 palliative resections and 42 radical resections. Six patients were excluded. Finally 18 cases in 5＇-DFUR group, 16 cases in CF ± 5-FU group, and 20 cases in control group were analyzed. RESULTS： There was no significant difference in patient mean age, gender, white blood cell count, haernatoglobin （HB）, thromboplastin, perioperative complication incidence, radical or palliation resection, invasion depth （T）, Iymphonode involvement （N）, metastasis （M） and TNM staging among the three groups. However, the PCNA index （PI） in 5＇-DFUR group （40.51 ± 12.62） and 5-FU ±CF group （41.12± 15.26） was significantly lower than that in control group （58.33± 15.69） （F=9.083, P= 0.000）. The apoptotic index （AI） in 5＇-DFUR group （14.39 ±9.49） and 5-FU±CF group （14.11±9.68） was significantly higher than that in control group （6.88 ± 7.37） （F= 4.409, P= 0.017）. The expression rates of Fas and FasL in group one and group three were 66.7% （12/18） and 50% （9/18）, 43.8% （7/16） and 81.3% （13/16）, 45.0% （9/20） and 85% （17/20）, respectively. The expression rate of FasL in 5＇-DFUR group was significantly lower than that in the other two groups （X^2=6.708, P= 0.035）. Meanwhile, the expression rate of PD-ECGF was significantly lower in 5＇-DFUR group （4/18, 28.6%） than in CF±5-FU group （9/16, 56.3%） and control group （13/20, 65.0%） （7,2= 7.542, P= 0.023）. The frequency of Fas expression was significantly correlated with palliative or radical resection （X^2= 7.651, P= 0.006）, invasion depth （X^2= 8.927, P= 0.003）, lymphatic spread （7,2= 4.488, P=0.034） and UICC stages （X^2=8.063, P=0.045） respectively. By the end of March 2005, 45 patients were followed up. The 0.5-, 1-, 2-, 3-year survival rates were 96%, 73%, 60%, 48%, respectively, which were related with T, N, M and Fas expression, but not with PDECGF and FasL expression. CONCLUSION： Preoperative oral 5＇-DFUR administration may induce apoptosis of gastric carcinoma cells and decrease tumor cell proliferation index, but cannot improve the prognosis of patients with gastric cancer. Downregulation of FasL and PD-ECGF expression mediated by 5＇-DFUR may be one of its anti-cancer mechanisms. Fas expression correlates with the progression of gastric carcinoma and may be an effective prognostic factor.

瞄准：为了学习， apoptosis 在胃的腺癌和它行动的机制由外科手术前的口头的 5'-DFUR 管理导致了。方法：六十个胃的癌症病人在手术前随机被划分成三个组(20 每组) ：在为 3 的 800-1200 mg/d 的剂量的组 one:5'-DFUR 口服 - 5 d，组织二：500 mg 5-FU + 200 mg/d CF 由静脉为 3 滴下 - 5 d，组三(控制组) 。在化疗以后的一或二天，病人被操作。Fas/FasL， PD-ECGF 和 PCNA 被免疫组织化学检验， apoptotic 肿瘤房间被原位 TUNEL 方法检测。54 个病人收到了胃切除术，包括 12 辩解的切除术和 42 激进的切除术。六个病人被排除。最后，在 5'-DFUR 组，在 CF+5-FU 组的 16 个盒子，和在控制组的 20 个盒子的 18 个盒子被分析。结果：在耐心的吝啬的年龄没有有效差量，性，白血房间计数， haematoglobin (HB ) ，凝血致活酶，在三之中的复杂并发症发生，基或减轻切除术，侵略深度(T) ， lymphonode 参与(N) ，转移(M) 和 TNM 阶段组织的起作用的仙子。然而， PCNA 索引(PI ) 在 5'-DFUR，组(40.51+/-12.62 ) 和 5-FU+CF 组(41.12+/-15.26 ) 在控制组(58.33+/-15.69 ) 是比那显著地低的(F=9.083， P=0.000 ) 。在 5'-DFUR 组(14.39+/-9.49 ) 和 5-FU+CF 组(14.11+/-9.68 ) 的 apoptotic 索引(AI ) 在控制组(6.88+/-7.37 ) 比那显著地高(F=4.409， P=0.017 ) 。船边交货和 FasL 在的表示率组一和组三是 66.7%(12/18 ) 并且 50%(9/18 ) ， 43.8%(7/16 ) 并且 81.3%(13/16 ) ， 45.0%(9/20 ) 并且 85%(17/20 ) 分别地。在 5'-DFUR 组的 FasL 的表示率在另外的二个组是比那显著地低的(chi2=6.708， P=0.035 ) 。同时， PD-ECGF 的表示率比在 CF+5-FU 组(9/16,56.3%) 和控制组(13/20,65.0%) 在 5'-DFUR 组(4/18,28.6%) 是显著地更低的(chi2=7.542， P=0.023 ) 。船边交货表示的频率显著地与辩解或激进的切除术被相关(chi2=7.651， P=0.006 ) ，侵略深度(chi2=8.927， P=0.003 ) ，淋巴的传播(chi2=4.488， P=0.034 ) 并且 UICC 阶段(chi2=8.063， P=0.045 ) 分别地。在 3 月 2005,45 日底，病人们被跟随起来。0.5- ， 1- ， 2- ，分别地， 3 年的幸存率是 96%,73%,60%,48% 它与 T， N， M 和船边交货表示，然而并非与 PD-ECGF 和 FasL 表示是相关的。结论：外科手术前的口头的 5'-DFUR 管理可以导致胃的癌房间和减少肿瘤房间增长索引的 apoptosis，但是不能与 FasL 和 PD-ECGF 表示的胃的 cancer.Down 规定改进病人的预后由 5'-DFUR 调停了可以是它的反癌症机制之一。有胃的癌的前进的船边交货表示相互关联并且可以是一个有效预示的因素。