5-氟尿嘧啶缓释剂瘤内植入治疗胰腺癌的实验研究和临床研究(英文)  

EXPERIMENTAL AND CLINICAL STUDY OF INTRA-TUMOR INJECTION OF SLOW-RELEASED 5-FU TO TREAT PANCREATIC CARCINOMA

作　　者：杜卫东[1] 袁祖荣[1] 倪泉兴[2] 华鲁纯 沈达明[1] 唐健雄[1] 张群华 竺越[3] 

机构地区：[1]上海华东医院普外科,200040 [2]上海华山医院普外科 [3]上海华东医院消化科

出　　处：《外科研究与新技术》2005年第2期147-154,共8页Surgical Research and New Technique

摘　　要：目的纲察5-氟尿嘧(5-FU)缓释剂对荷胰腺癌裸鼠肿瘤细胞及胰腺癌患者血清肿瘤标记物和细胞免疫的影响。方法(1)5-FU缓释剂的体外释放实验和体外抑瘤实验。(2)将荷胰腺癌细胞株PC3裸鼠60只,姑且机分成静脉对照组(A组)、5-Fu缓释剂植组(E组)治疗前、后14D测肿瘤大小。治疗2周后观察肿瘤组织学变化。免疫组化法测定bcl-2和Bax的蛋白表达水平;TUNEL法检测凋亡指数(AI)。(3)手术探查不能切除之胰腺癌69例随机分成3组。将5-FU缓释剂瘤内植入治疗组、术后行5-FU静脉化疗组和对照组。分别于术前1d和术后第14天采血,测定各组血清中NK细胞,T细胞亚群和CEA,CA50 ,CA19-9 ,CA242血清肿瘤记物水平。结果5 mg 5-FU缓释剂第1天释放量最大,为0 .85 mg,第3天为0 .45 mg,其后在0 .25 mg水平维持稳定的缓慢释放;释放时间长达14d以上。5-FU缓释剂第1天的浸出液对人胰腺癌细胞株PC-3的抑制率达60 .27 %,第3天为34 .25 %,以后稳定在25 %左右。5-FU缓释剂瘤内注谢治疗组裸鼠移植瘤生长速度减慢,bcl-2ad基因表达明显低于其他各组,而Bax基因表达明显高于其他各组,肿瘤细胞的AI明显高于其他各组。D组和E组肿瘤组织中炎症反应和血管内膜增厚程度明显高于其他各组。术后治疗组CD4+/CD8+和NK细胞水平高于静脉5-FU化疗组,而血清中上述5种肿瘤标记物低于对照组和静脉化疗组。结论5-FU缓释剂能在2周内在体外较稳定地特续释放,对人胰腺癌细胞株PC-3有持续抑制作用。该剂瘤内注射可明显抑制荷胰腺癌瘤裸鼠瘤体的生长,其作用机与药物在肿瘤组织中引起的炎症反应和血管内膜增厚等因素有关;并可能与诱导肿瘤细胞的凋亡有关。该剂植入胰腺癌实体内,能明显降低5种血清肿瘤标记物水平,同时对患者的细胞免疫功能影响较小,5-FU缓释剂可望成为治疗不能切除之胰腺癌的较好的制剂。Objective The purpose of the experiment is to study the effect and mechanism of intra-tumor injection of slow-released 5-FU in pancreatic carcinoma and to determine the therapeutic effectiveness of intra-tumor embedding of slow-released 5-fluorouracil (5-FU) in patients with unresectable pancreatic carcinoma.Methods 1.Releasing action and anti-tumor effect of slow-releasel 5-FU 2.Human pancreatic carcinoma strain PC-3 were cultured and inoculated into 70 athymic mice subcutaneously under their right armpits. We chose 60 mice unamious in size 4 weeks afer inoculation .All the mice were divided into 5 groups according to the treatment they received: A.intravenous NS injection as the control group,injecting 0.1ml NS each mouse through angularis vein. B.Injection of 5-FU through vein group,0.1 ml NS solution and 5-FU(10 mg/kg) was injected through angularis vein.C.Intra-tumour injection of basic stuff as another control group.D.Intra-tumor injection of slow-released 5-FU (4mg/kg)as the treatment group. E. Intra-trumor injection of slow-released 5-FU (1mg/kg) as treatment group. Tumor sizes were measured before and 3,6,10,14 days after the treatment. At the 2nd week,tumors were excised. the apoptosis index(AI)was detected by terminal-deoxynucleotide transferase mediated d-UTP nick end labeling (TUNE) and expression of bcl-2 and Bax with immunohistochemistry.3.69 cases with unresectable pancreatic carcinoma were divided into 3 groups randomly: intra-tumor embedding of slow-released 5-FU treated group,intravenous injection of 5-FU continued in treaed group and control group. The serous values of CD3.+,CD4.+,CD8.+,CD4.+/CD8.+,NK cells,CEA,CA50,CA50,CA19-9,CA125 and CA242 were measured in each 1 day before and 14 days after the operation.Results 0.85mg 5-FU was released at the first day and 0.45 mg 5-FU released at the 3.rd day. The releasing reached a stable level as 0.25 mg and lasted about 14 days. The anti-tumor rate was 60.27% in the first day liquid of slow-released 5-FU and was 34.25% in the 3.rd day.It reached sta

关 键 词：胰腺肿瘤 细胞株 5-氟尿嘧啶 瘤内注射 

分 类 号：R735.9[医药卫生—肿瘤]