术前口服5'-DFUR对胃肠道恶性肿瘤组织中PyNPase的影响及意义

Effect of Preoperative Oral 5'-DFUR on PyNPase Level in Gastrointestinal Malignant Tumor Tissues

背景与目的:嘧啶核苷磷酸化酶(pyrimidinenucleosidephosphorylase,PyNPase)主要分布在肿瘤组织,去氧氟尿苷(5'-deoxy-5-fluorouridine,5'-DFUR)可以降低PyNPase在肿瘤组织中的含量。但术前口服5'-DFUR不同时间后对肿瘤组织中PyNPase的影响如何尚未见报道。本研究通过观察术前口服5'-DFUR不同时间后对胃肠道恶性肿瘤组织中PyNPase水平的影响,探讨术前化疗的适宜时间。方法:胃肠道恶性肿瘤患者共73例,根据术前口服5'-DFUR(600～1200mg/d)至手术时间的不同分为A组(3天组)27例,B组(1周组)22例,C组(2周组)15例,D组(2月组)9例;E组(对照组)24例为同期住院手术的胃肠道恶性肿瘤患者。上述患者术前均未接受化疗或放疗。采用逆转录-聚合酶链反应(reversetranscriptionpolymerasechainreaction,RT-PCR)和免疫组织化学(immunohistochemistry,IHC)等方法检测各组肿瘤组织中PyNPase的表达水平。结果:(1)在电镜下,C组肿瘤细胞常出现不可逆的致死性改变,但在光镜下所见肿瘤细胞形态正常,仅D组可见肿瘤间质中纤维结缔组织增多;(2)与E组肿瘤组织中的PyNPasemRNA及蛋白表达水平(0.95±0.09,29.34±1.82)相比,A组(0.79±0.08,19.26±1.65)已明显降低,C组(0.43±0.07,5.91±1.45)最为明显,而C组与D组(0.42±0.04,5.36±1.19)

BACKGROUND &OBJECTIVE:Pyrimidine nucleoside phospho-rylase(PyNPase)exists mainly in tumor tissues.5'-d eoxy-5-fluorouridine(5'-DFUR)can decrease its level in tumor tissu es.However,the effect of preoperat ive oral 5'-DFUR on PyNPase level in the diffe rent time after administration has n ot been reported.This study was desig ned to investig ate the suitable duration o f preoperative chemotherapy throug h observing the chang es of PyNPase levels in g astrointestinal malig nant tumors after preoperative oral administra tion of 5'-DFUR in different duration.METHODS:Seventy-three patients with g astro intestinal malig nant tumors were divided into f our g roups by the duration of preoper ative oral 5'-DFUR(600-1200mg ·d -1 ):g roup A,three days ,27cases ;g roup B,one week,22cases ;g roup C,two weeks,15cases ;g roup D,two months ,9cases.Meanwhile,g roup E,control g roup,had 24inpatients with g astroi ntestinal malig nant tumors at the same term.Al l the above-mentioned patients did n ot receive the other chemotherapy or ra diotherapy.The chang es of PyNPase l evels in tumor tissues of different g roups were tested using reverse transcrip tion polymerase chain reaction(RT-PCR)and immunohistochemistry(IHC),etc.RESULTS :(1)Under electron microscope,there we re many irrecoverable,lethal chang es in tumor cells of g roup C.The outlines of the tumor cells were norm al under lig ht microscope,and more fib roconnective tissues were seen only in the stroma of g roup D.(2)The expressing levels of PyNPase mRN A and protein production in tumor tissues reduced obviously in g roup A (0.79±0.08,19.26±1.65),and decreased most obviously in g ro up C (0.43±0.07,5.91±1.45)comparing with g roup E (0.95±0.09,29.34±1.82).However,there was no sig nificant difference between g ro up C and g roup D (0.42±0.04,5.36±1.19)for the levels of PyNPase mRNA and pro tein production.The correlation coefficient between the levels of Py NPase mRNA and protein in tumor tissu es of different g roup was r=0.92(P<0.0001).CONCLUSION:5'-DFUR by oral administration before operation mi g ht destroy g astrointestinal malig nant tumor cells.As the duration prolong ed,th e content of PyNPase in tumor tissues decreased prog ressively,being low est level in two weeks after chemotherapy.So two-week duration mig ht be suitab le for the treatment.