The Influence Of Sustained 5-Flurouraril Particles Implanted Into Rectal Mucosa Before Operation On Apoptosis And Expression Of Control Gene In Colorectal Carcinoma

Purpose To explored the pharmacokinetic,harmful effect, apoptosis and expression of p53 bcl-2 of turner cell,after implantation of sustained 5-Flurouraril particles into rectal mucosa. Methods sustained 5-Flurouraril particles 500mg was implanted into six to eight points of rectal mucosa distancing tooth- line 2 to 4 centimetre in 13 patiens.Otherl2 patiens with similar clinical characteristic were used as control. The peripheral blood was collected at 24h,48h,72h after treatment.The operation and the collection of the mesentery venous blood,tissue of tumor and adjacent tissue were respectively made at 72h.The drug concentration of blood and tissue was detected by high performance liquid chromatography.Apoptosis was oberserved by HE dyeing.Immunohistoichemistry was performed to detect the expression of p53 and bcl-2 gene.The examination of liver and renal function,blood routine,and electrocardiogram were performed before and after therapy. Result The drug concentration of peripheral blood was respectively 0.182?.l36ugIml,0.195?.088 ug/ml,0.219?.162 ug/ml at 24h,48h,72h.The difference was no significance(p>0.05).The drug concentration of mesentery venous blood(0.418?.261 ug/ml) was higher than that of the peripheral blood(p=0.013).The drug concentration in tissue of tumor(l.478?1.333 ug/g) was higher than that of adjacent tissue (0.646?.6000 ug/g),p=0.010.The histiopathology showed that the point of implantation were infiltrated with minor inflamed cells.The results of blood examination were norrnal.In treated patiens,the proportion of apoptosis was increased,and the expression of bcl-2 was decreased.There was inapparent in controls.The expression of bcl-2 in patients with and without p53 mutation wre 3 decreased at postoperation(p=O.0441 and p=O.O232). Conclusion Implanting antitumor drug into rectal mucosa is the best way for neoadjuvant chemotherapy. After implantation of sustained 5-Flurouraril particles into rectal mucosa,the sustained stable effective drug concentration in peripheral blood could be obtained,moreover,the drug concentration in carcinoma district and portal venous system could be enhanced.The expression of bcl-2 was downregulated and the apoptosis of turner cells was increased.. The effect is no significance in pations with p53 mutation and without.So the therapeutics was effective safe,and also suitable for patiens with p53 mutation.