ABSTRACT
Objective To evaluate the effects of perioperative probiotics administration on patients with colorectal cancer and to explore its possible mechanism.Methods Seventy patients with colorectal cancer who were scheduled to undergo radical colorectomy at Shanghai Sixth People's Hospital between May 2011 and July 2011 were randomly divided with random number table into the control group (n =35) and the treatment group (n =35).The two groups in 5 days preoperatively and 7 days postoperatively were given daily doses of probiotics preparation consisting of two combined live bacteria and placebo,respectively.The structure of intestinal epithelial tight junction was observed by electron microscopy in colorectal tissue specimens collected during the operation.The expression of tight junctional protein was detected using Western blot and real-time RT-PCR technology.Intestinal epithelial permeability was evaluated by Ussing Chamber system.Stool samples and blood samples were collected on the 7th day after operation.The diversity of faecal flora was analyzed by terminal restriction fragment length polymorphism (T-RFLP) technique,and the quantitative detection of specific bacteria was conducted by bacterial culture.Clinical parameters including the first exhaust and defecate time,distension and diarrhea incidence,systemic inflammatory response,and postoperative infective complications were recorded.Results Compared with the control group,the treatment group showed better intestinal epithelial tight junction ultrastructure.The expression of tight junction proteins occludin,claudin-1,and ZO-1 (protein:all P ＜ 0.001 ; mRNA:P =0.005,0.001,0.006) and the transepithelial electrical resistance [(28.3 ±5.2) Ω · cm2 vs.(22.1 ± 4.7) Ω · cm2,P =0.002] were significantly increased,the large molecule permeability [(0.91 ± 0.17) ％ vs.(1.65 ± 0.33) ％,P ＜ 0.001] reduced,the diversity of intestinal flora (P=0.006) increased,the growth of intestinal Bifidobacteria [(143.4 ±35.9) vs.(100.0 ±0.0),P=0.002] and Lactobacilli [(111.3 ± 52.9) vs.(100.0 ± 0.0),P ＜ 0.001] promoted,and the growth of Clostridium perfringens [(66.2 ±23.7) vs.(100.0 ±0.0),P ＜0.001] inhibited in the treatment group.The treatment group also showed shorter postoperative exhaust [(2.5 ± 1.7) d vs.(4.5 ±2.0) d,P ＜0.001] and defecate time [(5.0 ± 1.3) d vs.(6.3 ± 1.1) d,P =0.002],lower incidence of diarrhea (20％ vs.40％,P =0.005) and abdominal distension (35 ％ vs.60％,P =0.021).Conclusion Probiotics used perioperatively in patients with colorectal cancer can effectively enhance the intestinal epithelia barrier function,maintain the homeostasis of gut flora,shorten the postoperative first exhaust and defecate time,reduce the incidence of diarrhea and abdominal distension,and promote the recovery of intestinal function.
ABSTRACT
Objective To explore the effect of fat on 1,2-dimethylhydrazine (DMH)-induced colon tumors.Methods A total of 50 7-week-old male Wistar rats were further divided into four groups:standard diet feed control group (n =10),standard diet feed plus DMH-induced tumor group (SDT,n =15),high-fat diet feed control group (n =10) and high-fat diet feed plus DMH-induced tumor group (HFDT,n =15).Rats were killed 18 weeks later,and enzyme-linked immunosorbent assay was used to detect serum triglyeeride,tumor necrosis factor (TNF-α),and colonic TNF-α,interleukin-6.After the intestinal tracts were removed,the location,amount,and size of the tumors were observed.The pathological changes of the tissue sections were observed,and the distributions of TNF-α and Ki-67 in the normal tissues and tumors were detected by immunohistochemistry.Results Upon the completion of the study,the mortality rate of rats was 20.00％ in the SDT group and 26.67％ in the HFDT group,the tumor formation rate was 75.00％ in the SDT group and 81.82％ in the HFDT group,and the tumor-bearing rate was 117％ in the SDT group and 191％ in the HFDT group.No statistical significance difference between the two groups in mortality rate,tumor formation rate (P =0.545) and tumor bearing rate (x2 =1.343,P =0.247).The average tumor volume was significantly different between the standard diet feed control group and high-fat diet feed control group (28.57％ vs 66.67％,P =0.030).Also,the serum triglyceride and TNF-α levels significantly differed between the SDT group and HFDT group [TG (1.39 ± 0.31) mmol/L and TNF-α (124.80 ± 21.69) ng/L in the HFDT group and TG (0.46 ±0.20) mmol/L and TNF-α (85.83 ± 17.45) ng/L in the SDT group] (P =0.000).The expressions of TNF-α,IL-6,and Ki-67 in colonic mucosa were significantly higher in the high-fat diet feed control group than in the standard diet feed control group [TNF-α:(6.22 ± 0.63) ng/g vs (2.33 ± 0.44) ng/g,P=0.020; IL-6:(13.50±0.67) ng/gvs (7.31 ±0.41) ng/g,P=0.000; and Ki-67:40％ vs 10％,P =0.028].The Ki-67 expression rate was 90.48％ in the HFDT group,compared to 50％ in the SDT group (P =0.015).Conclusions High-fat diet can increase the serum triglyceride and TNF-α levels in rats,upregulate the expressions of TNF-α,IL-6 and Ki-67,and thus promote inflammation and cell proliferation,and ultimately affect the tumor formation and development.However,the effect of fat on DMH-induced colon tumors warrants further studies.
ABSTRACT
Protein phosphatase 2A(PP2A)is a major Ser/Thr phosphatase involved in sevelral cellular signal transduction pathways.The reversible phosphorylation of proteins is accomplished by opposing activities of kinases and phosphatases.PP2A controls the specific dephosphorylation of thousands of phosphoprotein substrates and thus regulates physiological and biochemical processes of organism.The changes of the physiological activities of PP2A closely relate to apoptosis and regeneration of injured intestinal epithelial cell,and PP2A may be a regulatory factor in balancing the apoptosis and regeneration of intestinal epithehal cell.