ABSTRACT
Objective To investigate the expressions of P53,topoisomeraseⅡ(TopoⅡ)and multidrug resistance associated protein(MRP)in tissues of colorectal cancer of patients combined with chronic schistosomiasis.Method The retrospective case-control study was adopted.The clinicopathological data of 338 colorectal cancer patients who were admitted to the Zhejiang Cancer Hospital between January 2008 and December 2010 were collected.Cancer tissue specimens from surgical resection were collected.Among 338 patients,80 were combined with chronic schistosomiasis and 258 were combined with non-chronic schistosomiasis.The expressions of P53,TopoⅡand MRP were dectected using immunohistochemistry(IHC).Ranked data were presented as percentage and analyzed using the non-parametric test.Results The negative,weak positive,positive and strong positive expressions of P53 were respectively 5.00％(4/80),87.50％(70/80),3.75％(3/80),3.75％(3/80)in tissues of colorectal cancer of patients combined with chronic schistosomiasis and 28.68％(74/258),19.38％(50/258),16.67％(43/258),35.27％(91/258)in tissues of colorectal cancer of patients combined with non-chronic schistosomiasis,with a statistically significant difference(Z=-2.962,P＜0.05).The negative,weak positive,positive and strong positive expressions of TopoⅡwere respectively 8.75％(7/80),51.25％(41/80),22.50％(18/80),17.50％(14/80)in tissues of colorectal cancer of patients combined with chronic schistosomiasis and 12.01％(31/258),55.43％(143/258),22.48％(58/258),10.08％(26/258)in tissues of colorectal cancer of patients combined with non-chronic schistosomiasis,with no statistically significant difference(Z=-1.551,P＞0.05).The negative,weak positive,positive and strong positive expressions of MRP were respectively 7.50％(6/80),40.00％(32/80),28.75％(23/80),23.75％(19/80)in issues of colorectal cancer of patients combined with chronic schistosomiasis and 24.42％(63/258),38.37％(99/258),24.03％(62/258),13.18％(34/258)in tissues of colorectal cancer of patients combined with non-chronic schistosomiasis,with a statistically significant difference(Z=-3.408,P＜0.05).Conclusion There are abnormal expressions of P53 and MRP in tissues of colorectal cancer of patients combined with chronic schistosomiasis,which may be involved in the hypothetical mechanism of chronic schistosomiasis inducing carcinogenesis of colorectal cancer.
ABSTRACT
Objective: This study aimed to detect the expression levels of the key proteins involved in the insulin-like growth factor signaling pathway of patients with ovarian cancer. These proteins include insulin-like growth factor-1 (IGF1), insulin-like growth factor-1 receptor (IGF1R), and protein kinase B (AKT). Methods: Ovarian cancer tissues were subjected to drug resistance tests using the ATP-TCA method. IGF1, IGF1R, AKT, and multidrug resistance protein2 (MRP2) expressions were detected in the sera of patients with ovarian cancer by conducting enzyme-linked immunosorbent assay. IGF1, IGF1R, and AKT protein expressions were detected in the surgical specimens by immunohistochemistry. Patients were instructed to monitor their cancer antigen 125 (CA125) levels monthly from the date a patient was discharged to the last day of chemotherapy (or until chemotherapy was completed). A color Doppler ultrasound, CT, or MRI scan was required if CA125 value is abnormal. The total follow-up time was one year. Results: IGF1, IGF1R, and AKT expressions were significantly higher in the cisplatin-resistant group than in the cisplatin-sensitive group (P =0.000 1). Immunohistochemical results showed that IGF1, IGF1R, and AKT expressions were significantly higher in the cisplatin-resistant group than in the cisplatin-sensitive group (P<0.05). The monthly CA125 values of 40 patients were obtained after chemotherapy. In the cisplatin-sensitive group, 18 of the 24 cases exhibited normal CA125 values for more than one year, and the remaining 6 cases maintained normal values for more than half a year. In the cisplatin-resistant group, 16 cases revealed higher than normal CA125 values for half a year after chemotherapy. Recurrent lesions were observed in their color Doppler ultrasound results or MRI scans. Conclusion: Cisplatin resistance in ovarian cancer is strongly correlated with the expressions of IGF1, IGF1R and AKT. IGF1 is a potential candidate for the targeted therapy of ovarian cancer.
ABSTRACT
The mechanism of drug resistance of refractory epilepsy has remained unclear.In recent years,studies have shown that the multi-drug resistance associated protein(MRP) is related with refractory epilepsy.The mechanism responsible for the drug resistance may have something to do with the higher expression of MRP1 mRNA in brain tissues of refractory epilepsy patients.Through the use of drugs in cells to cells from the pump,it can reduce the drug concentration in brain and make the creation bears the medicine and inhibitors specific for MRP,which can significantly improve the effect of some antiepileptic drugs.Thus,further studies may provide new ways for the treatment of refractory epilepsy and find targets for new antiepileptic drugs.
ABSTRACT
Objective To study the effect of inhibitors of the multidrug transporters including P-glycoprotein (PGP)and multi-drug resistance-associated protein(MRP)on the regulation of concentration of oxcarbazepine in the extra-cellular fluid of the hippocampus after pilocarpine induced seizures in rats.To investigate whether oxcarbazepine are sub-strate for PGP and MRP and whether brain expressions of PGP and MRP are involved in muhidrug resistance mechanisms of refractory epilepsy.Methods The epileptic rats model were established by repeated peritoneal injection treatment with pi-locarpine.Thirty-two Wistar rats were divided into four groups:control group,pilocarpine epileptic model group,verapamil treated group and probenecid treated group.At 30,60,90,120 and 150 min following systemic injection of oxcarbazepine (80 mg/kg),dialysate was collected and the concentration of oxcarbazepine in the extracellular fluid of hippocampus was determined by microdialysis and high-performance liquid chromatography technique.Results After systemic injection of oxcarbazepine,the concentration of oxcarbazepine in extracellular fluid of the hippocampus during 90～150 min(1.26±0.09、0.93±0.10)were much higher in verapamil treated group than in pilocarpine epileptic model group(0.87±0.06、0.66±O.04)(P<0.05)and the concentration of oxcarbazepine in the hippocampus during 60～150 min(1.07 4±0.11、1.32±O.13、1.02±0.10、0.87±0.08)were higher in probenecid treated group than in pilocarpine epileptic model group (0.81±0.08、0.87±0.06、0.66.4±0.04、0.58±0.06)(P<0.05).Conclusions Oxcarbazepine are substrates for PGP and MRP and,penetration of oxcarbazepine through blood-brain barrier are restricted by PGP and MRP.Increased expres-sions of PGP and MRP in brain maybe involved in the mechanisms of multidrug resistance of refractory epilepsy.