ABSTRACT
Objective To study the reliability of 99Tcm-(hydrazinonicotinamide (HYNIC)-BMS-200261) (tricine) (trisodium triphenylphosphine-3,3',3"-trisulfonate (TPPTS)) as a radiotracer for protease activated receptor-1 (PAR-1) expression in breast cancer.Methods Fifteen nude mice bearing MDA-MB-435,MDA-MB-231 and MCF-7 human breast cancer xenografts (5 mice for each cell line) with different PAR-1 expression were used for 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) γ imaging,and tumor/non-tumor (T/NT) ratios were obtained with region of interest (ROI) technique.Afterwards,the biodistribution of 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) was analyzed in tumor-bearing nude mice,and the radioactivity in tumor (percentage activity of injection dose per gram of tissue,％ID/g) was calculated.The immunostaining was performed to examine PAR-1 expression in tumor tissue and semi-quantitative analysis was used.One-way analysis of variance and Pearson correlation analysis were used to analyze data.Results At 2 h postinjection,the T/NT ratios were 3.03±0.32,2.27±0.25 and 1.51±0.13 respectively in nude mice bearing MDA-MB-435,MDA-MB-231 and MCF-7 xenografts;the tumor uptakes of 99Tcm-(HYNIC-BMS-200261)(tricine)(TPPTS) were (1.03±0.15),(0.56±0.14) and (0.30±0.06) ％ID/g;PAR-1 expression levels were (17.22±2.71) ％,(10.78± 1.95) ％ and (2.80± 1.18) ％,respectively (F values:47.66,46.36,62.35,all P＜0.05).The T/NT ratios and tumor uptake of 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) at 2 h post-injection were correlated with PAR-1 expression (r values:0.934 and 0.929,both P＜0.05).Conclusions 99Tcm-(HYNIC-BMS-200261) (tricine) (TPPTS) imaging could be a noninvasive and effective method for monitoring PAR-1 expression in human breast cancer.
ABSTRACT
Objective To investigate the expression of protease-activated receptors (PARs) in colon mucosal tissue of patients with diarrhea-predominant irritable bowel syndrome (D-IBS). Methods Colon mucosa tissues were obtained from 28 D-IBS patients and 18 normal controls by colonoscopy.The expression of PARs was detected using Western blotting and real-time PCR. Data were analysed by SPSS 18. 0 softwave, and comparisons between groups were done using Mann-Whitney U test.Results There was no difference in expression of PAR1 between D-IBS patients and normal controls (P=0. 300). The expressions of PAR2 and PAR4 were higher in D-IBS patients than those in normal controls (0.99±0.67 vs 0.63±0.38, P=0.038 and 0.37±0. 14 vs 0.25±0. 11, P=0.013,respectively). The results of real-time PCR were in accordance with those of Western blotting.Conclusion The increased expressions of PAR2 and PAR4 in colon mucosa of D-IBS patients indicate that these two PAR receptors may be involved in the process of D-IBS.