Correlation of serum ß2-microglobulin levels with prostate-specific antigen, Gleason score, clinical stage, tumor metastasis and therapy efficacy in prostate cancer.

BACKGROUND AND AIMS: Despite previous reports implying a role of ß2-microglobulin (ß2M) in the development of prostate cancer (PCa), the correlation of serum ß2M with the clinicopathological features, therapy efficacy and prognosis of patients with PCa have not been fully clarified. The present study aims to investigate the serum levels of ß2M in patients with PCa and explore the potential use of ß2M as a tumor marker for diagnosis, treatment and prognosis of PCa. METHODS: Serum ß2M levels in 120 patients with PCa, 50 patients with benign prostate hyperplasia (BPH) and 85 healthy age-matched controls were measured by enzyme immunoassay. The correlation of serum ß2M with the clinicopathological features, therapy efficacy and the prognosis of PCa were subsequently assessed. RESULTS: Our results showed that: (i) PCa patients had significantly higher levels of ß2M compared to those of patients with BPH or those of healthy controls. (ii) Serum ß2M were markedly elevated in patients with high stage or grade PCa as compared to patients with low stage or grade PCa. (iii) We measured significantly higher levels of ß2M in patients with metastasis as compared to patients lacking metastasis. (iv) During follow-up, serum ß2M showed a marked decrease after successful therapy and a significant further increase in recurrent disease. CONCLUSIONS: Our results demonstrate that serum ß2M is correlated closely with the clinical stage, Gleason grade, PSA, distant metastasis and therapy efficacy in patients with PCa. Serum ß2M may be a useful biomarker for clinical diagnosis, follow-up and prognosis of PCa.

Effects of genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 on cyclosporine pharmacokinetics after renal transplantation.

1. The calcineurin inhibitor cyclosporine is widely used to prevent allograft rejection after solid organ transplantation. It has a narrow therapeutic index and shows considerable interindividual differences in its pharmacokinetics. Interindividual differences in the activity and expression of the metabolising enzymes cytochrome P450 (CYP) 3A4 and 3A5 and the multidrug efflux pump P-glycoprotein (P-gp) contribute considerably to cyclosporine pharmacokinetics. Variability in the activity of CYP3A4, CYP3A5 and P-gp could be considered to result from genetic polymorphisms encoding their genes. 2. The aim of the present study was to evaluate retrospectively the effects of genetic polymorphisms of CYP3A4, CYP3A5 and MDR1 on cyclosporine dose adjusted trough blood concentration during the early period after renal transplantation in Chinese patients. 3. One hundred and six renal transplant recipients in China were genotyped by polymerase chain reaction-restriction fragment length polymorphism for CYP3A4*18A, CYP3A5*3 and MDR1 C3435T. Cyclosporine whole blood levels were measured by fluorescence polarization immunoassay. Dose-adjusted trough blood concentrations (C(0)) were determined and compared among the different genotype groups. 4. The frequency of the CYP3A4*18A, CYP3A5*3 and MDR1 C3435T variant alleles were 0.005 (95% confidence interval (CI) 0.048, 0.0049), 0.783 (95% CI 0.781, 0.785) and 0.528 (95% CI 0.526, 0.531), respectively, and these alleles exhibited incomplete linkage disequilibrium. The median cyclosporine dose-adjusted C(0) in CYP3A5*1/*1 genotype subjects (n = 6) was 14.8 ng/mL per mg per kg (range 11.1-26.8 ng/mL per mg per kg), in CYP3A5*1/*3 patients (n = 34) it was 23.7 ng/mL per mg per kg (range 9.0-61.0 ng/mL per mg per kg) and for CYP3A5*3/*3 patients (n = 66) it was 26.4 ng/mL per mg per kg (range 9.8-85.8 ng/mL per mg per kg; P = 0.012, Kruskal-Wallis test). Accordingly, cyclosporine dose-adjusted C0 was larger in CYP3A5 non-expressors than expressors in the first week after renal transplantation. In addition, wild-type homozygotes (n = 21) for MDR1 C3435T had a slight but significantly lower dose-adjusted C0 compared with heterozygotes (n = 58): 17.7 (10.3-60.8) versus 26.4 (9.0-67.3) ng/mL per mg per kg, respectively (P = 0.014, Mann-Whitney U-test). 5. In conclusion, the present study shows that genetic polymorphisms in CYP3A5 may be responsible, in part, for the large interindividual variability of cyclosporine pharmacokinetics during the early phase after renal transplantation in Chinese patients. Patients with the CYP3A5*3 variant genotype require a low dose of cyclosporine to reach target levels compared with those with the CYP3A5*1 allele.

Free graft two-stage urethroplasty for hypospadias repair.

OBJECTIVE: To evaluate the effectiveness of free graft transplantation two-stage urethroplasty for hypospadias repair. METHODS: Fifty-eight cases with different types of hypospadias including 10 subcoronal, 36 penile shaft, 9 scrotal, and 3 perineal were treated with free full-thickness skin graft or (and) buccal mucosal graft transplantation two-stage urethroplasty. Of 58 cases, 45 were new cases, 13 had history of previous failed surgeries. Operative procedure included two stages: the first stage is to correct penile curvature (chordee), prepare transplanting bed, harvest and prepare full-thickness skin graft, buccal mucosal graft, and perform graft transplantation. The second stage is to complete urethroplasty and glanuloplasty. RESULTS: After the first stage operation, 56 of 58 cases (96.6%) were successful with grafts healing well, another 2 foreskin grafts got gangrened. After the second stage operation on 56 cases, 5 cases failed with newly formed urethras opened due to infection, 8 cases had fistulas, 43 (76.8%) cases healed well. CONCLUSIONS: Free graft transplantation two-stage urethroplasty for hypospadias repair is a kind of effective treatment with broad indication, comparatively high success rate, less complications and good cosmatic results, indicative of various types of hypospadias repair.