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The objective of this study was to examine E-cadherin and alpha-catenin expression at the junctions between adjacent Sertoli cells in testicular specimens from patients with varicocele in order to determine the presence of a possible link between blood-testis barrier and pathophysiology of varicocele. A total of 51 testicular biopsies were obtained from 28 infertile men with unilateral or bilateral varicocele. Twenty-three patients had bilateral and 5 had unilateral varicocele, Grade I varicocele was detected in 30 (59%), grade II in 15 (29%) and grade III in 6 (12%) patients. Abnormal expression of E-cadherin and alpha-catenin at the junctions between adjacent Sertoli cells was demonstrated in 100% and 90% of the patients with varicocele, respectively. In those with grade I-III varicocele, the mean E-cadherin and alpha-catenin expression were 7.6 +/- 11.4 and 39 +/- 36; 7.6 +/- 0.0 and 49 +/- 30; 8.3 +/- 9.3 and 58 +/- 33, respectively, but the difference was not significant. Reduced E-cadherin and alpha-catenin expression at the junctions between adjacent Sertoli cells may be associated with disruption of blood-testis barrier in varicocele.

Despite the fact that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in cancer cells, TRAIL resistance in cancer cells has challenged the use of TRAIL as a therapeutic agent. First, prostate carcinoma cell lines (DU145, LNCaP and PC3) were screened for sensitivity to adenovirus delivery of TRAIL (Ad5hTRAIL). As amplified Ikappa B kinase (IKK) activity is responsible for the constitutive nuclear factor-kappaB (NF-kappaB) activation leading to uncontrolled cell growth and metastasis, a dual vector approach using both an adenovirus vector (Ad) expressing the dominant-negative mutant of IKKbeta (AdIKKbetaKA) and Ad5hTRAIL was employed to determine if prostate cancer cells were sensitized to TRAIL in the setting of IKK inhibition. Inhibition of the NF-kappaB pathway through IKK blockade sensitized all three prostate cancer cell lines to TRAIL, regardless of NF-kappaB activation or decoy receptor gene expression. Moreover, a novel quantitative real-time RT-PCR assay and conventional flow cytometry analysis indicated that TRAIL-resistant DU145 and LNCaP cells, but not TRAIL-sensitive PC3 cells, expressed substantial amounts of TRAIL Decoy Receptor 4. In conclusion, TRAIL decoy receptor expression appeared to be the chief determinant of TRAIL resistance encountered in prostate carcinoma cell lines.