ABSTRACT
PURPOSE: Angiogenesis and vascular endothelial growth factor (VEGF) expression are associated with a poor outcome in bladder cancer. To understand more about the mechanisms, we studied the role of delta-like 4 (DLL4), an endothelial-specific ligand of the Notch signaling pathway, in bladder cancer angiogenesis. EXPERIMENTAL DESIGN: The expression of DLL4, CD34, and VEGF were studied in a cohort of 60 bladder tumors and 10 normal samples using quantitative PCR. In situ hybridization was used to study the pattern of DLL4 expression in 22 tumor and 9 normal samples. Serial sections were also stained for CD34 and alpha-smooth muscle actin (alpha-SMA) using conventional immunohistochemistry. RESULTS: The expression of DLL4 was significantly up-regulated in superficial (P < 0.01) and invasive (P < 0.05) bladder cancers. DLL4 expression significantly correlated with CD34 (P < 0.001) and VEGF (P < 0.001) expression. The in situ hybridization studies showed that DLL4 was highly expressed within bladder tumor vasculature. Additionally, DLL4 expression significantly correlated with vessel maturation as judged by periendothelial cell expression of alpha-SMA, 98.7% of DLL4-positive tumor vessels coexpressed alpha-SMA, compared with 64.5% of DLL4-negative tumor vessels (P < 0.001). High DLL4 expression may have prognostic value in superficial and invasive bladder. CONCLUSION: DLL4 expression is associated with vascular differentiation in bladder cancer; thus, targeting DLL4 may be a novel antiangiogenic therapy.
Subject(s)
Carcinoma, Transitional Cell/blood supply , Intercellular Signaling Peptides and Proteins/biosynthesis , Urinary Bladder Neoplasms/blood supply , Actins/biosynthesis , Actins/genetics , Adaptor Proteins, Signal Transducing , Adult , Aged , Aged, 80 and over , Antigens, CD34/biosynthesis , Antigens, CD34/genetics , Calcium-Binding Proteins , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/metabolism , Cohort Studies , Female , Humans , Immunohistochemistry , Intercellular Signaling Peptides and Proteins/genetics , Male , Middle Aged , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/metabolism , Polymerase Chain Reaction , Prognosis , Up-Regulation , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Vascular Endothelial Growth Factor A/biosynthesis , Vascular Endothelial Growth Factor A/geneticsABSTRACT
PURPOSE: We evaluated the efficacy and tolerance of topical 0.2% glyceryl trinitrate (GTN) paste vs placebo to decrease pain associated with transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS: Between October 2003 and April 2004, 134 consecutive patients referred for a first prostate biopsy were randomized to receive topical 0.2% GTN paste or placebo 30 minutes prior to biopsy. Participants completed a 10 point visual analog pain score following the procedure. RESULTS: Mean patient age was 68.5 years in the GTN group and 68.8 in the placebo group. There was a significant decrease in mean pain score in the GTN group compared with placebo (3.7 vs 4.8, p <0.05). Six patients (10%) in the GTN group complained of headache. CONCLUSIONS: Topical GTN paste is an effective and well tolerated method of decreasing pain associated with transrectal ultrasound guided prostate biopsy. It is safe and easy to use, and it should be offered to patients undergoing this procedure.
