ABSTRACT
The apoptosis-inducer Fas and the apoptosis-suppresser Bcl-2 are members of the tumor necrosis factor receptor and Bcl-2 gene superfamilies, respectively. Bcl-2 is overexpressed in hormonally refractory prostate cancer. Fas is expressed in several prostatic carcinoma cell lines but its in vivo expression in normal prostate and in prostate cancer is poorly understood. Formalin-fixed tissue sections from 10 benign prostatic hyperplasias, 10 low-grade and 10 high-grade organ-confined prostate cancers, and 6 metastatic prostate cancers were evaluated for immunoreactivity with Fas and Bcl-2 monoclonal antibodies. In addition, Fas expression was quantitated by computerized cytometry. The results were compared by one-way analysis of variance followed by Bonferroni tests. In benign prostate samples, Bcl-2 and Fas were expressed on basal cells and secretory cells, respectively. Bcl-2 was not expressed in any organ-confined tumors and only in one of six metastatic tumors (17%). Fas was expressed in all organ-confined tumors and in two of six metastatic tumors (33%). Fas expression was significantly decreased (P < 0.001) in prostate cancer (0.20 pg/cell) compared with benign prostate (0.79 pg/cell). The decrease was inversely related to the malignant grade of the tumors (0.30 pg/cell in low-grade tumors, 0.19 pg/cell in high-grade tumors, and 0.003 pg/cell in metastatic tumors). Based on these preliminary data, decreased expression of Fas appears to be an early molecular event in prostate cancer. The decline begins in low-grade tumors. The lowest expression occurs in metastatic carcinomas, which are often Fas negative. Overexpression of Bcl-2 appears to be a later and unrelated molecular event. Both abnormalities may be implicated in tumor progression by prolonging tumor cell survival.
ABSTRACT
Objective: To characterize urodynamic changes among patients who underwent a continent urinary reservoir (Florida Pouch).Methods: Patients who had a continent urinary diversion performed between January 1988 and December 1991 were asked to undergo sequential urodynamic evaluation to compare early (24 mo) changes in reservoir function. The difference in reservoir function was evaluated by defining change in maximum enterocystometric capacity of >/=100 mL, changes in pressure of 5 cm H(2)O, changes in segmental contractions were >/=3. High pressure contractions were those >/=30 mm H(2)O.Results: Seventeen patients underwent sequential urodynamic evaluation. The mean timing of the early study was 12.2 months (range 3-24 mo). The mean timing of the late study was 47.1 months (range 30-58 mo). The mean capacity of the reservoir initially was 698 mL (range 474-1000 mL). On long-term study the mean was 793 mL (range 400-1000 mL). The capacity remained unchanged or increased in 88% of patients. The pressure within the reservoir remained unchanged in seven patients, decreased in eight, and increased in two. Segmental contractions originally occurred in 15 patients with 11 low pressure and 4 high pressure type contractions. On long-term evaluation, 13 patients demonstrated contractions with 10 low pressure and 3 high pressure in character. Of note, 75% of those with initial high pressure contractions had no (1) or low pressure (2) contractions on subsequent evaluation.Conclusion: In long-term urodynamic evaluation of the continent urinary reservoir the reservoir capacity remained unchanged or increased in 88% of patients, while reservoir pressure remained unchanged or decreased in 88%. This long-term evaluation, therefore, demonstrates the continent urinary reservoir to be a low pressure system of adequate capacity thereby minimizing the risk of reflux.
ABSTRACT
BACKGROUND: The incidence of bladder cancer has been steadily increasing and, despite improvements in treatment, many patients will not survive five years. Gene therapy is a promising approach that may improve the management of this disease. METHODS: Gene therapy involves two steps: (1) selection of an appropriate gene and (2) transfer of that gene to the target cells. RESULTS: Five broad categories of cancer gene therapy are undergoing clinical evaluation: (1) immunological augmentation by cytokine or (2) foreign gene transfer into tumor cells, (3) insertion of a suicide gene into tumor cells, (4) tumor suppressor gene reconstitution, and (5) bone marrow protection by insertion of a multidrug resistance gene. CONCLUSIONS: Although many gene transfer approaches have great intuitive appeal, several constraints, including problems with methods of gene transfer, must be overcome before this biologic approach can reach its potential.
