Apoptosis of Prostate Cancer by Bax Gene Expression / 대한비뇨기과학회지

PURPOSE: To evaluate the antitumor effect of the proapoptotic Bax gene in prostate cancer cells, in vitro, using a plasmid vector expressing the human Bax gene. MATERIALS AND METHODS: cDNA of the human Bax gene, amplified by RT-PCR, was cloned to pCR@3.1. The expression of the cloned Bax (pCR3.1-Bax) was observed by RT-PCR and Western blot analyses. The efficacy of growth inhibition by the cloned Bax gene was tested, in vitro, on PC-3 and DU145 human prostate cancer cell lines using the MTT assay. Immunoblot analysis for the expressions of Bcl-2 and Bcl-xL were performed. Assays were also performed to evaluate the apoptosis, DNA fragmentation and CPP32. RESULTS: The Bax protein was expressed in the parental PC-3 cells, but not in the DU-145 cells. The expressions of Bax mRNA in the transfected PC-3 and DU-145 cells had increased by 24 hr, and those of Bax protein in the transfected PC-3 and DU-145 cells had increased by 48 and 24 hr, respectively, compared with the control cell lines. The cytotoxicity of pCR3.1-Bax on PC-3 and DU-145 cells increased significantly compared with an empty vector, pCR3.1 (p<0.05, respectively). An increased cytotoxicity of the Bax-transfected cell lines was associated with enhanced apoptosis. The Bcl-2 protein was not expressed in the transfected cells, and the levels of Bcl-xL protein expression in transfected cells were no different to those in the parenteral cells. The Bax/Bcl-xL ratio was increased by the transfection of the Bax expression vector. CONCLUSIONS: Our results show that the cloned Bax-expression plasmid vector efficiently inhibits the growth of PC-3 and DU145 human prostate cancer cell lines. These data suggest that exogenous Bax expression may have therapeutic applications in prostate cancer.

Prognostic Significance of the Nadir Prostate Specific Antigen Level after Hormone Therapy for Prostate Cancer Patients / 대한비뇨기과학회지

PURPOSE: We tried to find out whether the nadir PSA level after hormone therapy affected the progression into hormone-refractory prostate cancer (HRPC). MATERIALS AND METHODS: We reviewed the progressive status and the survival of the 177 patients with stage C or D prostate cancer who had received hormone therapies. The relative efficacy of the nadir PSA level for predicting the progression into HRPC was evaluated by the receiver operating characteristic (ROC) analysis. RESULTS: 85.4% of patients responded to the treatment and 78% of responders progressed into HRPC. Median time to nadir PSA level after hormone therapy and to HRPC were 8.1 and 24.0 months, respectively. The nadir PSA levels were under 0.2ng/ml in 31%, 0.2-1.0ng/ml in 23%, 1.1-10ng/ml in 42%, and over 10ng/ml in 5% of the responders (n=151). As the nadir PSA levels were lower, pretreatment PSA levels, Gleason score and the number of cases progressing into HRPC were significantly lower (p<0.05). In addition, the nadir PSA level was inversely correlated with the interval to the establishment of HRPC (r= 0.465, p<0.05). By univariate analysis, the bone metastasis, the nadir PSA level, PSA level at six months after treatment and pretreatment PSA level were associated with the progression into HRPC. Only the nadir PSA level was an independent factor by multivariate analysis. ROC analysis disclosed an accuracy of 86.2% for the nadir PSA level to predict the progression into HRPC after two years. By setting the lower limit of the nadir PSA level to 1.1ng/ml, the sensitivity was 80.3% and the specificity was 83.8%, being most adequate. CONCLUSIONS: The nadir PSA level after hormone therapy may be the most important factor that can predict the progression into HRPC. Also, in consideration of sensitivity and specificity, it would be adequate to set the lower limit of the nadir PSA level to 1.1ng/ml.

The Expression of Vascular Endothelial Growth Factor and Thrombospondin-1 in Wilms' Tumor / 대한비뇨기과학회지

PURPOSE: With the process of neoangiogenesis being linked to the growth and metastasis of various tumors, anticancer therapeutics with a basis in the suppression of neoangiogenesis has recently been receiving attention. In this study, we tried to clarify the immunoreactivities of vascular endothelial growth factor (VEGF), major angiogenic inducer and thrombospondin-1 (TSP-1), major angiogenic inhibitor in human Wilms' tumor and its clinicopathological significance. MATERAILS AND METHODS: Utilizing immunohistochemical staining, we assessed the immunoreactivities of VEGF and TSP-1 in archival tissues of 29 Wilms' tumors and 25 normal kidneys. Also, we assessed the relationship between expression of each factor and clinicopathological parameters in 29 cases of Wilms' tumors. RESULTS: Immunoreactivities of VEGF and TSP-1 were detected mainly in the cytoplasm of the tubular cells in normal kidneys. In Wilms' tumors, whereas VEGF was detected in the cytoplasm of the tumor cells and peritumoral stromal tissues, but TSP-1 only in the peritumoral stromal tissues. Immunohistochemical expression patterns of each factor were divided into two groups according to the area of immunoreactivity (negative: OR =10%). VEGF immunoreactivity was detected in 25 (100%) normal kidneys and in 20 (69%) Wilms' tumors. However, TSP-1 immunoreactivity was detected in 24 (97%) normal kidneys and in 3 (10%) Wilms' tumors. Therefore, although no significant difference was observed between the expressions of VEGF and TSP-1 in normal kidney, the TSP-1 immunoreactivity was significantly lower than VEGF immunoreactivity in Wilms' tumors. A relatively higher rate of positive expression of TSP-1 was observed in the patients with no demonstrable lymph node metastasis. Also, as for the VEGF, maximal diameter of the tumor was larger in the positive expression group. However, it proved otherwise for TSP-1 as the negative expression group demonstrated tumors with larger maximal diameters. CONCLUSIONS: Our study demonstrated that the TSP-1 immunoreactivity was significantly lower than VEGF immunoreactivity in Wilms' tumors, and disease progression has a tendency to be found in the VEGF-positive cases and TSP-1 negative cases. We suggest that the growth and metastasis of Wilms' tumor may be influenced mainly by TSP-1 decrease rather than VEGF increase.