ABSTRACT
OBJECTIVE: To evaluate the effect of post-treatment PSA kinetics on the prognosis of prostate cancer (PCa). METHODS: We retrospectively reviewed the clinical data of 114 cases of locally advanced PCa treated by maximal androgen blockade (MAB) combined with brachytherapy, and analyzed the association of the changes in PSA kinetics with the prognosis of the patients. RESULTS: The median survival time of the patients was 81 (15 - 144) months, with 1-, 3- and 5-year survival rates of 91. 23%, 78.07% and 68.42% , respectively. Univariate analysis indicated that the baseline PSA level, PSA nadir, the time of PSA decreasing to nadir, PSA doubling time, and the extent of PSA declining were all predictive factors for the survival time of the PCa patients. Multivariate analysis demonstrated that PSA nadir, the time of PSA decreasing to nadir, and the extent of PSA declining were three independent prognostic factors, which prolonged the long-term survival of the patients by 1.7, 3.2 and 6.8 times, respectively. CONCLUSION: For locally advanced PCa treated by MAB combined with brachytherapy, PSA nadir <1 micro g/L, the time to nadir <3 months, and the extent of PSA declining >96% are independent prognostic factors.
Subject(s)
Androgens/administration & dosage , Prostate-Specific Antigen/metabolism , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/therapy , Aged , Aged, 80 and over , Androgens/therapeutic use , Brachytherapy , Humans , Male , Middle Aged , Prognosis , Retrospective StudiesABSTRACT
Although cancer stem cells (CSCs) play a crucial role in seeding the initiation of tumor progression, they do not always possess the same potent ability as tumor metastasis. Thus, precisely how migrating CSCs occur, still remains unclear. In the present study, we first comparatively analyzed a series of prostate CSCs, which exhibited a dynamically increasing and disseminating ability in nude mice. We observed that the transcriptional activity of HIF-1α and ß-catenin became gradually elevated in these stem cells and their epithelial-mesenchymal transition (EMT) characteristic altered from an epithelial type to a mesenchymal type. Next, we further used cancer-associated fibroblasts (CAFs), which were cultured from surgically resected tissues of prostate cancer (PCa) to stimulate prostate CSCs. Similar results were reconfirmed and showed that the protein levels of both HIF-1α and ß-catenin were markedly improved. In addition, the EMT phenotype displayed a homogenous mesenchymal type, accompanied with increased aggressive potency in vitro. Most importantly, the aforementioned promoting effect of CAFs on prostate CSCs was completely repressed after "silencing" the activity of ß-catenin by transfection of stem cells with ShRNA. Taken together, our observations suggest that prostate migrating CSCs, with a mesenchymal phenotype, could be triggered by CAFs in a HIF-1α/ß-catenin-dependent signaling pathway.
Subject(s)
Epithelial-Mesenchymal Transition , Fibroblasts/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Neoplastic Stem Cells/physiology , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , beta Catenin/metabolism , Animals , Fibroblasts/pathology , Gene Expression Regulation, Neoplastic , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Male , Mice , Mice, Nude , Neoplastic Stem Cells/metabolism , Prostatic Neoplasms/genetics , RNA, Small Interfering/genetics , Signal Transduction , Tumor Cells, Cultured , beta Catenin/geneticsABSTRACT
OBJECTIVE: To explore the prognostic factors of prostate cancer (PCa) patients and evaluate the effect of brachytherapy on survival time. METHODS: A total of 289 PCa were recruited to collect their clinical and survival data. And their possible prognostic factors were analyzed. A further comparison of 5-year cumulative survival rate was made between the patients treated by maximal androgen blockade (MAB) and those on MAB plus brachytherapy. RESULTS: Their median survival time was 73 (7-144) months. And the 1, 3 and 5-year survival rates were 93.1%, 81.0% and 60.2% respectively. Univariate analysis indicated that prostate volume, basal level of prostate-specific antigen (PSA), Gleason score, tumor stage, PSA nadir, time PSA decreasing to nadir and brachytherapy were all predictive factors for survival time. And multivariate analysis further demonstrated that Gleason score, tumor stage and PSA nadir were independent prognostic indicators. And the combination therapy based on brachytherapy could significantly increase the 5-year cumulative survival rate than MAB-based monotherapy. CONCLUSION: Gleason score, tumor stage and PSA nadir may predict the prognosis of PCa patients. And brachytherapy significantly improves patient survival.
