ABSTRACT
Objective:To explore the efficacy and mechanism of Guben Qingyuan prescription combined with androgen deprivation therapy （ADT） in the treatment of castration-resistant prostate cancer （CRPC）. Method:A CRPC-bearing mouse model was established. When the tumor volume reached about 100 mm<sup>3</sup>， 50 CRPC-bearing BALB/c nude mice were randomly divided into the model group， ADT group， and ADT+low-， medium-， high-dose Guben Qingyuan prescription groups， with 10 mice in each group. After grouping， it was ensured that there was no statistically significant difference in tumor volume between groups. The mice in the model group was treated with the same amount of normal saline （10 mL·kg<sup>-1</sup>） by gavage， twice a day， while those in the other groups were provided with bicalutamide （5 mg·kg<sup>-1</sup>） for intragastric administration， once a day， and then with goserelin （0.36 mg·kg<sup>-1</sup>） for intraperitoneal injection on the 10th day. On the basis of ADT， the ones in the ADT+Guben Qingyuan prescription groups further received Guben Qingyuan prescription at the low （2.5 g·kg<sup>-1</sup>）， medium （25 g·kg<sup>-1</sup>）， and high doses （50 g·kg<sup>-1</sup>） by gavage， twice a day. After 25 days of continuous administration， the tumor tissue was harvested for recording the tumor growth and calculating the tumor inhibition rate. The mRNA and protein expression levels of androgen receptor （AR）， androgen receptor splice variant-7 （AR-V7）， and prostate-specific antigen （PSA） were detected by real-time polymerase chain reaction （Real-time PCR） and Western blot assay. Result:The tumor inhibition rates of the ADT+low-， medium-， and high-dose Guben Qingyuan prescription groups were 27.95%， 46.71%， and 44.46%， respectively， and the inhibition rates in the ADT+medium- and high-dose Guben Qingyuan prescription groups were significantly increased as compared with that in the ADT group （<italic>P</italic><0.05）. As revealed by comparison with the ADT group， Guben Qingyuan prescription at the medium and high doses significantly down-regulated the mRNA and protein expression levels of AR， AR-V7， and PSA （<italic>P</italic><0.05）. Conclusion:Guben Qingyuan prescription combined with ADT is efficient in controlling the tumor growth in CRPC-bearing mice， which is related to the regulation of AR/AR-V7 signaling pathway.
ABSTRACT
To identify novel genes in castration-resistant prostate cancer (CRPC), we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus (GEO). R packages affy and limma were performed to identify differentially expressed genes (DEGs) between primary prostate cancer and CRPC. After that, we performed functional enrichment analysis including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway. In addition, protein-protein interaction (PPI) analysis was used to search for hub genes. Finally, to validate the significance of these genes, we performed survival analysis. As a result, we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets. Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosterone-regulated sodium reabsorption pathway. PPI network identified hub genes like cortactin-binding protein 2 (CTTNBP2), Rho family guanosine triphosphatase (GTPase) 3 (RND3), protein tyrosine phosphatase receptor-type R (PTPRR), Jagged1 (JAG1), and lumican (LUM). Based on PPI network analysis and functional enrichment analysis, we identified two genes (PTPRR and JAG1) as key genes. Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer. In conclusion, PTPRR and JAG1 are key genes in the CRPC, which may serve as promising biomarkers of diagnosis and prognosis of CRPC.
ABSTRACT
The incidence and mortality of prostate cancer have steadily increased. As such, the prevention and treatment of prostate cancer are important. Standardized drug therapy in patients with castration-resistant prostate cancer (CRPC) is crucial for improving survival and quality of life. Here, we review the current situation and latest research progress in drug therapy for CRPC.
ABSTRACT
Objective: To evaluate the prognostic value of serum phosphorus level in castration-refractory prostate cancer (CRPC). Methods: The clinical data of 56 patients with CRPC who were admitted to the Second Hospital of Tianjin Medical University between January 2009 and January 2012 were retrospectively analyzed. The patients were assigned into three groups according to their phos-phorus levels as follows: low (blood phosphorus level<0.8 mmol/L), normal (0.8 ±1.5 mmol/L), and high (>1.5 mmol/L) phosphorus groups.This study was aimed at comparing the clinicopathological features of the three groups and analyzing the influence of blood phosphorus level on patient prognosis. Results: Among the 56 patients with CRPC, 13 (23.2%) were in the low phosphorus group; 39 (69.6%) in the normal phosphorus group; and 4 (7.2%) in the high phosphorus group. The median survival time of the three groups were 18,27, and 24 months, respectively. Significant differences were found among the groups (P<0.05). A single-factor analysis re-vealed that the survival time was affected by clinical stage (χ2=3.940, P=0.047), distant metastasis (χ2=5.369, P=0.020), and hypophos-phatemia (χ2=6.695, P=0.010). A multivariate analysis of the Cox model revealed that hypophosphatemia, hypercalcemia, and distant metastasis were risk factors related to patient prognosis, with hazard ratios (95% confidence interval) of 5.448 (1.532-19.379), 5.868 (1.897-18.147), and 3.708 (1.300-10.578), respectively. Conclusions: The prognosis of the patients with CRPC who had low blood phos-phorus levels was poor. Hypophosphatemia, hypercalcemia, and distant metastasis are prognostic risk factors in patients with CRPC. Blood phosphorus level can predict the prognosis of patients with CRPC to a certain extent.
ABSTRACT
Background & objectives: There is lack of data on natural history and progression of prostate cancer (PC) which have implications in the management of the disease. We undertook this retrospective study to analyze factors predicting progression of metastatic PC to castration-resistant prostate cancer (CRPC) in Indian men. Methods: Complete records of 223 of the 489 patients with metastatic PC were obtained from computerized data based system in a tertiary care hospital in north India between January 2000 to June 2012. Patients with follow up of < 6 months were excluded. Age (≤ and > 65 yr), baseline PSA (< and ≥ 50 ng/ml), bone scan and Gleason score (≤7 and >7) were recorded. Extent of bone disease (EOD) was stratified according to the number of bone lesions i.e., < 5, 5-10, > 10. CRPC was defined as two consecutive PSA rise of > 50 per cent from nadir or an absolute value of > 5 ng/ml. Results: Mean age of patients was 61.5 ± 12.45 yr and their PSA level was 325.6 ± 631.35 ng/dl. Of the 223 patients, 193 (86%) progressed to CRPC at median time of 10.7 (4-124) months. Median follow up was 24 (6-137) months. On univariate and multivariate analyses EOD on bone scan was found to be a significant predictor (P=0.006) for time to CRPC. Median time to CRPC was 10 months (CI 95%, 7.5-12.48) with >10 lesions or super scan versus 16 months (CI 95%, 10.3-21.6) with <10 bone lesion (P=0.01). Ninety (46.6 %) patients of CRPC died with median time to death from time of CRPC 21 (10-120) months. Interpretation & conclusions: Median time for progression of metastatic PC to CRPC ranged from 10-16 months depending on the extent of the bone involvement. In Indians, the aggressive course of advanced prostate cancer warrants further clinical trials to explore the need for additional treatment along with initial castration.