Background: Although up to 30% of men who undergo radical prostatectomy for clinically organ-confined prostate cancer will relapse with disseminated disease, currently it is not possible to predict these patients.
Methods: Androgen receptor (AR) immunoreactivity in stromal and epithelial compartments of tumor foci was evaluated by video image analysis in 53 radical prostatectomy specimens. Kaplan-Meier and Cox Regression analyses were used to determine whether AR immunostaining was related to rate and risk of relapse, respectively.
Results: Ninety-eight percent (52/53) of the tumors contained AR positive malignant epithelial cells. Kaplan-Meier analysis indicated that patients with high AR levels (>64% AR positive nuclear area) in the malignant epithelial cells or low AR levels (
Conclusions: These findings suggest that AR is an important determinant of disease relapse in early stage prostate cancer, and that altered AR levels in the malignant epithelial cells or in the peritumoral stroma is indicative of non-organ confined prostate cancer.
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http://dx.doi.org/10.1002/pros.20154 | DOI Listing |
Clin Genitourin Cancer
December 2024
Medical and Translational Oncology, Department of Oncology, Azienda Ospedaliera Santa Maria, Terni, Italy.
The recent evidences provided in metastatic hormone sensitive prostate cancer (nmHSPC) and in nonmetastatic castration resistant (nmCRPC) introduced the possibility to adopt Androgen Receptor Signaling inhibitor (ARSi) alone (both settings) or with chemotherapy (in mHSPC). In daily clinical practice there are some opening questions regarding the inclusion of next generation imaging, mainly PSMA-PET, how integrate local treatment as radiotherapy, how to select patients or drugs in a multiple-choice scenario, and how to manage patients with comorbidities and polypharmacy. These issues led the Italian Society for Uro-Oncology (SIUrO) to develop a consensus project involving all of the most important Italian scientific societies engaged in the multidisciplinary and multiprofessional management of the disease.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Department of Biochemistry and Molecular Biology, LSU Health Shreveport, Shreveport, LA 71103, USA.
For nearly a century, fundamental observations that prostate cancer (PCa) cells nearly always require AR stimulation for sustained proliferation have led to a unidirectional quest to abrogate such a pathway. Similarly focused have been efforts to understand AR-driven processes in the context of elevated expression of its target genes, and much less so on products that become overexpressed when AR signaling is suppressed. Treatment with ARSI results in an increased expression of the TLK1B splice variant via a 'translational' derepression driven by the compensatory mTOR activation and consequent activation of the TLK1 > NEK1 > ATR > Chk1 and NEK1 > YAP axes.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Faculty of Pharmacy, University of Montreal, 2940 Chem. de Polytechnique, Montreal, QC H3T 1J4, Canada.
Background/objectives: Through phase III clinical trials, PARP inhibitors have demonstrated outcome improvements in mCRPC patients with alterations in BRCA1/2 genes who have progressed on a second-generation androgen receptor pathway inhibitor (ARPI). While improving outcomes, PARP inhibitors contribute to the ever-growing economic burden of PCa. The objective of this project is to evaluate the cost-effectiveness of PARP inhibitors (olaparib, rucaparib, or talazoparib) versus the SOC (docetaxel or androgen receptor pathway inhibitors (ARPI)) for previously progressed mCRPC patients with BRCA1/2 mutations from the Canadian healthcare system perspective.
View Article and Find Full Text PDFCancers (Basel)
December 2024
CeRePP, 75020 Paris, France.
Purpose: To identify molecular changes during PCa invasion of adipose space using Spatial Transcriptomic Profiling of PCa cells.
Methods: This study was performed on paired intraprostatic and extraprostatic samples obtained from radical prostatectomy with pT3a pathological stages.
Results: Differential gene expression revealed upregulation of heat shock protein genes: DNAJB1, HSPA8, HSP90AA1, HSPA1B, HSPA1A in PCa PanCK+ cells from the adipose periprostatic space.
Int J Mol Sci
December 2024
Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
Prostate cancer (PCa) remains a critical global health challenge, with high mortality rates and significant heterogeneity, particularly in advanced stages. While early-stage PCa is often manageable with conventional treatments, metastatic PCa is notoriously resistant, highlighting an urgent need for precise biomarkers and innovative therapeutic strategies. This review focuses on the dualistic roles of sirtuins, a family of NAD+-dependent histone deacetylases, dissecting their unique contributions to tumor suppression or progression in PCa depending on the cellular context.
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