Background: Prostate cancer (PCa) management can benefit from novel concepts/biomarkers for reducing the current 20-30% chance of false-negative diagnosis with standard histopathology of biopsied tissue.
Method: We explored the potential of selected epigenetic markers in combination with validated histopathological markers, 3D high-content imaging, cell-by-cell analysis, and probabilistic classification in generating novel detailed maps of biomarker heterogeneity in patient tissues, and PCa diagnosis. We used consecutive biopsies/radical prostatectomies from five patients for building a database of ∼140,000 analyzed cells across all tissue compartments and for model development; and from five patients and the two well-characterized HPrEpiC primary and LNCaP cancer cell types for model validation.
Results: Principal component analysis presented highest covariability for the four biomarkers 4',6-diamidino-2-phenylindole, 5-methylcytosine, 5-hydroxymethylcytosine, and alpha-methylacyl-CoA racemase in the epithelial tissue compartment. The panel also showed best performance in discriminating between normal and cancer-like cells in prostate tissues with a sensitivity and specificity of 85%, correctly classified 87% of HPrEpiC as healthy and 99% of LNCaP cells as cancer-like, identified a majority of aberrant cells within histopathologically benign tissues at baseline diagnosis of patients that were later diagnosed with adenocarcinoma. Using k-nearest neighbor classifier with cells from an initial patient biopsy, the biomarkers were able to predict cancer stage and grade of prostatic tissue that occurred at later prostatectomy with 79% accuracy.
Conclusion: Our approach showed favorable diagnostic values to identify the portion and pathological category of aberrant cells in a small subset of sampled tissue cells, correlating with the degree of malignancy beyond baseline.
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http://dx.doi.org/10.18632/oncotarget.18985 | DOI Listing |
Angew Chem Int Ed Engl
December 2024
Institut Chimie radicalaire ICR-UMR 7273, Facult� de Saint jerome, avenue Escadrille-Normandie-Niemen, service 562, 13397, Marseille, FRANCE.
Efforts to understand radical stability have led to considerable progress in radical chemistry. In this article, we investigated a novel approach to enhancing the radical stability of carbon-centered radicals through space electron delocalization within [2,2]-paracyclophanes. Alkoxyamines possessing a paracyclophane scaffold exploit face-to-face π-π-interactions between the aromatic rings to effectively lower bond dissociation energy (BDE) for NO-C bond homolysis.
View Article and Find Full Text PDFScand J Urol
December 2024
Department of Urology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Urology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
N/A.
View Article and Find Full Text PDFFront Genet
December 2024
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Objective: This study evaluated the real-world efficacy and safety of combining PARP inhibitors with novel hormonal therapy (NHT) as a first-line treatment in Chinese patients with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene mutations.
Methods: We enrolled 41 mCRPC patients who received at least 1 month of combined treatment with PARP inhibitors and NHT. Patients were divided into two groups: Cohort A (mutations in BRCA1, BRCA2, or ATM genes) and Cohort B (mutations in other HRR genes).
Front Oncol
December 2024
Department of Magnetic Resonance Imaging (MRI), The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, China.
Purpose: The aim of this study was to evaluate the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) derived kinetic parameters with high spatiotemporal resolution in discriminating malignant from normal prostate tissues.
Methods: Fifty patients with suspicious of malignant diseases in prostate were included in this study. Regions of interest (ROI) were manually delineated by experienced radiologists.
Supraphysiological androgen (SPA) treatment can paradoxically restrict growth of castration-resistant prostate cancer with high androgen receptor (AR) activity, which is the basis for use of Bipolar Androgen Therapy (BAT) for patients with this disease. While androgens are widely appreciated to enhance anabolic metabolism, how SPA-mediated metabolic changes alter prostate cancer progression and therapy response is unknown. Here, we report that SPA markedly increased intracellular and secreted polyamines in prostate cancer models.
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