Background: Prostate cells can produce 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) from 25-hydroxyvitamin D3 (25(OH)D3) to regulate their own growth. Here, the questions of whether prostate cells express vitamin D-25-hydroxylase (25-OHase) and can convert vitamin D3 to 1alpha,25(OH)2D3 were investigated.
Materials And Methods: Protein and receptor binding assays were used to determine 25(OH)D3 and 1alpha,25(OH)2D3, respectively. Measurements of proliferation by 3H-thymidine incorporation, and 1alpha,25(OH)2D-responsive gene expression by real-time qPCR and by Western blot were used as functional assays for the presence of 25-OHase activity.
Results: Prostate cells metabolized vitamin D3 to 1alpha,25(OH)2D3. Vitamin D3 up-regulated 25(OH)D-24R-hydroxylase and IGFBP3, two 1alpha,25(OH)2D-responsive genes, in prostate cells. CYP2R1 was the major form of 25-OHase expressed in normal and cancerous prostate cells as determined by qPCR.
Conclusion: The autocrine synthesis of 1alpha,25(OH)2D3 from vitamin D3 suggests that maintaining adequate levels of serum vitamin D could be a safe and effective chemo-preventive measure to decrease the risk of prostate cancer.
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Naunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, , 11829, Cairo, Egypt.
Globally, the incidence and death rates associated with cancer persist in rising, despite considerable advancements in cancer therapy. Although some malignancies are manageable by a mix of chemotherapy, surgery, radiation, and targeted therapy, most malignant tumors either exhibit poor responsiveness to early identification or endure post-treatment survival. The prognosis for prostate cancer (PCa) is unfavorable since it is a perilous and lethal malignancy.
View Article and Find Full Text PDFGenome Med
January 2025
Department of Systems Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA.
Background: Despite extensive analysis, the dynamic changes in prostate epithelial cell states during tissue homeostasis as well as tumor initiation and progression have been poorly characterized. However, recent advances in single-cell RNA-sequencing (scRNA-seq) technology have greatly facilitated studies of cell states and plasticity in tissue maintenance and cancer, including in the prostate.
Methods: We have performed meta-analyses of new and previously published scRNA-seq datasets for mouse and human prostate tissues to identify and compare cell populations across datasets in a uniform manner.
EJNMMI Radiopharm Chem
January 2025
Department of Medicinal Chemistry, Uppsala University, Uppsala, 751 23, Sweden.
Background: Gastrin releasing peptide receptor (GRPR)-directed radiopharmaceuticals for targeted radionuclide therapy may be a very promising addition in prostate and breast cancer patient management. Aiming to provide a GRPR-targeting theranostic pair, we have utilized the Tc-99m/Re-188 radiometal pair, in combination with two bombesin based antagonists, maSSS-PEG2-RM26 and maSES-PEG2-RM26. The two main aims of the current study were (i) to elucidate the influence of the radiometal-exchange on the biodistribution profile of the two peptides and (ii) to evaluate the feasibility of using the [Tc]Tc labeled counterparts for the dosimetry estimation for the [Re]Re-labeled conjugates.
View Article and Find Full Text PDFEur Urol Oncol
January 2025
Cancer Heterogeneity Plasticity and Resistance to Therapies (CANTHER) Research Group, CHU Lille, Institut Pasteur de Lille, and University of Lille, Lille, France; Department of Urology, Hospital Claude Huriez, CHU Lille, Lille, France. Electronic address:
Background And Objective: It has been shown that androgen receptor pathway inhibitor (ARPIs) treatment for metastatic castration-resistant prostate cancer (mCRPC) improves overall survival rates, but ARPIs appear to be associated with a higher frequency of treatment-related neuroendocrine prostate cancer (t-NEPC). Our aim was to quantify the proportion of prostate adenocarcinoma cases that transition to t-NEPC following ARPI therapy.
Methods: We conducted a comprehensive search of the literature on t-NEPC using databases including MEDLINE and Scopus.
Am J Transl Res
December 2024
Laboratory of Translational Oncology and Experimental Cancer Therapeutics, The Warren Alpert Medical School, Brown University Providence, RI 02903, USA.
Objectives: Prostate cancer (PCa) is a leading cause of cancer death in men worldwide. Approximately 30% of castrate-resistant PCa becomes refractory to therapy due to neuroendocrine differentiation (NED) that is present in <1% of de-novo tumors. First-in-class imipridone ONC201/TIC10 therapy has shown clinical activity against midline gliomas, neuroendocrine tumors, and PCa.
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