Prostate cancer is a leading cause of morbidity and cancer-related death worldwide. Androgen deprivation therapy (ADT) is the cornerstone of management for advanced disease. The use of these therapies is associated with multiple side effects, including metabolic syndrome and truncal obesity. At the same time, obesity has been associated with both prostate cancer development and disease progression, linked to its effects on chronic inflammation at a tissue level. The connection between ADT, obesity, inflammation and prostate cancer progression is well established in clinical settings; however, an understanding of the changes in adipose tissue at the molecular level induced by castration therapies is missing. Here, we investigated the transcriptional changes in periprostatic fat tissue induced by profound ADT in a group of patients with high-risk tumours compared to a matching untreated cohort. We find that the deprivation of androgen is associated with a pro-inflammatory and obesity-like adipose tissue microenvironment. This study suggests that the beneficial effect of therapies based on androgen deprivation may be partially counteracted by metabolic and inflammatory side effects in the adipose tissue surrounding the prostate.
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http://dx.doi.org/10.1530/EC-19-0029 | DOI Listing |
Andrology
January 2025
Department of Pharmacology, Faculty of Pharmacy, Ankara University, Ankara, Turkey.
Background: Androgen deprivation is associated with erectile dysfunction (ED). In different animal models, sulfur dioxide (SO) donors NaSO and NaHSO reduced oxidative stress, fibrosis, and inflammation which contribute to the pathogenesis of androgen deprivation-induced ED, however the effect of SO donors on ED in castrated rats were not known.
Objective: To investigate the therapeutic effect of SO donors, NaSO/NaHSO, on ED in castrated rat model.
Prostate Cancer Prostatic Dis
January 2025
South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, Australia.
Background: Patients treated with RT and long-term androgen deprivation therapy (ltADT) for high-risk localized prostate cancer (HRLPC) with 1 high-risk factor (any of Gleason ≥8, PSA > 20 ng/mL, ≥cT3; "high-risk") have better outcomes than those with 2-3 factors and/or cN1 disease ("very high risk"). We evaluated whether this risk stratification could determine benefit from ltADT versus short-term (stADT).
Methods: The Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) repository of randomized trials was queried to identify eligible patients and trials.
Pharm Res
January 2025
Penn State Cancer Institute, Pennsylvania State University, Hershey, PA, 17033, USA.
Angelica gigas Nakai (AGN) root is a medicinal herbal widely used in traditional medicine in Korea. AGN root ethanolic extracts have been marketed as dietary supplements in the United States for memory health and pain management. We have recently reviewed the pharmacokinetics (PK) and first-pass hepatic metabolism of ingested AGN supplements in humans for the signature pyranocoumarins decursin (D, C 1x), decursinol angelate (DA, C ~ 10x) and their common botanical precursor and hepatic metabolite decursinol (DOH, C ~ 1000x).
View Article and Find Full Text PDFObjectives: Attaining castration resistance in metastatic prostate cancer (mCRPC) represents a pivotal juncture in the progression of the patient's illness and treatment regimen. Within this therapeutic context, novel hormonal agents (NHA) constitute a fundamental component of pharmacological intervention. However, the efficacy of NHA therapy remains uncertain for patients with a compromised general condition, as indicated by an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of ≥2.
View Article and Find Full Text PDFClin Med Insights Oncol
January 2025
Ted Rogers School of Information Technology Management, Toronto Metropolitan University, Toronto, ON, Canada.
Despite the expanding therapeutic options available to cancer patients, therapeutic resistance, disease recurrence, and metastasis persist as hallmark challenges in the treatment of cancer. The rise to prominence of generative artificial intelligence (GenAI) in many realms of human activities is compelling the consideration of its capabilities as a potential lever to advance the development of effective cancer treatments. This article presents a hypothetical case study on the application of generative pre-trained transformers (GPTs) to the treatment of metastatic prostate cancer (mPC).
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