Metabolomic effects of androgen deprivation therapy treatment for prostate cancer

ADT is standard therapy for advanced and metastatic PC with negative metabolic consequences. We determined the metabolomic effects of ADT during the PC treatments. Such analysis identify the unexpected reduced ketogenesis and microbiome ‐associated metabolites during ADT AbstractAndrogen deprivation therapy (ADT) is the main treatment strategy for men with metastatic prostate cancer (PC). However, ADT is associated with various metabolic disturbances, including impaired glucose tolerance, insulin resistance and weight gain, increasing risk of diabetes and cardiovascular death. Much remains unknown about the metabolic pathways and disturbances altered by ADT and the mechanisms. We assessed the metabolomic effects of ADT in the serum of 20 men receiving ADT. Sera collected before (baseline), 3 and 6  months after initiation of ADT was used for the metabolomics and lipidomics analyses. The ADT‐associated metabolic changes were identified by univariable and multivariable statistical analysis, ANOVA, and Pearson correlation. We found multiple key changes. First, ADT treatments reduced the stero id synthesis as reflected by the lower androgen sulfate and other steroid hormones. Greater androgen reduction was correlated with higher serum glucose levels, supporting the diabetogenic role of ADT. Second, ADT consistently decreased the 3‐hydroxybutyric acid and ketogenesis. Third, many acyl‐ carnitines were reduced, indicating the effects on the fatty acid metabolism. Fourt...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research

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British Journal of Cancer, Published online: 29 May 2020; doi:10.1038/s41416-020-0910-yThe association of diabetes with risk of prostate cancer defined by clinical and molecular features
Source: British Journal of Cancer - Category: Cancer & Oncology Authors: Source Type: research
Authors: Holly JMP, Biernacka K, Perks CM Abstract Introduction: Preclinical, clinical, and population studies have provided robust evidence for an important role for the insulin-like growth factor (IGF) system in the development of prostate cancer.Areas covered: An overview of the IGF system is provided. The evidence implicating the IGF system in the development of prostate cancer is summarized. The compelling evidence culminated in a number of clinical trials of agents targeting the system; the reasons for the failure of these trials are discussed.Expert opinion: Clinical trials of agents targeting the IGF system...
Source: Expert Review of Endocrinology and Metabolism - Category: Endocrinology Tags: Expert Rev Endocrinol Metab Source Type: research
Circular RNAs (circRNAs), which act as initiators and promoters of various diseases, were thought to be mostly noncoding RNAs (ncRNAs) in eukaryotes, until recent studies confirmed that some circRNAs have the function of encoding proteins. Accumulating research findings have proved that dysregulation of circRNAs is associated with the developmental process of multiple cancers. circHIPK3, an example of circRNA, is frequently expressed in many diseases, such as diabetes, age-related cataract, idiopathic pulmonary fibrosis, preeclampsia, osteoblasts, and retinal vascular dysfunction, leading to disease development and progres...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
RARITAN, NJ, May 13, 2020 – The Janssen Pharmaceutical Companies of Johnson &Johnson announced today results from the final analysis of the pivotal Phase 3 SPARTAN study demonstrating ERLEADA® (apalutamide) in combination with androgen deprivation therapy (ADT) significantly improved overall survival (OS), compared to ADT alone, in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who were at high risk of developing metastases.[i] Results will be presented at the American Society of Clinical Oncology (ASCO) Virtual Scientific Program (Abstract #5516) beginning May 29th. ERLEADA® i...
Source: Johnson and Johnson - Category: Pharmaceuticals Tags: Innovation Source Type: news
Abstract Mitochondrial-derived peptides (MDPs) are a novel class of bioactive microproteins that modify cell metabolism. To date, eight MDPs have been characterized (e.g., humanin, MOTS-c, SHLPs1-6) and attenuate disease pathology, including Alzheimer's disease, prostate cancer, macular degeneration, cardiovascular disease, and diabetes. Human genetic variation in these MDPs is underexplored, but two polymorphisms in humanin and MOTS-c associate with cognitive decline and diabetes, respectively, suggesting a precise role for MDPs in disease-modification. There could be hundreds of additional MDPs that have yet to ...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research
The objective is to start treating chronic diseases from the root and not the symptoms of the disease. As we are starting to enroll patients in "senolytics-clinical trials," it will be imperative to assess if senolysis efficiently targets the primary cause of disease or if it works best in combination with other drugs. Additional basic science research is required to address the fundamental role of senescent cells, especially in the established contexts of disease. Notes on Self-Experimentation with Sex Steroid Ablation for Regrowth of the Thymus https://www.fightaging.org/archives/2020/04/notes-on-se...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
ConclusionOur study suggests that central adiposity as measured by WHR may improve long-term survival among men of African ancestry. Metabolic studies to understand the mechanism for this association are needed.
Source: Cancer Causes and Control - Category: Cancer & Oncology Source Type: research
Authors: Zhou J, Song Q, Liu X, Ye H, Wang Y, Zhang L, Peng S, Qin H Abstract Long non-coding (lnc) RNA Erbb4-IR has been associated with diabetic renal injury; however, its roles in other diseases remain unknown. Therefore, the present study investigated the involvement of Erbb4-IR in prostate carcinoma. Reverse transcription-quantitative PCR was used to analyze gene expression in tissue samples collected from patients with prostate carcinoma. Overexpression experiments via cell transfection were performed to determine the association between Erbb4-IR and microRNA (miR)-21. Furthermore, Cell Counting Kit-8 and cel...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Conclusion: Better chronic disease management is needed among prostate cancer survivors through more effective survivorship care planning and interventions that promote health behaviors. PMID: 32269460 [PubMed - in process]
Source: Ethnicity and Disease - Category: International Medicine & Public Health Tags: Ethn Dis Source Type: research
ConclusionsForced expression of GLP ‐1R attenuates prostate cancer cell proliferation by inhibiting cell cycle progressionin  vitro andin  vivo. Therefore, GLP ‐1R activation might be a potential therapy for prostate cancer.
Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: Original Article Source Type: research
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