Prostate cancer is the second most commonly diagnosed cancer and the fifth leading cause of death among men worldwide. Androgen deprivation therapy is a common prostate cancer treatment, but its efficacy is often hindere...Prostate cancer is the second most commonly diagnosed cancer and the fifth leading cause of death among men worldwide. Androgen deprivation therapy is a common prostate cancer treatment, but its efficacy is often hindered by the development of resistance, which results in reducing survival benefits. Immunotherapy showed great promise in treating solid tumours; however, clinically significant improvements have not been demonstrated for patients with prostate cancer, highlighting specific drawbacks of this therapeutic modality. Hence, exploring novel strategies to synergistically enhance the efficacy of prostate cancer immunotherapy is imperative. Clinical investigations have focused on the combined use of targeted or gene therapy and immunotherapy for prostate cancer. Notably, tumour-specific antigens and inflammatory mediators are released from tumour cells after targeted or gene therapy, and the recruitment and infiltration of immune cells, including CD8 T cells and natural killer cells activated by immunotherapy, are further augmented, markedly improving the efficacy and prognosis of prostate cancer. Thus, immunotherapy, targeted therapy and gene therapy could have reciprocal synergistic effects in prostate cancer in combination, resulting in a proposed synergistic model encompassing these three therapeutic modalities, presenting novel potential treatment strategies for prostate cancer.
Endocrine-disrupting chemicals (EDCs) are natural or synthetic compounds that are ubiquitous in the environment and in daily-usage products and interfere with the normal function of the endocrine system leading to advers...Endocrine-disrupting chemicals (EDCs) are natural or synthetic compounds that are ubiquitous in the environment and in daily-usage products and interfere with the normal function of the endocrine system leading to adverse health effects in humans. Exposure to these chemicals might elevate the risk of metabolic disorders, developmental and reproductive defects, and endocrine-related cancers. Prostate cancer is the most common hormone-dependent cancer in men, and the fifth leading cause of cancer-related mortality, partly owing to a lack of knowledge about the mechanisms that lead to aggressive castration-resistant forms. In addition to the dependence of early-stage prostate cancer on androgen actions, the prostate is a target of oestrogenic regulation. This hormone dependence, along with the fact that exogenous influences are major risk factors for prostate cancer, make the prostate a likely target of harmful actions from EDCs. Various sources of EDCs and their different modes of action might explain their role in prostate carcinogenesis.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a bladder disorder with no definite aetiology and currently no effective treatment. Its clinical symptoms vary widely, and the bladder condition and extra-bladder d...Interstitial cystitis/bladder pain syndrome (IC/BPS) is a bladder disorder with no definite aetiology and currently no effective treatment. Its clinical symptoms vary widely, and the bladder condition and extra-bladder dysfunction also show different clinical presentations. This condition is considered to have multiple factors affecting the bladder and clinical symptoms, including urothelial dysfunction, mast cell activation, autoimmune response, neurogenic inflammation, viral or bacterial infection, autonomic nervous dysfunction and central nervous sensitization. Several non-pharmacological, medical, intravesical and novel bladder therapies have been advocated, but the efficacy and durability of these treatments have not been well elucidated. Multimodal therapy has been suggested based on possible pathological mechanisms; however, the most appropriate therapeutic strategy for this disorder has not been well defined. Thus, a rational algorithm for concomitant multimodal therapy for IC/BPS has been proposed.
Gender identity (GI) and sexual orientation (SO) are key aspects of an individual's sexual identity, which is a major driver of human sexuality. Although definitions for GI and SO have been long established and represent...Gender identity (GI) and sexual orientation (SO) are key aspects of an individual's sexual identity, which is a major driver of human sexuality. Although definitions for GI and SO have been long established and represented in clinical and theoretical research, often without acknowledgement of their relationship to one another, the ideal means by which they should be measured is unclear. Various tools for measurement have been proposed, each presenting different methodological approaches along with their respective flaws and issues. By providing a comprehensive overview of the major instruments for measuring GI and SO, the XYGO tool aims to integrate their strengths by developing a new, cohesive and inclusive perspective on sexual identity, taking into consideration both dimensions of this unique characteristic of human sexuality. This holistic perspective integrates these components into a single construct capable of providing a more immediate and tailored interpretation to facilitate everyday clinical practice and potentially improve research in sexual medicine and psychosexology.
Testosterone has a pivotal role in spermatogenesis, erectile function, libido and expression of secondary sexual characteristics. The prevalence of symptomatic, laboratory-proven testosterone deficiency increases with ag...Testosterone has a pivotal role in spermatogenesis, erectile function, libido and expression of secondary sexual characteristics. The prevalence of symptomatic, laboratory-proven testosterone deficiency increases with age and is often treated with testosterone replacement therapy (TRT). Treatment with exogenous androgens suppresses gonadotropin levels, inhibits endogenous testosterone production and drastically reduces intratesticular testosterone, consequently impairing spermatogenesis. Sperm production often slowly resumes after TRT cessation. However, the rate of recovery shows highly variable kinetics that might complicate family planning. Medical therapies (including aromatase inhibitors and selective oestrogen receptor antagonists) and exogenous gonadotropins (including human chorionic gonadotropin and follicle-stimulating hormone) may be used to preserve or restore spermatogenesis in select populations receiving TRT. Exogenous testosterone is contraindicated in men trying to conceive, but new short-acting formulations, including oral testosterone undecanoate and nasal testosterone gel, might incompletely suppress the hypothalamic-pituitary-gonadal axis and partially preserve spermatogenesis.
Stephens Shields AJ, Clemens JQ, Pontari MA
… +12 more, Lai HH, Moldwin R, Williams DA, Bradley CS, Farrar JT, Landis JR, Mullins C, Naliboff BD, Sutcliffe S, Walker SJ, Yang CC, Clauw DJ
Randomized clinical trials have resulted in few approved therapies for the treatment of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively referred to as urolog...Randomized clinical trials have resulted in few approved therapies for the treatment of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively referred to as urologic chronic pelvic pain syndrome. Heterogenous patient populations, mismatches of treatments to patient phenotypes, non-specific outcomes and use of standard study designs not leveraging phenotypic heterogeneity might have contributed to the inability of previous trials to demonstrate existing efficacy. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network has identified important phenotypic characteristics associated with differential symptom severity and treatment responsiveness. Based on Multidisciplinary Approach to the Study of Chronic Pelvic Pain findings and external research, empirically informed strategies were generated for defining patient populations, specifying treatments and selecting primary outcomes for future randomized clinical trials in urologic chronic pelvic pain syndrome. Explicitly specifying the scope of eligibility criteria across heterogeneous patient subgroups defined by pain widespreadness, the presence of Hunner lesions, the presence of pain with bladder filling or relieved by voiding, the extent of chronic overlapping pain conditions, and pelvic floor tenderness is needed. Therapies should be selected based on the mechanism of action and relevance to the mechanism of pain and dominant symptomology that the patient experiences. Evidence suggests that pain and urinary symptoms should be evaluated separately. Promising trial designs for identifying effective therapies in this heterogeneous patient population include sequential multiple assignment randomized trials and adaptive designs.
Liquid biopsies, indicating the sampling of body fluids rather than solid-tissue biopsies, have the potential to revolutionize cancer care through personalized, noninvasive disease detection and monitoring. Circulating t...Liquid biopsies, indicating the sampling of body fluids rather than solid-tissue biopsies, have the potential to revolutionize cancer care through personalized, noninvasive disease detection and monitoring. Circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) are promising blood-based biomarkers in bladder cancer. Results from several studies have shown the clinical potential of ctDNA and CTCs in bladder cancer for prognostication, treatment-response monitoring, and early detection of minimal residual disease and disease recurrence. Following successful clinical trial evaluation, assessment of ctDNA and CTCs holds the potential to transform the therapeutic pathway for patients with bladder cancer - potentially in combination with the analysis of urinary tumour DNA - through tailored treatment guidance and optimized disease surveillance.