Search Results (301)

Radical prostatectomy is the standard of care for the treatment of early, clinically localized prostate cancer (PC). In addition to known clinical prognosticators, perioperative conditions and the type of anesthesia may affect clinical outcomes through several mechanisms that favor a tumor-propagating state, including activation of the sympathetic system, increased opioid requirements, and inflammation. In this review, we provide an overview of the impact of the perioperative period on PC prognosis and patient outcomes. A non-systematic literature review was conducted to investigate the possible association between neuraxial anesthesia and outcomes after radical prostatectomy (RP) for prostate cancer. The following keywords were used: “cancer recurrence” OR “cancer prognosis” OR “metastasis” AND “neuraxial anesthesia” AND “prostate cancer”. Eligible studies were summarized in the form of a narrative review. In the era of limited use of ERAS protocols, the implementation of neuraxial anesthesia was found to reduce mortality after RP for primary prostate cancer when compared to general anesthesia. Although there was no significant association between anesthetic technique and radiological or biochemical-free survival, regional anesthesia may have an impact on short-term survival in patients with severe comorbidities, involving pulmonary complications and thrombosis. The effect of anesthetic technique on PC patient outcomes remains elusive, although preliminary retrospective evidence suggests a possible positive effect of neuraxial anesthesia on patient outcomes. As the perioperative period is considered a vulnerable timeframe for these patients, the role of the leadership dyad of surgeon and onco-anesthesiologist is crucial. Full article

Prostate cancer is not only the most common type of cancer in elderly American men but also the 2nd leading cause of cancer death in American men. The currently available treatments in clinics target male hormones that are majorly required for maintaining many physiological functions, including muscle strength, leading to poor life quality and subsequent patient-opted intermittent treatment. Aging is a key factor in prostate cancer that is associated with increased levels of oxidative stress. Several lines of evidence indicated elevated levels of reactive oxygen species (ROS) in prostate cancer, including its precursor, prostate intraepithelial neoplasia (PIN). In this current study, we utilized 4-hydroxynonenal (4HNE) as a general readout for overall oxidative stress to demonstrate the imbalance between ROS and antioxidants in human prostate cancer and its precursor lesion in both human culture cell lines and tissue samples. Our results showed that the production of 4HNE adducts was increased in human prostate cancer cells and was non-linearly correlated with prostate cancer stage. They also provided insight into prevention and potential therapeutic strategies for prostate cancer. Full article

Background: The outgrowth of castration-resistant prostate cancer (CRPC) dictates patient morbidity and mortality. Recurrence of prostate cancer (PC) following androgen-deprivation therapy (ADT) often occurs due to constitutively active androgen receptor (AR) splice variants (AR-Vs), primarily AR-V7. Therefore, safe and effective therapies enabling the suppression of both full-length AR (AR-FL) and AR-Vs are urgently needed. The natural compound dimethyl sulfoxide (DMSO) has negligible cytotoxicity at concentrations below 5% and has anticancer potential. DMSO has been broadly used in biomedical research as a solvent for pharmaceuticals, as a cryoprotectant for cells, and as a topical treatment to suppress pain and inflammation. We investigated the effect of low-dose DMSO on AR expression, cell viability, and metastatic ability in PC cell lines expressing both AR-FL and AR-V7 (e.g., 22Rv1) and those expressing only AR-FL (e.g., C4-2B). Methods: MTT cell viability assays were performed to measure DMSO-induced cytotoxicity. Wound-healing assays were conducted to monitor the effect of DMSO on the migratory phenotype of cancer cells. Western blot analyses were performed to study the efficacy of DMSO in suppressing the protein levels of AR-FL and AR-V7, and expression of heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) was measured as a possible mechanism. Results: At concentrations of 0.1–1% (v/v), DMSO treatment showed minimal cytotoxicity, whereas the highest concentration used (2.5%) showed approximately 20% cytotoxicity at 96 h. Interestingly, however, DMSO treatment at concentrations of 1.0 and 2.5% significantly inhibited the migration of PC cells. Treatment with DMSO led to a dose-dependent inhibition of both AR-FL and AR-V7. Notably, in 22Rv1 cells, DMSO potently downregulated the expression of hnRNPH1, a splicing factor often associated with AR expression and signaling. Conclusions: Our findings suggest that low concentrations of DMSO may have potential as an effective anticancer agent, both at the initial and later stages when PC cells become castration resistant. Full article

Background: Currently, it is a priority to develop prognostic biomarkers that would allow the identification of patients with progressing prostate diseases with a low risk of progression, so that unnecessary treatment and patient burden can be avoided. Objectives: This study aimed to assess the clinical features and concentrations of selected mediators of apoptosis, markers of inflammation, and immunoexpression of Ki67 and selected mediators of inflammation in patients with PCa after prostatectomy procedures and who underwent palliative radiotherapy for bone metastases, as well as patients with benign prostatic hyperplasia (BPH). Methods: A total of 88 patients, including 54 cases with PCa and 34 with BPH, were included. Stage and tumor grades were determined according to Gleason’s grading system. Immunoenzymatic methods were used to determine apoptotic and inflammatory mediators in serum, as well as deoxynucleotidyl transferase-mediated dUTP Nick End Labeling (TUNEL) reaction, and immunohistochemistry to determine selected markers of inflammation and Ki67 expression. Results: Strong differentiating indicators were revealed, such as Ki67, and tumor necrosis factor receptor 2. Ki-67 expression was significantly associated with the Gleason score. In turn, the tumor necrosis factor receptor 2 (TNFRII) showed the highest expression in the inflammatory environment of cancer in the metastatic stage. Conclusions: Ki67 and TNFRII can be classified as high-value clinical markers. These factors may be treated as markers regarding future information about the implementation or withdrawal of more aggressive treatment to possibly avoid toxic complications associated with both increased doses in radiotherapy and prolonged hormonal therapy. Full article

The prostate gland, a male accessory reproductive organ, is regulated by hormonal inputs and autonomic innervation from the major pelvic ganglion. This study examined the effects of major pelvic ganglion denervation on prostate histology, immune cell infiltration, and systemic levels of prolactin, testosterone, and cytokines in rats. Male Wistar rats (300–350 g) were divided into groups receiving bilateral axotomy of the hypogastric nerve, the pelvic nerve, or both, alongside with a sham-operated control. After 15 days, the animals were killed, and prostate tissue was dissociated in DMEM medium containing DNase I and collagenase. The dissociated cells were stained with fluorochrome-conjugated antibodies, and cell characterization was performed using a flow cytometer. Hematoxylin and eosin (H&E) staining was used to analyze histological characteristics, while testosterone, prolactin, and interleukin levels were measured via ELISA. Histological analysis revealed inflammatory atypical hypertrophy e hiperplasia. Immunological assessments demonstrated increased leukocytes, T lymphocytes (CD4⁺ and CD8⁺), B lymphocytes, and macrophages following double nerve axotomy. Serum analyses showed elevated pro-inflammatory cytokines IL-1β, IL-6, and IFN-γ, as well as anti-inflammatory IL-10, in denervated animals. Hormonal assessments revealed significant increases in serum prolactin and testosterone levels after double axotomy. Loss of neural control may promote pathological prostate changes via inflammation and hormonal dysregulation, offering insights into neuroimmune and neuroendocrine mechanisms underlying prostate pathologies. Full article

Benign prostatic hyperplasia (BPH) is a multifactorial condition that is highly prevalent and affects aging males. It frequently results in lower urinary tract symptoms (LUTS) and a reduced quality of life. While hormonal dysregulation and chronic inflammation have long been implicated in BPH pathogenesis, recent evidence highlights the role of physical activity in modulating prostate health. In this narrative review, evidence from quantitative studies examining the effect of exercise on BPH risk and symptom severity was first synthesized. Collectively, these studies suggest that regular physical activity is associated with a lower incidence and reduced progression of BPH. The potential mechanisms through which exercise may exert protective effects on the prostate were then explored. These include modulation of sympathetic nervous system activity, alterations in hormonal profiles (e.g., testosterone and insulin), suppression of chronic inflammation and oxidative stress, and the promotion of autophagy within prostatic tissue. Central to these mechanisms is the role of myokines—signaling molecules secreted by skeletal muscle during exercise. Key myokines, such as irisin, interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and myostatin, are reviewed in the context of prostate health. These molecules regulate inflammatory pathways, metabolic processes, and tissue remodeling. For instance, exercise-induced reductions in myostatin are linked to improved insulin sensitivity and decreased fat accumulation, while elevated irisin and BDNF levels may exert anti-inflammatory and metabolic benefits relevant to BPH pathophysiology. Although direct causal evidence linking myokines to BPH is still emerging, their biological plausibility and observed systemic effects suggest a promising avenue for non-pharmacological intervention. Future research should focus on identifying the specific myokines involved, elucidating their molecular mechanisms within the prostate, and evaluating their therapeutic potential in clinical trials. Full article

Inflammation, oxidative stress, and androgen activity are key features in benign prostate hyperplasia (BPH). Risks associated with the long-term use of 5α-reductase inhibitors have led to the search for alternative therapies, including food supplements. This study investigates the effectiveness of the combination of pollen extracts, namely Graminex^®G96^® (G) and Teupol 25P (T), towards oxidative stress and inflammation on human macrophages and benign prostate hyperplasia cells (BPH-1), both of which are LPS stimulated. The Nrf2-dependent antioxidant intracellular cascade as well as the NF-ĸB-driven inflammatory cascades were analyzed. The anti-proliferative effect of G and T, alone and in association, were evaluated on prostatic adenocarcinoma cells (PC-3) and BPH-1 cells. Finally, the inhibitory activity of GT on 5α-reductase was investigated in PC-3 cells by measuring epiandrosterone amounts, with the 5α-reductase inhibitor finasteride administered for comparison. All experiments were conducted in triplicate; data are presented as mean values ± standard deviations. Statistical analysis was performed using one-way analysis of variance. Our work demonstrates that GT promotes Nrf2-dependent antioxidant responses and counteracts the NF-ĸB-driven pathway in macrophages. GT is effective in counteracting the expression of pro-inflammatory cytokines and the generation of reactive oxygen species by promoting HO-1-dependent antioxidant responses in BPH-1 cells. GT reduces PC-3 and BPH-1 proliferation when associated with finasteride through a statistically significant inhibition of 5α-reductase activity. Data obtained in vitro and in silico demonstrate the potential efficacy of a multitargeted approach in the treatment of BPH. Full article

Oxidative stress and hypoxia-induced inflammation contribute to benign prostatic hyperplasia (BPH) progression. This study investigated the roles of urinary inflammatory and oxidative stress biomarkers in BPH patients. This prospective study enrolled 62 clinical BPH patients (33 treated medically, 29 surgically) and 20 controls. Symptom scores, uroflowmetry, and urinary biomarker levels were assessed at baseline and three months post-treatment. Before treatment, BPH patients exhibited elevated urinary levels of total antioxidant capacity (TAC), PGE2, IL-1β, and IL-6. Post-treatment, successful outcomes were reported in 63.6% of the medical treatment group and 86.2% of the surgical treatment group, with improvements in symptom scores and urinary flow rate, along with reductions in urinary 8-isoprostane, TAC, and IL-1β. Prior to treatment, voiding efficiency (VE) was negatively correlated with urinary IL-1β, IL-6, and IL-8 levels, while bladder wall thickness was positively correlated with TAC. After treatment, changes in VE were negatively correlated with changes in IL-1β, and changes in post-void residual urine were positively correlated with changes in IL-1β, IL-6, IL-8, and TNF-α. Urinary inflammatory and oxidative stress biomarkers may serve as non-invasive indicators of disease severity and treatment response in clinical BPH. Their significant correlations with clinical improvements underscore their potential utility in monitoring treatment efficacy. Full article

The polyunsaturated fatty acids of the omega-3 class have been widely investigated due to their antitumor properties, including in prostate cancer (PCa). Among them is docosahexaenoic acid (DHA, C22:6 ω-3), whose biological activity is higher than other omega-3s, exhibiting a stronger impact on PCa. The specific mechanisms triggered by DHA are blurred by studies that used a blend of omega-3s, delaying the understanding of its biological role, and hence alternative therapeutic approaches. DHA is differentially processed between normal and malignant epithelial PCa cells, which suggests its function as a tumor suppressor. At cell-specific level, it downregulates key pathways in PCa, such as androgen signaling and lipid metabolism, but also changes membrane composition by disrupting phospholipid balance and increasing unsaturation status, arrests the cell cycle, and induces apoptosis and reactive oxygen species (ROS) overproduction. At the tissue level, DHA seems to influence stromal components, such as the inhibition of cancer-associated fibroblast differentiation and resolution of inflammation, which generates a microenvironment favorable to PCa initiation and progression. Considering that such effects are misunderstood and assigned to omega-3s in general, this review aims to discuss the specific effects of DHA on PCa based on in vitro and in vivo evidence. Full article

Prostate cancer is one of the most prevalent malignancies in men, posing a significant public health challenge due to its high incidence and long-term treatment-related toxicities. Long-lived patients often experience prolonged side effects that can severely diminish their quality of life. Despite advancements in radiotherapy techniques like IMRT and VMAT, some patients still experience acute and late side effects. Current treatment protocols do not account for individual variability in normal-tissue radiosensitivity, highlighting the need for predictive tools and a personalised treatment approach. Genetic factors and molecular regulators like microRNAs (miRNAs) contribute to these variations by influencing DNA repair, inflammation, and apoptosis. This review explores potential biomarkers of radiotoxicity, focusing on immune-related factors such as IL-6 and TGF-β1, SNPs influencing radiosensitivity, miRNAs involved in radiation responses, and functional assays including the radiation-induced lymphocyte apoptosis (RILA) test. These approaches offer promising tools for identifying radiosensitive patients and enabling risk-adapted radiotherapy. Full article

Background: Prostate cancer is a leading malignancy among men globally, with its incidence expected to rise due to aging populations and shifting lifestyles. While established risk factors include age, ethnicity, and genetics, the role of modifiable dietary factors, particularly sugar intake, remains less clear. Emerging evidence suggests that high sugar consumption may promote carcinogenesis through insulin resistance, chronic inflammation, and hormonal dysregulation. This systematic review aimed to evaluate the current evidence on the association between dietary sugar intake and prostate cancer risk. Methods: A systematic search was conducted across six databases for observational studies published between January 2005 and April 2025. Eligible studies assessed the associations between quantitative sugar intake and prostate cancer outcomes. Screening, data extraction, and a risk of bias assessment (using ROBINS-E) were performed independently by multiple reviewers. Results: Six studies met the inclusion criteria, comprising four prospective cohorts, one case–control study, and one cross-sectional study, with a combined sample of 11,583 men from the USA, Canada, Sweden, and France. Three studies reported a significant positive association between a high intake of dietary sugars and prostate cancer risk, two found no association, and one showed mixed findings depending on the type of sugar. Heterogeneity in the exposure assessments and confounder control limited the comparability. Conclusions: This review suggests a possible association between high dietary sugar intake and increased prostate cancer risk, especially from added sugars and sugar-sweetened beverages. However, inconsistent findings and methodological limitations highlight the need for robust, prospective studies with standardized assessments to understand this relationship better. Full article

Goji berries (Lycium barbarum), rich in antioxidant and immunomodulatory compounds, have shown potential benefits for male reproductive health. This study aimed to evaluate the impact of dietary Goji berry (GB) supplementation on immune-related and antioxidant gene expression in the male reproductive tract of rabbits. Eighteen 7-month-old New Zealand White rabbit bucks were randomly assigned to two groups: a control group (n = 9) receiving a standard diet, and a Goji group (n = 9) receiving the same diet supplemented with 1% GB. After 60 days of nutritional adaptation and then 60 days of treatment, tissues from the testes, epididymis, seminal vesicles, prostate, and bulbourethral glands were collected and analyzed using quantitative real-time PCR. Gene expression analysis focused on immune markers (TLR4, IL-1β, IL-10, and TNFα) and antioxidant enzymes (SOD1, CAT, and GPX). Significant modulation was observed only in the epididymis, where TLR4 and GPX were significantly downregulated in the Goji group (p = 0.0274 and p = 0.007, respectively), while IL-1β and TNFα showed a downward trend. No significant differences were found in the other tissues. These results suggest that Goji berry supplementation exerts tissue-specific effects, particularly in the epididymis, by modulating inflammation and oxidative stress. This supports its potential use as a natural nutraceutical strategy to enhance male fertility in rabbits. Full article

Caffeine, one of the most widely consumed bioactive compounds worldwide, is gaining recognition for its potential anticancer properties beyond its well-known neurological and metabolic effects. Mechanistically, caffeine exerts anti-tumor activity by modulating key cellular pathways involved in carcinogenesis, including the inhibition of phosphodiesterases, antagonism of adenosine A2A receptors, and disruption of the DNA damage response through ATR-Chk1 pathway inhibition. These actions collectively promote apoptosis, suppress tumor cell proliferation, and impair metastatic spread. In vitro and in vivo studies have demonstrated that caffeine can enhance the cytotoxic effects of chemotherapeutic agents and radiation therapy, suggesting a synergistic role in conventional cancer treatments. Epidemiological data further supports an inverse association between habitual caffeine consumption and the incidence of several cancers, notably liver, colorectal, breast, and prostate cancers. Among these, the most consistent experimental and clinical evidence exists for liver and colorectal cancer, where caffeine’s modulatory effects on inflammation and cell proliferation have been repeatedly observed. Additionally, caffeine’s anti-oxidant and anti-inflammatory properties may contribute to a microenvironment less conducive to tumor initiation and progression. While promising, the anticancer effects of caffeine are influenced by factors such as dosage, individual genetic variability, and cancer type, underscoring the need for further clinical investigation. This review explores the emerging role of caffeine as a potential chemopreventive and adjuvant therapeutic agent in oncology. Full article

Bardoxolone methyl, also known as CDDO-Me or RTA 402, is a synthetic oleanane triterpenoid that has garnered significant attention as a potent pharmacological activator of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Nrf2 is a master regulator of cellular redox homeostasis, controlling the expression of genes involved in antioxidant defense, detoxification, and mitochondrial function. By inducing Nrf2 and promoting the transcription of downstream antioxidant response element (ARE)-driven genes, bardoxolone methyl enhances cellular resilience to oxidative stress and inflammation. This mechanism is central not only to its cytoprotective effects but also to its emerging role in oncology. A number of studies investigated the effects of bardoxolone methyl in several malignancies including breast cancer, lung cancer, pancreatic ductal adenocarcinoma, prostate cancer, colorectal cancer, oral and esophageal squamous cell carcinoma, ovarian cancer and glioblastoma. Studies in the literature indicate that bardoxolone methyl exhibits anticancer activity through several mechanisms, including the suppression of cell proliferation, induction of cell cycle arrest and apoptosis, inhibition of epithelial–mesenchymal transition (EMT), and impairment of cancer cell stemness. Additionally, bardoxolone methyl modulates mitochondrial function, reduces glycolytic and oxidative phosphorylation capacities, and induces reactive oxygen species (ROS)-mediated stress responses. In this review, we summarize the available literature regarding the studies which investigated the effects of bardoxolone methyl as anticancer agent. Full article

Poplar leaves (Populi folium) are a herbal remedy traditionally used for the treatment of rheumatic diseases and prostate inflammation. The aim of our study was a comprehensive identification of secondary metabolites occurring in the leaves of Populus alba, Populus × candicans, and Populus nigra, in order to search for a source of raw plant material rich in active compounds. Total salicylate (TSC), flavonoid (TFC), and phenolic compound (TPC) contents were determined, and the antioxidant potential was assessed using DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azino-bis(3-ethylbenzothiazoline- 6-sulfonic acid) diammonium salt), and FRAP (ferric reducing antioxidant power) assays as well as 2D-TLC (two-dimensional thin layer chromatography) bioautography using DPPH, riboflavin-light-NBT (nitro blue tetrazolium chloride), and xanthine oxidase inhibition tests. Secondary metabolites present in the analyzed poplar leaves were identified under the developed HPLC-DAD-ESI/MS (high performance liquid chromatography with photodiode array detection and electrospray ionization mass spectrometric detection analysis conditions and using the 2D-TLC method. Among the 80 identified compounds, 13 were shown for the first time in the genus Populus. The most diverse and similar set of flavonoids characterized the leaves of P. × candicans and P. nigra, while numerous salicylic compounds were present in the leaves of P. alba and P. × candicans. All analyzed leaves are a rich source of phenolic compounds. The highest flavonoid content was found in the leaves of P. × candicans and P. nigra, while the leaves of P. alba were characterized by the highest content of salicylates. All examined poplar leaves demonstrated antioxidant potential in all the assays used, which decreased in the following order: P. nigra, P. × candicans, P. alba. Full article