Search Results (8,204)

Background/Objectives: Prior studies have reported a complex interplay between Parkinson’s disease (PD) and malignancy. Although patients with PD often present a lower general risk for several types of cancer, some forms—including melanoma—show elevated frequency. The present work aimed to evaluate the occurrence of cancers other than melanoma among individuals with sporadic and genetic PD. Methods: We examined medical histories from 1888 participants with PD and 438 healthy controls (HCs) using the Parkinson’s Progression Markers Initiative (PPMI) dataset, with a focus on neoplastic disease. In cases with positive cancer history, genetic information was additionally assessed [carriers of mutations in the most prevalent PD-related genes were evaluated]. Results: Our results demonstrate that cancer incidence was antecedent to PD diagnosis for the majority of PD patients, while the most common cancer types apart from malignant melanoma were non-melanoma skin cancer and prostate cancer. Conclusions: Regarding genetic PD patients, the most common cancer types in the LRRK2 and GBA1 groups were skin cancer and lymphoma, while PRKN/PARK2 carriers appeared with an overall increased incidence of cancer. No statistically significant results were observed comparing cancer incidence in PD patients to that in healthy control individuals. Interesting results were obtained by dividing the patients by gender, showing increased cancer risk in female PD patients and female LRRK2 carriers, along with increased breast cancer risk in female PD patients compared to healthy controls. Full article

Cancer metabolomics has become a powerful way of understanding tumor biology, identifying biomarkers and metabolites, and helping precision oncology. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), among many other analytical platforms, has gained popularity over the past two and a half decades due to its unique ability of directly analyzing metabolites in tissue with spatial resolution. This review will study 2000–2025 MALDI-based strategies for cancer metabolite detection, spanning from early proof-of-concept protein profiling to the development of high-resolution MALDI-MS imaging (MALDI-MSI), which is capable of mapping thousands of metabolites at near single-cell resolution. Its applications include the differentiation of tumor versus normal tissue, discovery of stage and subtype specific biomarkers, mapping of metabolic heterogeneity, and the visualization of drug metabolism in situ. Breakthrough technological milestones, such as the advanced matrices, on-tissue derivatization, MALDI-2 post-ionization, and the integration with Orbitrap or Fourier-transform ion cyclotron resonance (FT-ICR) platforms, have significantly improved the overall sensitivity, metabolite coverage, and spatial fidelity. Clinically, MALDI-MS has shown its purpose in breast, prostate, colorectal, lung, and liver cancers by providing metabolic fingerprints that are linked to tumor microenvironments, hypoxia, and therapeutic response. However, challenges such as the inclusion of matrix interface with low-mass metabolites, limited quantitation, ion suppression, and the lack of standardized procedures do not yet allow for the transition from translation to routine diagnostics. Even with these hurdles, the future of MALDI-MS in oncology remains in a good position with major advancements in multimodal imaging, machine learning-based data integration, portable sampling devices, and clinical validation studies that are pushing the field towards precision treatment. Full article

Currently, new cultivation methods are increasingly sought to create functional foods that could reduce the risk of certain diseases. Benign prostatic hyperplasia represents significant health challenges worldwide and because of that, we investigated the effect of microgravity and total darkness on the anti-proliferative, anti-inflammatory, and anti-androgenic activity of white clover sprouts. The use of clover sprouts, a widely studied plant from the Fabaceae family, can be promising due to their rich phytochemical profile, including isoflavones, known for estrogenic properties. Anti-proliferation activity was determined using a crystal violet assay. Analysis of the prostate-specific antigen (PSA) and 5-α-reductase level was performed using ELISA kits, similarly to anti-inflammatory activity. White clover sprouts exerted anti-proliferative activity against PNT2 prostate cells stimulated by testosterone, and total darkness increased this activity. In addition, anti-androgenic activity of white clover sprouts was demonstrated, through the inhibition of PSA and 5-α-reductase activity, which was most visible in 7-days-old sprouts growing in conditions of microgravity and standard light. In turn, the anti-inflammatory activity of the tested sprouts was rather moderate, but most observed in the inhibition of pro-inflammatory interleukin 6 (IL-6). White clover sprouts cultivated in microgravity and darkness may represent a candidate for novel functional food with anti-androgenic activity. Full article

Background/Objective: Biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer indicates disease progression. Although type 2 diabetes mellitus (T2D) shows a paradoxical association with prostate cancer risk, the prognostic role of T2D-related genetic variants remains unclear. Methods: We analyzed 113 common T2D susceptibility-related single-nucleotide polymorphisms (SNPs) in 644 Taiwanese men with localized prostate cancer (D’Amico risk classification: 12% low, 34% intermediate, and 54% high) treated with RP. Associations between SNPs and BCR were assessed using Cox regression, adjusting for key clinicopathological factors. Functional annotation was performed using HaploReg and FIVEx, while The Cancer Genome Atlas transcriptomic data were analyzed for C2 calcium-dependent domain-containing 4A (C2CD4A) expression. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were applied to explore related biological pathways. Results: C2CD4A SNP rs4502156 was independently associated with a reduced risk of BCR (hazard ratio = 0.80, p = 0.035). The protective C allele correlated with higher C2CD4A expression. Low C2CD4A expression is associated with advanced pathological stages, higher Gleason scores, and disease progression. GSEA revealed negative enrichment of mitotic and chromatid segregation pathways in high-C2CD4A-expressing tumors, with E2F targets being the most suppressed. GSVA confirmed an inverse correlation between C2CD4A expression and E2F pathway activity, with CDKN2C as a co-expressed functional gene. Conclusions: The T2D-related variant rs4502156 in C2CD4A independently predicts a lower risk of BCR, potentially via suppression of the E2F pathway, and may serve as a germline biomarker for postoperative risk stratification. Full article

Background: Physical plasma, the fourth state of matter formed through gas ionization, has shown promise in various clinical applications, including wound healing and antimicrobial therapy. Recently, Non-invasive physical plasma (NIPP) selectively disrupts tumor cell proliferation and metabolism without inducing cytoprotective stress responses, positioning it as a promising adjunct in oncological therapies, though its underlying mechanisms remain insufficiently understood. Methods: In this study, we investigated the effects of NIPP (Plasma Care device) on six tumor cell lines, ovarian (SKOV-3, OVCAR-3), prostate (LNCaP, PC-3), and breast (MCF-7, MDA-MB-231). Cell proliferation and migration were assessed using CASY analysis and scratch assays, while cytoskeletal integrity, heat shock protein (HSP) expression, and key metabolic indicators were evaluated through immunofluorescence, Western blotting, and biochemical assays. Results: NIPP treatment significantly inhibited tumor cell proliferation and migration, disrupted cytoskeletal organization, and altered metabolic activity in a time-dependent manner. These effects were associated with increased intracellular reactive oxygen species (ROS), decreased mitochondrial membrane potential (MMP), enhanced glycolysis, and elevated lactate production. Notably, despite cellular stress, neither HSP expression nor superoxide dismutase (SOD) activity showed significant changes, suggesting a lack of classical stress-response activation. Conclusions: Our findings indicate that NIPP selectively impairs tumor cell function by inducing oxidative stress and metabolic disruption, without triggering protective HSP-mediated resistance pathways commonly seen in radiotherapy and chemotherapy. These results highlight the therapeutic potential of NIPP, particularly via the Plasma Care device, as a novel anticancer strategy. Full article

Background/Objectives: To investigate the efficacy and safety of treatment with [¹⁷⁷Lu]Lu-PSMA-I&T Radioligand Therapy (PSMA-RLT) in older patients (≥80 years) vs. younger ones with metastatic castration-resistant prostate cancer (mCRPC). Methods: In this retrospective single-center analysis, 103 patients treated with PSMA-RLT between 2019 and 2024 were included. Overall survival (OS) and therapeutic response were assessed by PSA serum and based on PET/CT Imaging according to the RECIP 1.0 criteria, respectively. Toxicity was additionally assessed via laboratory (hemoglobin, cell counts, and serum creatinine). Adverse events (AEs) were detected according to CTCAE V.5. Results: Median OS did not differ significantly in patients ≥ 80 years vs. <80 years (13.7 vs. 16.1 months, respectively). PSA decline of ≥50% was achieved in 32% patients in total, comparably in both groups (29.4% vs. 34.8%). According to RECIP 1.0, the majority of patients with both ≥80 and <80 years demonstrated stable disease or partial responses in imaging (64% and 71%, post two cycles). Concerning toxicity, the most frequently observed AE was anemia, which occurred in both <80 and ≥80 subgroups (grade 3: 2.8% vs. 5.9%); however, no grade 4 anemia was recorded. Renal function remained stable throughout treatment, and no AE grade 3 or higher was observed. Overall, the safety profile was comparable between age groups. Conclusions: Treatment with PSMA-RLT can be both effective and well tolerated in patients with mCRPC aged 80 years and older. Full article

Fatty acid-binding protein 4 (FABP4) is an important adipokine associated with inflammatory responses and metabolic regulation. Although a high-fat diet (HF) and/or HF-mediated obesity have been clearly linked to the progression of prostate cancer, with FABP4 potentially playing a critical role in this relationship, the mechanisms by which FABP4 facilitates this interaction remain unclear. After generating FABP4 knockout (FABP4^−/−) transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, it was found that FABP4^−/− TRAMP mice presented significantly ameliorated prostate tumorigenesis and tumor progression along with decreased body weight, protumorigenic cytokine secretion, and pan-amino acid synthesis when compared to TRAMP mice under the HF condition. Additionally, treatment with BMS309403—a chemical inhibitor of FABP4—was observed to abrogate the HF-mediated TRAMP tumor progression, along with reductions in body weight and cytokine production. Thus, FABP4 plays an essential role in the progression of HF-mediated prostate cancer through the modulation of metabolic and inflammatory pathways, providing a potential therapeutic target for prostate cancer. Full article

Environmental pollution, driven by industrialization, urbanization, and agricultural practices, has intensified global ecological degradation. Among the most concerning pollutants is PFOS, a synthetic compound known for its chemical stability, environmental persistence, and bioaccumulative potential. Widely utilised in industrial and consumer products, PFOS infiltrates ecosystems and food chains, posing substantial risks to human and animal health. Upon exposure, PFOS disrupts lipid metabolism, damages cellular membranes, and alters signaling pathways through partial metabolism by cytochrome P450 enzymes. Accumulating evidence links PFOS to oxidative stress, mitochondrial dysfunction, endocrine disruption, neurotoxicity, and immunotoxicity. Critically, PFOS contributes to the development and progression of prostate, breast, and ovarian cancers via mechanisms such as hormonal interference, chronic inflammation, and epigenetic modifications. Epidemiological studies further associate elevated PFOS serum levels with increased cancer risk, particularly in occupationally and environmentally exposed populations. This review brings together the latest knowledge on PFOS emissions, mechanistic toxicity, and cancer-causing potential, highlighting the urgent need for focused research and improved regulatory measures to safeguard public health. Full article

Background: Prostate cancer is one of the most common malignancies in men and a leading cause of cancer-related mortality. Early detection is essential to ensure curative treatment and favorable outcomes, but traditional diagnostic approaches—such as serum prostate-specific antigen (PSA) testing, digital rectal examination (DRE), and histopathological confirmation following biopsy—are limited by suboptimal accuracy and variability. Multiparametric magnetic resonance imaging (mpMRI) has improved diagnostic performance but remains highly dependent on reader expertise. Artificial intelligence (AI) offers promising opportunities to enhance diagnostic accuracy, reproducibility, and efficiency in prostate cancer detection. Objective: To evaluate the diagnostic accuracy and reporting timeliness of AI-based technologies compared with conventional diagnostic methods in the early detection of prostate cancer. Methods: Following PRISMA 2020 guidelines, PubMed, Scopus, Web of Science, and Cochrane Library were searched for studies published between January 2015 and April 2025. Eligible designs included randomized controlled trials, cohort, case–control, and pilot studies applying AI-based technologies to early prostate cancer diagnosis. Data on AUC-ROC, sensitivity, specificity, predictive values, diagnostic odds ratio (DOR), and time-to-reporting were narratively synthesized due to heterogeneity. Risk of bias was assessed using the QUADAS-AI tool. Results: Twenty-three studies involving 23,270 patients were included. AI-based technologies achieved a median AUC-ROC of 0.88 (range 0.70–0.93), with median sensitivity and specificity of 0.86 and 0.83, respectively. Compared with radiologists, AI or AI-assisted readings improved or matched diagnostic accuracy, reduced inter-reader variability, and decreased reporting time by up to 56%. Conclusions: AI-based technologies show strong diagnostic performance in early prostate cancer detection. However, methodological heterogeneity and limited standardization restrict generalizability. Large-scale prospective trials are required to validate clinical integration. Full article

The growing global aging population is contributing to an increasing burden of benign prostatic hyperplasia (BPH), highlighting the need for novel, highly effective and low-toxicity therapies. In light of its well-documented anti-inflammatory and anti-tumor properties, we investigated the potential of the natural product Pulsatilla saponin D (PSD) in treating BPH. For the first time, we demonstrate that PSD significantly inhibits the proliferation of and induces apoptosis in the immortalized human normal prostatic stromal cell line, human prostate fibroblasts, and the human benign prostatic hyperplasia epithelial cell line. Mechanistic studies involving transcriptome analysis and RT-qPCR validation revealed that PSD likely exerts its effects by downregulating the expression of the androgen receptor and by modulating multiple signaling pathways synergistically, including the Phosphatidylinositol 3-kinase/Protein Kinase B, Tumor Necrosis Factor, Hypoxia-Inducible Factor-1 and Interleukin-17 pathways. Full article

Castration-resistant prostate cancer (CRPC) remains difficult to treat with conventional chemotherapy. We evaluated a stem cell-based enzyme-prodrug strategy using hTERT-immortalized adipose-derived stem cells engineered to express rabbit carboxylesterase 2 (hTERT-ADSC.CE2) in combination with irinotecan (CPT-11). hTERT-ADSC.CE2 cells were generated via lentiviral transduction and confirmed to overexpress CE2. Their tumor-homing capacity toward PC3 prostate cancer cells was assessed, along with prodrug activation, apoptosis induction, and in vivo tumor suppression in a CRPC mouse model. hTERT-ADSC.CE2 cells demonstrated enhanced migration toward PC3 cells and higher expression of tumor-homing factors than the controls. Under CPT-11, they exhibited a strong “suicide” effect and induced selective killing of PC3 cells, with upregulation of BAX and cleaved caspase-3 and downregulation of BCL-2. By day 14, the combination arm showed significantly lower tumor burden than both the control and irinotecan-alone arms (p < 0.05). The pattern is consistent with intratumoral activation and localized SN-38 exposure. hTERT-ADSC.CE2 combined with irinotecan provides potent, tumor-targeted cytotoxicity and markedly suppresses CRPC progression. This cell-mediated prodrug activation system may represent a promising therapeutic approach for advanced prostate cancer. Full article

Background and Objectives: Benign prostatic hyperplasia (BPH) is one of the most common chronic conditions in older men, significantly impairing quality of life (QoL) by causing lower urinary tract symptoms (LUTSs). 5-alpha-reductase inhibitors (5-ARIs), including finasteride and dutasteride, remain a cornerstone of pharmacotherapy for BPH; however, comparative real-world data remain limited. The aim of this retrospective clinical study was to compare the therapeutic efficacy and safety of finasteride and dutasteride in patients with BPH. Materials and Methods: A total of 401 patients with BPH were retrospectively analyzed: 162 received finasteride and 239 received dutasteride. Clinical parameters, including the International Prostate Symptom Score (IPSS), Quality of Life (QoL) index, and International Index of Erectile Function-5 (IIEF-5) score; urodynamic outcomes, including maximum urinary flow rate (Qmax), average flow rate (Qave), and post-void residual urine volume (PVR); and biochemical markers, including prostate-specific antigen (PSA) and serum creatinine levels, were evaluated at baseline and after at least 6 months of continuous therapy. Statistical significance was defined as p < 0.05. Results: Both treatment groups demonstrated significant within-group improvements in LUTS severity and urodynamic outcomes (p < 0.001 for IPSS, Qmax, and QoL). Compared with finasteride, dutasteride achieved greater reductions in prostate volume (−26.3% vs. −18.1%, p = 0.008) and PSA levels (−43.7% vs. −32.5%, p = 0.014), as well as a slightly greater improvement in IPSS (−6.8 ± 3.9 vs. −5.9 ± 3.6, p = 0.042). Both drugs showed comparable effects on erectile function, as indicated by similar IIEF-5 score changes (Δ = −0.9 ± 2.8 vs. −0.7 ± 2.5, p = 0.51), confirming that neither agent demonstrated a clinically meaningful difference in sexual outcomes. Renal function parameters remained stable in both cohorts. Multivariate analysis identified higher BMI and older age as independent predictors of lower IIEF-5 scores in the finasteride group, while baseline prostate volume was the principal determinant of response in the dutasteride group. Conclusions: Both 5-ARIs effectively reduced LUTS severity and improved urodynamic parameters in men with BPH. Dutasteride demonstrated superior reductions in prostate volume and PSA, while both agents had comparable effects on sexual and renal function. These findings provide real-world evidence supporting the individualization of 5-ARI therapy according to patient-specific clinical characteristics. Full article

Background/Objectives: Prostate cancer (PCa) has the highest incidence and mortality rates among men in Puerto Rico. However, screening and early detection programs remain limited and fragmented. This study presents the design and implementation of a community-based educational program to increase PCa screening and knowledge in three southeastern rural communities with high African ancestry and elevated PCa mortality. Methods: Conducted between 2021 and 2025, this mixed-method study followed Community Engagement principles and was guided by the Intervention Mapping framework. A Community Advisory Committee informed each step of the intervention, which included PSA and digital rectal examination (DRE) testing via a mobile clinic staffed by urologists. Pre- and post-tests measured knowledge gains and willingness to screen, while satisfaction surveys evaluated the program’s impact. Results: After the intervention, knowledge scores increased significantly (t = −5.5, p < 0.001), and 76% of participants reported greater confidence in making health decisions. In total, 95 men accessed screening services through a mobile clinic, 33 were referred for follow-up, and 4 PCa cases were detected. Conclusions: Combining culturally tailored education with accessible screening helped overcome sociocultural and structural barriers, showing promise for reducing PCa disparities in underserved Puerto Rican populations. Full article

Breast and prostate cancers, two of the most prevalent malignancies worldwide, pose significant therapeutic challenges owing to their resistance to conventional treatments and complex tumor microenvironments. The integration of innovative therapies into current clinical frameworks is essential for improving patient outcomes. SN-38, an active metabolite of irinotecan, exerts potent antitumor effects by inhibiting topoisomerase I and modulating the tumor microenvironment. In addition to direct cytotoxicity, SN-38 induces immunogenic cell death, promotes damage-associated molecular pattern (DAMP) release, and enhances antitumor immune responses. These dual mechanisms support the potential of combining it with chemotherapy, targeted therapy, and immunotherapy, particularly in breast and prostate cancers. However, challenges such as poor solubility, rapid degradation, and dose-limiting toxicity hinder its clinical translation. Novel delivery systems, including liposomal formulations, antibody–drug conjugates, and nanoparticle-based strategies, are being developed to address these limitations. This review summarizes the current evidence on SN-38 alone and in combination with emerging therapies, highlighting its potential as a dual cytotoxic and immune-modulating agent in resistant and aggressive cancers. Full article