Search Results (4,595)

Thyroid cancer (TC) is the most common endocrine malignancy, and challenges persist in preoperative diagnosis of indeterminate nodules and postoperative monitoring when thyroglobulin (Tg) assays are compromised by interfering anti-Tg antibodies (Tg-Ab). Extracellular vesicles (EVs) carry molecular cargo reflective of cells of origin and are increasingly explored as biomarker sources. In this study, we investigated whether thyroid-derived EVs retain the expression of thyroid-specific thyrotropin-receptor (TSHR), a suitable target in immunoaffinity-based EV isolation, and explored the presence of Tg in EV cargo as potential surrogate for serum Tg. EVs from thyroid cell lines (Nthy-Ori 3-1, TPC-1, OCUT2) and plasma of patients with benign, malignant tumors and recurrent TC were isolated by differential ultracentrifugation and characterized via nanoparticle tracking and Dot and Western blot analyses. EVs derived from Nthy-Ori 3-1 and TPC-1 cell lines were positive for surface TSHR and vesicular Tg, but not OCUT2. All plasma-derived EVs were positive for TSHR and Tg, while their electrophoretic profiles from vesicles differed compared to tissue lysate. Tg was detectable in EVs isolated from recurrent TC samples, even in Tg-Ab positive cases. Together, these results support the use of TSHR for targeted EV isolation and point to vesicular Tg as a potential recurrence marker. Full article

Circulating tumor cells (CTCs) are essential biomarkers for cancer prognosis, yet their extreme rarity and biological heterogeneity pose significant challenges for label-free detection. This study presents an automated, non-invasive classification framework integrating a self-assembly cell array (SACA) microfluidic chip with hyperspectral imaging (HSI) and deep learning. By utilizing the SACA chip’s 5 µm gap design, patient-derived blood samples were organized into a flattened monolayer, ensuring high-purity spectral acquisition by minimizing cell overlapping. We implemented two deep-learning pipelines: an Attention-Based Adaptive Spectral–Spatial Kernel ResNet (A²S²K-ResNet) for pixel-level feature extraction and a modified ResNet50 for structural image analysis. While spectral classification achieved ~80% accuracy for cultured cell lines, its performance on patient-derived CTCs was hindered by subtle spectral overlap with white blood cells (WBCs). To overcome this, a multi-band ensemble strategy using majority voting across seven optimized spectral bands (470–900 nm) was developed. This hybrid approach significantly enhanced detection robustness, achieving an overall accuracy of >93.5% and precision exceeding 92%. These results demonstrate that combining microfluidic spatial control with multi-band deep learning offers a reliable, label-free pipeline for clinical liquid biopsy and real-time cancer monitoring. Full article

Non-coding RNAs (ncRNAs) have emerged as important regulators of gene expression and cellular homeostasis, and their dysregulation is now recognized as a hallmark of cancer. Over the past decades, extensive research has demonstrated that diverse ncRNA classes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and other small ncRNA species, participate in complex regulatory networks that influence tumor initiation, progression, metastasis, and therapy response. Through mechanisms such as transcriptional regulation, post-transcriptional gene silencing, epigenetic modulation, and competitive endogenous RNA interactions, ncRNAs shape the molecular circuitry underlying cancer development. In addition to their functional roles in tumor biology, many ncRNAs are released into biological fluids and can be detected as circulating molecules in blood, urine, saliva, and other biofluids. Their remarkable stability in extracellular environments has generated considerable interest in their use as minimally invasive biomarkers in liquid biopsy applications. Emerging evidence has shown that circulating ncRNAs (c-ncRNAs) can support cancer detection, disease stratification, and treatment monitoring. This narrative review provides an integrated view that links ncRNA-mediated regulatory networks with their application as liquid biopsy biomarkers, positioning ncRNAs as comprehensive indicators of tumor conditions. Particular emphasis is placed on c-ncRNA biomarkers, the integration of multiple ncRNA classes, and multi-analyte biomarker strategies that combine ncRNAs with complementary circulating molecules such as cell-free DNA and protein markers. Finally, we discuss the technical and clinical challenges that currently limit the translation of ncRNA-based diagnostics into clinical practice and highlight future directions for advancing ncRNA-guided liquid biopsy approaches in precision oncology. Full article

Background: Poly(ADP-ribose) polymerase inhibitors (PARPis) are established maintenance therapies in epithelial ovarian cancer (EOC). Although considered relatively safe, their impact on renal function remains unclear. Increases in serum creatinine (SCr) are frequently observed during treatment, but the clinical significance of these changes is uncertain. We conducted a systematic review and meta-analysis to assess the risk of renal adverse events associated with PARPis in randomized controlled trials (RCTs). Methods: PubMed/MEDLINE, Embase, and the Cochrane Library were searched for phase II–III, placebo-controlled RCTs published through 30 June 2025. Eligible studies enrolled patients with ovarian cancer receiving maintenance monotherapy with olaparib, niraparib, rucaparib, or fuzuloparib and reported renal adverse events. The primary endpoint was creatinine increase (all grades). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects models according to heterogeneity. Results: Nine high-quality RCTs comprising 2578 patients met the inclusion criteria. PARPi therapy was associated with a significantly increased risk of creatinine elevation compared with placebo (OR 5.04; 95% CI 3.51–7.24; p < 0.001). Heterogeneity was moderate (I² = 31.7%). High-grade renal adverse events (≥grade 3) were rare (<1%) and could not be reliably pooled. No significant publication bias was detected. Conclusions: PARP inhibitors significantly increase the likelihood of SCr elevation in EOC; however, severe nephrotoxicity appears uncommon in RCTs. Observed SCr increases may partly reflect inhibition of renal tubular creatinine transport rather than true reductions in glomerular filtration. Careful renal monitoring and prospective studies incorporating direct GFR assessment are warranted. Full article

Background/Objectives: Macrophage phenotype and function are highly sensitive to environmental cues; however, most in vitro studies rely on 2D culture systems that lack physiologically relevant structural context. The spatial dimensionality can influence immune cell signaling, yet the roles of these cells in regulating macrophage behavior remain incompletely understood. This study aimed to investigate how cultural dimensionality affects the phenotype, signaling, and functional activity of monocyte-derived macrophages. Methods: GFP-expressing THP-1 monocytes were differentiated into M0, M1, and M2 macrophages and cultured either on planar substrates or within 3D matrices composed of Matrigel or type I collagen. Macrophage morphology and viability were monitored. Membrane receptor expression and secreted cytokines were examined and quantified. Functional activity was further assessed through coculture experiments with RFP-expressing MDA-MB-231 breast cancer cells. Results: Compared with 2D culture, 3D environments induced distinct morphological and viability changes in macrophages. Collagen matrices supported sustained growth, subtype-specific morphologies, and enhanced functional activity, whereas Matrigel promoted aggregation and reduced viability. Core lineage markers remained stable across conditions, but activation-associated receptors and cytokine profiles were strongly influenced by dimensionality. 3D culture enhanced TNF-α expression and altered serglycin glycosylation patterns. In coculture assays, macrophage effects on tumor cell growth depended on polarization state and were more pronounced in 3D systems. Conclusions: These findings demonstrate that culture dimensionality and ECM composition are key regulators of macrophage phenotype and function. Collagen-based 3D systems better reproduce physiologically relevant macrophage behaviors than conventional 2D platforms, highlighting the value of structurally biomimetic models for immunological studies and therapeutic screening. Full article

The urea cycle (UC) is usually described as the hepatic metabolic pathway responsible for ammonia detoxification, but its role extends far beyond nitrogen (N) elimination to include cellular biosynthesis and metabolic signalling. In cancer cells, the UC is reconfigured/reorchestrated to support high anabolic demand, often involving the dysregulation of key enzymes such as ASS1, ASL, OTC and CPS1. While these changes support biomass production and stress resistance, they also generate measurable biochemical signatures through kinetic and thermodynamic isotope effects (¹⁴N/¹⁵N). In this review, we summarise UC biochemistry and recall key enzymatic mechanisms. Together, these elements provide a mechanistic framework to interpret changes in ¹⁵N abundance observed in tumour tissues and cells. We discuss how the redirection of N flux toward nucleotide and polyamine synthesis, coupled with partial excretion of ¹⁵N-depleted urea, may shape the isotopic composition of cancer cells. By integrating molecular oncology with stable isotope analysis, this review highlights the potential of natural isotope abundance as a functional readout of tumour metabolism and supports further investigation of its translational relevance in cancer phenotyping and monitoring. Full article

The high morbidity and mortality of cancer pose a severe challenge to human health. Traditional diagnostic and therapeutic strategies still exhibit obvious limitations in early diagnostic sensitivity, therapeutic precision, and real-time monitoring of treatment efficacy. The development of nanotechnology has provided novel solutions for precision cancer theranostics. Among nanomaterials, gold nanoparticles (AuNPs) have become a research hotspot in tumor nanomedicine due to their tunable size and morphology, excellent localized surface plasmon resonance (LSPR) effect, and favorable biocompatibility. However, despite encouraging preclinical outcomes, several challenges hinder their clinical translation, including an incomplete understanding of long-term toxicity, complex in vivo biological interactions, the lack of standardized evaluation protocols, and regulatory uncertainties and manufacturing reproducibility issues. This paper systematically reviews the physicochemical and biological mechanisms of AuNPs in cancer theranostics, and summarizes the latest research advances of AuNPs in cancer detection and diagnosis (including biomarker detection and multimodal imaging) as well as in therapeutic fields, covering photothermal therapy (PTT), photodynamic therapy (PDT), radiosensitization, targeted drug and nucleic acid delivery, and immunotherapy-assisted strategies. Furthermore, we discuss the development of intelligent and stimuli-responsive theranostic nanoplatforms based on AuNPs, and outline their future prospects in precision medicine and personalized cancer therapy, with particular emphasis on the requirements for clinical translation, including safety evaluation, large-scale production, and regulatory approval pathways. Full article

Endometriosis and endometrial cancer are distinct gynecological conditions that share overlapping biological mechanisms with implications for clinical management. Endometriosis is a chronic, benign disorder characterized by the ectopic implantation of functional tissue lining the uterus, primarily affecting women of reproductive age. It commonly causes chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. The disease is marked by persistent inflammation, hormonal dysregulation, and alterations in cellular signaling, which mirror some neoplastic processes despite lacking malignant potential. Endometrial cancer is a malignant tumor of the uterine lining, most frequently diagnosed in postmenopausal women. Its incidence is rising due to aging, obesity, and prolonged estrogen exposure. Epidemiological studies suggest a modest increase in endometrial cancer risk among women with endometriosis. However, detection bias and metabolic confounders may influence this association. Both conditions share estrogen dependence, chronic inflammatory microenvironments, and dysregulated pathways such as PI3K/AKT/mTOR. Somatic mutations in genes, including PTEN and ARID1A, further underline molecular intersections. Clinical management is tailored to disease type and severity. Endometriosis therapy emphasizes stepwise hormonal treatment, multidisciplinary pain management, and surgery when indicated. Endometrial cancer management relies on staging, with particular emphasis on molecular classification and histopathology to guide surgery, radiotherapy, chemotherapy, hormone therapy, and immunotherapy in advanced cases. Emerging noninvasive biomarkers and precision medicine strategies may enhance diagnosis, monitoring, and targeted treatment in both conditions. Understanding their shared and divergent mechanisms aids risk stratification, individualized therapy, and improved quality of life. Further prospective studies are needed to optimize patient-specific management and translate mechanistic insights into clinical practice. Full article

Background/Objectives: This study aimed to describe and quantify facial soft tissue changes in two patients who underwent radiotherapy (RT) for head and neck cancers, using three-dimensional (3D) stereophotogrammetry and surface deviation analysis. The aims were (i) to assess the progression of morphological alterations over time (ii) and to evaluate the clinical potential of 3D surface mapping in documenting RT-related aesthetic changes. Methods: Two patients with head and neck cancer undergoing RT were analyzed using three-dimensional stereophotogrammetry (3dMD Trio-system, Atlanta, GA, USA) at three timepoints: before RT (T0), 45 days after the start of RT (T1), and 6 months after the start of RT (T2). Facial 3D scans were processed using Geomagic Control 2014 software (v.3D Systems, Morrisville, NC, USA) to perform standardized alignments and calculate volumetric deviations, create colorimetric deviation maps, and conduct Root Mean Square (RMS) analysis. Results: Between T0 and T1, both patients showed soft tissue volume reduction, primarily in the mandibular and submental regions, likely reflecting acute treatment effects and weight loss. Between T0 and T2, an increase in soft tissue volume was observed, especially in the lower face and neck, consistent with late radiation effects such as lymphedema and post-treatment weight gain. RMS values ranged from 5.53 mm to 6.87 mm across patients and time points, indicating measurable morphological changes. The upper third of the face remained stable and served as a reliable reference region for alignment. Conclusions: RT may be associated with significant, region-specific changes in facial and cervical soft tissues in HNC patients, but these preliminary observations must always be correlated with weight loss and confirmed by further studies. 3D stereophotogrammetry is a reliable, non-invasive method for detecting and quantifying these alterations over time. This technique can offer valuable insights for clinical monitoring and could promote better patient counseling and potentially mitigate the psychological burden associated with facial changes. Full article

UV radiation causes health effects and repeated excessive sun exposure during childhood increases the risk of skin cancer in adulthood. The French region of Occitanie combines conditions conducive to sun exposure with a wide range of healthcare services. The study aims to describe temporal variations related to sun overexposure and patient characteristics, and evaluate the relevance of each data source. We conducted a retrospective analysis (2019–2022) on pharmacy sales, emergency care provided by SOS Médecins (SOSM), and emergency departments (EDs). More than 220,000 customers purchased products associated with sun overexposure, while 71 SOSM procedures and 417 ED visits were recorded. The activity is clearly seasonal, but remains five to ten times higher for pharmacies than for other sources. About 80% of ED patients were under 40 years of age, while 50% lived within 20 km of the consultation location. The impacts on healthcare systems vary, and each provides complementary insights into care related to sun overexposure. Increases in pharmacy sales are observed as early as spring, underscoring the need to strengthen prevention messaging from the start of the season. The study confirms the value of pharmacy sales data for assessing the impact of sun exposure, but ED or SOSM data enable real-time monitoring and patient characterization. Full article

Background and Objectives: Menopausal hormone therapy (MHT) is the most efficacious treatment for vasomotor symptoms and genitourinary conditions associated with menopause. Modern menopause care increasingly encompasses women with multimorbidity, renal or hepatic impairment, previous malignancies or thromboembolic disorders, advanced age, and polypharmacy—groups frequently underrepresented in randomized clinical trials. This evidence gap prompts significant inquiries about the relevance of trial-based recommendations to actual clinical practice. Materials and Methods: This narrative review offers a concentrated assessment of prominent worldwide clinical guidelines regarding menopausal hormone therapy through thematic synthesis. We examined position statements from the North American Menopause Society (NAMS), the European Menopause and Andropause Society (EMAS), NICE clinical guidelines, the ACOG Practice Bulletin on menopausal symptom management, the Endocrine Society clinical practice guideline, and pertinent UK guidance from RCOG, BMS, and BGCS. Data from systematic reviews, meta-analyses, and extensive observational studies were analyzed to contextualize guideline recommendations for populations often underrepresented in clinical trials, including women aged ≥65 years and individuals with multimorbidity or polypharmacy. Results: Only the NICE and EMAS recommendations expressly acknowledge clinical vulnerability or complexity (multimorbidity, frailty, and cancer survivorship) as foundational principles. NAMS and ACOG delineate risk categories but fail to offer a cohesive taxonomy of vulnerability. Polypharmacy and drug–drug interactions are inconsistently addressed across guidelines, and there is a deficiency of standardized prescribing algorithms. While routine safety monitoring is universally advocated, the intervals for follow-up and methods for risk categorization differ. Observational evidence consistently indicates route-dependent variations in cardiovascular and thromboembolic risk, with transdermal estrogen linked to a more advantageous safety profile in higher-risk individuals. Conclusions: Present menopausal therapy guidelines are methodologically sound; however, they insufficiently address the complexities of multimorbidity, polypharmacy, and organ dysfunction. A systematic conceptual framework that incorporates areas of clinical vulnerability may facilitate personalized benefit–risk evaluation in practical applications. Future guideline revisions should enhance clarity by incorporating polypharmacy concerns, monitoring strategies, and systematic risk stratification methods for clinically complicated patients. Full article

Protein glycation is a nonenzymatic modification that links sugar chemistry to molecular aging and chronic disease. Sequential reactions involving Schiff bases, Amadori products, and reactive α dicarbonyl intermediates generate advanced glycation end products (AGEs) that irreversibly alter protein structure and function. AGEs also act as ligands for the receptor for advanced glycation end products (RAGE), initiating oxidative stress, inflammation, and tissue remodeling. This review synthesizes the molecular pathways of AGE formation, their structural diversity, and the biological factors influencing glycation kinetics. Advances in analytical detection methods—including fluorescence spectroscopy, LC–MS/MS, and immunochemical approaches—are highlighted for their role in monitoring AGE accumulation. Particular attention is given to the contribution of glycation to diabetes, cardiovascular disease, neurodegeneration, and cancer, alongside emerging therapeutic strategies to limit AGE formation or block AGE–RAGE signaling. Glycation thus represents a central mechanism in human disease pathogenesis and an emerging therapeutic frontier. Full article

Background/Objectives: This study aimed to assess the feasibility and acceptability of a 3-month health coaching intervention to promote PNF and healthy diet for men on ADT for PCa. Methods: The study was carried out via a two-armed randomized controlled trial including 40 patients with PCa at a medical center in Philadelphia. During the 3-month period, the intervention group (PNF+) received health coaching utilizing an interactive text message system, and the control group received healthy eating text messages for the same duration. The outcome variables were feasibility and acceptability. Results: The PNF+ group (n = 27) had high adherence to health coaching (82%), picture response (85%) and moderate adherence to the PNF window (69%). The intervention was rated highly acceptable with no reported A/E associated with the intervention, and most participants planning to continue in some capacity. At 3 months, the PNF+ group had numerically lower BMI (29.1) and body weight (195.2 lbs) compared to the control group (n = 13; BMI 31.6, weight 223.3 lbs). Improvements in patient-reported outcomes were observed in both groups. FACIT-F scores (higher scores indicate less fatigue) increased in the PNF+ group (43.6 to 45.2) and in the control group (42.5 to 45.5). FACT-P scores (higher scores indicate better quality of life) increased in the PNF+ group (121.3 to 125.5) but decreased slightly in the control group (121.1 to 119.8). Between-group comparisons of change from baseline showed no statistically significant differences across outcomes (all p > 0.05). Conclusions: The intervention demonstrated partial feasibility and high acceptability. It was associated with numerically lower BMI and body weight and favorable changes in patient-reported outcomes, particularly quality of life; however, no statistically significant differences were observed between groups. These findings should be interpreted cautiously given the small sample size and require confirmation in larger, adequately powered trials. Full article

Oral squamous cell carcinoma (OSCC) remains a major clinical challenge, highlighting the need for novel therapeutic strategies. Natural bioactive compounds such as curcumin (Cu) and cordycepin (Co) have shown anticancer potential; however, their effects on cancer cell morphology and behavior remain incompletely characterized. This study assessed the individual and combined effects of Cu and Co on oral squamous cell carcinoma cells (OECM-1) and normal human gingival epithelial cells (HGEpiC) over 24 and 48 h. Metabolic activity, membrane integrity, oxidative stress, apoptosis, and inflammatory responses were evaluated using MTT, LDH, ROS-H₂O₂, caspase 3/7, and NO assays. Label-free digital holographic microscopy enabled real-time monitoring of morphology, motility, and proliferation. Both compounds induced ROS-mediated cytotoxicity, but responses were notably more pronounced in OECM-1 than in HGEpiC cells. Real-time morphological profiling revealed distinct response patterns: Co primarily exerted cytostatic effects, whereas Cu induced cell shrinkage, impaired motility, and inhibited cell division. The combination treatment (CC) largely reflected Cu-driven morphological and functional changes, with Co coexisting without counteracting Cu’s effects. Taken together, these findings reveal compound-specific mechanisms of action for Cu and Co in OSCC therapy. Full article