Search Results (9,705)

Cancer development is influenced not only by genetic alterations but also by epigenetic dysregulation driven by environmental and lifestyle factors, particularly diet. Nutrigenomics investigates how dietary components interact with the genome to influence gene expression, while nutritional epigenetics focuses on diet-induced modifications such as DNA methylation, histone modifications and non-coding RNA regulation. Increasing evidence indicates that bioactive dietary compounds can modulate epigenetic mechanisms involved in carcinogenesis, highlighting their potential role in cancer prevention. This narrative review synthesizes recent evidence, with emphasis on literature published between 2015 and 2025 and an updated search through September 2026 on the molecular interplay between diet, epigenetic regulation and cancer risk. We examine how key dietary factors—including methyl donors involved in one-carbon metabolism, polyphenols, short-chain fatty acids and omega-3 fatty acids—modulate epigenetic regulators such as DNA methyltransferases and histone deacetylases. Particular emphasis is placed on the emerging Nutrigenomics–Microbiome–Epigenome Axis, whereby microbiota-derived metabolites influence host chromatin architecture and gene expression pathways relevant to tumor suppression and inflammation. In addition, we discuss current evidence linking dietary patterns, including Mediterranean and Western diets, with distinct epigenomic signatures associated with cancer susceptibility. The review further explores the potential of epigenetic biomarkers and epigenome-wide association studies to support precision nutrition strategies for cancer prevention. Collectively, accumulating evidence suggests that diet-driven epigenetic plasticity may contribute to cancer prevention. However, the human evidence remains heterogeneous, and large, well-designed intervention studies with standardized epigenetic endpoints are required before mechanistic findings can be translated into clinically actionable precision nutrition strategies. Full article

Scutellaria barbata D. Don (SBD) has been widely investigated for antitumor activity, but its immune- and tumor microenvironment (TME)-related mechanisms remain fragmented. This study synthesized preclinical evidence on SBD and contextualized the findings using network pharmacology. A scoping review was conducted according to established scoping review methodology and PRISMA-ScR guidance. Preclinical in vitro and in vivo cancer studies published between January 2016 and December 2025 were searched in PubMed, Embase, CENTRAL, and OASIS. Network pharmacology analysis was performed using TCMSP, SwissTargetPrediction, ImmPort, GeneCards, STRING, Cytoscape, MCODE, DAVID, GO, and KEGG analyses. Fifty-six preclinical studies were included. SBD extracts, fractions, polysaccharides, diterpenoids, flavonoids, and isolated constituents suppressed cancer cell proliferation, induced cell-cycle arrest, promoted apoptosis and ferroptosis, modulated autophagy, induced endoplasmic reticulum stress-associated cell death, inhibited migration, invasion, angiogenesis, and metastasis, and enhanced chemosensitivity across diverse cancer models. Immune- and TME-related effects included activation of natural killer cells and CD8⁺ T cells, reduction in regulatory T cells, T helper 17 cells, myeloid-derived suppressor cells, and M2-like tumor-associated macrophage polarization, modulation of cytokine and inflammatory signaling, and regulation of epithelial–mesenchymal transition, matrix remodeling, angiogenesis, and metastatic niche formation. Network pharmacology identified 32 active candidate compounds, 408 predicted targets, and 152 immune/TME-overlapping targets. Protein–protein interaction and enrichment analyses highlighted AKT1, TNF, SRC, EGFR, and BCL2 as candidate hub targets and implicated PI3K-Akt, MAPK, Ras, EGFR tyrosine kinase inhibitor resistance, and proteoglycans in cancer. SBD-derived interventions showed antitumor, immunomodulatory, and TME-remodeling activities across diverse preclinical models. The integrated findings identify recurrent biological processes and candidate molecular targets, while differences in preparation, chemical characterization, dose, and experimental design limit direct comparison across studies. This framework supports further mechanistic, pharmacokinetic, and translational evaluation of chemically characterized SBD preparations and candidate compounds. Full article

Background: Melanoma disproportionately affects older adults, who account for a growing share of cases as populations age. Its incidence rises with age, and the number of ultra-octogenarians (≥85 years) is expected to triple by 2050, particularly in high-incidence regions such as Australia, North America and Europe. Moreover, older adults frequently present with substantial comorbidities, making management complex and complicating treatment decisions. Methods: This comprehensive review summarizes evidence concerning the clinicopathological characteristics, treatment patterns, systemic therapy outcomes, and geriatric considerations relevant to patients aged 75 years or older with melanoma. PubMed/MEDLINE was searched from January 2000 to March 2026. Reference lists of eligible articles and relevant reviews were examined to identify additional studies. Priority was given to studies reporting age-stratified outcomes for patients aged at least 75 years. Because relatively few studies reported outcomes specifically for patients aged ≥75 years, evidence using thresholds of ≥65, ≥70, or ≥80 years was included when directly relevant. Age thresholds are reported for each study and should not be considered interchangeable. Results: Most evidence specific to patients aged ≥75 years derives from retrospective cohorts and registries. Compared with younger patients, elderly patients more often present with melanomas of the head, neck, hands and feet, a higher prevalence of the nodular subtype, greater Breslow thickness, higher mitotic rates and lower tumor-infiltrating lymphocyte density. Diagnosis is frequently delayed due to difficulties with self-examination, visual impairment, benign age-related skin changes and social factors. Despite presenting such a high-risk disease, older patients are less likely than their younger counterparts to receive immunotherapy or BRAF/MEK-targeted agents. This treatment gap may reflect comorbidities, altered pharmacokinetics, concerns about toxicity, under-representation in pivotal trials, and limited caregiver support. Available real-world data suggest that the efficacy of immune checkpoint inhibitors and targeted therapies is comparable to that in younger adults, although treatment selection, discontinuation, hospitalization, and dose modification differ across studies. Conclusions: Melanoma in older adults has distinct clinical and pathological patterns, but treatment evidence for patients aged ≥75 years remains limited and subjected to selection bias. Tailored, geriatric-informed treatment strategies integrating tumor biology, comorbidity, functional status and patient preferences are needed to optimize outcomes for patients aged 75 years and older. Full article

Tumors of the spine and spinal cord, including primary and metastatic vertebral tumors, intramedullary gliomas, and refractory intradural lesions, are challenging to treat because curative local therapy is limited by the eloquent, nonregenerating neural tissue surrounding them. Oncolytic virotherapy may offer a rational alternative by combining tumor-selective oncolysis with the induction of systemic antitumor immunity, while sparing normal neural cells. This review summarizes the current field of oncolytic viruses, including adenovirus, herpes simplex virus, reovirus, and others, in the context of spinal and spinal cord tumors. Clinical data in the spine remain scarce; however, the rationale is based on histological evidence from sarcomas and other tumors, extensive glioma experience, including diffuse intrinsic pontine glioma, and preclinical activity in nerve sheath and meningioma models. We discuss the telomerase-specific oncolytic adenovirus OBP-301 and its derivatives, whose hTERT-driven replication provides histology-agnostic tumor selectivity, while sparing the telomerase-silent spinal cord. This telomerase dependence, however, limits activity against tumors that maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, such as many osteosarcomas and some spinal cord astrocytomas. We also discuss delivery and safety within the confined spinal canal, combination strategies, and future directions, such as extracellular vesicle-mediated delivery and biomarker-guided patient selection. Although clinical translation to the spine will require dedicated preclinical and early-phase studies, virotherapy represents a promising, mechanistically grounded modality for these therapeutically challenging tumors. Full article

Cholesterol is increasingly recognized as a regulator of hematolymphoid malignancy biology, by influencing tumor proliferation, immune function, and therapeutic response. This review summarizes current evidence regarding the relationship between cholesterol metabolism and hematologic malignancies, integrating mechanistic studies with retrospective and emerging prospective clinical data. Cholesterol contributes to immune dysfunction by promoting CD8⁺ T-cell exhaustion within the tumor microenvironment. Clinical studies have reported associations between serum lipid profiles, statin use, and outcomes across multiple hematologic malignancies, although findings remain heterogeneous and are largely derived from retrospective analyses. Preclinical studies demonstrate that statins disrupt cholesterol-dependent signaling and inhibit tumor growth, whereas retrospective clinical studies generally support the safety of statin use and suggest possible therapeutic benefits in some lymphoma subtypes. Clinically, low high-density lipoprotein cholesterol (HDL) has been associated with advanced disease across multiple hematological malignancies. However, prospective, interventional data remain limited. Collectively, this review highlights the possible relationship between cholesterol metabolism and hematologic malignancy biology, with a focus on potential impacts on disease related outcomes. Full article

Background: Feline mammary carcinoma (FMC) is an aggressive neoplasm in cats and has attracted interest in comparative oncology because selected clinicopathological and molecular features overlap with human breast cancer. Methods: This integrative review synthesized literature was identified in PubMed/MEDLINE, Scopus, and Web of Science from database inception to 30 March 2026, focusing on epidemiology, pathology, biomarkers, tumor microenvironment, omics, therapy, and comparative oncology. Feline-derived evidence was distinguished from the human breast cancer literature, and findings were synthesized qualitatively because of substantial methodological and clinical heterogeneity. Results: FMC shows recurrent associations with aggressive histological features, hormone receptor-negative phenotypes, HER2-related signaling, immune checkpoint pathways, and emerging molecular and liquid-biopsy biomarkers. However, differences in molecular classification, methodology, treatment, cohort size, and clinical validation limit direct cross-species inference. Conclusions: FMC may serve as a complementary, question-specific comparative oncology system for studying selected aspects of aggressive mammary tumor biology, metastasis, tumor–host interactions, biomarkers, and therapeutic response. Its translational relevance remains hypothesis-generating and requires standardized methods and independent clinical validation. Full article

Background: Glioblastoma (GBM) remains difficult to treat, and natural bioactive formulations are being explored as experimental modifiers of tumor-associated cellular processes. This study examined a fixed-ratio olive polyphenol–bromelain formulation in U87MG cells and performed targeted phenolic characterization of its olive-derived component. Methods: Seven phenolics were quantified by LC–MS/MS. U87MG cells were exposed to the formulation or a bromelain comparator. The MTT metabolic signal, DNA-content cell-cycle distribution, IL-6, IL-10, and extracellular total antioxidant capacity (TAC) were assessed. Results: The total quantified phenolics were 483.22 mg/kg, with oleocanthal, oleuropein, and 3,4-DHPEA-EDA predominating. The formulation reduced the MTT signal more than bromelain at lower and intermediate concentrations, although the response became non-monotonic at higher concentrations. Combination-treated cells showed greater G0/G1 accumulation. Culture supernatants showed lower IL-6 and higher IL-10 and TAC relative to untreated controls. Conclusions: The formulation was associated with changes in metabolic activity, cell-cycle distribution, and extracellular cytokine/redox readouts in U87MG cells. Because no polyphenol-only arm, direct cell-death assay, complete replicate-level inferential analysis, or non-tumoral comparator was available, the findings are descriptive and do not establish synergy, cytotoxicity, mechanism, tumor selectivity, or therapeutic efficacy. Full article

Background: Thymosin alpha 1 (Tα1, thymalfasin) is a thymus-derived immunomodulatory peptide investigated as an adjunctive therapy in cancer care. Although studied across malignancies, its evidence landscape has not been systematically mapped. This scoping review characterized treatment contexts, intervention patterns, outcome domains, and safety reporting of clinical studies evaluating Tα1 in patients with cancer. Methods: PubMed, Embase, and CENTRAL were searched for clinical studies of Tα1 in patients with cancer published from January 2016 to March 2026. Eligible studies included randomized controlled trials, non-randomized studies, observational studies, and case-based reports. Data on study characteristics, cancer type, intervention features, comparators, outcomes, and adverse-event reporting were charted and synthesized descriptively. Results: Twenty-six clinical publications were included. Most were conducted in China, and retrospective observational studies and case reports predominated. Hepatobiliary, thoracic, and gastrointestinal cancers were the most frequently studied clusters. Classical Tα1 was administered mainly by subcutaneous injection, most commonly at 1.6 mg, and used primarily as an adjunct to chemotherapy, radiotherapy, chemoradiotherapy, targeted therapy, immune checkpoint inhibitors, or postoperative and supportive care. Outcomes included tumor response, survival, recurrence, immune and inflammatory markers, treatment-related toxicity, functional status, and quality of life. Several studies reported favorable clinical, immune-related, or treatment-tolerance signals, but heterogeneity limited comparability. Safety reporting was inconsistent. One case described severe multisystem immune-related toxicity during combination treatment without establishing Tα1-specific causality. Conclusions: Tα1 has been investigated mainly as an adjunctive immunomodulatory strategy in cancer care. Prospective controlled studies with standardized dosing, defined treatment contexts, consistent outcomes, and systematic harms reporting are needed. Full article

This study explored the potential of gold nanorods (AuNRs) functionalized with polyethylene glycol (PEG) and loaded with non-steroidal anti-inflammatory drugs (NSAIDs) fenamic acid (fenH) or its bromo-derivative (4′BrfenH) for targeted drug delivery and preclinical cancer research, given their pH-dependent drug-release profiles and in vitro cytotoxicity in breast cancer cell models. Both formulations demonstrated strong π–π stacking interactions with calf-thymus DNA, suggesting intercalation, and exhibited significant binding affinity to bovine and human serum albumins. Drug release was markedly higher at alkaline pH. As the fenamates are weak acids that are practically insoluble in their neutral form, this pH dependence is attributed principally to the ionization and solubility of the released drug rather than to a responsive carrier. Cytotoxicity assays revealed that AuNRs@PEG@4′BrfenH significantly reduced cell viability in both aggressive (MDA-MB-231) and less metastatic (MCF-7) breast cancer cell lines, particularly at higher concentrations, and caused structural disorganization in 3D spheroid cultures. These findings highlight the promise of AuNRs@PEG@4′BrfenH as a nanoplatform showing pH-dependent release and significant in vitro anticancer activity in breast cancer cell lines and spheroids, supporting its further investigation in relevant tumor models. Full article

Imines, commonly known as Schiff bases, are widely investigated compounds because of their structural versatility and biological properties. In this study, we aimed to evaluate the antioxidant potential of salicylaldehyde-derived imines and to determine how their reduction to the corresponding secondary amines affects their radical-scavenging activity and mechanism of action. Two series of phenolic derivatives, imines I1–I6 and amines A1–A6, were synthesized and assessed using an integrated experimental and theoretical strategy combining five in vitro antioxidant assays with density functional theory calculations. Antioxidant evaluation by DPPH, ABTS, FRAP, phenanthroline, and CUPRAC assays revealed distinct activity profiles for the two series. The imine derivatives were more effective in electron-transfer-based assays, whereas the reduced amines showed stronger DPPH radical-scavenging activity. Compound A6 exhibited the highest overall antioxidant activity, with IC₅₀ values (e.g., DPPH IC₅₀ = 26.7 ± 0.97 µM; ABTS IC₅₀ = 11.69 ± 0.43 µM) lower than BHT (DPPH IC₅₀ = 85.85 ± 3.69 µM) and BHA (DPPH IC₅₀ = 59.39 ± 1.9 µM) in most assays. DFT calculations in aqueous medium indicated that the phenolic OH groups govern antioxidant reactivity and identified SPLET as the dominant mechanism for A6, supported by a remarkably high rate constant (k = 1.40 × 10⁵ M⁻¹s⁻¹) and a 100% branching ratio (G), completely outcompeting the HAT mechanism (k = 2.28 × 10⁻² M⁻¹s⁻¹). In addition to the antioxidant investigation, cytotoxicity was assessed in MDA-MB-231 breast cancer cells and Vero normal cells, revealing that the chlorinated derivatives such as I5 combine moderate anticancer activity (MDA-MB-231 IC₅₀ = 122.6 ± 2.23 µM) with lower toxicity toward non-tumor cells (Vero IC₅₀ > 400 µM). Molecular docking studies were conducted to elucidate the binding modes of the active derivatives within the active sites of EGFR, Tubulin, and Topoisomerase IIβ, while subsequent 100 ns molecular dynamics simulations validated the structural stability and sustained interaction energies of these predicted complexes. Full article

Accurate preoperative discrimination between indolent and aggressive renal lesions is essential for personalized risk-stratified management and improves the clinical outcomes of renal tumor patients. This study aimed to establish and externally validate a non-invasive computed tomography (CT)-derived radiomic model for identifying aggressive renal tumors and predicting long-term postoperative survival. A total of 3407 patients with pathologically confirmed renal tumors from multiple centers were retrospectively enrolled and divided into three independent cohorts: a training cohort (n = 1840), an internal validation cohort (n = 789), and an external test cohort (n = 778). Based on preoperative multiphasic CT images, a support vector machine (SVM)-based radiomic model was constructed to evaluate tumor aggressiveness. Cox proportional hazards regression analysis was performed to identify independent prognostic factors, and a comprehensive nomogram combining radiomic aggressiveness score and clinicopathological parameters was further developed for survival prediction. The established SVM radiomic model yielded stable discriminatory performance, with an area under the receiver operating characteristic curve (AUC) of 0.740 in the internal validation cohort and 0.763 in the external test cohort. Multivariate Cox regression analysis demonstrated that radiomics-predicted tumor aggressiveness remained an independent adverse prognostic factor for recurrence-free survival (HR = 3.656), overall survival (HR = 1.981), and disease-specific survival (HR = 3.673). Moreover, the integrated nomogram demonstrated favorable calibration for predicting 5-year and 8-year overall survival in the internal validation cohort. This novel CT-based radiomic model provides a robust non-invasive tool for preoperative differentiation of renal tumor aggressiveness. As an independent prognostic biomarker, it can assist clinicians in precise preoperative risk evaluation and facilitate individualized therapeutic decision-making for renal tumor patients. Full article

Obesity influences breast cancer risk, progression, and therapeutic response through endocrine, inflammatory, metabolic, stromal, and vesicular mechanisms. Circulating and extracellular vesicle (EV)-associated microRNAs are attractive liquid biopsy candidates; however, in obesity-associated breast cancer, they should not be interpreted as tumor-only biomarkers. This narrative review analyzes circulating/EV-miRNAs as mixed host–tumor signals and separates association-based biomarker evidence from functional EV-mediated transfer. We performed a narrative and integrative review of studies on miRNA biogenesis, circulating miRNA transport, EV biology, adipose tissue dysfunction, adipose-tumor communication, biomarker development, therapy response, and methodological reporting standards. The current literature is read along two independent axes: human relevance and source attribution, from non-breast models to obesity-stratified human cohorts, and mechanistic causality, from association only to EV-level function, miRNA-level function, and causality with rescue; clinical validation is treated as a separate qualifier rather than as the top of a single scale. For example, EV-let-7a in overweight/obese breast cancer patients mainly supports an obesity-stratified biomarker candidate. Breast adipose tissue-derived EV cargoes enriched in miR-155-5p, miR-10a-3p, and miR-30a-3p provide stronger functional support for metabolic reprogramming, whereas EV-associated miR-221/222 has mediator-level evidence in endocrine resistance but is not obesity specific. Conclusions: The main contribution of this review is an operational interpretation framework in which circulating miRNAs are evaluated according to probable source, evidence level, and clinical purpose. Future studies should report EV workflow quality, sample type, hemolysis and platelet control, normalization strategy, external validation, tumor subtype, and obesity phenotyping beyond BMI, including waist circumference or waist-to-hip ratio, insulin resistance, diabetes, menopausal status, and inflammatory markers. Full article

Radiomic features derived from longitudinal imaging offer a non-invasive approach to quantify tumor heterogeneity, but their integration with clinical variables in small cohorts remains methodologically challenging. We analyzed 23 patients with advanced non-small cell lung cancer (NSCLC) enrolled in a Phase I study of pembrolizumab and vorinostat. Radiomic features were extracted from baseline and two-month follow-up computed tomography scans, aggregated to the patient level, and transformed into delta features representing early changes over time. A unified modeling framework was implemented using strict leave-one-out cross-validation (LOOCV), incorporating both radiomic and clinical variables. Within each training fold, outcome-guided feature screening was performed using elastic net penalized Cox regression, followed by category-aware principal component analysis and ridge-penalized Cox modeling. Model performance was evaluated using out-of-fold concordance indices for overall survival (OS) and progression-free survival (PFS). Radiomics-only models demonstrated moderate discrimination for OS (C-index 0.609) and favorable discrimination for PFS (C-index 0.770), whereas clinical-only models showed weaker performance (OS 0.605; PFS 0.571). The combined radiomics and clinical model demonstrated numerically higher discrimination without statistically distinguishable differences for OS (C-index 0.648) while maintaining favorable discrimination for PFS (C-index 0.718). Stable features were predominantly texture-based and included Laws filter and co-occurrence-derived metrics associated with spatial heterogeneity. In this exploratory analysis, early changes in radiomic features reflecting tumor heterogeneity suggest potential associations with survival outcomes in advanced NSCLC. Integration of radiomic and clinical variables showed trends toward improved performance for overall survival while maintaining favorable discrimination for progression-free survival. These findings support further investigation of longitudinal radiomic features as candidate imaging biomarkers in larger, independently validated cohorts. Full article

Platelets are key components of the tumor microenvironment that contribute to colorectal cancer (CRC) progression. However, effective platelet-related prognostic tools for CRC risk stratification and prognostic assessment are lacking. Therefore, we aimed to develop a platelet-related prognostic model to improve risk stratification and prognostic evaluation. A tumor-cell-expressed platelet-related transcriptional signature, termed platelet-related risk score (PLRS), was established using LASSO and Cox regression based on TCGA-COADREAD, GSE39582 and GSE183635. After strict screening for intact survival information, 573, 531 and 85 tumor samples were retained correspondingly. Patients were stratified into high- and low-PLRS groups according to the median cutoff value of PLRS derived from the training cohort. A single-cell dataset GSE178341 was utilized for single-cell transcriptomic validation. All analyses were performed in R. Wilcoxon test, Kaplan–Meier method, log-rank test, multivariate Cox regression and ROC curves were applied with two-sided p < 0.05. qRT-PCR was conducted for hub gene validation. The PLRS model involved six prognostic genes (TIMP1, TTYH3, GPX4, PLCB4, CA2, and LITAF). The high- and low-PLRS groups showed significant differences in disease stage and survival in TCGA datasets, which was confirmed in the GEO dataset (GSE39582). The multivariate analysis established the PLRS as an independent prognostic factor. Single-cell analyses revealed distinct transcriptional trajectories, immune microenvironments, and communication patterns between the PLRS groups. Stromal, immune, and ESTIMATE scores positively correlated with PLRS, whereas tumor purity was inversely correlated. Exploratory drug sensitivity analysis using GDSC and CCLE cell line datasets suggested potential associations between PLRS and multiple therapeutic agents, warranting validation in clinical cohorts. qRT-PCR in RKO cells compared with the CCD-18Co fibroblast control partially confirmed the expression trends of four PLRS genes (TIMP1, GPX4, LITAF, and PLCB4), whereas TTYH3 showed no significant difference and CA2 was not tested due to primer-design failure. Validation in normal colonic epithelial cells is warranted. The PLRS model demonstrated statistically significant prognostic value and may serve as a complementary tool for CRC risk stratification, providing a basis for further investigation into platelet-related transcriptional programs. Full article

Background: Fresh ovarian cancer tissue is a demanding starting material for cellular workflows, particularly when the aim is to obtain tumor-derived suspensions suitable for further TIL-oriented procedures. In this study, we evaluated post-isolation cell concentration and viability in ovarian cancer specimens processed according to a standardized mechanical–enzymatic protocol. Methods: Biological material was collected from 24 patients undergoing routine surgery for ovarian cancer or suspected advanced ovarian malignancy. After macroscopic assessment and exclusion of extensively necrotic tissue, 19 specimens were included in the final analysis. The cohort was dominated by high-grade serous ovarian carcinoma, which accounted for 15 of 19 analyzed cases. Tissue specimens varied markedly in mass, with a median processed tissue weight of 2.05 g and a range from 0.11 to 14.93 g. Results: The median final cell concentration was 8.10 × 10⁶ cells/mL, with values ranging from 6.40 × 10³ to 9.26 × 10⁸ cells/mL. Median viability was 80.8%, although individual results ranged widely from 2.3% to 98.7%. The calculated median concentration of viable cells was 6.17 × 10⁶ viable cells/mL. Tissue mass showed a moderate positive association with final cell concentration (Spearman’s rho = 0.50, p = 0.028), but not with viability. Conclusions: These findings show that standardized processing of ovarian cancer surgical specimens can generate cell suspensions suitable for post-isolation quality assessment, even when the input material is highly variable. The present study focused on early post-isolation quality-control readouts obtained after tumor dissociation and did not evaluate TIL expansion capacity, detailed TIL phenotype, or antitumor function. The wide range of final cell concentrations underlines the biological and practical heterogeneity of ovarian cancer tissue and supports the need for careful reporting of early tissue-processing parameters in TIL-oriented workflows. Full article