The development of effective viroimmunotherapies for cancer relies on the ability of replicating viruses to infect the entire tumor tissue and induce comprehensive inflammation within the tumor microenvironment (TME). In this study, we investigate the impact of mutations in the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV) on tumor cell infectivity, replication, and the immune response. Specifically, we focus on two key positions in GP1 (181 and 185) that significantly enhance tumor cell infectivity and improve CD8⁺ T cell function in the GP-mutated LCMV strain LCMV P52. Our findings demonstrate that LCMV strain LCMV P52 replicates preferentially in vivo in tumors, exhibits improved tumor penetration, attracts functional CD8⁺ T cells more effectively to the tumor, and reprograms the tumor toward a more immunogenic microenvironment to allow for effective checkpoint inhibitor combination.

Epstein-Barr virus (EBV) is an oncogenic human gammaherpesvirus that is prevalent worldwide. Although over 95% of the world's population harbors this pathogen, the vast majority of infections are asymptomatic, largely due to immune system involvement. However, in certain situations, such as when individuals are immunocompromised, the immune system can lose control of EBV suppression, leading to oncogenesis. While standard chemotherapeutic regimens can be effective against some EBV-associated cancers, these treatments can be toxic to some patients, and disease relapse and/or drug resistance can develop. Additionally, no human vaccine currently exists for EBV. In recent years, biotherapy has become a promising avenue for the clinical management of EBV-positive cancers. As early detection is often correlated with a more positive prognosis, identification of reliable EBV biomarkers has also come into focus. In this review, we summarize advancements made over the last five years in immunotherapy use for EBV-positive cancers and in EBV biomarker identification to detect both EBV infection and biotherapy response.

Immune checkpoint inhibitors (ICIs) have transformed the treatment of several malignancies, but their efficacy and gastrointestinal (GI) immune-related adverse events (irAEs) vary considerably among patients. Growing evidence suggests that the gut microbiota and intestinal barrier integrity are associated with both therapeutic response and toxicity, although their causal contribution and clinical utility remain incompletely defined. Dysbiosis may disrupt epithelial homeostasis, increase intestinal permeability, and promote mucosal immune activation, potentially influencing antitumor immunity and susceptibility to ICI-induced colitis. Current biomarkers of intestinal permeability are limited by their indirect nature, lack of standardization, or poor spatial resolution. Probe-based confocal laser endomicroscopy (pCLE) enables real-time, in vivo visualization of epithelial abnormalities associated with barrier dysfunction, including fluorescein leakage, epithelial gaps, and cell shedding. In parallel, dietary and microbiota-directed interventions are being investigated as potential strategies to modulate intestinal homeostasis during ICI therapy, although evidence for their clinical benefit and effects on intestinal barrier integrity remains limited. This review summarizes current evidence linking the gut microbiota, intestinal barrier dysfunction, and cancer immunotherapy and discusses the potential role of pCLE as a candidate functional imaging tool in ICI-treated patients. We highlight current knowledge gaps and propose a translational framework integrating pCLE with microbiome profiling, circulating biomarkers, histopathology, and clinical outcomes to determine whether this approach can improve patient stratification and the early identification and monitoring of GI toxicity.

Cisplatin resistance remains a significant challenge in the effective treatment of breast cancer, underscoring the need for novel combination-based therapeutic strategies. Background: This study investigated the anticancer effects of ellagic acid (EA) and metformin (MET), both individually and in combination, against parental and cisplatin-resistant breast cancer models. To our knowledge, this is the first study to evaluate the EA-MET combination in the context of cisplatin resistance in breast cancer. Methods: The in vitro antiproliferative and apoptotic effects of EA and MET were assessed using MTT and caspase-3 assays in parental (EMT-6/P) and cisplatin-resistant (EMT-6/CPR) cells. An in vivo study was also conducted to evaluate the anti-tumor effects of the treatment combinations in mice bearing EMT-6/P or EMT-6/CPR tumors. Liver enzymes and creatinine levels were measured to assess potential hepatic and renal toxicity. Results: In vitro combination index analysis indicated a synergistic interaction between EA and MET in EMT-6/P cells (CI = 0.45) and a strong synergistic interaction in EMT-6/CPR cells (CI = 0.29) under the tested conditions. In vivo, the addition of the combination to cisplatin resulted in significant tumor size reductions of 73.83% and 56.25% in EMT-6/P and EMT-6/CPR bearing mice, respectively, along with tumor regressions of 66.6% and 50%, respectively. Conclusions: Thecombination of metformin and ellagic acid shows promise as a potential treatment for cisplatin-resistant breast cancer. Further research is needed to elucidate the precise anticancer mechanisms underlying this combination.

Background and Objectives: Drug repurposing provides an opportunity to identify anticancer activities among established pharmacological agents. Labetalol (LB), an α₁- and non-selective β-adrenergic receptor antagonist, has been insufficiently investigated in melanoma. This study evaluated the potential anti-melanoma activity of LB in A375 human melanoma cells, compared its effects with those observed in HaCaT immortalized non-tumoral keratinocytes, and investigated the cellular mechanisms associated with LB-induced cytotoxicity. Materials and Methods: A375 and HaCaT cells were exposed to 75-500 μM LB for 24 h. Cell viability and lysosomal dye retention were assessed using MTT and NRU assays. A DMSO-only concentration series (0.075-0.50% v/v) was additionally evaluated by MTT in both cell lines. Mitochondrial membrane potential, mitochondrial staining patterns, nuclear morphology, cytoskeletal organization, caspase-3/7 and caspase-9 activities, and plasma membrane integrity were evaluated using JC-1, MitoTracker Red CMXRos, immunofluorescence, luminescence-based caspase assays, and AO/PI staining. The acute irritation potential of 500 μM LB was assessed using the HET-CAM assay. Results: DMSO alone did not significantly reduce viability over the investigated concentration range in either cell line. LB reduced A375 cell viability in a concentration-dependent manner, with a 24 h IC₅₀ of 422.5 μM and a viability of 33.61% at 500 μM. Under the same experimental conditions, HaCaT viability remained at 89.01% at 500 μM, and an IC₅₀ was not reached within the investigated concentration range. At the highest concentration, neutral red uptake and the JC-1 aggregate/monomer ratio decreased to approximately 33% and 24% of the corresponding control values, respectively. The apoptotic index increased from approximately 3% in control cells to 31%, while caspase-3/7 and caspase-9 activities increased to approximately 482% and 324% of the control. Qualitative imaging demonstrated mitochondrial staining redistribution, cytoskeletal disorganization, apoptosis-associated morphology, and loss of plasma membrane integrity at higher concentrations. In the HET-CAM assay, 500 μM LB produced a mean irritation score of 0.71 ± 0.27, within the non-irritant range. Conclusions: LB displayed concentration-dependent in vitro cytotoxicity in A375 melanoma cells, whereas HaCaT keratinocytes showed limited changes under the investigated conditions. LB treatment was also associated with mitochondria-associated apoptotic signaling in A375 cells. These findings provide preliminary evidence supporting further investigation of LB within a melanoma-directed drug-repurposing strategy. Additional studies are required to establish receptor dependence, achievable local exposure, safety, and translational relevance.

Background and Objectives: Hereditary medullary thyroid carcinoma (hMTC) exhibits substantial clinical heterogeneity according to the underlying germline RET pathogenic variant. Although the germline RET M918T pathogenic variant is associated with aggressive disease, its associations with clinical outcomes have not been comprehensively quantified. We aimed to evaluate the associations between the M918T variant and adverse clinical outcomes in patients with hMTC. Materials and Methods: PubMed, Scopus, and Embase were searched from database inception to May 2026 in accordance with PRISMA 2020. Eligible studies compared patients with the germline RET M918T pathogenic variant with those harboring other germline RET pathogenic variants. Random-effects models were used to pool odds ratios (ORs) and 95% confidence intervals (CIs) for lymph node metastasis, metastatic disease, advanced-stage disease, and mortality. Risk of bias was assessed using the Quality in Prognosis Studies tool. The protocol was prospectively registered in PROSPERO (CRD420261377120). Results: Nine cohort studies involving 1485 participants were included, with outcome-specific sample sizes varying. Three studies had a low overall risk of bias and six had a moderate risk. The M918T variant was associated with increased odds of lymph node metastasis (OR 7.86, 95% CI 2.58-23.94), metastatic disease (OR 6.50, 95% CI 3.72-11.37), advanced-stage disease (OR 4.88, 95% CI 2.30-10.33), and mortality (OR 7.32, 95% CI 3.14-17.10). The association was stronger for disease-specific than all-cause mortality, although the subgroup difference was not statistically significant. Conclusions: The germline RET M918T pathogenic variant was associated with adverse clinical outcomes compared with other germline RET pathogenic variants. However, heterogeneous comparator groups and residual confounding preclude causal interpretation.

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.

The inequities observed during the COVID-19 pandemic were not an accident. They reflect deeper patterns of injustice already embedded in rules, financing models and power arrangements in global health governance. This paper argues that the paradigm of ethical health sovereignty offers a moral countermodel to the dependency shaping global health relations. It examines how sovereignty, solidarity and justice are being reinterpreted after the pandemic by drawing on the WHO Pandemic Agreement (A78/10, 2025) and Africa's regional responses through the African Union and Africa Centres for Disease Control and Prevention. The Agreement represents a partial moral advance by acknowledging equity and shared responsibility while still leaving hierarchy intact through voluntarism and sovereignty-based limits. In contrast, Africa's pooled procurement, regulatory harmonisation and coordinated diplomacy show solidarity as shared governance rather than charity. The paper concludes that global health equity requires redesigning governance so that fairness is built into institutions and sovereignty is understood as shared and cooperative decision-making.

To describe real-world management of connective tissue disease-associated interstitial lung disease (CTD-ILD) and explore associations between progressive pulmonary fibrosis (PPF) onset and clinical outcomes. This international, retrospective cohort included adults with rheumatoid arthritis (RA), systemic sclerosis (SSc), mixed connective tissue disease, and other CTD with associated ILD. PPF was identified using INBUILD and/or ATS/ERS/JRS/ALAT criteria applied in routine care. Analyses were descriptive and exploratory; time-to-event methods assessed selected outcomes and factors associated with PPF onset. Among 357 patients (mean age 61.6 years; 58% female), SSc-ILD (31%) and RA-ILD (29%) were most common. At ILD diagnosis, 21.6% had no respiratory symptoms. During a mean follow-up of 60.5 months, 147 patients (41.2%) met the PPF criteria, at a median of 30.6 months after CTD-ILD diagnosis. Following PPF onset, the most frequently prescribed therapies were corticosteroids (72.8%), mycophenolate mofetil (52.4%), and antifibrotics (51.0%). Lung function data were available for 37.8% at diagnosis and 53.7% at year 5. PPF was associated with greater observed lung function decline compared to non-PPF patients. ILD-related hospitalizations was numerically more frequent within PPF patients (37.4% vs. 28.6%), but the difference was not statistically significant (P = 0.078). Among patients with PPF, earlier versus later onset, defined by a subtype-specific median split, was associated with poorer observed survival (P < 0.001). In this retrospective cohort, PPF was observed frequently in CTD-ILD patients, particularly those with SSc-ILD, and was associated with greater lung function decline and higher healthcare utilisation. Earlier PPF onset was associated with higher mortality risk, but missing lung function data, surveillance differences, time-related bias, and residual confounding limit causal interpretation. Prospective studies using harmonised PPF adjudication and time-dependent analyses are needed.

This study investigated whether umbilical subcutaneous fat thickness (USFT), measured opportunistically on abdominal computed tomography (CT) images obtained for clinical indications, was associated with perioperative obstructive sleep apnea (OSA) risk assessed using the STOP-BANG questionnaire. In this cross-sectional observational study, 64 adult participants completed the STOP-BANG questionnaire, and USFT was measured on existing abdominal CT images using a standardized protocol. Associations between USFT and continuous variables were assessed using Spearman correlation, while comparisons across STOP-BANG risk categories were performed using the Kruskal-Wallis test. Exploratory logistic regression was used to assess the association between USFT and high STOP-BANG risk after adjustment for age. No significant correlation was observed between USFT and STOP-BANG score (ρ = 0.142, p = 0.264), and USFT did not differ significantly across STOP-BANG risk categories (p = 0.677). USFT was significantly higher among participants reporting snoring (p = 0.026) and showed positive correlations with body mass index (BMI; ρ = 0.663, p < 0.001) and neck circumference (ρ = 0.544, p < 0.001). USFT was not significantly associated with high STOP-BANG risk after adjustment for age. Overall, CT-measured USFT was not associated with STOP-BANG-based OSA risk in this study. Larger studies incorporating polysomnography (PSG)-confirmed OSA and adequately powered multivariable analyses are needed to determine the potential role of CT-derived adiposity measures in perioperative OSA risk assessment.