Search Results (304)

Background: Platinum-based chemotherapy, including cisplatin and carboplatin, is widely used to treat various cancers, including ovarian cancer. However, its clinical application is limited by dose-limiting toxicities and resistance, with a poor 5-year overall survival rate for ovarian cancer (35–40%). In this study, we used ionisable lipids and developed pH-responsive lipid nanoparticles (LNPs) to address platinum-resistance in ovarian carcinoma. Methods: Cisplatin was loaded into three LNP systems containing monoolein (MO) and synthetic cationic ionisable lipids (OE-Mo, OA-Py, and OA-Pi) dispersed in Pluronic F-127 with 0.9% NaCl. Cisplatin-loaded LNPs (Cis-OE-Mo-NP, Cis-OA-Py-NP, and Cis-OA-Pi-NP) were characterised for size, zeta potential, and internal mesophase structure. Encapsulation efficiencies were determined via HPLC after removing free drug by ultrafiltration. In vivo efficacy was tested using cisplatin-resistant human patient-derived xenograft (PDX) models. Results: The LNPs were well dispersed with particle size of 219–250 nm and a drug loading of ~1.2 mg/mL. Encapsulation efficiencies were 62%, 59%, and 64%, for Cis-OE-Mo-NP, Cis-OA-Py-NP, and Cis-OA-Pi-NP, respectively. Small angle X-ray scattering (SAXS) results showed that the LNPs are pH responsive with structural transitions from a cubic to a hexagonal phase at an acidic pH. Among the tested formulations, Cis-OA-Py-NP resulted in the most significant reduction in tumour volume by ~60% compared to treatment with cisplatin alone. However, they also showed significant toxicity, including >10% weight loss and gross lung and kidney damage, as confirmed by histology. Conclusions: These findings highlight the potential of Cis-OA-Py-NP in reducing tumour volume but underscore the need for further optimisation to improve safety and therapeutic applicability. Full article

Breast cancer surgery has evolved from radical procedures to increasingly individualized and less invasive approaches. This narrative review contextualizes this evolution, synthesizes current evidence supporting surgical de-escalation, and examines emerging strategies that may further reduce the need for surgery. The manuscript is based on a structured appraisal of PubMed/MEDLINE literature and major international guidelines, prioritizing randomized trials, prospective studies, and consensus statements. Contemporary practice is characterized by progressive reduction in both breast and axillary surgery, enabled by advances in tumour biology, neoadjuvant systemic therapy, sentinel node strategies, and oncoplastic techniques. Emerging approaches—including selective omission of axillary surgery, targeted axillary dissection, and investigational strategies aiming at omission of breast surgery in exceptional responders—highlight a shift toward response-adapted and biology-driven care. While technological innovations such as robotic surgery and intraoperative radiotherapy may influence surgical practice, their role in true de-escalation remains limited or context-dependent. Overall, the field is moving toward minimizing surgical burden without compromising oncological safety, with future progress likely driven by improved patient selection, imaging, and integration of systemic therapy response. Full article

Background/Objectives: Accurate intraoperative tumour localisation remains challenging in minimally invasive colorectal surgery, where conventional tattooing methods suffer from marker migration, tissue diffusion, and potential allergic reactions. Radio frequency identification (RFID) technology offers a promising alternative through implantable passive transponders detectable via electromagnetic coupling, eliminating ionising radiation exposure. Methods: This preclinical feasibility study evaluated three RFID frequency bands for surgical tumour marking: 134 kHz (low frequency, LF), 13.56 MHz (high frequency, HF), and 868 MHz (ultra-high frequency, UHF). Finite element electromagnetic simulations characterised antenna field distributions, while experimental validation employed glass-encapsulated transponders in air and tissue-simulating saline (0.9% NaCl, σ ≈ 1.5 S/m). Detection ranges were measured across 28 angular configurations with expanded measurement uncertainty (k = 2) ranging from ±0.9 to ±3.2 mm. Results: Maximum detection distances in air were 25.0 ± 0.9 mm (LF), 23.0 ± 1.1 mm (HF), and 68.0 ± 2.3 mm (UHF). In saline, ranges decreased to 22.5 ± 1.0 mm, 20.7 ± 1.2 mm, and 18.0 ± 1.4 mm, respectively, demonstrating tissue attenuation of 10% at LF/HF vs. 74% at UHF. Angular characterisation revealed 64–70% range reduction at orthogonal orientation for LF/HF systems. Computational–experimental correlation yielded r² = 0.975 across 154 paired observations. Conclusions: The 13.56 MHz HF band emerges as the optimal candidate for clinical translation, offering adequate tissue penetration (20.7 mm), superior antenna miniaturisation potential (5 mm diameter), established biocompatibility pathways, and mature near-field communication ecosystem support. Future development should address angular sensitivity through multi-axis antenna configurations and validation in anatomically realistic tissue phantoms. This study establishes the electromagnetic evidence base for clinical system development; translation to clinical practice requires sequential preclinical and clinical evaluation. Full article

Background: Organised colorectal cancer (CRC) screening programmes have been widely implemented across Europe; however, robust population-level evaluations of their real-world effectiveness, particularly for programmes based exclusively on faecal immunochemical testing (FIT), remain limited. The Galician CRC screening programme was progressively implemented between 2013 and 2019. Methods: We conducted a population-based ecological time-series study using data from the Galician Tumour Registry (ICD-10 C18–C21) for 2015–2023. Age-standardised mortality (ASMR) and incidence (ASIR) rates were analysed. They were calculated using the direct standardisation method, applying age-specific rates to the 2013 European Standard Population (ESP2013). Structural changes associated with programme implementation were evaluated using interrupted time-series (ITS) models, estimating annual percent change (APC) before and after implementation and the net change in slope (ΔAPC). Absolute and relative changes in ASMR and ASIR were calculated by comparing 2015–2017 and 2019–2023. Analyses were performed for the overall population and for individuals aged 50–69 years. Results: Between 2015 and 2023, overall CRC mortality declined significantly (APC −3.00%; 95% CI −3.37 to −2.63). ITS analysis demonstrated a marked modification of mortality trajectories following programme implementation. Mortality shifted from an increasing pre-implementation slope (APC +13.70%; 95% CI 10.12, 17.39) to a significant annual decline post-implementation (APC −3.62%; 95% CI −4.47, −2.76), yielding a ΔAPC of −17.32. In individuals aged 50–69 years, the structural change was more pronounced (ΔAPC −19.88), with post-implementation mortality decreasing by −8.08% annually (95% CI −10.43, −5.66). Incidence showed a comparable structural modification. Overall APC changed from +15.26% (95% CI 5.48, 25.95) before implementation to −2.48% (95% CI −5.29, 0.41) afterwards (ΔAPC −17.74). In the screening-eligible population, APC shifted from +21.32% (95% CI 4.60, 40.71) to −3.74% (95% CI −7.62, 0.30), corresponding to a ΔAPC of −25.06. Descriptively, ASMR declined from 41.92 to 35.91 per 100,000 (−14.33%), and ASIR from 98.37 to 85.16 per 100,000 (−13.42%) between 2015 and 2017 and between 2019 and 2023. Relative reductions were larger in individuals aged 50–69 years and were more pronounced for colon cancer than for rectal cancer. Conclusions: Implementation of an organised FIT-based screening programme was associated with a structural change in CRC mortality and incidence trends, particularly among individuals aged 50–69 years. Full article

Population aging has markedly increased the burden of cancer in older adults, in whom frailty, sarcopenia, and reduced physiological reserve limit tolerance to treatment and worsen clinical outcomes. Aging is accompanied by progressive functional decline and by biological processes such as cellular senescence, characterized by irreversible cell cycle arrest, chronic low-grade inflammation, and impaired immune surveillance. The accumulation of senescent cells and the persistence of a senescence-associated secretory phenotype contribute to tissue dysfunction and generate a microenvironment that favors tumor initiation and progression. Physical exercise has been associated with attenuation of inflammation, improvements in metabolic and immune function, and with lower levels of senescence-related biomarkers. Although aerobic exercise has been extensively studied in this setting, resistance training holds relevance for older adults due to its capacity to counteract sarcopenia, preserve muscle strength and power, and sustain functional independence. Structured and periodized approaches to resistance exercise may further enhance these benefits by delivering targeted stimuli aligned with age-related physiological deficits. Block strength training (BST), a periodized model that concentrates training adaptations into sequential phases of maximal strength, power, and muscular endurance, has demonstrated consistent improvements in functional performance and reductions in frailty risk in community-dwelling older adults. BST improves physical function. It may also influence biological processes related to aging and cancer; however, mechanistic evidence specific to BST remains to be established. We hypothesized that the exercise in block as a targeted, a structured and physiologically grounded resistance training intervention highlights the potential of BST to promote functional aging and healthy. In the case of cancer biology, and the environment near to tumour, the relationship between aging mechanisms in older adults and controlled exercise effects are currently in advance, but mechanistic trials are still lacking. Finally, we propose a novel training method, structured and personalized, that could impact different clinical outcomes in older patients with cancer. Full article

Introduction: Evidence on the use of dopamine agonists (DAs) for managing residual or recurrent non-functioning pituitary adenomas (NFPAs) is limited. We aim to evaluate the use of cabergoline (CAB) for NFPAs. Methods: A retrospective cohort study was conducted at a single UK centre, between November 2011 and December 2025. Twenty-six patients were identified. Ten patients were excluded due to CAB intolerance or discontinuation (n = 5), insufficient data (n = 4), or invalid scan due to patient movement (n = 1). The remaining 16 patients (mean age 68.9 ± 4 years (range 42–89 years old), 7/16 females) were included. CAB was initiated in cases where surgery or radiotherapy were not appropriate (e.g., due to age and/or comorbidities, or patient choice). Radiological response was assessed using at least two scans separated by a minimum interval of six months. Tumour shrinkage was defined as a reduction in volume of 20% or more, growth as an increase of 20% or more, and stabilisation as interval change of less than 20%. Results: Overall, tumour shrinkage was observed in 7/16 (43.8%) patients, stabilisation in the remaining 9/16 (56.3%) patients, over 503 ± 51 days (range of 117–934 days) (from the date of CAB initiation to latest MRI scan). There was a statistically significant reduction in tumour volume (p = 0.0335). In five patients with documented tumour growth prior to CAB initiation, growth rates retarded or reversed post-CAB initiation. Conclusions: Our findings in this small cohort potentially suggests that cabergoline can retard, arrest, or even reverse tumour growth in selected patients with NFPAs. Our review also highlights ongoing uncertainty regarding optimal dosing, approaches to dose up-titration, follow-up imaging intervals, and objective criteria for defining radiological response. Our results may provide a proof of concept for future, larger-scale prospective studies and controlled trials to validate the conclusions drawn. Full article

Ethnopharmacological relevance. Withania somnifera (L.) Dunal, widely used in traditional medical systems such as Ayurveda, Unani, and Middle Eastern folk medicine, is valued for its adaptogenic, anti-inflammatory, neuroprotective, antimicrobial, and anticancer properties. These activities are primarily attributed to withanolides, with Withaferin A recognized as one of the most bioactive constituents. Although traditional preparations often rely on the root, leaf use provides a more sustainable alternative and may yield significant quantities of active metabolites. Identifying efficient, modern extraction technologies that can enhance the recovery of bioactive compounds from leaves is essential for developing effective, standardized ethnopharmacological formulations. Materials and methods. Plants of W. somnifera grown from seeds were subjected to different environmental conditions (control, drought, cold, yeast extract treatment). Leaves were extracted using Pressurized Cyclic Solid–Liquid Extraction (PCSLE) with hydroalcoholic solvents and compared with conventional infusion of dried leaves. Extracts were fractionated with solvents of varying polarity and analyzed by TLC, HPLC, and NMR for quantification of Withaferin A. Expression levels of key withanolide-biosynthetic genes (CAS, SMT1, DWARF1, CYP71, CYP76) were assessed using qRT-PCR. Antimicrobial activity of pure Withaferin A, aqueous extract, and hydroalcoholic PCSLE extract was evaluated through MIC and MBC assays against Gram-positive and Gram-negative strains. Cytotoxic activity was measured via MTT assays in six human cancer cell lines after 3, 6, and 24 h of treatment. Results. PCSLE yielded substantially higher levels of Withaferin A than traditional infusion, especially in medium-polarity fractions (chloroform and ethyl acetate), with concentrations reaching 0.70% in fresh leaf mass (4.8% dry weight), compared to 0.11% obtained by infusion. Gene expression analysis revealed that 24-week-old plants exhibited the highest transcription of withanolide-biosynthetic genes, and drought stress significantly upregulated CAS, SMT1, DWARF1, CYP71, and CYP716, indicating enhanced metabolic flux toward withanolide production. Hydroalcoholic PCSLE extracts showed broad-spectrum antimicrobial activity, with MIC and MBC values comparable to pure Withaferin A and demonstrating bactericidal effects against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes. The aqueous extract showed activity only against Gram-positive strains. Cytotoxicity assays demonstrated an optimistic, dose-dependent reduction in cell viability across all tumour cell lines treated with the hydroalcoholic PCSLE extract, closely mirroring the activity of pure Withaferin A and consistently exceeding the effect of the aqueous extract. IC50 values confirmed the high bioactive content of PCSLE extracts and suggested mechanisms like those known for Withaferin A. Conclusions. PCSLE proved to be a highly efficient extraction technology for obtaining leaf extracts rich in Withaferin A, outperforming conventional extraction methods while exploiting sustainable plant tissue. Developmental stage and drought stress significantly modulated the expression of genes involved in withanolide biosynthesis, highlighting agronomic strategies capable of enhancing metabolite production. Hydroalcoholic PCSLE extracts exhibited antimicrobial and cytotoxic activities comparable to pure Withaferin A, supporting their relevance as promising therapeutic candidates. These findings advocate for the use of W. somnifera leaves as a sustainable source of bioactive compounds and demonstrate that advanced extraction technologies can contribute to the development of innovative ethnopharmacological preparations for antimicrobial and anticancer applications. Full article

Background: Exercise modulates the immune system and may enhance anti-cancer activity, offering potential synergy with cancer immunotherapy. Tumours with low immune cell infiltration (“cold” tumours) often respond poorly to immunotherapy and are associated with poor prognosis. Here, we demonstrate that exercise can reshape the immune landscape of tumours across the cold spectrum. Methods: C57BL/6 mice underwent orthotopic implantation of PANC02 (murine pancreatic adenocarcinoma) cells and BALB/c mice underwent intraperitoneal injections of AB-1 (murine mesothelioma) cells. Mice were then divided into groups; exercise with anti-Programmed Cell Death Protein 1 (PD-1), exercise with isotype, no exercise with anti-PD-1 and no exercise with isotype. Treadmill-running was performed for 20 min/day, 4 days/week at a speed of 12 metres/minute. Resistance training consisted of hanging upside down on a wire-mesh screen for 1 min 2 days/week. Flow cytometry was used to measure TME immune populations. Tumour and liver samples were harvested, paraffin wax-embedded/sectioned and analysed using SlideViewer 2.9.0™. A total of 22 healthy volunteers underwent a single bout of high-intensity interval cycling. Blood was collected pre- and post-exercise. Flow cytometry was used to measure leucocyte subpopulations. MSTO-211H (mesothelioma) and PANC-1 (pancreatic cancer) cells were cultured with pre- and post-exercise serum, with/without HSV1716, and viability determined using alamarBlue^®. PANC-1 apoptosis and migration were assessed using caspase-3/7 and scratch assays, respectively. Results: In an orthotopic pancreatic cancer mouse model, combining exercise with immunotherapy significantly increased tumour necrosis and reduced metastatic potential. In both pancreatic cancer and mesothelioma models, this combination remodelled the tumour microenvironment, enhancing cytotoxic CD8⁺ T cell infiltration, upregulating Programmed Cell Death Protein 1 (PD-1), and reducing Myeloid-Derived Suppressor Cells and regulatory T cells (Tregs). Complementary human studies revealed an acute systemic release of Natural Killer cells and a reduction in Tregs following high-intensity interval exercise in healthy volunteers. Moreover, exercise-conditioned serum from these participants exerted anti-cancer effects on pancreatic cancer and mesothelioma cell lines. Conclusions: Altogether, these findings highlight exercise as a promising adjunct to immunotherapy for poorly immunogenic cancers such as pancreatic cancer and mesothelioma. Full article

Chronic rhinosinusitis (CRS) is a persistent inflammatory disorder of the nasal and paranasal mucosa, typically attributed to local infection or anatomical obstruction. However, recent evidence suggests that CRS may also reflect systemic inflammatory dysregulation influenced by the gut microbiome, establishing a potential ‘gut–sinus axis’. This systematic review aims to synthesise current evidence linking gut microbiome alterations to the pathogenesis and clinical course of CRS and to explore emerging therapeutic strategies targeting this axis. Five databases were comprehensively searched for studies published between January 2000 and October 2025. Data were extracted and evaluated for quality using the JBI and SYRCLE tools. A total of 441 records were retrieved, of which 20 studies met the inclusion criteria. Human studies consistently showed gut dysbiosis in CRS, characterised by reductions in Roseburia, Bifidobacterium, Faecalibacterium and Akkermansia species. These microbial shifts correlated with increased levels of systemic cytokines, such as interleukin-6, interleukin-17 and tumour necrosis factor-α, and disease severity. Animal and interventional studies confirmed that high-fibre diets and short-chain fatty acid (SCFA) supplementation modified airway inflammation, whereas antibiotic-induced dysbiosis exacerbated it. Current evidence substantiates a gut–sinus axis mediated by immune, metabolic and neuroendocrine pathways. Dysbiosis-driven reductions in SCFA-producing bacteria appear central to systemic pro-inflammatory signalling implicated in CRS. Full article

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis in which inflammation plays a central pathogenic role. Endovascular revascularisation may transiently amplify inflammation due to vascular injury, but successful restoration of perfusion could reduce inflammatory burden over time. This prospective, observational, single-centre pilot study aimed to characterise the temporal dynamics of inflammatory biomarkers during the first three months following endovascular revascularisation of the lower limbs. Consecutive patients with PAD who underwent successful percutaneous femoropopliteal revascularisation at the Department of Vascular Diseases, University Medical Centre Ljubljana, Slovenia, between January 2022 and January 2024 were enrolled. Venous blood was obtained one hour before the procedure, one day afterwards, and again approximately three months later. Concentrations of high-sensitivity C-reactive protein (hsCRP), interleukins (IL-6, IL-8, IL-10), and tumour necrosis factor-alpha (TNFα) were measured. Temporal changes in biomarker levels were analysed using Friedman and Wilcoxon signed-rank tests where appropriate. Clinical outcomes were evaluated at three months and one year post-procedure and were further verified through patient telephone interviews. The observed outcomes were worsening of PAD symptoms, newly diagnosed angina pectoris, myocardial infarction, stroke, transient ischaemic attack (TIA), or death. Twenty-eight patients (median age 69 years) completed all blood samplings. IL-6 concentrations increased significantly one day after revascularisation and decreased below preprocedural levels at three months, with significant differences observed across all time points (p < 0.001). IL-10 and TNFα decreased significantly between the postprocedural and three-month measurements (p = 0.012 and p = 0.016, respectively), but not below preprocedural levels. No significant changes were observed in hsCRP or IL-8. Over a median follow-up of 732 days, 9 patients experienced worsening PAD symptoms in the treated limb, 2 developed new-onset PAD symptoms in the contralateral limb, and 1 was newly diagnosed with angina pectoris. No myocardial infarction, stroke, TIA, or death occurred. To conclude, endovascular femoropopliteal revascularisation induces distinct short-term inflammatory responses, with IL-6 showing the most pronounced peri-procedural dynamics. The observed reductions in some inflammatory biomarker levels at three months suggest that restored limb perfusion may modulate systemic inflammation. Larger studies are warranted to clarify the prognostic relevance of these biomarkers. Full article

Background: Aberrant signalling through the urokinase-type plasminogen activator receptor (uPAR) is a key driver of tumour invasion and progression in prostate cancer, yet linking molecular-level perturbations to emergent spatial invasion phenotypes remains challenging. Methods: In this study, we developed a multiscale in silico framework combining molecular docking, mechanistic ordinary differential equation (ODE) modelling, and agent-based modelling (ABM) to investigate uPAR-driven invasion dynamics. Results: Molecular docking and MM-GBSA analyses were used to prioritise caffeic acid phenethyl ester (CAPE) as a candidate uPA/uPAR modulator, while uPAR inhibition was implemented mechanistically at the signalling level within the ODE model rather than through direct energetic parametrisation. Steady-state signalling outputs were mapped to effective proliferation and motility rates, which served as inputs to a spatial ABM of tumour invasion. The integrated simulations showed that uPAR inhibition results in statistically significant reductions in spatial invasion and tumour growth compared with baseline conditions, whereas enhanced uPA signalling produced only modest, non-significant trends. Conclusions: These findings demonstrate how subtle intracellular signalling perturbations can translate into pronounced population-level invasion phenotypes when embedded in a spatial context. Overall, the proposed digital-twin framework provides a coherent and extensible approach for connecting molecular prioritisation with quantitative predictions of tumour invasion behaviour in prostate cancer. Full article

Background/Objectives: Transurethral Laser Ablation (TULA) is fast evolving as a surgical procedure, especially for small or recurrent bladder tumours. It offers a safe alternative for patients who are unsuitable for general anaesthetic (GA) or who cannot obtain timely pre-operative assessments for Transurethral Resection of Bladder Tumour (TURBT). Patients are identified for TULA in ‘Bladder Cancer Surgery Planning Meetings’ (BSPMs) and this significantly reduces their cancer waiting time (CWT). Its effectiveness as a diagnostic and therapeutic tool, including its complications and costs, has been assessed. Methods: All TULA procedures performed at the Trust were studied in two cycles. The first between August 2023 and November 2024, prior to initial audit, and then up to September 2025. Case notes, operation notes, and multidisciplinary team (MDT) outcomes were retrospectively reviewed. All procedures were performed with a flexible cystoscope and ‘cold cup’ biopsies with further ablation and haemostasis using a 1470 nm diode laser at 4 watts and 400 µm laser fibre. Patients were identified for TULA based on tumour size, location, and fitness for general anaesthetic. Results: During the study period, 95 TULA procedures were performed with a follow-up period between 4 weeks and 1 year. A total of 86 patients (90.5%) had local anaesthetic (LA) ± intravenous (IV) sedation, with 50% having LA alone in the second phase of the study; of the remaining patients, 8 had GA (8.4%) and 1 (1.1%) had spinal anaesthetic. None of the cases were considered to have missed a significant finding. One case (1.1%) was complicated, with ongoing bleeding requiring bladder washout under GA. BSPMs were introduced in July 2024 and audited in the first phase of this study. A total of 24 (39%) of patients were identified for TULA. Of those, 7 (29%) were originally scheduled for TURBT and were having difficulties obtaining pre-operative assessment (POA) clearance. Cost figures were provided by the hospital’s accountants. Conclusions: TULA has been implemented with a low complication rate and appropriate sampling. In the next phase, TULA will be rolled out to an outpatient setting, performed exclusively under LA. This will lead to a significant cost reduction. Full article

Background: In triple-negative breast cancer (TNBC), the addition of immunotherapy has significantly improved outcomes. Immune-related adverse events (irAEs) can be accelerated in patients with pre-existing autoimmune (AI) conditions. The treatment-response standardized protocol used in clinical care raises concerns about the need for right-sizing strategies. As the use of immunotherapy expands, recognizing toxicity from recurrence and optimizing response-adapted approaches are essential to balance cure with quality of survival. Case Presentation: A 38-year-old pregnant woman with a distant history of uveitis and psoriasis was discovered to have pregnancy-associated TNBC. Postnatally, she was treated with neoadjuvant chemotherapy and pembrolizumab, followed by wire-guided left breast wide local excision and sentinel lymph node biopsy of the left axilla. After surgery, residual cancer was noted. She continued adjuvant pembrolizumab and adjuvant radiotherapy 40.05 Gy/15 fr to the breast and nodes, followed by a 13.35 Gy/5 fr boost to the tumour bed (breast). Despite a persistent residual tumour, pembrolizumab was continued as per protocol in a response-agnostic manner. At the end of one year of adjuvant pembrolizumab, she developed progressive numbness and weakness in the ipsilateral arm, initially raising suspicion for local recurrence. Comprehensive MRI and PET-CT imaging did not identify recurrent tumour or new metastatic disease. Electromyography confirmed a lower-trunk brachial plexopathy without a structural cause. An immune-mediated process was diagnosed by a process of elimination. Despite treatment with 1st-line high-dose corticosteroids and 2nd-line intravenous immunoglobulin (IVIG), improvement was limited. Therapeutic plasmapheresis led to marked functional recovery and symptom resolution 20 months later. Discussion: Four main challenges are identified: (1) the diagnostic difficulty in identifying local recurrence or radiation injury from immune-related neuropathy; (2) the emerging therapeutic role of plasmapheresis in steroid-refractory irAEs; (3) the possible inconsistencies between rare toxicities observed in clinical trials vs. clinical practice; and (4) the limitations in response in adjuvant therapy, particularly in patients with coexisting AI conditions. Conclusions: Early recognition and accurate distinction from tumour recurrence, as well as support for plasmapheresis as a potential option in steroid-refractory presentations, have been shown to improve patient survival and symptom reduction. With increasing use of immunotherapy, real-world toxicity data, predictive biomarkers, and personalized treatment strategies are urgently needed to balance cure with long-term functional outcomes. Full article

Tight junction (TJ) proteins, such as Junctional Adhesion Molecule-A (JAM-A), claudins, and occludin, play increasingly recognized roles in cancer biology beyond their structural functions, influencing tumour proliferation, invasion, metastasis and therapy resistance. Understanding how these proteins modulate tumour progression in vivo requires models that are both physiologically relevant and ethically viable. The chick chorioallantoic membrane (CAM) xenograft model has emerged as a powerful and cost-effective in vivo system that aligns with the 3Rs (replacement, reduction, and refinement), offering unique advantages such as vascular accessibility, rapid tumour growth kinetics and immunotolerance. This review explores how the CAM model can be leveraged to study the mechanistic role of TJ proteins in tumour–stroma interactions, angiogenesis, extracellular matrix (ECM) remodelling and mechanotransduction, including the YAP/TAZ pathway. While limitations remain, particularly with respect to immune modelling and long-term studies, recent advances in imaging, genetic manipulation and integration of patient-derived xenografts (PDXs) are expanding the model’s translational relevance. Standardizing methodologies and embracing new molecular tools will further elevate the utility of this approach as a complementary platform to traditional rodent models, with significant promise for TJ-focused cancer research and therapeutic innovation. Full article

Background: Obesity-associated inflammation arises from adipose dysfunction and intestinal disturbances, including altered microbiota and short-chain fatty acid (SCFA) metabolism. Beans (Phaseolus vulgaris) are rich in non-digestible carbohydrates and polyphenols, but whether kidney bean varieties differing in seed coat colour exert distinct effects on inflammation in obesity remains unclear. Objective: To determine whether supplementation of an obesogenic high-fat (HF) diet with white or dark red kidney beans modulates gut microbiota, SCFAs, and intestinal, systemic, and neuroinflammatory outcomes. Methods: Male C57Bl/6N mice (n = 12/group) were fed a basal diet (BD; modified AIN-93G), an HF diet (60% kcal from fat), or an HF diet supplemented with 15% cooked white (HF + WK) or dark red kidney beans (HF + DK) for nine weeks. Outcomes included cecal microbiota composition, predicted KEGG pathways with taxon contributors mapped with BURRITO (a tool for linking predicted microbial functions to contributing taxa), and SCFA-related pathways; cecal and fecal SCFA concentrations; colon histomorphometry and expression of gut barrier junction and inflammatory genes; serum cytokines and adipose hormones; and hippocampal inflammatory and barrier genes. Results: Mice consuming bean-supplemented HF diets had higher microbial diversity, enrichment of SCFA-producing taxa (Prevotella, Lactobacillus, Muribaculaceae), and lower obesity-associated genera versus HF alone (Mucispirillum, rc4-4). Bean diets elevated cecal acetate and butyrate concentrations, which aligned with increases in predicted acetate kinase in both bean groups versus HF and BD, and butyrate kinase in HF + DK versus BD. Bean supplementation attenuated HF-induced reduction of goblet cells and systemic interleukin (IL)-10. The HF + DK group had lower colonic tumour necrosis factor (TNF)-α and partially attenuated hippocampal IL-6. SCFAs were inversely associated with systemic and neuroinflammatory markers in HF + DK mice. Conclusions: Kidney bean supplementation mitigated HF diet-induced intestinal, systemic, and neuroinflammatory disturbances in male mice, with microbiota and SCFA modulation. Further, dark red beans exerted stronger anti-inflammatory effects, highlighting the role of seed coat colour in bean-mediated obesity outcomes. Full article