Search Results (20,409)

Solid-organ transplant (SOT) recipients have an increased risk of malignancies and poor oncological prognosis compared to the general population. A central reason for both is that various factors unique to transplantation coalesce to dampen anti-tumor immunity. These include graft or immunosuppressive therapy-related T-cell dysfunction, microenvironmental changes in grafts due to ischemic/reperfusion injuries peri-transplant and comorbidities such as metabolic syndrome. Both innate and adaptive immunity are heavily implicated in cytotoxicity effected by systemic therapeutic agents, not just immune checkpoint inhibitors (ICIs) but also conventional chemotherapy and targeted therapies. Hence, impaired anti-tumor immunity may also affect the treatment efficacy of these agents. Generally, clinical data for systemic therapies in transplant recipients is constrained to retrospective and heterogenous case reports and series only, with a low level of evidence and significant risk of bias. For ICIs, the efficacy in SOT recipients is relatively well preserved in cutaneous squamous cell carcinomas but seems diminished in other tumor types compared to non-transplant recipients. Data for other agents are limited, but the efficacies of chemotherapy in SOT recipients with colorectal cancer and sorafenib/lenvatinib in LT recipients with recurrent hepatocellular carcinoma seem preserved. Given the prevailing trend of broadening the use of transplantation in patients with cancer, further clinical and translational studies to develop strategies to enhance anti-tumor immunity while ensuring graft preservation are urgently needed. Full article

Ovarian cancer (OC) remains one of the leading causes of gynecologic cancer mortality, largely due to late diagnosis, frequent relapse, and the emergence of chemoresistance. An important but often-overlooked contributor to treatment failure is the heterogeneous penetration of anticancer drugs within tumors. Structural and biochemical barriers—including abnormal vasculature, elevated interstitial pressure, dense extracellular matrix, drug efflux transporters, and malignant ascites—generate steep intratumoral concentration gradients that conventional preclinical models fail to capture. As a result, systemic pharmacokinetic measurements frequently provide limited insight into tumor-level drug exposure. Patient-derived organoids (PDOs) have emerged as physiologically relevant 3D models that preserve the genetic, architectural, and functional characteristics of the original tumor. These systems enable controlled investigation of pharmacokinetic and pharmacodynamic processes, including drug penetration, metabolism, retention, and exposure–response relationships. Adding cell-free malignant ascites supernatant enhances PDOs’ ability to mimic the metastatic peritoneal microenvironment of OC. This review discusses recent advances in PDO technologies and examines how PDO-derived data can inform intratumoral pharmacokinetics and dosing strategies using physiologically based pharmacokinetic modeling and in vitro–in vivo extrapolation. Emerging hybrid platforms, including organoid-on-chip systems, vascularized co-cultures, and multi-omics integration, are crucial to improve translational prediction and support precision oncology. Full article

Dihydroartemisinin (DHA), the active metabolite of artemisinin derivatives, is a clinically established antimalarial agent that has recently gained significant attention for its anticancer properties. This review systematically examines the molecular mechanisms underlying DHA’s antitumor effects and explores innovative strategies to enhance its bioavailability and therapeutic efficacy. DHA demonstrates substantial potential in combination therapies with conventional clinical agents, with its broad anticancer applications being strongly supported by both preclinical and clinical evidence. Furthermore, this article outlines future research directions, discusses challenges in clinical translation, and summarizes current scientific approaches addressing these limitations. Collectively, this review highlights DHA’s promising role in cancer treatment and provides a foundation for developing improved therapeutic strategies. Full article

Colorectal cancer (CRC) remains a leading cause of cancer mortality, yet no systematic effort has linked druggable CRC driver genes to downstream ion channel effectors. We integrated differential expression analysis, weighted gene co-expression network analysis (WGCNA), and protein–protein interaction (PPI) network pharmacology to identify CRC hub genes and their ion channel connections, validated by dual single-cell perturbation approaches: variational graph autoencoder-based virtual knockout (VGAE-KO) and experimental HCT116 CRISPRi Perturb-seq (6 genes, 8445 cells). WGCNA identified 100 hub genes spanning three functional programs. Ribosomal proteins link to K${}^{+}$ channels (RPS21→KCNQ2, targetable by EMA-approved ataluren, passed dual validation at 97.8th–98.7th percentile). RNA processing genes connect to Cl${}^{-}$ channels (LSM7→CLIC1, strongest signal at 99.8th–99.4th percentile). Immune checkpoint receptors (LAG3, CD27) connect via PPI intermediates to Ca${}^{2+}$ and K${}^{+}$ channels, targetable by relatlimab (FDA-approved) and varlilumab (Phase 2). This work maps previously unknown links between CRC driver genes and ion channel regulation, with the ataluren-RPS21-KCNQ2 axis ready for pharmacological testing. Full article

Traditional cancer therapies such as surgery, chemotherapy, and antibody-based treatments often face significant barriers, including systemic toxicity, a lack of selectivity, and the emergence of drug resistance. These issues demand innovative and targeted solutions. Peptide-based therapeutics have gained prominence for their ability to disrupt cancer pathways and facilitate targeted drug delivery, offering structural flexibility, precise targeting, and low immunogenicity with minimal effects on healthy tissues. Concurrently, aptamers, which are structured nucleic acid molecules capable of high-affinity molecular recognition, are being developed as both direct therapeutic agents and as targeting ligands for the improved delivery of anticancer drugs. Combining peptide and aptamer technologies with engineered exosomes provides a modular drug delivery system that enhances targeting specificity, stability, and the ability to cross complex biological barriers such as the blood–brain barrier. The emergence of peptide-decorated, aptamer-decorated exosomes represents a new frontier in precision oncology, promising highly selective, biocompatible, and tunable cancer therapies. Further advances are required to overcome challenges in pharmacokinetics, scalable production, and regulatory compliance, but ongoing bioengineering and nanotechnology research continues to accelerate the translation of these innovative strategies toward improved cancer diagnostics and treatment outcomes. This review discusses the synergistic integration of peptides and aptamers with exosome-based delivery systems, highlighting their current applications and future possibilities. Full article

Background/Objectives: Accurate assessment of pulmonary function is essential before planning radical lung cancer treatment. While spirometry reflects global lung function, perfusion imaging provides detailed information on regional perfusion patterns. This study aimed to characterize the pre-treatment profile of patients and compare the impact of surgical resection, radiotherapy, and thermal ablation on global pulmonary function and regional perfusion using SPECT/CT. Methods: In this prospective study of 68 patients, pre- and post-treatment assessments were conducted using lung perfusion SPECT/CT. While the entire cohort underwent imaging, longitudinal global pulmonary function (spirometry and gas diffusion) was analyzed for 45 patients who completed the three-month follow-up. Quantitative analysis included perfusion percentages and lung volumes, while a semi-quantitative scoring system evaluated the severity of perfusion defects. Results: In the overall cohort, the affected lung perfusion and volume significantly decreased (p = 0.002). Subgroup analysis revealed that the surgical resection group experienced significant reductions in perfusion (from 54.0% to 41.0%, p = 0.002) and volume (p < 0.001) of the affected lung, whereas no statistically significant changes were observed in the thermal ablation and radiotherapy groups (p > 0.05). Notably, 60.3% of patients presented with perfusion defects before treatment. Post-treatment spirometry parameters, particularly FEV1% (threshold 83.5%, AUC = 0.783), served as reliable predictors of persistent perfusion impairment. Conclusions: Radiotherapy and thermal ablation are lung-perfusion-sparing treatments compared to surgical resection. The high prevalence of pre-existing perfusion defects emphasizes the importance of incorporating lung perfusion SPECT/CT into routine pre-treatment evaluation to optimize treatment selection. Full article

Background/Objectives: Systemic inflammation and nutritional status are two factors known to influence the prognosis of cancer patients. The Naples Prognostic Score (NPS) includes two inflammatory and two nutritional markers and combines them in a single score to better predict survival of cancer patients. In this study, we aimed to critically evaluate the NPS for its significance in head and neck cancer patients. Methods: We retrospectively analyzed the preoperative NPS and its association with overall survival (OS) and disease-free survival (DFS). We evaluated 140 patients with head and neck squamous cell carcinoma (HNSCC) who were treated with primary surgical therapy at a tertiary center between 2001 and 2019. OS and DFS were analyzed using Kaplan–Meier estimators, the log-rank test and uni- and multivariable Cox models. Results: The median postoperative follow-up was 6.7 years. Higher NPS showed numerically, but not significantly shorter OS and DFS. Sensitivity analysis for all markers included in the NPS revealed only the neutrophil-to-lymphocyte ratio (NLR) as a significant predictor for OS and DFS. Conclusions: These findings suggest that the overall NPS may have limited prognostic value in this cohort. In contrast, NLR appears to be a more robust and clinically relevant marker for survival outcomes in patients with head and neck squamous cell carcinoma. Full article

Skin and its appendages form an integrated system of ectodermal mini-organs that rely on Wnt signaling for lifelong homeostasis and regeneration; yet, the pathway operates in a highly organ-specific manner in each compartment. In interfollicular epidermis, the Wnt activity is spatially graded, thus maintaining the balance between basal progenitor proliferation and terminal differentiation. The hair follicle is governed by an intrinsic oscillator based on cross-regulation between Wnt and BMP signaling, providing a cell-autonomous layer of control over hair cycle dynamics. Finally, the nail organ is characterized by the spatial compartmentalization of Wnt activity, with a distal matrix activation zone supported by specialized mesenchymal niche cells that sustain continuous nail plate growth and coordinate the digit tip regeneration. Understanding these divergent regulatory architectures provides a conceptual framework for targeted regenerative strategies aimed at enhancing repair in skin and its appendages. Therefore, in this review, we synthesize recent molecular studies on Wnt signaling in the adult skin, hair follicles, and nail mini-organs, highlighting appendage-specific features that underlie their distinct regenerative capacities. We further discuss how dysregulated Wnt signaling contributes to skin, hair, and nail pathologies such as alopecia, chronic wounds, excessive scarring, skin cancer, and nail deformations, and summarize the emerging strategies that target Wnt pathway to therapeutically enhance hair regrowth, wound repair, cancer treatment, and digit tip regeneration. Full article

Ubiquitination is a reversible post-translational modification crucial for cellular homeostasis and protein degradation. It is orchestrated by a cascade of ubiquitin-activating enzymes (E1), conjugating enzymes (E2), and ligases (E3) that tag proteins with ubiquitin, and deubiquitinating enzymes (DUBs) that remove these tags. Through this tightly regulated ubiquitination/deubiquitination system, cells control protein turnover, localization, and activity, thereby governing processes ranging from cell cycle progression and DNA repair to immune and stress responses. Here, we review the structural and functional mechanisms of each class of enzymes in the ubiquitin–proteasome system, including E1, E2, E3, and DUBs, and highlight their roles in key signaling pathways and physiological processes. We further discuss how the dysregulation of these enzymes leads to diseases such as cancer, neurodegenerative disorders, and immune diseases, underlining the potential of targeting ubiquitination pathways for therapeutic intervention. 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

Background: The aim of this study is to determine the safety of a locally implemented Standard of Practice (SOP) in patients with cardiac implantable electronic devices (CIEDs). With increasing use of radiotherapy in cancer treatment and the widespread adaptation of CIEDs, the British Heart Rhythm Society introduced new guidance in 2025. There remains ambiguity between various international, as well as manufacturer, guidelines on the management of these patients. Methods: This was a retrospective single-centre observational study analysing patients with CIEDs receiving radiotherapy after the implementation of our Standard of Practice in 2021. Patients were identified using the Cardiobase system. Patients were divided into non-pacemaker-dependent, pacemaker-dependent and implantable-cardioverter–defibrillator (ICD) groups. Lead sensing and impedance values were gathered pre- and post-treatment and analysed using a paired Student’s T-test. Results: A total of 320 patients were included in this study. There were no statistically significant changes in lead sensing capabilities in any of the groups pre- and post-radiotherapy with a p value of >0.05. There were no statistically significant changes in lead impedance in the ICD and non-pacemaker-dependent groups. Although statistically significant (p = 0.039), there was no clinically significant reduction in atrial lead impedance in the pacemaker-dependent cohort. Conclusions: From the obtained results, we can conclude that our locally implemented SOP is a safe alternative to BHRS guidelines. Full article

Despite advances in surgical technique and perioperative care, pancreatic ductal adenocarcinoma (PDAC) remains associated with poor survival. Sarcopenia is highly prevalent in PDAC and is consistently associated with inferior survival and reduced tolerance of systemic therapy. However, interventions primarily aimed at increasing muscle mass through nutritional supplementation and resistance-based exercise have yielded limited improvements in clinically meaningful postoperative outcomes. This has prompted increasing interest in sarcopenia as a marker of broader biological vulnerability rather than isolated physical deconditioning. Emerging clinical, translational, and experimental evidence demonstrates that skeletal muscle and adipose tissue function as active immunometabolic organs, and that cancer-associated inflammatory pathways drive early muscle loss, immune dysfunction, and impaired physiological recovery. Across multiple clinical cohorts, sarcopenia is reproducibly associated with worse overall survival and failure to complete adjuvant therapy, but not consistently with increased postoperative complications, suggesting that its prognostic relevance lies in impaired recovery and oncological fitness rather than immediate surgical risk. Translational studies further indicate that sarcopenia identifies patients with reduced antitumor immune competence, particularly in early-stage disease. This review synthesizes current evidence linking sarcopenia, immune dysfunction, and surgical outcomes in PDAC and examines implications for perioperative care. We propose that immunometabolic-informed prehabilitation, integrated with existing nutritional and exercise strategies, may represent a more effective approach to improving recovery, treatment tolerance, and durable oncological outcomes following PDAC resection. Full article

Background: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and one of the few solid tumors with a steadily rising incidence, paralleling global trends in obesity and insulin resistance. Its strong epidemiologic association with systemic metabolic dysfunction positions EC as a uniquely accessible model for metabolically informed chemoprevention. Methods: This narrative review was conducted through a systematic search of PubMed/MEDLINE and Embase using the following terms: “endometrial cancer” AND (“insulin resistance” OR “metabolic syndrome” OR “PI3K” OR “chemoprevention” OR “bariatric surgery” OR “metformin” OR “cellular senescence”). Searches were limited to English-language publications; no date restriction was applied for foundational molecular studies, while clinical and translational evidence was reviewed from 2000 to 2025. Additional references were identified through manual review of reference lists of included articles. Results: We examine metabolic amplification as a conceptual framework in which hyperinsulinemia, inflammatory reinforcement, and redox-epigenetic modulation intensify proliferative signaling in biologically susceptible endometrial tissue, particularly within molecular subtypes enriched for PI3K pathway activation such as tumors lacking a specific molecular profile (NSMP). Bariatric surgery offers the strongest human evidence supporting the principle that durable metabolic correction can substantially reduce EC incidence. In contrast, pharmacologic interventions including metformin, anti-inflammatory agents, and nutraceutical compounds demonstrate variable or limited preventive efficacy, and short-term biomarker modulation cannot substitute for validated reduction in cancer risk. The endometrial intraepithelial neoplasia (EIN) model provides a uniquely accessible platform for biomarker-guided intervention. Conclusions: Integration of genomic subtype classification with metabolic profiling may enable precision prevention strategies in clearly defined high-risk populations. Effective chemoprevention will require molecular enrichment, confirmation of tissue-level target engagement, and clinically meaningful endpoints, while acknowledging the translational limits of pathway-directed approaches. Full article

Tissue repair is a finely organized process that progresses via a series of phases, including hemostasis, inflammation, proliferation, and remodeling, which are coordinated by immune–stromal interactions. Aging profoundly dysregulates these processes through mechanisms such as immunosenescence and inflammaging, cellular senescence, chronic inflammation, and extracellular matrix alterations, ultimately contributing to typical age-related progression. This review discusses the immune mechanisms that govern physiological tissue healing, as well as the age-related perturbations that lead to ulcerative and fibrotic diseases. It also highlights the potential application of extracellular vesicles (EVs), both mammalian and plant-derived, as a stable and low-immunogenicity mediator to modulate and re-establish repair homeostasis. Translational hurdles such as EV standardization, dosing, safety assessment, and manufacturing are critically discussed to promote their use in geroscience, regenerative medicine, and dermatology. 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