Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality, and treatment efficacy is frequently limited by acquired resistance and systemic toxicity. Glutathione-responsive abasic site-trapping prodrugs have shown selective anticancer activity in prior experimental studies, but whether their released metabolites also show meaningful interactions with cancer-relevant proteins remains to be established. Here, an integrated in silico workflow combining network pharmacology, molecular docking, molecular dynamics (MD), and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis was used to prioritize testable protein-interaction hypotheses for two glutathione-responsive prodrugs (Compound 1 and Compound 2), their aminooxy-containing products (Compound 4 and Compound 5), and a matched non-trapping control pair (Compound 3 and Compound 6). Twenty-one intersecting compound- and disease-associated targets were identified, and AKT serine/threonine kinase 1 (AKT1), epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF), matrix metalloproteinase 9 (MMP9), and SRC proto-oncogene non-receptor tyrosine kinase (SRC) were prioritized by protein-protein interaction topology. Compound 5 produced the most favorable single AutoDock Vina score with MMP9 (-8.418 kcal·mol⁻¹) and showed comparatively persistent docking-derived poses across the MMP9 and SRC MD trajectories. However, the top-ranked MMP9 pose did not show direct coordination of the catalytic Zn²⁺ ion or direct engagement of His401, Glu402, His405, or His411, so it cannot be assigned a canonical MMP9 inhibitory binding mode. MD and MM-PBSA analyses characterize only trajectory behavior and the relative energetic ranking of these complexes; they do not demonstrate intracellular target engagement, enzyme inhibition, or pathway regulation. The established abasic-site-trapping activity and the newly predicted protein interactions are therefore treated as separate, potentially parallel hypotheses rather than a demonstrated mechanistic chain. Overall, the results prioritize specific compound-target pairs for future testing but do not establish a multi-target anti-NSCLC mechanism.

Incidental thyroid nodules (ITNs) detected on nonthyroid imaging contribute to thyroid cancer overdiagnosis, largely through downstream evaluation initiated by thyroid ultrasound (TUS). However, TUS follow-up rates for ITNs and their drivers in routine practice remain unclear. We quantified TUS utilization after ITN detection and identified patient, imaging, nodule, and reporting factors associated with this first step in the diagnostic cascade.

We conducted a retrospective cohort study of adults without prior thyroid disease who underwent imaging that incidentally captured the thyroid at Mayo Clinic sites (2017-2023). A validated natural language processing pipeline identified ITNs and extracted nodule characteristics from radiology reports across multiple imaging modalities. The main outcome was the rate of TUS within 180 days after ITN detection. Clinical outcomes, including thyroid biopsy, thyroidectomy, and thyroid cancer diagnosis, were compared between patients who underwent TUS and those who did not. Factors associated with TUS utilization were assessed using multivariable logistic regression with penalized variable selection.

Among 115,683 patients who underwent thyroid-capturing imaging, 8426 (7.3%) had an ITN. These patients were predominantly female (64.6%) and White (89.7%), with a mean age of 61.7 years (standard deviation 15.2). Most nodules were detected on computed tomography (80.8%), most commonly from chest imaging (52.3%). Overall, 1677 patients with ITNs (19.9%) underwent TUS. In multivariable analysis, TUS use was independently associated with higher body mass index (odds ratio [OR], 1.20 per 10-unit increase; confidence interval [CI] [1.08-1.33]), nodule size ≥1.5 cm (OR, 1.79; CI [1.52-2.10]), and a radiologist recommendation (OR, 2.51; CI [2.12-2.98]), whereas older age was associated with lower odds of TUS (OR, 0.89 per 10-year increase; CI [0.84-0.93]). Patients undergoing TUS had higher rates of thyroid biopsy, partial thyroidectomy, and total thyroidectomy compared with those without it. All detected thyroid cancers (103 cases) occurred in the TUS group, representing 6.1% of that cohort.

One in five patients with ITNs underwent TUS, representing a critical gateway to downstream diagnostic procedures and thyroid cancer detection. Factors associated with TUS utilization highlight opportunities to better define appropriateness of ultrasound after incidental nodule detection and to reduce unnecessary testing and treatment.

Intimal sarcoma is a malignant mesenchymal tumour arising in large blood vessels of systemic and pulmonary circulation, depicted as undifferentiated and aggressive. Clinical presentation of these cardiac masses is often subtle, making misdiagnosis possible. We discuss the case of a 27-year-old woman with a recent history of delivery, admitted for dyspnoea and signs of right-heart failure. A diagnosis of pulmonary embolism was made on a computed tomography angiogram and transoesophageal echocardiography basis. Emergency surgery was performed due to haemodynamic instability. Pulmonary arteriotomy revealed a large solid polylobate mass instead of a thrombus. Surgical debulking, with reconstruction of the right ventricle outflow tract, and pulmonary valve replacement were therefore necessary. Partial pulmonary annulus reconstruction was furthermore performed with a strip of heterologous pericardium with a 'sandwich technique'. Prompt diagnosis of intimal sarcoma was made, permitting initiation of timely treatment with anthracycline. Surgical resection of malignancies involving either the heart or great vessels is uncommonly performed because of the potential morbidity and mortality and the unknown probability of significant cure. Preoperative imaging is then of paramount importance in determining the diagnosis and planning for surgery. In this specific case, the haemodynamic instability, the high suspicion of a thrombotic nature of the mass, and young age precluded the performing of any second-level examination, leading surgeons to an unexpected reconstruction.

Liver transplantation (LT) and liver resection (LR) are curative options for early-stage hepatocellular carcinoma (HCC), but the optimal approach for single-nodule disease remains debated. This systematic review and meta-analysis compared long-term outcomes of LT versus LR in patients with single-nodule HCC.

PubMed and Cochrane Library were searched (2012-2023) following PRISMA guidelines. Studies comparing LT and LR in adults with single-nodule HCC were included. Overall survival (OS) and disease-free survival (DFS) at 1, 3, 5, and 10 years were analyzed using random-effects models.

Eight studies including 5094 patients (LT: 2289; LR: 2805) were analyzed. No randomized clinical trials were identified. LT showed significantly higher OS at 3, 5, and 10 years, while 1-year OS was similar. DFS was superior in the LT group at all time points, with progressively larger benefits over time. ITT and tumor-size sensitivity analyses showed similar findings.

LT was associated with better long-term OS and DFS than LR in patients with single-nodule HCC. The consistency of these findings, particularly for DFS, suggests a potential oncological benefit of LT in appropriately selected patients. However, the observational design and substantial baseline differences limit causal interpretation and warrant further comparative research.

This study was registered prospectively in the International Prospective Register of Systematic Reviews (PROSPERO) under the ID number CRD42024512589.

Thyroid cancer (THCA) has recently become one of the most common endocrine malignancies worldwide. Dihydroartemisinin (DHA) exhibits well-documented antitumor activity, but its therapeutic potential in THCA remains largely unclear.

The relative mRNA and protein expression levels of the apoptosis-related markers Bax, Bcl-2, and Caspase-3 in the human THCA cell line TPC-1 were evaluated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. Potential active targets of DHA were obtained from the TCMSP, SwissTargetPrediction and SuperPred databases. The THCA-related targets were collected from TCGA, DisGeNET and GeneCards. Protein-protein interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict key targets and pathways of DHA against THCA.

DHA treatment significantly modulated the expression of apoptosis-related markers, including upregulation of Bax and Caspase-3 and downregulation of Bcl-2, suggesting that DHA may promote apoptosis in TPC-1 cells. A total of 230 potential targets were identified from the overlap between DHA- and THCA-related targets. Indeed, STAT3, PIK3R1, PIK3CA, PIK3CD, MAPK1, MAPK3, EGFR, HSP90AA1, ESR1, PTPN11 were identified as the top 10 hub genes. In total, 2214 biological processes, 118 cellular components, and 220 molecular functions were enriched. KEGG analysis indicated that DHA may suppress THCA primarily via the chemical carcinogenesis-receptor activation pathway.

These findings suggest that DHA is a promising candidate for THCA treatment and warrant further investigation, including direct apoptosis assays and in vivo validation.

Thiopurines remain a cornerstone of treatment for pediatric acute lymphoblastic leukemia (ALL); however, interindividual variability in drug metabolism, largely driven by polymorphisms in the thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genes, can predispose patients to severe, dose-dependent toxicities. Latin American populations have been underrepresented in several global pharmacogenomic (PGx) datasets, limiting the applicability of current dosing recommendations.

Thus, this study aimed to analyze TPMT and NUDT15 variants in 302 pediatric patients diagnosed with hematological malignancies at the Instituto Nacional de Salud del Niño-San Borja (INSN-SB). Targeted sequencing of the coding regions was performed using custom AmpliSeq™ panels and Illumina platforms, followed by variant annotation and star allele classification based on the Clinical Pharmacogenetics Implementation Consortium (CPIC) and PharmGKB guidelines.

Among the TPMT alleles, *3A (8.97%) was the most prevalent actionable variant, followed by *2 (0.32%) and *3C (0.32%). For NUDT15, the most frequent reduced-function allele was *2 (9.29%), with additional findings of *4 (0.64%), *6 (0.32%), *3 (0.16%), and *15 (0.16%). A substantial proportion of the cohort was classified as intermediate or poor metabolizer categories, indicating an increased risk of thiopurine-related toxicity. The observed allele distribution suggests potential geographic variation, although these patterns should be interpreted as exploratory given the limited regional sample size.

This study provides one of the first comprehensive characterizations of clinically relevant TPMT and NUDT15 variants in a Peruvian pediatric population. The findings highlight a substantial burden of actionable pharmacogenetic variants and support the implementation of preemptive genotyping to guide thiopurine dosing. These results help addressing the underrepresentation of Latin American populations in PGx research and provide a foundation for advancing precision medicine in the region.

Multiple myeloma (MM) is a biologically and clinically heterogeneous plasma cell malignancy characterized by clonal expansion in the bone marrow and a highly variable clinical course. Despite major therapeutic advances, MM remains incurable, largely due to the associated genomic complexity, clonal evolution, and the emergence of treatment resistance. In this context, next-generation sequencing (NGS) has emerged as a transformative tool for improving disease characterization, risk stratification, and clinical management. This review summarizes current evidence on the application of NGS technologies, including whole-exome sequencing, whole-genome sequencing, and targeted gene panels-in the diagnosis, prognostic assessment, and monitoring of MM. Genomic profiling has consistently revealed recurrent alterations in key driver genes, copy number abnormalities, and structural variants that underlie disease heterogeneity and influence clinical outcomes. In addition to baseline characterization, NGS enables high-resolution analysis of clonal architecture and evolution, offering critical insights into mechanisms of relapse and therapeutic resistance. Importantly, NGS-based assessment of minimal residual disease (MRD) has demonstrated superior sensitivity compared with conventional techniques, providing a powerful prognostic marker and a promising tool for treatment monitoring and response-adapted strategies. Indeed, by integrating genomic and MRD data, NGS supports a more precise and dynamic approach to patient management. Overall, the growing body of evidence highlights NGS as a central component of precision medicine in multiple myeloma. Continued efforts toward standardization, validation of emerging biomarkers, and clinical implementation of sequencing-guided strategies are expected to enhance personalized treatment further and improve patient outcomes.

As the global population ages, the incidence of meningiomas rises, and the demand for clinical management of elderly patients also rises. Meningiomas are common intracranial tumors, and their incidence increases with age. Elderly patients with meningiomas are prone to comorbidities, reduced reserve function, atypical manifestations, increased perioperative risks, and impaired functional recovery, making management more difficult. The application of neuroimaging leads to more elderly patients with asymptomatic or incidentally discovered meningiomas. Choosing the best strategy among monitoring, surgery, radiotherapy, and other strategies is therefore key to clinical decision-making. For asymptomatic, small, and radiologically low-risk meningiomas in elderly patients, active surveillance is generally the preferred initial strategy. Surgery is more appropriate for symptomatic tumors, lesions with mass effect, documented growth, progressive peritumoral edema, neurological deterioration, or other high-risk clinical and radiological features. However, the treatment goal for elderly patients should emphasize symptom relief, preservation of neurological function, and quality of life more than pursuing gross total resection as routine. Stereotactic radiosurgery and fractionated radiotherapy provide important supplementary treatments for very elderly patients, high surgical risk patients, and postoperative residual lesions. This article reviews recent advances in understanding meningiomas in elderly and very elderly patients, focuses on epidemiology, clinical characteristics, prognostic factors, and treatment strategies, and also discusses the core principles of individualized management for this population to guide clinical practice.

Cholangiocarcinoma (CCA) is an aggressive bile duct malignancy with a high incidence and mortality rate in Southeast Asia, particularly in Thailand. However, current treatments offer only limited clinical benefit. Aberrant mRNA splicing, driven by hyperactivation of serine/arginine-rich splicing factors (SRSFs) and their upstream kinases SRPK1 and SRPK2, contributes to the progression of CCA. Although SRPK inhibitors suppress tumor growth, their effects remain incomplete, highlighting the need for rational combination strategies.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic profiling was performed on CCA cell lines (KKU-213A and KKU-055) treated with the SRPK inhibitors SRPIN340 and SPHINX31. Subsequently, commonly upregulated differentially expressed proteins (UpDEPs) were identified and cross-validated with data from the Cancer Genome Atlas (TCGA) using GEPIA, followed by reverse transcription-quantitative polymerase chain reaction (qRT-qPCR) validation. The functional effects of combined SRPK and mitogen-activated protein kinase kinase (MEK) inhibition (with U0126) were evaluated using cell viability and colony formation assays, and by analyzing signaling pathways.

A total of 34 common UpDEPs were identified following SRPK inhibition. Laminin subunit beta 1 (LAMB1) was prioritized as a candidate combination target due to robust upregulation, concordant overexpression in TCGA datasets, and increased mRNA levels after SRPK inhibitor treatment. Given prior evidence linking MEK signaling to LAMB1 regulation, we also evaluated the MEK inhibitor U0126. Combined treatment with SRPK inhibitors (SRPIN340 or SPHINX31) and U0126 produced greater suppression of viability and clonogenic growth in KKU-213A cells than either treatment alone. These effects were accompanied by reduced ERK phosphorylation and cellular Jun proto-oncogene (c-JUN) expression.

LAMB1 represents a potential adaptive response target following SRPK inhibition in CCA. Dual targeting of SRPK and MEK signaling pathways exerts greater antitumor effects than either treatment alone and may provide a promising therapeutic strategy for CCA management.

Breast cancer continues to be a major global health burden, with a significant proportion of patients developing metastatic or treatment-resistant disease. Novel therapeutic strategies are urgently needed. Nectin cell adhesion molecule 4 (Nectin4), an adhesion molecule overexpressed in aggressive breast cancer subtypes, represents a promising target for immunotherapy due to its restricted expression in normal tissues. This study investigated the therapeutic potential of Nectin4-directed chimeric antigen receptor natural killer (CAR-NK) cell therapy against triple-negative breast cancer (TNBC) at the preclinical stage.

Human natural killer (NK) cells obtained from peripheral blood from healthy donors were engineered to express an anti-Nectin4 chimeric antigen receptor (CAR) via lentiviral transduction, expanded ex vivo, and then used for functional studies. Cytotoxic activity was assessed in vitro against Nectin4-high-expressing breast cancer cells using luciferase-based killing assays at various effector-to-target ratios. In vivo efficacy was evaluated in NOD/SCID/IL2rγnull (NSG) mice bearing subcutaneous breast cancer tumors treated with CAR-NK cells, compared to untransduced NK cells and phosphate-buffered saline controls. Tumor growth was monitored using bioluminescence imaging and harvested tumors were subsequently analyzed for Nectin4 expression using immunohistochemistry.

CAR-NK cells potently and specifically lysed Nectin4-positive breast cancer cells in vitro, with up to 95% target cell lysis at an effector-to-target ratio of 5:1. In vivo, CAR-NK treatment reduced tumor burden and prolonged survival compared with controls. Immunohistochemical analysis revealed a marked reduction in Nectin4 expression within tumors from the CAR-NK-treated group, consistent with targeted tumor cell elimination.

CAR-NK cells targeting Nectin4 demonstrated potent cytotoxic activity in vitro and effectively suppressed tumor growth in vivo, supporting the further evaluation of Nectin4 as a therapeutic target for CAR-NK-based immunotherapy in TNBC, particularly for aggressive subtypes with limited treatment options.