Enhancer of zeste homolog 2 (EZH2), the catalytic component of the polycomb repressive complex 2, is frequently overexpressed in lung adenocarcinoma and contributes to transcriptional programs that support tumor proliferation and cellular plasticity. However, its role in regulating senescence-associated signaling and tumor-stromal interactions in lung cancer remains incompletely understood. In this study, we combined transcriptomic analysis of The Cancer Genome Atlas lung adenocarcinoma cohort with functional characterization of EZH2 targeting in A549 cells using the catalytic inhibitor EPZ6438 and the EZH2 degrader MS1943. Elevated EZH2 expression was associated with enrichment of cell cycle-related transcriptional pathways. Pharmacological targeting of EZH2 reduced proliferation, migration, stemness-associated features, and sphere-forming capacity, with more pronounced effects observed following EZH2 degradation. Both compounds promoted features consistent with senescence-associated phenotypic remodeling characterized by increased expression of p16 and p21, enhanced β-galactosidase activity, G0/G1 cell cycle arrest, and increased expression of cytokines commonly associated with senescence-related secretory signaling, including IL-6, CCL2, and CXCL8. Conditioned medium from treated tumor cells promoted activation of primary lung fibroblasts, indicating functional paracrine microenvironmental remodeling. Importantly, EZH2 targeting elicited cytostatic responses without induction of apoptosis. Collectively, these findings suggest that EZH2 contributes to regulation of proliferation-associated and senescence-associated phenotypic programs together with stromal signaling in lung adenocarcinoma.

Thermal ablation (TA) is an increasingly adopted minimally invasive treatment for benign thyroid nodules. However, TA induces marked histological alterations that may simulate thyroid malignancy, creating significant diagnostic pitfalls for pathologists. The present study expands our previous institutional series and further characterizes the morphologic, immunohistochemical, and molecular features of thermally ablated thyroid nodules in order to refine the differential diagnosis with thyroid carcinoma. Fourteen surgically excised thyroid nodules previously treated with laser thermal ablation were retrospectively analyzed. Histopathological evaluation focused on architectural changes, nuclear atypia, capsule alterations, degenerative phenomena, and evidence of invasion. Immunohistochemical analysis included galectin-3 (Gal-3), HBME-1, BRAF V600E, p53, and Ki-67. In addition, molecular profiling for the principal thyroid cancer-related alterations, including BRAF, RAS family genes, TERT promoter mutations, PIK3CA alterations, and RET rearrangements, was performed using targeted next-generation sequencing. All nodules showed treatment-related reactive and degenerative changes, including fibrosis/sclerosis, subcapsular hemorrhage, focal oncocytic metaplasia, and architectural distortion. No true capsular or vascular invasion was identified. Immunohistochemically, all cases were negative for Gal-3 and BRAF V600E, while HBME-1 expression was absent or only focally weak. Ki-67 proliferative activity remained consistently low (<3%) in all cases. Molecular analyses did not identify pathogenic alterations involving BRAF, RAS, TERT promoter, PIK3CA, or RET genes in any case. Thermal ablation induces reproducible reactive and degenerative histologic alterations that may closely mimic follicular or papillary thyroid neoplasms. The absence of malignancy-associated immunohistochemical and molecular alterations strongly supports the benign nature of these lesions and highlights the importance of an integrated morphologic, immunohistochemical, and molecular diagnostic approach in challenging post-ablation specimens. Thermally ablated thyroid nodules may display significant pseudo-neoplastic changes that can lead to overdiagnosis of carcinoma. Awareness of these treatment-related alterations, combined with immunohistochemical and molecular profiling, represents a reliable strategy to distinguish reactive post-ablation changes from true thyroid malignancy and to avoid inappropriate clinical management.

Extracellular vesicles (EVs) and liposomes are nanoscale drug delivery systems extensively investigated in oncology for their ability to improve pharmacokinetics, biodistribution, and therapeutic efficacy of anticancer agents. Liposomes are clinically validated synthetic nanocarriers characterized by high versatility, scalable production, and established regulatory approval; however, their performance is limited by tumor heterogeneity, vascular barriers, adverse effects and inefficient intracellular drug release. EVs are naturally derived nanoparticles involved in intercellular communication and exhibit intrinsic biocompatibility, low immunogenicity, and biological targeting potential; yet their translation is constrained by heterogeneity, limited loading capacity, and manufacturing challenges. Different studies indicate complementary advantages between both systems, with EVs favoring biological targeting and immune modulation and liposomes enabling controlled formulation and pharmacokinetic optimization. These features have driven the development of hybrid EV-liposome nanovesicles, which integrate synthetic and biological properties to enhance tumor targeting, therapeutic efficacy, and payload diversity, including drugs, nucleic acids, and gene-editing systems. Despite promising preclinical results, challenges remain in scalability, standardization, and mechanistic understanding of in vivo behaviour. Overall, these hybrid strategies represent a promising platform for next-generation precision nanomedicine in cancer therapy and for advancing clinical translation by addressing key limitations of current delivery systems and improving therapeutic index and patient outcomes.

Urolithin A (UA) is a gut microbiota-derived postbiotic generated from dietary ellagitannins, while urinary 6-sulfatoxymelatonin (6-SMT) is a surrogate marker of nocturnal melatonin output. We explored whether dysbiosis, UA depletion, and low 6-SMT define an ordered biomarker pattern across healthy aging, salt-sensitive hypertension, and advanced cancer. In this pilot observational study, patients with advanced solid tumors were classified as Cancer Group 1 (higher aggressiveness; n = 231) or Cancer Group 2 (lower aggressiveness; n = 118) and compared with healthy older controls (n = 117) and elderly participants with salt-sensitive hypertension (n = 333). Plasma UA decreased stepwise from controls (2.24 [1.38-3.12] nmol/L) to salt-sensitive hypertension (1.20 [0.76-1.89] nmol/L), Cancer Group 2 (0.60 [0.32-0.91] nmol/L), and Cancer Group 1, in which most samples were at or below the assay limit (overall p < 0.0001; trend p < 0.0001). Twenty-four-hour urinary 6-SMT declined in parallel, whereas the dysbiosis score, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), and malondialdehyde (MDA) increased, and antioxidant indices decreased across the ordered groups (all p < 0.0001). These cross-sectional findings support a hypothesis-generating biomarker framework linking dysbiosis, postbiotic depletion, circadian disruption, inflammation, and redox imbalance across age-related disease states.

To evaluate the diagnostic performance and clinicopathologic relevance of a multi-locus circulating tumor DNA methylation assay, in this prospective, single-center, case-control exploratory study, we enrolled 35 patients with colorectal cancer undergoing surgery and 57 healthy controls undergoing screening colonoscopy at the Asan Medical Center, Seoul, Republic of Korea between July 2024 and January 2025. Peripheral blood was collected before surgery or colonoscopy, and circulating tumor DNA methylation was analyzed using a multi-locus panel targeting Septin9, IKZF1, BCAT1, Septin9-2, BCAN, and VAV3. The main outcomes were test accuracy (sensitivity, specificity, and area under the curve [AUC]) and associations between methylation marker positivity and clinicopathologic features. Circulating tumor DNA was positive in 74.3% of the patients and 12.3% of controls, yielding a sensitivity of 74.3%, specificity of 87.7%, and an AUC of 0.837, whereas serum carcinoembryonic antigen exhibited lower sensitivity (25.7%). Sensitivity in stage I disease was limited (36.4%). Circulating tumor DNA-positive tumors were larger (5.7 cm vs. 2.2 cm, p < 0.001) and had more advanced T and N stages. The number of positive markers increased with pathologic stage (p = 0.003). Individual marker analysis revealed that BCAT1, Septin9-2, and VAV3 were associated with higher T stage, whereas BCAN positivity was linked to nodal metastasis. The six-marker circulating tumor DNA methylation assay demonstrated acceptable diagnostic accuracy, with multi-locus patterns associated with tumor burden and invasive features. However, sensitivity for early-stage disease was limited. The assay may serve as a complementary tool for screening and risk stratification.

Frontline systemic treatment selection for advanced leiomyosarcoma (LMS) remains variable in routine practice. Gemcitabine-based regimens are frequently used despite randomized evidence of non-superiority compared with doxorubicin-based regimens and greater complexity in treatment delivery.

This multi-centre retrospective cohort study included advanced/metastatic LMS patients treated with frontline doxorubicin- or gemcitabine-based chemotherapy at four Canadian sarcoma centres (2010-2022). The primary endpoint was overall survival (OS). Secondary endpoints were time to second-line treatment (T2T) and number of subsequent systemic treatment lines. Subgroup analyses were conducted by primary tumor site (uterine vs. non-uterine LMS).

Among 217 patients, median OS was 17.1 months (95% CI 14.8-21.1). OS did not differ between frontline doxorubicin- and gemcitabine-based regimens (17.8 vs. 16.1 months; p = 0.16), nor did T2T (5.8 vs. 6.3 months; p = 0.77). Non-uterine primary site and surgery following frontline systemic treatment were independently associated with improved OS. Median OS was longer for non-uterine versus uterine LMS (23 vs. 12.8 months; p < 0.001).

In this large real-world LMS cohort, outcomes were not influenced by frontline chemotherapy choice. These findings support prioritizing toxicity, quality of life, cost, and treatment delivery burden when selecting frontline therapy, particularly where doxorubicin/trabectedin use is limited.

Patients' expectations may influence how chemotherapy side effects are perceived and could contribute to symptom amplification. Psychological distress and prior treatment experiences are assumed to shape these expectations, yet their interplay and impact on side-effect burden remain unclear.

This study examined how prior treatment experiences, psychological distress, hope, and self-efficacy affect expectations of side effects and predict the severity of chemotherapy-related symptoms such as nausea, peripheral neuropathy, and fatigue.

In a prospective longitudinal study, 101 adult patients with cancer initiating outpatient chemotherapy were assessed at T1 (start of the second cycle) and T2 (8-12 weeks later). Expectations of side effects (G-EEE), chemotherapy-related symptom severity (GASE), hope (HHI-D), self-efficacy (CBI-B-D), and psychological distress (PHQ-2, GAD-2) were assessed using standardized questionnaires. Prior treatment experiences, sociodemographic and illness-related variables were documented. Multiple linear regressions identified predictors of expectations and symptom severity.

Of 101 patients, 73 completed both assessments. Higher side effect expectations were predicted by prior chemotherapy, anxiety, lower hope, and negative treatment reports from others. At T2, depressive symptoms predicted neuropathy and fatigue; lower self-efficacy predicted neuropathy; and lower hope predicted fatigue. Expectations improved model fit but did not independently predict symptom severity.

Findings highlight the relevance of personal and vicarious treatment experiences, psychological distress, and resilience factors in shaping both expectations and patients' symptom experiences related to chemotherapy side effects. While expectations were linked to psychological variables, hope, self-efficacy, and depression were stronger predictors of symptom severity. These patient characteristics may help identify patients who could benefit from supportive care and patient-centered communication in oncology.

German Clinical Trials Register (DRKS00028791).

Several epidemiological studies have explored the potential associations between allergy, asthma, and cancer incidence, but the findings remain inconclusive. This study investigates the association between a history of allergy, asthma, and cancer risk in a Japanese population. Data were obtained from the Japan Public Health Center-based Prospective Study (JPHC Study). Participants reported in a self-administered questionnaire whether they had been diagnosed by a physician for allergy, asthma, or both (hereafter referred to as "allergy and/or asthma"). They were followed until December 2013. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and site-specific cancers for allergy, asthma, and combined allergy and/or asthma. Subgroup analyses were performed by smoking status. Among participants, 17,679 cancer cases were identified, and 6.5% reported a history of allergy and/or asthma. A borderline association was observed between allergy and/or asthma and thyroid cancer (HR 1.54, 95% CI 1.00-2.35). Subgroup analysis revealed that men with a history of smoking and allergy and/or asthma had an increased risk of colorectal cancer (HR 1.30, 95% CI 1.03-1.63), while never-smoking women with allergy and/or asthma showed an increased risk of cervical cancer (HR 1.98, 95% CI 1.01-3.86). These findings showed no overall association of allergy, asthma, or their combined exposure with cancer risk in a Japanese population, warranting further investigation.

This study aimed to construct a nomogram incorporating preoperative laboratory parameters and clinical pathological factors for the first time to predict the probability of adjuvant therapy requirement following radical surgery in IB stage cervical squamous cell carcinoma (SCC) with tumor size ≤ 4 cm.

Clinical pathological parameters and relevant laboratory indicators were collected from IB stage cervical SCC with tumor size ≤ 4 cm patients who underwent radical surgery at our hospital. Patients included in the study were randomly divided into a training set and a validation set in a 7:3 ratio. In the training set, the least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to determine the final variables for constructing the nomogram. Finally, the performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) in both the training and validation sets.

The nomogram ultimately included seven predictive variables. The area under the ROC curve (AUC) for the nomogram in the training and validation sets was 0.863 and 0.767, respectively. Moreover, the calibration curve of the nomogram was relatively close to the ideal curve. The DCA showed that using the nomogram to predict the probability of adjuvant therapy requirement over a wide range of threshold values is beneficial.

This study constructed and validated a model for predicting adjuvant therapy requirement in IB stage cervical SCC with tumor size ≤ 4 cm. The model can help clinicians determine the risk of postoperative adjuvant therapy before surgery, promoting personalized treatment choices and patient management.

Meningiomas in pediatric and adolescent/young adult patients are poorly characterized biologically and clinically, and risk stratification is largely extrapolated from adult tumors. We analyze 293 tumors from patients aged 0-39 years using integrated histopathological and molecular profiling. Youth-onset meningiomas are enriched for NF2 and SMARCE1 alterations and exhibit a gain-dominated copy-number landscape, including recurrent chr17q gain, whereas canonical adult high-risk features, such as chr1p loss, lack prognostic significance. Adult-derived prognostic frameworks, including WHO grade, methylation-based stratification and integrated risk scores, fail to predict progression in patients ≤21 years of age. Tumors segregate into age-enriched epigenetic clusters defined by SMARCE1, NF2 and BAP1 alterations. Among NF2-altered tumors, patterns of Merlin inactivation, shaped by germline status and co-occurring copy-number variations, delineate biologically divergent subsets. In patients ≤21 years, extent of resection is the dominant predictor of outcome, while molecular features further refine risk assessment. These findings define pediatric and young adult meningiomas as a distinct molecular entity and support age-adapted risk refinement that integrates molecular features with strong clinical determinants.