To investigate the association between gut-airway microbiota dysbiosis, serum queuine levels, and early malignant transformation in patients with chronic obstructive pulmonary disease (COPD). We further explored whether the potential mechanistic role of queuine in enhancing lung epithelial cell viability under cigarette smoke exposure.

Stable COPD patients were stratified into a high relative abundance of Proteobacteria group (CH) and a low relative abundance of Proteobacteria group (CL) using 16S rRNA gene sequencing of fecal samples. Airway microbiota profiles were analyzed in parallel to assess gut-lung axis coupling. Serum queuine concentrations were quantified using LC-MS/MS in healthy controls, COPD subgroups (CL and CH), and COPD patients complicated by lung cancer. Clinical symptoms (CAT, mMRC, SCSS) and spirometry (FEV₁/FVC, FEV₁, FEV₁% predicted, FVC, FEF_25-75%) were assessed. In vitro experiments were performed using cigarette smoke extract (CSE)-stimulated lung cancer epithelial A549 cells and bronchial epithelial BEAS-2B cells to determine the effects of queuine on cell viability. Chest CT imaging was analyzed to quantify pulmonary nodules as an indicator of in vivo epithelial proliferative activity.

The α-diversity of gut microbiota did not differ between CH and CL. In contrast, β-diversity showed separation (PERMANOVA P = 0.062), with CH characterized by Proteobacteria enrichment and relative depletion of Firmicutes, Bacteroidota, and Actinobacteriota. Airway communities showed concordant remodeling with shifts in taxa consistent with dysbiosis. Serum queuine concentrations increased stepwise from healthy controls to COPD, were higher in CH than CL, and were highest in COPD complicated by lung cancer. Despite comparable pulmonary function and symptom scores between CH and CL groups, the CH group exhibited a significantly higher number of pulmonary nodules on CT imaging, particularly ground-glass nodules. In vitro, queuine significantly enhanced the viability of CSE-stimulated A549 lung cancer cells but failed to rescue CSE-induced growth inhibition in BEAS-2B cells.

COPD-associated gut microbiota dysbiosis, particularly enrichment of Proteobacteria, is closely associated with elevated systemic queuine levels. Excess queuine enhances cell viability of smoke-exposed lung cancer epithelial cells and is associated with increased pulmonary nodules in vivo. These findings identify queuine as a microbiota-derived metabolic mediator that may connect COPD-related dysbiosis to abnormal proliferation of lung epithelial cells.

Solid pseudopapillary neoplasm is a rare epithelial tumor of the pancreas with low malignant potential and a marked predilection for adolescent girls and young women. Although the overall prognosis is favorable after complete resection, preoperative characterization and surgical planning become more challenging in giant tumors with intratumoral degeneration, hemorrhage, and adjacent vascular compression. We report a 15-year-old girl who presented with acute abdominal pain persisting for 24 hours after strenuous physical activity. Imaging revealed a giant mixed solid-cystic mass in the pancreatic body and tail, and computed tomography angiography and venography demonstrated narrowing of the splenic vein with collateral venous circulation. After multidisciplinary assessment of oncologic safety and perioperative bleeding risk, the patient underwent laparoscopic distal pancreatectomy with splenectomy. Histopathology confirmed solid pseudopapillary neoplasm with negative margins and no nodal metastasis; ectopic splenic tissue was identified in the peripancreatic fat. Immunohistochemistry showed nuclear/cytoplasmic positivity for beta-catenin, loss of E-cadherin, positivity for CD10 and CD56, and partial positivity for lymphoid enhancer-binding factor 1, supporting the diagnosis. The postoperative course was uneventful, and no evidence of recurrence was detected on short-term follow-up. This case suggests that giant solid pseudopapillary neoplasm may have been related to acute abdominal pain in the setting of intratumoral degeneration, hemorrhagic change, and local tension effect. Surgical strategy should balance oncologic safety, bleeding risk, and organ preservation. In patients requiring splenectomy, long-term infection prevention should include immunization planning, fever emergency counseling, and individualized antibiotic prophylaxis according to local guidance and risk stratification.

Radiomics can quantify intratumoral heterogeneity on MRI, providing complementary information beyond clinical predictors. This study aimed to evaluate whether integrating radiomic features from pre-operative biparametric MRI (bpMRI) with standard clinical variables improves pre-treatment prediction of biochemical recurrence after radical prostatectomy. We further assessed whether radiomic features add prognostic value to established predictors and compared model performance against the D'Amico classification.

In this retrospective single-center study (2015-2023), 395 men who underwent pre-operative bpMRI (3T Siemens Magnetom Skyra) before radical prostatectomy were included. Lesions were automatically detected using the in-house developed PROVIZ framework, and radiomic features were extracted from index lesions using PyRadiomics v3.1.0. A total of 153 features, including first-order, textural, shape, and anatomical descriptors, were derived from T2-weighted (T2W), ADC, and high b-value diffusion-weighted (DWI, b=1500 s/mm²) images. Clinical variables included prostate specific antigen (PSA), Gleason Grade Group (GGG), PI-RADS v2.1, clinical T stage, and age. A stacked ensemble model (Random Forest and regularized Logistic Regression as base model; Logistic Regression as meta-model) was developed using five-fold stratified cross-validation, SMOTE balancing, Optuna hyperparameter tuning, and isotonic regression-based probability calibration. Performance was evaluated using AUC, calibration, and decision-curve analysis (DCA). Prognostic value was assessed with Kaplan-Meier and Cox regression analyses.

The combined model achieved an AUC of 0.85 (95% CI 0.83-0.87), outperforming radiomics-only (0.78) and clinical-only (0.72) models. Calibration was strong (slope = 1.01; Brier = 0.13). DCA showed higher net benefit than D'Amico classification. High-risk patients (probability ≥ 0.26) had significantly shorter recurrence-free survival (log-rank p<0.001; HR = 5.03, 95% CI 2.7-9.9). The most influential predictors were Gleason Grade Group and PSA, together with radiomic first-order/texture features.

Integrating bpMRI-derived radiomic features with standard clinical variables improved pre-treatment prediction of biochemical recurrence after radical prostatectomy. The combined model provided better discrimination between high-risk and low-risk recurrence groups and showed higher clinical net benefit than D'Amico. The results support the potential role of radiomics for refining individualized recurrence risk assessment in prostate cancer. External validation in independent cohorts is required before clinical implementation.

Friend and/or family caregivers (FCGs) of those with terminal cancer are heavily relied upon to address the emotional and physical needs of the patient facing death. Although increasing research has focused on testing supportive interventions for FCGs who deliver home-based care at end of life, limited attention has targeted strategies that support grief processing for bereaved FCGs during the months following the patients' death. Both natural environments and meditation practices are shown to support directed attention, reflection, and the capacity to remain present with painful thoughts and emotions that are essential for grief processing. This mixed-method study assesses the potential of a new tailored online audio nature-meditative intervention to support grief recovery and healing among 70 bereaved cancer caregivers who are in the first year of bereavement. A primary goal is to assess the acceptability and feasibility of both content and delivery methods. Measures for the 6-week intervention include numbers eligible vs. consented; numbers consented vs. completed; number of weeks using the intervention, and self-report feasibility/acceptability. Potential effect size estimate data for future larger scale work will be collected at three time points: baseline (Time 1; study week 0), at the intervention end (Time 2; week 6), and at follow-up (Time 3; study week 12) on quality of life, bereavement (grief), directed attention, anxiety and depressive symptoms. Additionally, semi-structured interviews with a diverse representative subsample of 15 caregivers will be conducted at the end of the 12-week study to further assess acceptability and feasibility in more depth. Data analyses will include descriptive statistics, linear mixed models, and content analysis. Findings will be used to assess and enhance the intervention prior to wider scale testing with the long-term goal of establishing an evidence-based intervention for supporting bereaved cancer caregivers as they process grief and adapt to their loss.

Artificial intelligence (AI) is increasingly influencing cancer diagnostics, with ongoing advancements into more refined and advanced applications. This review examines current applications of AI in cancer diagnosis. AI has demonstrated considerable success in screening and diagnosis of a range of cancer types, including breast, colorectal, and skin cancer, but challenges with specificity and false-positive rates remain. Within radiology and histopathology, AI shows promise in identifying cancers and augmenting clinician performance. Natural language processing and AI-driven clinical documentation tools can expedite diagnosis by reducing administrative burden and extracting clinically meaningful data from unstructured records. Additionally, AI models using unimodal and multimodal data can improve patient prognostication and risk stratification. Despite these advances, challenges relating to deployment, bias, interpretability, accountability and real-world efficacy persist. Prospective validation and careful implementation are required to ensure safe, equitable, and effective adoption of AI in cancer diagnostics.

Mammary tumors in sheep are exceedingly rare, with all reported cases being benign to noninvasive and slow growing. Here, we describe a squamous cell carcinoma (SCC) with widespread metastases presumptively arising from the mammary parenchyma in a 3.5-y-old ewe. Following a history of chronic mastitis and severe swelling of the udder, the udder was removed surgically and submitted for examination. Three weeks after surgery, because of poor prognosis, the animal was euthanized and autopsied. The udder had no cutaneous lesions but had parenchymal disorganization and extensive areas of necrosis delimiting large, fluid-filled cavities. Two cord-like masses extended from the mammary gland into the pelvic cavity and subcutis of the right hindlimb. Numerous nodules were observed within the mammary and abdominal lymph nodes, peritoneum, lungs, and heart. Histologically, mammary and extramammary lesions consisted of neoplastic squamous epithelial cells, often surrounding keratinized cores. Neoplastic cells had diffuse cytoplasmic immunolabeling for pancytokeratin, confirming their epithelial lineage. Non-keratinized neoplastic cells were positive for p63 and, infrequently, for cytokeratin 19, suggesting mammary histogenesis. Considering the lack of a primary extramammary mass and the tumoral immunophenotype, a presumptive diagnosis was made of primary mammary SCC with metastasis to multiple organs. The aggressive clinical behavior of this neoplasm contrasts with that of reported ovine mammary neoplasms and cutaneous SCCs.

Chimeric antigen receptor (CAR)-T-based strategies target the B-cell maturation antigen (BCMA) expressed on the surface of malignant plasma cells in patients with multiple myeloma (MM). Idecabtagene vicleucel (ide-cel), an anti-BCMA CAR-T therapy, has shown promising results in the treatment of relapsed or refractory multiple myeloma (R/RMM). Notably, the extent of CAR-T cell expansion correlates with objective response rates and complete responses, indicating that monitoring CAR-T cells is critical for predicting clinical outcomes in these patients. Although several tools are available to monitor CAR-T cells in patient blood samples, they remain costly, prompting us to develop novel fluorescent and soluble BCMA reagents for CAR-T cell labeling. BCMA is a type III transmembrane protein, and we found that a recombinant construct consisting of the BCMA extracellular domain fused to green fluorescent protein (GFP) failed to traffic through the Golgi apparatus and was not secreted. Incorporation of the interferon-α2 signal peptide restored intracellular trafficking and enabled efficient secretion of soluble BCMA-GFP and BCMA-mCherry fusion proteins. These reagents specifically labeled anti-BCMA CAR-T cells. Overall, our results establish a cost-effective method to generate soluble BCMA probes and provide accessible tools for monitoring CAR-T cells in translational settings.

No comparative analysis of the infrequently occurring B-cell neoplasms (BCNs) in the oral cavity has yet been reported in patients with non-immunosuppressiveness or immunosuppressiveness. To identify any differences in clinicopathological findings between patients with non-immunosuppressiveness and those with immunosuppressiveness, we compared the clinicopathological characteristics of oral-cavity BCNs in these patient groups. The clinical characteristics of 39 patients were analyzed from hospital records, including 24 with non-immunosuppressiveness and 15 with immunosuppressiveness. Histological and immunohistochemical evaluation was performed using formalin-fixed paraffin-embedded tissue sections. Comparisons between the two groups were conducted using cross-tabulations and the chi-squared or Fisher exact test. In patients with non-immunosuppressiveness, diffuse large B-cell lymphoma (DLBCL) was the most common type (14/24, 58%), followed by mucosa-associated lymphoid tissue lymphoma (MALT-L, 4/24, 17%). In patients with immunosuppressiveness, EBV-positive mucocutaneous ulcers (EBV-MCU) were the most common type (9/15, 60%), followed by DLBCL (3/15, 20%) and polymorphic/lymphoplasmacytic infiltration (3/15, 20%). Macroscopic findings showed 21 masses (88%) and 3 ulcers (13%) in patients with non-immunosuppressiveness and 11 ulcers (73%) and 4 masses (27%) in patients with immunosuppressiveness. Immunohistochemistry revealed that BCNs in patients with non-immunosuppressiveness expressed EBER in only 1 case (1/22, 5%), whereas those in patients with immunosuppressiveness expressed EBER in all cases (15/15, 100%). Our macroscopic findings and EBV status allowed us to distinguish BCNs between patients with non-immunosuppressiveness and those with immunosuppressiveness.

4-[4-(Bis(2-(nitrooxy)ethyl)amino)phenyl]butanoic acid (NPB), a phenylbutyrate-derived nitric oxide (NO) donor, has been developed as a potential anticancer agent for pancreatic cancer. In the present study, we investigated the cytotoxic effects of NPB under cellular stress conditions and examined its effects on autophagy-related pathways and hypoxia-inducible factor-1α (HIF-1α) signaling. NPB-induced cell death was enhanced under nutrient-deprived conditions in PANC-1 cells. In addition, NPB induced greater cell death under hypoxic conditions than under normoxic conditions in PANC-1 cells, whereas in BxPC-3 cells, NPB-induced cell death was slightly but significantly lower under hypoxic conditions than under normoxic conditions. Using GFP-LC3-RFP-LC3ΔG reporter cells, NPB suppressed starvation-induced autophagic flux. In pancreatic cancer cells, NPB decreased DAPGreen fluorescence, an indicator of autophagy-related vesicular activity, and increased propidium iodide-positive cells under hypoxic conditions. Western blot analysis showed that NPB induced the accumulation of p62 and LC3 under both normoxic and hypoxic conditions. Under hypoxic conditions, NPB also reduced HIF-1α expression. Under cobalt chloride (CoCl₂)-induced HIF-1α-accumulating conditions, NPB and the NO donor NONOate suppressed HIF-1α expression, whereas OH-PB, a non-NO-releasing analog, showed little effect. Furthermore, the proteasome inhibitor MG132 restored HIF-1α accumulation in NPB-treated cells. Time-course analysis under CoCl₂-treated conditions showed that NPB reduced HIF-1α expression concomitantly with p62 accumulation. These findings suggest that NPB induces pancreatic cancer cell death, particularly under nutrient-deprived and hypoxic conditions, accompanied by impairment of autophagy-related pathways and NO-dependent, proteasome-associated reduction of HIF-1α.

Curcumin is a naturally occurring bioactive compound with well-characterized anti-inflammatory and antitumor properties; however, its clinical utility is limited by poor bioavailability and chemical instability. To overcome these limitations, various curcumin analogs have been developed. In this study, we investigated the antitumor and antimetastatic effects of 3,5-bis(2'-ethoxybenzylidene)-piperidine-4-one (E145), a monocarbonyl curcumin analog, with a particular focus on its ability to inhibit nuclear factor-kappaB (NF-κB) signaling in breast cancer cells. We first evaluated the effects of E145 on cell proliferation in murine 4T1 and human MDA-MB-231 breast cancer cell lines. E145 inhibited cell proliferation in a dose-dependent manner and suppressed phosphorylation of the NF-κB p65 subunit. Furthermore, E145 blocked tumor necrosis factor alpha-induced NF-κB activation by inhibiting both p65 phosphorylation and nuclear translocation. Consistently, E145 reduced the expression of NF-κB-regulated pro-tumorigenic factors, including vascular endothelial growth factor, matrix metalloproteinase-9, interleukin-1β (IL-1β), and IL-6. Functional assays demonstrated that E145 markedly suppressed the migration and invasion of breast cancer cells in vitro. In addition, experimental lung metastasis assays revealed that E145 treatment significantly reduced metastatic colonization of 4T1 cells in vivo. Collectively, these findings indicate that E145 exerts potent antimetastatic effects by inhibiting cell-intrinsic NF-κB activation and downstream inflammatory mediators. These results suggest that E145 is a promising therapeutic candidate for targeting NF-κB-driven breast cancer progression and metastasis.