This study aimed to characterize molecular subtypes of Papillary thyroid carcinoma (PTC) and identify novel therapeutic targets and potential therapeutic compounds.

We performed integrative analysis of TCGA data, including consensus clustering, mutational profiling, copy number variation (CNV) analysis, functional enrichment (GO and GSEA), and immune microenvironment assessment (CIBERSORT). Validation utilized GEO datasets. The biological function of Plectin (PLEC) was investigated through expression analysis (TCGA, GEO, qRT-PCR and IHC), association with clinical parameters, and functional experiments such as siRNA knockdown or overexpression of PLEC in TPC-1 and B-CPAP cell lines assessing cell growth, proliferation, apoptosis, and migration both in vitro and in vivo. Drug candidates targeting PLEC were screened (DGIdb and DrugMap) and validated via molecular docking, dynamics simulations (RMSD, RMSF and Rg), and rescue experiments. Favorable biosafety was tested by ELISA kits and H&E staining.

Consensus clustering revealed four stable molecular subtypes (A1-A4) with distinct mutational landscapes (e.g., prevalent BRAF mutations (59%), subtype-specific alterations in CAND1/PCDH11X (A1) and PTEN (A4)), CNV gains (e.g., A1: 2p16.1/19p13.3), and immune features (A3 enriched in immune pathways). PLEC is up-regulated in PTC tissues compared with non-tumor thyroid tissues and was associated with lymph node metastasis, histological type, and residual tumor status in TCGA-THCA. Knockdown of PLEC significantly suppressed PTC cell growth, proliferation, and migration while inducing apoptosis. Whereas PLEC overexpression partially reversed these phenotypes. Among FDA-approved drugs predicted to target PLEC, Troglitazone exhibited the lowest binding affinity (-7.5 kcal/mol). Troglitazone's anti-tumor effects (inhibiting proliferation/migration, inducing apoptosis) were partially reversed by PLEC overexpression, suggesting that PLEC may participate in Troglitazone-associated anti-PTC effects.

These findings identify PLEC as a candidate molecule associated with aggressive PTC phenotypes and provide preliminary evidence supporting its biological relevance, although larger independent cohorts are required to validate its clinical significance.

Background: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer exhibits high metastatic potential, linked not only to intrinsic cancer cell traits but also to critical crosstalk with the tumor microenvironment. However, the coevolutionary mechanisms between cancer cells and multiple stromal subpopulations in driving distant metastasis remain poorly understood. Therefore, this study aimed to explore the microenvironmental regulatory mechanisms of breast tumor-initiating cells and their roles in HER2-positive breast cancer metastasis. Methods: Integrated multi-omics analyses (spatial transcriptomics, metabolomics, spatial in situ analysis, and proteomics) were used to identify novel cell subpopulations and their interactions. High-throughput sequencing of exosomal microRNAs (miRNAs) and single-nucleus RNA from the same tissue was performed to explore the molecular mechanisms underlying cell crosstalk. In vitro experiments were conducted to verify the interaction between stromal cells and prominin 1 (PROM1)⁺ SMAD family member 5 (SMAD5)⁺ cells. In vivo murine breast cancer models were established to confirm the role of stromal subpopulations in pulmonary metastasis, and parabiosis assays were carried out to compare key cell subpopulations between tumor-bearing mice and normal mice. Clinical samples were analyzed to correlate key cell subpopulations with clinicopathological features and prognosis. Results: A breast tumor-initiating subpopulation, PROM1⁺ SMAD5⁺ cells, and its interactions with stromal cells, specifically adiponectin (ADIPOQ)⁺ notch receptor 4 (NOTCH4)⁺ adipocytes and decorin (DCN)⁺ transmembrane 4 L six family member 1 (TM4SF1)⁺ fibroblasts, were identified by integrated multi-omics analyses. Mechanistically, these 2 stromal subpopulations delivered functional miRNAs and mediated coatomer protein complex subunit alpha (COPA)-dependent epidermal growth factor receptor (EGFR) activation in PROM1⁺SMAD5⁺ cells, thereby triggering the EGFR-SMAD5-cytochrome P450 family 3 subfamily A member 4 (CYP3A4) axis to induce partial epithelial-mesenchymal transition (pEMT) and metastasis. Additionally, stroma-secreted exosomal miR-671-3p down-regulated Claudin1 in PROM1⁺SMAD5⁺ cells, promoting their evolution into PROM1⁺SMAD5⁺Claudin1^- subpopulations with enhanced stemness and metastatic potential. In vivo experiments confirmed that the 2 stromal subpopulations markedly promoted pulmonary metastasis, and the 3 identified subpopulations preferentially accumulated in the primary tumors, lymph nodes, and pulmonary metastatic lesions of tumor-bearing mice. Clinically, these 3 subpopulations form a "trinity niche", whose aggregation associated with HER2 positivity, high malignancy, and lymph node/pulmonary metastasis, and predicted poor prognosis. Conclusion: This study clarified the microenvironmental regulation of breast tumor-initiating cells and provided new insights into precision therapy.

CAR T cell therapies have shown clinical success in several tumor types, though not in breast cancer, for which advanced stages remain incurable. CD70 is expressed in a broad range of solid tumor types and is emerging as a molecular target for CAR T cells in renal and ovarian malignancies. Here we show that a subset of breast cancer cell lines and patient-derived xenografts express CD70, albeit to varying levels. Leveraging a recently developed HLA-independent T cell (HIT) receptor with greater sensitivity to CD70 than conventional CAR designs, we assessed whether CD70 can be targeted to eliminate breast cancer cells. We observed that CD70-targeted HIT T cells showed antigen-specific activation in vitro, and cytotoxicity against breast cancer cell lines and patient-derived xenograft cells across a broad range of CD70 levels. Implanted in the murine mammary fat pad, high CD70-expressing patient-derived xenografts were readily eliminated by both conventional CAR and HIT T cells. Against xenografts with lower CD70 expression, however, CD70-targeted HIT T cells engineered with supplemental costimulation outperformed conventional CAR T cells by inhibiting tumor outgrowth in mice, and conferred a significant survival benefit. These findings establish that CD70 is a targetable antigen in breast cancer and highlight the potential of enhanced-sensitivity receptor designs such as HIT receptors to engage a broader range of tumors.

Secondary myelodysplastic syndrome (sMDS) is increasing as more individuals survive treatment for a primary cancer diagnosis, which is associated with many factors, such as prior alkylator therapy, topoisomerase II inhibitors and higher-dose pretransplant irradiation, hematopoietic cell transplantation (HCT) and graft purging.

We report a unique case of sMDS diagnosed 34 months after a sequential treatment regimen consisting of chemotherapy, autologous hematopoietic stem cell transplantation (auto-HSCT), and chimeric antigen receptor T (CAR-T) cell therapy for primary splenic diffuse large B-cell lymphoma (DLBCL). With reference to existing literature, we discuss plausible etiologic interpretations and research limitations.

The patient was diagnosed with therapy-related myelodysplastic syndrome (t-MDS) with multihit-TP53. The patient achieved complete remission after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and achieved sustained complete remission with full donor chimerism during 18 months of follow-up.

The case we reported highlights the cumulative risk of t-MDS associated with multi-modal intensive treatments for relapsed/refractory DLBCL, even with initial disease control. The etiology of sMDS is multifactorial. This case may provide novel hypothesis-generating clues for exploring the mechanisms underlying clonal evolution under multimodal hematopoietic stress. This single case raises the hypothesis that early allo-HSCT may contribute to favorable prognosis, which needs validation in larger cohorts.

Orbital solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is an exceedingly rare mesenchymal neoplasm in the pediatric population. While typical orbital tumors present with proptosis or mass effect, the clinical picture can be deceptively indolent, leading to diagnostic delay.

A 15-year-old male patient presented with a 2-year history of progressive right upper eyelid edema that had repeatedly been misdiagnosed as conjunctivitis and visual fatigue. Notably, there was an absence of proptosis, visual decline, or ocular motility restriction. Magnetic resonance imaging revealed an extraconal mass posterior to the right globe. The patient underwent lateral orbitotomy with en bloc resection of a 4.5 cm × 3.5 cm × 2.5 cm dark-red, pseudocapsulated tumor. Histopathology and immunohistochemistry (CD34+, CD31-, S-100-, SMA-, and Ki-67 3%) confirmed the diagnosis of SFT/HPC. Given the tumor size and the potential risk of recurrence, adjuvant low-dose radiotherapy was administered after a multidisciplinary discussion.

This case underscores that persistent, asymmetric eyelid edema in a child-even in the absence of classic orbital signs-warrants dedicated orbital imaging to exclude space-occupying lesions. Complete surgical resection via lateral orbitotomy provides the definitive diagnosis and effective local control for orbital SFT/HPC.

Distinguishing non-small lung cancer (NSCLC) with tuberculosis from pulmonary tuberculosis (PTB) is still a major clinical problem. Misdiagnosis or missed diagnosis can lead to missed opportunities for optimal treatment, making highly sensitive diagnostic criteria crucial.

Database analysis and histological analysis were used at the same time. A total of 55 patients were included in the histological analysis, including 20 patients with both NSCLC and PTB (NSCLC-PTB group), 20 patients with NSCLC alone (NSCLC group), and 15 patients with PTB alone (PTB group). The levels of NLRC4 and NLRP3 in each sample were analysed using the optical density method. Statistical analyses were performed, including the LIMMA algorithm, regression, and ROC analysis, to assess biomarker levels and their correlation with clinical outcomes.

The expression of NLRC4 and NLRP3 was significantly down-regulated in NSCLC tissues (both P < 0.001), and low expression of NLRC4 was associated with shorter overall survival (HR = 0.76, P < 0.001), while low expression of NLRP3 was associated with longer survival (HR = 1.21, P < 0.001). The level of NLRC4 in cancer nodules in the NSCLC-PTB group was significantly lower than that in the PTB group (0.0177 ± 0.0218 vs. 0.0299 ± 0.0117, P = 0.021). The level of NLRP3 in adjacent nodules in the NSCLC-PTB group was significantly higher than that in the PTB group (0.0398 ± 0.0282 vs. 0.0097 ± 0.0078, P < 0.001). At the same time, the results show that NLRC4 has the best diagnostic effect in squamous cell carcinoma, patients aged 60 and above, as well as NLRP3 in patients below 60, and the combination of NLRC4 and NLRP3 in adenocarcinoma.

The use of NLRC4 and NLRP3 as biomarkers can improve the certainty of NSCLC prediction and has great prospects.

Chimeric antigen receptor (CAR) T-cell therapy has shown limited efficacy against solid tumors due to antigen heterogeneity and scarcity of tumor-specific targets.

To address those challenges, we report a covalent CAR-T strategy that achieves programmable tumor recognition via oncolytic adenovirus-mediated (OAD) delivery of artificial antigens. An engineered OAD was designed to induce tumor-selective expression of a membrane-anchored SpyTag-containing artificial antigen on infected tumor cells. In parallel, we generated SpyCatcher CAR-T cells by replacing the conventional single-chain variable fragment (scFv) with SpyCatcher, which forms a spontaneous covalent bond with SpyTag and redirects CAR-T-cell activity toward virus-labeled tumor cells.

In vitro, optimized SpyCatcher CAR-T cells mediated selective cytotoxicity against SpyTag-positive tumor cells, achieving >85% specific lysis at an effector-to-target ratio of 1:1, while sparing antigen-negative cells. The OAD efficiently induced tumor-selective expression of membrane-anchored SpyTag-fused antigens across multiple cell lines. Combined treatment with OAD and SpyCatcher CAR-T cells resulted in substantially greater antitumor activity than either monotherapy alone. In vivo, the combinatorial strategy significantly inhibited tumor growth and increased intratumor CD3⁺, CD8⁺ T-cell infiltration in both immunodeficient and immunocompetent mouse models. Importantly, patient-derived prostate cancer organoids were effectively transduced by OAD and supported robust SpyCatcher CAR-T cell infiltration and cytotoxicity, demonstrating the translational potential of this approach.

This study establishes a modular platform for solid tumor immunotherapy therapy by integrating covalent SpyCatcher CAR-T cells with SpyTag-delivering OAD. By decoupling tumor recognition from endogenous antigen expression, this approach provides a generalizable strategy to overcome antigen heterogeneity and scarcity of tumor-specific targets in solid tumors.

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, highlighting the urgent need for more effective and clinically translatable therapeutic agents. In recent years, drug discovery strategies integrating computational modeling with experimental validation have gained increasing attention; however, their predictive consistency across biological scales remains a critical challenge. This review systematically synthesises evidence from eleven primary studies that evaluated anti-lung cancer agents across computational, cellular, and organism-level platforms within a single developmental continuum. Eligible studies were required to report either in silico target prediction/molecular docking or network pharmacology analysis (or both), in direct conjunction with in vitro cytotoxic evaluation and in vivo efficacy assessment. Relevant studies were identified using a structured Boolean keyword strategy integrating computational, cellular, animal-based, and lung cancer-specific terms. Across the analyzed studies, computational and network approaches consistently converged on key oncogenic signaling hubs, particularly PI3K/AKT-centered pathways and receptor tyrosine kinases. These predictions were corroborated by cellular assays demonstrating selective antiproliferative activity in lung cancer cell lines and subsequently validated in animal models showing significant tumor growth suppression with acceptable safety profiles. Notably, agents optimized through targeted delivery systems, formulation strategies, or rational combination therapies exhibited the most consistent cross-platform performance. Collectively, the findings highlight that robust anti-lung cancer efficacy is most reliably achieved when molecular interaction data, systems-level network engagement, cellular responses, and in vivo outcomes are coherently integrated. This integrated evaluation framework provides a rational and predictive foundation for future anti-lung cancer drug discovery and development.

Head and neck cancer (HNCs) is a major health issue worldwide, and India has contributed to approximately 2.4 lakh new cases in 2022. Definitive chemoradiation is the standard treatment for locally advanced disease but carries a risk of lower respiratory tract infections (LRTI) that add to morbidity, hospitalization, cost, and possible delay in treatment. The increasing incidence of antimicrobial resistance (AMR) has also contributed to management burden. This study aimed to assess the microbiological profiles and antimicrobial resistance patterns of lower respiratory tract infections in patients with head and neck cancer receiving chemoradiation.

Patients who underwent definitive radiotherapy with or without chemotherapy and who developed LRTIs were included in the study. Sputum and tracheostomy suction tip cultures were obtained and processed using standard microbiological techniques such as Gram staining, biochemical tests, and VITEK-2 automated systems. Antimicrobial susceptibility was tested according to the Clinical and Laboratory Standards Institute (CLSI) and EUCAST recommendations. Clinical and treatment-related factors were documented and compared using SPSS version 23.0, with descriptive statistics, chi-square tests, t-tests, ANOVA, and logistic regression models.

Pseudomonas aeruginosa was the most frequently isolated pathogen (35.0%), followed by Klebsiella pneumoniae (16.7%), and Acinetobacter baumannii (10.0%). The pathogens were strongly resistant to fluoroquinolones and third-generation cephalosporins but were susceptible to carbapenems and aminoglycosides in the majority of isolates. Pseudomonas aeruginosa was the most frequent pathogen in all age groups and chemotherapy regimens (p<0.001).

LRTIs in patients with HNC treated with chemoradiation were mainly caused by multidrug-resistant Pseudomonas aeruginosa and Klebsiella pneumoniae. Resistance patterns are crucial for directing empirical antibiotic therapy, minimizing treatment delays, and enhancing clinical outcomes.

Newly emerging influenza viruses pose a constant threat as they encounter a population lacking neutralizing antibodies against the new strain. However, cross-reactive non-neutralizing antibodies (nnABs) may be present and help mitigate disease symptoms through various effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Although nnABs to influenza virus have received more attention lately, little information is available on their age-related prevalence, steady-state levels, functional properties, and changes in these parameters over time. Using longitudinal samples from adolescents, adults, and older adults, collected before and after the 2009 swine flu pandemic, we comprehensively characterized the specificity and functionality of nnAB responses against H1N1 pandemic 2009 (H1N1pdm09) virus. Remarkably, all participants exhibited cross-reactive antibodies to this virus before having encountered it through infection or vaccination, with the highest baseline levels observed in older adults. The levels of these IgG antibodies showed a strong correlation with engagement of fragment crystallizable γ receptor IIIa (FcγRIIIa) and NK cell activation, both of which were notably lower in adolescents than in adults and older adults. Without infection or vaccination, average amounts of H1N1pdm09-reactive antibodies remained relatively stable on the population level over the 5-year study period. However, on an individual level, substantial increases and decreases occurred. H1N1pdm09 infection or vaccination significantly enhanced specific antibody levels and the FcγRIIIa-engaging capacity of these antibodies in all age groups. ADCC-mediating antibodies increased, however, only in adolescents, reaching the same level as observed in the adult groups. Taken together, our results demonstrate the presence of cross-reactive, non-neutralizing, functional, and boostable antibodies against a never-encountered influenza virus strain across all age groups. These antibodies might contribute to protection from severe disease. Accordingly, in case of a newly emerging influenza virus, their further enhancement by vaccination could be beneficial as an immediate protective measure before a strain-specific vaccine becomes available.