B-cell lymphoma 6 (BCL6) is a transcriptional repressor whose overexpression is closely linked to the progression of diffuse large B-cell lymphoma (DLBCL), making it a promising therapeutic target. This study aims to identify a novel small molecule, synthesized via proteolysis-targeting chimeras (PROTACs), capable of degrading BCL6, thereby inhibiting DLBCL growth and providing a foundation for future preclinical studies.

The expression of BCL6 in DLBCL was analyzed using The Cancer Genome Atlas (TCGA) database and the Human Protein Atlas. Western blotting assays confirmed BCL6 expression in tumor cell lines, leading to the identification of the small molecule compound DZ-865B. To evaluate DZ-865B's in vitro efficacy, multiple assays were performed, including protein immunoblotting, immunofluorescence, reverse transcription quantitative PCR, EDU proliferation, and soft agar cloning assays.

TCGA analysis revealed significant overexpression of BCL6 in DLBCL (p < 0.05), corroborated by immunohistological staining and western blotting. DZ-865B induced BCL6 degradation in DLBCL cell lines (OCI-LY-1 and SU-DHL-4) in a concentration- and time-dependent manner, and induced the degradation of nuclear BCL6 through the ubiquitin-proteasome pathway. Notably, DZ-865B did not alter BCL6 mRNA levels but modulated downstream gene expression, leading to the activation of apoptosis pathway proteins and inhibition of DNA synthesis, effectively suppressing DLBCL cell growth.

This study demonstrates that the small molecule DZ-865B targets and degrades BCL6 in DLBCL cells, promoting apoptosis and inhibiting cellular proliferation. These findings highlight DZ-865B as a potential therapeutic agent for diffuse large B-cell lymphoma.

Tamoxifen is a key drug that provides endocrine therapy for estrogen receptor (ER) α-positive breast cancer; however, resistance remains a significant clinical challenge. This study aims to investigate the molecular mechanisms of tamoxifen resistance in ERα-positive breast cancer, with particular focus on the role of SET Domain Containing 1A (SETD1A)-driven forkhead box A2 (FOXA2) as a key regulator of this resistance.

FOXA2 expression and its regulation by SETD1A were assessed via (quantitative polymerase chain reaction), western blotting, transcriptome profiling, and chromatin immunoprecipitation analyses. The effects of FOXA2 on cell proliferation, migration, invasion, and cancer stem cell traits were evaluated using small interfering RNA (siRNA)-mediated silencing. Clinical relevance was examined by analyzing patient datasets and tumor tissue microarrays.

FOXA2 expression was significantly elevated in tamoxifen-resistant (TamR) and ERα-negative breast cancer cells compared to that in ERα-positive MCF-7 cells, regardless of tamoxifen treatment or ERα depletion. Transcriptome and chromatin immunoprecipitation analyses revealed that SETD1A, a histone methyltransferase, directly regulated FOXA2 expression. Functionally, FOXA2 knockdown inhibited the proliferation, migration, invasion, and cancer stem cell properties of TamR cells while restoring tamoxifen sensitivity. High FOXA2 expression was correlated with poor survival and reduced responsiveness to tamoxifen in patients with ER-positive breast cancer.

Our findings identified FOXA2 as a key mediator of tamoxifen resistance regulated by SETD1A and suggested that targeting the SETD1A-FOXA2 axis may offer a novel strategy for overcoming endocrine resistance in breast cancer.

Accumulating evidence indicates that the neuro-immune axis is central to gastric cancer pathogenesis. Dynamic, bidirectional signaling between neural circuits and immune cells promotes tumor progression, shapes an immunosuppressive microenvironment, and contributes to therapeutic resistance. We synthesize current knowledge on how autonomic (sympathetic and parasympathetic) and sensory innervation regulate gastric cancer biology. These circuits act through neurotransmitters (catecholamines, acetylcholine) and neuropeptides (substance P [SP], calcitonin gene-related peptide [CGRP]) to foster tumor growth and angiogenesis, facilitate perineural invasion, and enable immune evasion by recruiting suppressive myeloid and lymphoid populations and by inducing checkpoint molecule expression. We also examine how chronic stress and the microbiota-gut-brain axis intensify immunosuppression via glucocorticoid signaling and microbially derived metabolites. In parallel, we discuss why current immunotherapies achieve only modest response rates (approximately 10%-20%) in many settings, emphasizing neurally mediated mechanisms of resistance. We evaluate therapeutic strategies that target the neuro-immune axis-including pharmacological neuromodulation, selective neural ablation, and rational combination regimens-and outline how single-cell approaches and neural-tumor-microenvironment organoid models can accelerate mechanism-driven translation. This review aims to integrate current evidence from neuroscience and immuno-oncology to construct a conceptual framework for neuro-immune regulation in gastric cancer and to identify potential therapeutic strategies to overcome treatment resistance by targeting neural-tumor-immune crosstalk.

A clear goal in cold tumor research is to identify strategies for converting them into immunologically 'hot' tumors with enhanced immune cell infiltration and activity, thereby improving their responsiveness to immunotherapy. The genesis of cold tumors is exceedingly intricate. In recent times, as the analysis of this phenomenon has been pursued with greater depth, a suite of advanced diagnostic and therapeutic technologies has surfaced. These novel approaches and tactics are anticipated to modulate the tumor immune microenvironment across various dimensions, thereby facilitating the advancement of personalized and precise treatment modalities for cold tumors. The present article addresses the challenge of diminished therapeutic responsiveness to "cold tumors" within clinical settings. It systematically elucidates the multi-faceted regulatory mechanisms underlying immune evasion in cold tumors and offers a detailed analysis of advanced therapeutic strategies that incorporate nanotechnology, gene editing, and artificial intelligence methodologies. Furthermore, the future development trends of immunotherapy were explored in greater depth. It was posited that the convergence of artificial intelligence, multidimensional genomics, and emerging biotechnologies has presented positive prospects for the treatment of cold tumors, and has offered a theoretical foundation and technical framework for the transformation of cold tumors into "hot tumors".

Classical Hodgkin lymphoma (cHL) is characterized by rare Hodgkin/Reed-Sternberg (HRS) tumor cells that uniformly express cluster of differentiation (CD)30 molecules and orchestrate an immunosuppressive tumor microenvironment, making CD30 an attractive and selective therapeutic target. We summarize the biological rationale for CD30 as a therapeutic target and the preclinical and clinical evidence across major platforms: antibody-drug conjugates (brentuximab vedotin), monoclonal antibodies (including acimtamig and its combinations with Natural Killer cells), second- and third-generation chimeric antigen receptor (CAR)-T cells, and alternative modalities. Particular attention is given to standardized response assessment (IWG, Lugano, RECIL criteria), which enables appropriate cross-trial comparisons. Taken together, the data indicate that beyond the established role of brentuximab vedotin, CD30-directed CAR-T cells and bispecific antibodies demonstrate high activity in refractory cHL, especially when used with fludarabine-containing lymphodepletion, combined with programmed cell death 1 (PD-1) receptor blockade as a strategy to eradicate minimal residual disease. Key challenges include durable effector-cell persistence and optimization of sequencing and combinations; notably, loss of CD30 as an escape mechanism appears uncommon. Integrating mechanistic insights into HRS biology with clinical trial data highlights strategies to enhance the efficacy, safety, and accessibility of CD30-directed immunotherapy. This review aims to provide a concise overview of CD30-targeted approaches in cHL, emphasizing therapeutic outcomes and the evolution of CAR-T technologies.

Photodynamic therapy (PDT) is a minimally invasive method used in the treatment of various cancers and skin diseases, but it is not widely used in bone cancer, where the current therapy is often not effective and accompanied by side effects. Alternative and more effective therapies like PDT are needed. In this in-vitro study, the effect of the photosensitizer (PS) chlorin e6 (Ce6) on cancerous bone tumor cells using PDT was examined.

A total of 27 tissue specimens from patients with primary bone cancers or bone metastases of different origins were genetically characterized and treated with PDT. Following a 24-h incubation, cell viability was determined, and the effect of PDT on cell migration was analyzed over 48 h.

We could demonstrate that the effect on proliferation of PDT in combination with the PS Ce6 was best in cells isolated from primary osteosarcoma and in bone metastases from mammary carcinomas. Besides proliferation, PDT was also effective in inhibiting the migration of these cells. A statistically significant correlation between the PDT effect and CD164 gene expression was detected, indicating that a high expression of this gene could result in a higher effectiveness of the photodynamic treatment.

This study analyzes for the first time the effect of PDT in bone cancers and metastases and shows the potential of treating these cancer types with Ce6 PDT.

Large language models (LLMs) are increasingly used by the public to obtain health information, yet the relationship between content quality and readability in LLM-generated patient education remains unclear.

We benchmarked five LLMs (Doubao, DeepSeek, Wenxin Yiyan, Tongyi Qianwen, and GPT-5) using an identical set of 20 Mandarin Chinese skin-cancer FAQs (100 total outputs). Quality was assessed using c-PEMAT-P and the Global Quality Scale (GQS), and readability was assessed using seven indices (ARI, FRES, GFOG, FKGL, CL, SMOG, and LW). Group differences and correlations were evaluated with appropriate statistical tests.

Models showed comparable understandability/actionability (c-PEMAT-P), while overall quality (GQS) differed, with GPT-5 scoring highest. Readability varied substantially by both model and content category, and no single model performed best across all readability metrics. Correlation analyses indicated that quality and readability were largely decoupled.

High-quality outputs do not necessarily have high readability. Optimizing AI-generated skin-cancer education requires multi-faceted strategies that jointly consider model choice and content topic.

This study aims to develop and clinically evaluate EarlyTect BCD Plus, a urine-based assay measuring two methylation sites of the PENK gene, and to assess its diagnostic performance and clinical utility according to haematuria risk stratification.

A dual-target quantitative methylation-specific PCR assay was optimized using the PENK gene and evaluated in 892 patients with haematuria from Korea and the United States who underwent cystoscopy and histopathology. Urine DNA was analysed for two PENK methylation markers, and test results were interpreted using a combined algorithm. Diagnostic accuracy was assessed, and clinical utility was further analysed for patients stratified by the 2025 AUA/SUFU haematuria guideline risk categories.

In the pooled cohort (gross haematuria, n = 509; microhaematuria, n = 366; unspecified haematuria, n = 17), EarlyTect BCD Plus achieved a sensitivity of 87.7% (95% CI, 81.5%-92.5%), specificity of 82.5% (95% CI, 79.6%-85.2%) and negative predictive value (NPV) of 97.0% (95% CI, 95.5%-98.0%). Sensitivity for Ta-LG tumours improved to 60.5% compared with the original single-marker assay, while high-grade tumours were detected with 96.6% sensitivity. In the intermediate-risk group, NPVs were 99.1% for all BC and 100% for high-grade BC.

EarlyTect BCD Plus significantly enhances detection of Ta-LG bladder cancer while maintaining high specificity. Its high NPV supports use as a non-invasive adjunct and triage tool, allowing deferral of cystoscopy in selected haematuria patients.

Accurate delineation of tumor margins during prostate cancer surgery remains challenging due to limited intraoperative visualization and insufficient molecular specificity. Here, we developed a PSMA-targeted near-infrared fluorescent probe, PSMA-12-IRDye800CW, that leverages the clinically used IRDye800CW scaffold and its extended emission tail beyond 1000 nm to support NIR-II fluorescence imaging for intraoperative navigation and histopathological margin mapping.

PSMA-12-IRDye800CW integrates a PSMA-targeting ligand with an albumin-binding linker to enable active targeting and circulation-assisted tumor accumulation. Optical properties, targeting specificity, imaging performance, and biosafety were evaluated in vitro, in prostate cancer xenograft models with direct comparison to indocyanine green (ICG) across defined time points, and in clinical formalin-fixed paraffin-embedded (FFPE) prostate specimens with matched histopathology and PSMA immunohistochemistry.

In 22Rv1 (PSMA⁺) xenografts, PSMA-12-IRDye800CW achieved significantly higher tumor-to-background ratios than ICG at key surgical-relevant time points, including 24 h (4.31 ± 0.17 vs. 2.65 ± 0.15), providing a practical imaging window for fluorescence-guided resection. Ex vivo tissue analyses further confirmed significantly higher fluorescence in tumors than in muscle and skin. In human FFPE specimens, fluorescence showed pathology-aligned spatial correspondence with PSMA immunohistochemistry, and fluorescence intensity correlated strongly with PSMA H-scores (R² = 0.8616, P < 0.0001), enabling micron-scale histopathological margin mapping. Multimodal biosafety assessments indicated favorable biocompatibility with no evident acute toxicity and low immunogenic potential.

PSMA-12-IRDye800CW enables NIR-II fluorescence imaging-assisted intraoperative navigation and provides a quantitative, pathology-anchored readout for histopathological margin mapping in prostate cancer, supporting further clinical validation of this PSMA-targeted strategy for fluorescence-guided surgery and margin assessment.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality, and while immune checkpoint inhibitor (ICI) has transformed treatment, resistance remains a critical challenge. Beyond the T-cell-centric view, tumor-infiltrating B lymphocytes (TIL-Bs) and tertiary lymphoid structures (TLSs) have emerged as pivotal prognostic determinants; however, the mechanistic interplay within the B-cell-autoantibody axis remains underexplored. Unlike previous reviews that primarily catalogue B-cell abundance, this synthesis integrates emerging evidence from single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to dissect the spatiotemporal dynamics of B-cell subsets. We elucidate how the maturation status of TLSs dictates the functional plasticity of TIL-Bs, switching between anti-tumor effector phenotypes (e.g., antibody-secreting plasma cells) and pro-tumor regulatory roles (e.g., IL-10⁺ regulatory B cells). Furthermore, we systematically examine the dualistic role of autoantibodies-not merely as serological biomarkers but as active regulators of the tumor immune microenvironment (TIME) through complement activation and antibody-dependent cell-mediated cytotoxicity (ADCC). Finally, we highlight the clinical and translational implications of targeting this axis, proposing precision strategies such as B-cell-based vaccines and the modulation of TLS neogenesis to overcome ICIs resistance. This review provides a comprehensive roadmap for integrating B-cell biology into next-generation personalized immunotherapy for NSCLC.