Clinical and Experimental Medicine最新文献

{"title":"Oncolytic virotherapy for cancer: biological mechanisms, clinical advances, and future perspectives.","authors":"Esraa M Halawa, Sherihan G AbdelHamid, Mahmoud ElHefnawi","doi":"10.1007/s10238-026-02311-3","DOIUrl":"10.1007/s10238-026-02311-3","url":null,"abstract":"<p><p>Oncolytic virotherapy has emerged as a promising cancer treatment that combines selective tumor destruction with potent stimulation of antitumor immunity. Unlike conventional therapies, oncolytic viruses (OVs) preferentially infect and replicate within malignant cells while sparing normal tissues, leading to direct tumor lysis and the release of tumor-associated antigens, pathogen-associated molecular patterns, and damage-associated molecular patterns that activate both innate and adaptive immune responses. Advances in molecular virology and genetic engineering have transformed naturally occurring viruses into programmable therapeutic platforms capable of delivering immunomodulatory payloads that enhance antitumor efficacy and remodel the tumor microenvironment. Multiple DNA- and RNA-based viral platforms, including herpes simplex virus, adenovirus, vaccinia virus, reovirus, measles virus, Newcastle disease virus, vesicular stomatitis virus, and coxsackievirus, are currently under clinical investigation, with regulatory approval of talimogene laherparepvec (T-VEC) and G47Δ providing important proof of clinical feasibility. Increasing evidence indicates that OVs can convert immunologically \"cold\" tumors into \"hot\" tumors, thereby improving responsiveness to immune checkpoint inhibitors and other therapeutic modalities. Consequently, oncolytic virotherapy has become an attractive component of combination strategies involving immunotherapy, chemotherapy, radiotherapy, targeted therapies, and cellular therapies. Nevertheless, several challenges continue to limit its broader clinical application, including antiviral immune clearance, inefficient systemic delivery, restricted intratumoral spread, tumor heterogeneity, manufacturing complexity, and the lack of robust predictive biomarkers. This review provides a comprehensive overview of the biological foundations of oncolytic virotherapy, viral engineering strategies, mechanisms of tumor selectivity, direct oncolysis, immunogenic cell death, and immune remodeling of the tumor microenvironment. It further summarizes the major oncolytic virus platforms, recent preclinical and clinical advances, emerging combination strategies, current translational challenges, and future directions expected to advance precision oncolytic virotherapy and expand its role in modern cancer treatment.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammasome, clonal stability and the thrombotic circuit in myeloproliferative neoplasms: an antecedent framework.","authors":"Alessandro Lucchesi, Mariasanta Napolitano","doi":"10.1007/s10238-026-02343-9","DOIUrl":"10.1007/s10238-026-02343-9","url":null,"abstract":"<p><p>El-Sehrawy and colleagues recently proposed a model of clonal thrombo-inflammation in myeloproliferative neoplasms organised around the inflammasome, clonal stability and a multi-compartmental thrombotic niche. Each of these elements was addressed in two reviews published by our group in 2021, neither of which is cited. The first set out the pathogenetic role of the NLRP3 and AIM2 inflammasomes and their link to hypercoagulable states; the second formalised the vascular consequence as the Circulating Wound, a self-sustaining lesion in which tissue-factor-rich clonal platelets, thrombin generation, protease-activated receptor signalling and TGF-β crosstalk reinforce one another. This coagulative arm is absent from the more recent model. We summarise experimental findings from 53 therapy-naive patients that support the earlier formulation, and set out where the two accounts diverge and why the difference bears on the therapeutic reading.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149191861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mystery of BMI in Sjögren's disease: unravelling complex relationships between BMI and multiple laboratory parameters.","authors":"Yaya Ding, Xueqi Zhao, Xian Liu, Bingbing Yu, Rong Chang, Qian Sun, Yutao Fan, Yiran Wang, Quan Jiang, Man Han","doi":"10.1007/s10238-026-02354-6","DOIUrl":"10.1007/s10238-026-02354-6","url":null,"abstract":"<p><p>The relationship between body mass index (BMI) and laboratory parameters in Sjögren's disease (SjD) remains unclear. We evaluated associations of BMI with selected serological and haematological parameters and explored its relationship with the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). This single-centre retrospective cross-sectional study included 554 unique hospitalised patients with SjD. Multivariable linear regression models were adjusted for age, sex and disease duration. Effect estimates were expressed per 5 kg/m² higher BMI, and Benjamini-Hochberg false discovery rate correction was applied across all estimable laboratory outcomes. Generalised additive and segmented regression models examined nonlinear relationships. Natural-log-transformed CRP and TNF-α analyses and an ESSDAI score excluding both biological and haematological domains were used as sensitivity analyses. After adjustment for age, sex and disease duration, each 5 kg/m² higher BMI was associated with lower IgG and higher C3, HGB, WBC and RBC after false discovery rate correction. CRP showed a nominal inverse association (P = 0.038, q = 0.076). TNF-α showed no linear association, but U-shaped patterns were observed in raw and log-transformed analyses. BMI was weakly inversely correlated with ESSDAI (ρ=-0.160, P < 0.001) and very weakly with ESSDAI excluding the biological and haematological domains (ρ=-0.085, P = 0.044). BMI was associated with several laboratory parameters and weakly with ESSDAI in this hypothesis-generating cross-sectional study. The underlying mechanisms remain uncertain.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and exploratory external assessment of a machine learning model for early delirium prediction in non-mechanically ventilated patients with sepsis.","authors":"Bingjie Xiang, Yuan Gao, Yuanyuan Ren, Xiaoli Zhong, Jinxiu Li, Yan Zhang","doi":"10.1007/s10238-026-02306-0","DOIUrl":"10.1007/s10238-026-02306-0","url":null,"abstract":"<p><p>Delirium is a common and severe complication of sepsis in critically ill patients and is associated with increased mortality and prolonged hospitalization. Early identification of high-risk individuals remains challenging, particularly among non-mechanically ventilated patients who are less frequently represented in prediction studies. Using routinely collected electronic health record data, we performed a retrospective multicenter study to establish and validate an early prediction model for delirium in non-mechanically ventilated adults with sepsis. Patients from the MIMIC-IV database were used for model development, and an independent cohort from the eICU Collaborative Research Database was used for exploratory external assessment. A total of 3,015 patients in the development cohort and 1,119 patients in the exploratory test cohort were included. Among the evaluated algorithms, XGBoost achieved the best discrimination, with an area under the receiver operating characteristic curve of 0.807 in internal validation. The eICU cohort contained only 10 delirium cases (incidence < 1%), forming a sparse-event dataset; although the XGBoost model yielded an AUC of 0.833 in this cohort, the calibration and decision curve analysis results should be interpreted with extreme caution due to limited positive events. Lower Glasgow Coma Scale scores, higher illness-severity indices, exposure to sedative or analgesic agents, and metabolic disturbances such as elevated anion gap and abnormalities in hematocrit and calcium were the strongest contributors to prediction. These predictors align with recognized features of sepsis-associated brain dysfunction. This externally validated model may support early risk stratification and targeted preventive strategies in this vulnerable population.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"H19 and the PD-1/PD-L1 Axis in hepatocellular carcinoma and colorectal cancer: emerging evidence, mechanistic links, and therapeutic perspectives.","authors":"Mohammad Taha Nami, Fatemeh EmamiPari, Nooshin Farrokhi, Iliya Fattahyan, Maryam Yekkalam","doi":"10.1007/s10238-026-02319-9","DOIUrl":"10.1007/s10238-026-02319-9","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are major causes of cancer-related mortality, yet responses to immune checkpoint inhibitors (ICIs) remain heterogeneous. Although programmed death-ligand 1 (PD-L1) is a key component of immune checkpoint biology, antitumor immunity is shaped by multiple tumor-intrinsic and microenvironmental factors, and the contribution of the long non-coding RNA H19 to these processes remains incompletely defined. This narrative review synthesizes experimental and clinical evidence linking H19 to immune regulation in HCC and CRC, with particular emphasis on its potential intersection with PD-L1-mediated immune checkpoint signaling. Evidence was classified as experimentally demonstrated, indirectly supported, contextual, or hypothetical according to the strength, mechanistic resolution, and disease specificity of the available data. Current evidence indicates that H19 perturbation can influence PD-L1-associated phenotypes in selected experimental HCC models; however, a complete, mechanistically resolved H19-dependent PD-L1 regulatory axis, including validated intermediate mechanisms and causal rescue, has not been established in HCC or CRC. Proposed ceRNA and signaling mechanisms remain incompletely validated, while several mechanistic links are supported primarily by indirect or cross-cancer evidence. Beyond direct checkpoint regulation, H19-associated extracellular vesicles and H19-dependent signaling have been implicated in macrophage remodeling, intercellular communication, and T-cell dysfunction, although direct convergence of these processes on H19-mediated PD-L1 regulation remains unproven. Circulating H19 has also shown preliminary associations with tumor presence or burden, but its clinical utility as a diagnostic, prognostic, or predictive biomarker remains insufficiently validated, particularly for ICI response. Overall, H19 represents a biologically plausible interface between non-coding RNA regulation, tumor-intrinsic signaling, and the tumor immune microenvironment rather than an established central regulator of PD-L1. Disease-specific mechanistic studies incorporating H19 perturbation, PD-L1 measurement, pathway-specific rescue, and immune-functional assays are required to determine whether H19 can serve as a clinically actionable component of immune checkpoint regulation.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13638753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-based therapies of autoimmune diseases in the context of artificial intelligence development.","authors":"Diya Dinesh, Snigdha Suman Das, Barshana Bhattacharya, K Sreedhara Ranganath Pai","doi":"10.1007/s10238-026-02302-4","DOIUrl":"10.1007/s10238-026-02302-4","url":null,"abstract":"<p><p>Autoimmune diseases are comprised of several chronic inflammatory conditions characterized by activation of autoreactive T and B lymphocytes and produces autoantibodies. While most of the current treatment options mainly rely on non-specific immunosuppression, stem cell based therapies can be a promising candidate for promoting \"immune reset\" and restore long term tolerance against these complex diseases. Stem cell based therapy eliminate autoreactive clones and reconstitute immune tolerance. Besides, mesenchymal stromal cells (MSCs; also referred to as mesenchymal stem cells) have immunomodulatory effects via paracrine signalling, including anti-inflammatory cytokine and extracellular vesicles secretion. However, successful clinical translation is limited by complex high-dimensional datasets and patient heterogeneity. In this review, we have focused on the convergent journey of Artificial Intelligence (AI) and stem cell based therapies, which mainly evolved in recent times. We also discussed how machine learning and deep learning methods facilitate the analysis of single-cell multi-omics, spatial transcriptomics, and easily identify disease states. Furthermore, the role of AI in optimizing the design and potency of therapeutic modalities, including regulatory T cells (Tregs), Chimeric Antigen Receptor (CAR)-T cells, and mesenchymal stromal cells (MSCs) have also been explored. Altogether, this review highlights the emerging role of AI-guided approaches in bridging mechanistic immunology with future precision stem cell therapies, while several computational and preclinical studies are promising, prospective clinical validation remains necessary before widespread clinical implementation .</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13553666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium-glucose cotransporter-2 inhibitors and gastrointestinal neoplasm risk in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.","authors":"Yu-Fan Zhang, Jia-Jie Xie, Qi Wu, Xiao-Yu Zhou, Chen Zeng, Yan Zeng, Yi-Meng He, Man Guo, Fang-Yuan Teng, Yong Xu","doi":"10.1007/s10238-026-02300-6","DOIUrl":"10.1007/s10238-026-02300-6","url":null,"abstract":"<p><p>The potential carcinogenic effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) remain controversial, particularly regarding site-specific gastrointestinal (GI) neoplasms. This systematic review and meta-analysis aimed to determine the relationship between SGLT2 inhibitors and the risk of GI neoplasms in patients with T2DM. We searched PubMed, EMBASE, Cochrane CENTRAL, Scopus, and Web of Science through March 17, 2025, for RCTs in T2DM comparing SGLT2 inhibitors with placebo or active comparators. Two reviewers independently screened studies, extracted data, and assessed the risk of bias. The primary outcome was GI neoplasms reported in publications, supplementary materials, or trial registries, usually as adverse events rather than centrally adjudicated cancer endpoints. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in Stata 17.0. In 48 RCTs (n = 48,765), SGLT2 inhibitor therapy was not associated with overall GI neoplasm risk (OR = 1.10, 95% CI: 0.84-1.44; p = 0.46; I² = 0%). Site-specific analyses showed no statistically significant association for esophageal (OR = 1.12, 95% CI 0.37-3.45), gastric (1.20, 0.65-2.23), hepatic (0.62, 0.31-1.22), pancreatic (0.91, 0.51-1.64), colonic (1.28, 0.78-2.08), colorectal (0.76, 0.27-2.17), and rectal neoplasms (0.98, 0.49-1.97), with all p-values > 0.05. Subgroup analyses by agents (e.g., canagliflozin, dapagliflozin, empagliflozin), baseline age, body mass index (BMI), HbA1c, treatment duration, and dose were also non-significant (all p > 0.05). Approximately half of the trials had follow-up of one year or less, limiting our ability to evaluate long-term risk. Available RCT evidence does not show a clear increase in GI neoplasm risk with SGLT2 inhibitors in T2DM. However, limited follow-up, low event counts, and non-cancer-specific outcome ascertainment, the findings should be interpreted as reassuring but not definitive evidence of long-term oncologic safety.Systematic review registration: PROSPERO No. CRD42024619019.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13541834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An interpretable machine learning model for early prediction of subsequent observed CRRT initiation in patients with sepsis-associated acute kidney injury.","authors":"Yaoyao Tang, Shuai Zhang, Qiujun Wang, Qi Zhang, Liye Ji, Ruoxi Li, Mingxing Fang","doi":"10.1007/s10238-026-02305-1","DOIUrl":"https://doi.org/10.1007/s10238-026-02305-1","url":null,"abstract":"<p><p>We developed and externally validated an interpretable machine-learning model for observed continuous renal replacement therapy (CRRT) initiation in sepsis-associated acute kidney injury (SA-AKI) using a strict 24-hour landmark framework. This multicenter retrospective study used MIMIC-IV and eICU-CRD data. Predictors were restricted to the period from sepsis diagnosis to 24 h, and the outcome was first observed CRRT initiation after the landmark and within 7 days. Patients who died, initiated CRRT, or were no longer under observation by 24 h were excluded. Eight algorithms were evaluated, and a seven-predictor Gradient Boosting model was selected. Discrimination, calibration, incremental value, SHAP-based interpretation, and exploratory prediction-subgroup outcomes were assessed. The final MIMIC-IV cohort included 5,238 patients, with 239 CRRT events; 3,666 were assigned to training and 1,572 to internal validation. The eICU-CRD cohort included 4,683 patients and 157 events. The model retained serum creatinine, AKI stage, SOFA score, urine output, lactate, red blood cell distribution width, and peripheral oxygen saturation. AUCs were 0.905 internally and 0.816 externally, with an external calibration slope of 0.567. In an exploratory age- and sex-matched eICU analysis, the high predicted-risk/no observed CRRT subgroup had higher ICU, 7-day, and 28-day mortality than the true-negative subgroup. The model provided interpretable risk estimates for observed CRRT initiation, but external calibration and incremental value were limited. Findings should not be interpreted as evidence of CRRT indication, undertreatment, or treatment benefit. Prospective validation and local recalibration are required.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-associated fusion transcripts: mechanisms, functional roles, and clinical implications.","authors":"Md Faruq Hossain","doi":"10.1007/s10238-026-02303-3","DOIUrl":"10.1007/s10238-026-02303-3","url":null,"abstract":"<p><p>Fusion transcripts are hybrid RNA molecules generated through genomic rearrangements or RNA-level fusion mechanisms. They represent important molecular features of many cancers and can function as oncogenic drivers, diagnostic biomarkers, prognostic indicators, and therapeutic targets. Since the discovery of the BCR::ABL1 fusion in chronic myeloid leukemia, numerous cancer-associated fusion transcripts have been identified across hematologic malignancies and solid tumors. These fusion events encompass diverse biological mechanisms, including constitutively active kinases, aberrant transcription factors, epigenetic regulators, and non-coding fusion RNAs. This review summarizes current knowledge of the mechanisms underlying fusion transcript formation, including genomic rearrangement-dependent and rearrangement-independent processes, as well as fusion circular RNAs. The functional roles of fusion transcripts in cancer biology and their clinical relevance as diagnostic, prognostic, and predictive biomarkers are discussed. In addition, recent advances in fusion transcript detection and characterization are reviewed, including next-generation sequencing, long-read sequencing, single-cell approaches, artificial intelligence-assisted computational methods, and CRISPR/Cas9-mediated strategies for functional modeling and functional validation of fusion transcripts. Despite the rapid expansion of fusion transcript catalogs, the biological and clinical significance of most identified fusion events remains incompletely understood. Future progress will depend on integrating advanced sequencing technologies, artificial intelligence-assisted computational prioritization, and systematic functional validation to distinguish clinically actionable fusion transcripts from biologically neutral events. Such multidisciplinary approaches will be essential for translating fusion transcript research into precision oncology and improving cancer diagnosis, patient stratification, and targeted therapy.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13529871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental evaluation of Nilotinib and Paclitaxel co-delivered via albumin nanoparticles as a therapeutic strategy for lung squamous cell carcinoma.","authors":"Xingfang Wei, Leiyu Cao, Yan Gao, Chengcheng Qu, Zhongxiong Fan, Li Zhang","doi":"10.1007/s10238-026-02293-2","DOIUrl":"10.1007/s10238-026-02293-2","url":null,"abstract":"<p><p>Chemotherapy remains the primary treatment for advanced lung squamous cell carcinoma (LUSC); however, its severe toxic side effects significantly limit therapeutic efficacy. There is an urgent clinical need to integrate molecular targeting with chemotherapy to enhance treatment outcomes. Consequently, this study developed a co-loaded albumin-based nanodelivery system (NLB/PTX-NPs) for targeted delivery of nilotinib alongside the chemotherapeutic agent paclitaxel. We systematically evaluated its in vitro and in vivo anti-tumor activity, safety, and underlying molecular mechanisms. NLB/PTX-NPs were synthesized via the solvent displacement method, followed by characterization of their physicochemical properties, drug-loading performance, and biosafety. Using NCI-H520 cells as a model, the in vitro efficacy and molecular mechanisms were evaluated through cellular uptake studies, cytotoxicity assessments, in vitro cellular experiments, and Western Blot assays. Additionally, subcutaneous tumor and lung metastasis models were established in nude mice to evaluate in vivo targeted distribution, as well as anti-tumor and anti-metastatic activities. NLB/PTX-NPs exhibited a uniform spherical morphology, demonstrating excellent dispersibility, stability, and biosafety. In vitro experiments revealed that the nanoparticles significantly enhanced cellular uptake and inhibited the proliferation, migration, and invasion of NCI-H520 cells. Western blot analysis confirmed their ability to regulate the expression of proteins associated with apoptosis and epithelial-mesenchymal transition (EMT). Furthermore, in vivo experiments indicated that the nanoparticles significantly accumulated in tumor tissues, synergistically inhibiting tumor growth (P < 0.001) and lung metastasis (P < 0.05) through the downregulation of NF-κB and IKBα phosphorylation levels, as well as a reduction in the Ki67 index, without any apparent systemic toxicity. This study successfully developed NLB/PTX-NPs, achieving effective co-loading of dual drugs, efficient enrichment, and synergistic delivery at tumor sites. The system demonstrated promising preclinical anti-tumor and anti-metastatic effects in the NCI-H520 models by synergistically inhibiting the NF-κB pathway, thereby providing a novel strategy for the treatment of lung squamous cell carcinoma.</p>","PeriodicalId":10337,"journal":{"name":"Clinical and Experimental Medicine","volume":"26 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}