Background:Ex vivo lung perfusion(EVLP)has emerged as a critical technique for lung preservation and evaluation prior to transplantation.While conventional rat EVLP systems utilize closed-loop dual cannulation of pulm...Background:Ex vivo lung perfusion(EVLP)has emerged as a critical technique for lung preservation and evaluation prior to transplantation.While conventional rat EVLP systems utilize closed-loop dual cannulation of pulmonary artery(PA)and vein,the effect of the simplified model using single PA cannulation with passive venous drainage is unknown.Methods:We developed two EVLP models in rats:a semi-closed circuit with PA-only cannulation and left atrial incision for passive venous drainage(SC-EVLP),and a closed circuit employing both arterial and venous cannulation(C-EVLP).Donor lungs were perfused for a defined duration and subsequently orthotopically transplanted.We evaluated pulmonary function parameters,histopathological injury scores,inflammatory cytokine levels,and apoptotic marker expression at the end of perfusion and posttransplantation.Results:Compared to the conventional EVLP,the SC-EVLP group exhibited significantly lower PA pressure and improved dynamic lung compliance throughout perfusion.Although the levels of tumor necrosis factor-αin the perfusate were higher in the SC-EVLP group,other cytokine levels in the perfusate and bronchoalveolar lavage fluid exhibited no significant differences.Pulmonary edema was reduced in the SC-EVLP group,as indicated by a lower lung wet-to-dry ratio.After transplantation,lungs from the SC-EVLP group exhibited lower histological injury scores,reduced apoptosis,and decreased serum cytokine levels,suggesting attenuated inflammation and tissue damage.Conclusions:In a rat model,single PA cannulation with passive venous drainage reduced pulmonary edema during EVLP and reduced lung injury and systemic inflammation after transplantation.展开更多
Background:Triptolide(TP)exhibits various pharmacological activities.Our previous studies have confirmed the efficacy of TP against lung adenocarcinoma(LUAD).However,the potent pharmacological activity of TP is underp...Background:Triptolide(TP)exhibits various pharmacological activities.Our previous studies have confirmed the efficacy of TP against lung adenocarcinoma(LUAD).However,the potent pharmacological activity of TP is underpinned by its complex mechanisms.Exploring its potential mechanisms is of great value for promoting the clinical application of TP and extending its clinical use.Methods:Differentially expressed genes(DEGs)associated with LUAD were analyzed and acquired from the TCGA database,while DEGs related to TP were obtained through RNA sequencing.Hub genes were identified through LASSO and random forest models.The efficacy of TP against LUAD was validated using tumor-bearing mouse models and A549 cells.The validation of hub genes was conducted using RT-qPCR.The regulatory effect of hub genes on TP efficacy was validated through overexpression cell models.Furthermore,the potential mechanisms by which TP improves gemcitabine(GEM)resistance were explored using a GEM-resistant cell line in combination with the overexpression model.Results:This study validated the therapeutic effect of TP against LUAD in vivo and in vitro.Bioinformatics revealed that the mechanism of TP's effect against LUAD might be associated with amino acid-related biological processes.Five hub genes were screened and identified by combining bioinformatics methods and experiments.The overexpression model validated that PSAT1 plays an effective role in the efficacy of TP and in alleviating GEM resistance.Conclusion:This study preliminarily demonstrated that the anti-LUAD effect of TP was associated with the PSAT1-regulated serine biosynthesis pathway,and that TP effectively improves GEM resistance by inhibiting PSAT1 expression.展开更多
Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent...Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent challenges in its clinical management.Neddylation,a novel type of post-translational modification,was overactivated in lung cancer and was closely associated with its occurrence,development,metastasis,and drug resistance.This review systematically summarizes the biological process of neddylation and deeply explores the latest research progress on how neddylation affects lung cancer cell proliferation,metastasis,and drug resistance mechanisms,with a focus on its regulation of key molecules such as Cullin-RING E3 ligases and the SCCRO family.Meanwhile,it concludes the current advances in potential therapeutic agents targeting neddylation-related targets,including small-molecule compounds(such as Pevonedistat)and natural extracts(such as arctigenin).Finally,the review prospectively evaluates the application potential and questions requiring further exploration of neddylation in lung cancer treatment.In conclusion,we aim to systematically summarize the biological process of neddylation,critically explore its roles in lung cancer proliferation,metastasis,and drug resistance,and evaluate the therapeutic potential of neddylation-targeting agents.展开更多
Objective:Chemotherapy-based regimens remain the standard first-and second-line treatment options for patients with driver gene-negative non-small cell lung cancer(NSCLC).However,in real-world settings,certain patient...Objective:Chemotherapy-based regimens remain the standard first-and second-line treatment options for patients with driver gene-negative non-small cell lung cancer(NSCLC).However,in real-world settings,certain patients cannot tolerate chemotherapy or opt to decline it.Immune checkpoint inhibitors(ICIs)constitute the preferred chemotherapy-free alternative.To enhance patient prognosis,this study aimed to examine the efficacy of ICIs combined with anlotinib in real-world scenarios.Methods:This prospective,multicenter,real-world study evaluated the efficacy and safety of ICIs combined with anlotinib in patients with advanced NSCLC.Patients undergoing first-or second-line treatment were enrolled.The primary endpoint was progression-free survival(PFS),while the secondary endpoints included overall survival(OS),objective response rate(ORR),disease control rate(DCR),and safety.Results:In total,242 patients were enrolled from 28 centers.The median PFS for the entire cohort was 7.8[95%confidence interval(95%CI),7.0-9.5]months,OS events occurred in 112(46.3%)patients,with a current median OS of 17.0(95%CI,15.1-19.4)months.The ORR and DCR were 36.0%(95%CI,30.2%-42.2%)and97.9%(95%CI,95.3%-99.1%),respectively.The median PFS was 9.8(95%CI,7.4-12.5)months for first-line therapy and 6.9(95%CI,6.0-8.3)months for second-line therapy.Treatment-related adverse events(AEs)occurred in 198(81.8%)patients,with grade 3-4 AEs reported in 22(9.1%)patients.Conclusions:This multicenter,real-world study demonstrates that the anlotinib-ICI combination regimen exhibits clinically meaningful efficacy and tolerability as a chemotherapy-free alternative for advanced NSCLC,offering viable evidence to guide treatment for patients who are unsuitable for conventional chemotherapy.展开更多
Lung cancer remains the leading cause of cancer-related mortality worldwide,primarily driven by metabolic reprogramming and immune evasion mechanisms within tumor cells.To adapt to the nutrient-deprived tumor microenv...Lung cancer remains the leading cause of cancer-related mortality worldwide,primarily driven by metabolic reprogramming and immune evasion mechanisms within tumor cells.To adapt to the nutrient-deprived tumor microenvironment(TME),lung cancer cells undergo profound metabolic reprogramming,characterized by enhanced glycolysis(the Warburg effect),increased glutamine dependency(mediated by GLS1),and accelerated lipid synthesis(involving enzymes such as FASN).These metabolic alterations not only remodel the TME but also dampen antitumor immune responses by promoting immunosuppressive cell populations(e.g.,Tregs and M2 macrophages)and inhibiting effector functions of CD8^(+)T cells and natural killer(NK)cells.Critically,a bidirectional crosstalk operates between tumor cell metabolism and the immunosuppressive TME:metabolic reprogramming drives immune suppression through metabolite accumulation,whereas the immunosuppressive TME,in turn,promotes tumor cell adaptability—thus forming a positive feedback loop that reinforces immune evasion and therapy resistance.This review elucidates key molecular pathways governing metabolic reprogramming in lung cancer—spanning glucose,amino acid,and lipid metabolism—and their dynamic crosstalk with immune regulation,including epigenetic modifications and non-coding RNA-mediated mechanisms.Additionally,it evaluates emerging therapeutic strategies targeting the metabolic-immune axis,such as inhibitors of HK2 or GLS1 combined with anti-PD-1/PD-L1 agents,which aim to reverse immunosuppression and improve clinical outcomes.By synthesizing recent advances,this work provides a theoretical framework for precision oncology interventions,highlighting the potential of metabolic immunotherapies and future directions integrating AI and multi-omics data to overcome resistance in lung cancer.展开更多
Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This...Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This study aimed to assess longitudinal changes in lung function over a 5-year period and to identify predictors of airflow obstruction in a cohort of patients treated for active pulmonary TB.Methods Patients with active pulmonary TB were enrolled in this study and were followed during treatment,at treatment completion and five years post-treatment.Assessments included lung function and chest CT,analyzing longitudinal trends and airflow obstruction risk factors.Results Among 53 patients(mean age 36.9±13.9 years;64.2%male),7 patients(13.2%)exhibited airflow obstruction.At the 5-year follow-up,the mean FEV_(1)/FVC declined significantly(76.27%±12.04%vs.80.23%±11.02%,P<0.001)and 9 patients(17.0%)exhibited airflow obstruction.Seven of these patients predominantly showed air trapping consistent with small airway disease on chest CT,aligning with TB-COPD phenotype.Notably,four young-to-middle-aged patients(<60 years old)had persistent obstruction over the five years.Conclusion The initial test revealed that 13.2%of patients presented with airflow obstruction.By the 5-year follow-up,this proportion had increased to 17.0%,with most cases demonstrating imaging findings aligning with TB-COPD,even among younger,non-smoking individuals.These findings emphasize the importance of long-term follow-up and routine lung function assessments in TB survivors.展开更多
Down syndrome(DS)is caused by an extra copy of chromosome 21(Hsa21).Children with DS have an increased frequency of respiratory tract infections,impaired alveolar and vascular development,and pulmonary hypertension.Ho...Down syndrome(DS)is caused by an extra copy of chromosome 21(Hsa21).Children with DS have an increased frequency of respiratory tract infections,impaired alveolar and vascular development,and pulmonary hypertension.How trisomy 21 causes lung diseases remains poorly understood.In this study,we use the Dp16 mouse model,which contains a segmental chromosomal duplication of the entire Hsa21 syntenic region on mouse chromosome 16,to explore the gene dosage effects on DS-related lung diseases.The Dp16 mice present impaired alveolar development and inflammatory-like pathological changes.Single-cell RNA sequencing(scRNA-seq)analysis highlights increased APP-related interactions among male Dp16 lung cells.Specifically,altered antigen processing and presentation with increased MHC-II signaling are found in Dp16 immune cells.Reduced angiogenesis and altered inflammatory responses of Dp16 endothelial cells are also suggested.Moreover,scRNA-seq indicates hyperplasia of Dp16 vascular smooth muscle cells,which is validated by tissue immunofluorescence assessment.Transthoracic echocardiography further shows the existence of pulmonary hypertension in young Dp16 mice.Independent scRNA-seq analysis of the female lung cells recapitulates the majority of key findings identified in male mice,confirming the reproducibility of the results.Collectively,our results provide important clues for the further development of therapeutic approaches for DS-related lung diseases.展开更多
Background:Despite the promise shown by large language models(LLMs)for standardized tasks,their multidimensional performance in real-world oncology decision-making remains unevaluated.This study aims to introduce a fr...Background:Despite the promise shown by large language models(LLMs)for standardized tasks,their multidimensional performance in real-world oncology decision-making remains unevaluated.This study aims to introduce a framework for evaluating LLMs and physician decisions in challenging lung cancer cases.Methods:We curated 50 challenging lung cancer cases(25 local and 25 published)classified as complex,rare,or refractory.Blinded three-dimensional,five-point Likert evaluations(1–5 for comprehensiveness,specificity,and readability)compared standalone LLMs(DeepSeek R1,Claude 3.5,Gemini 1.5,and GPT-4o),physicians by experience level(junior,intermediate,and senior),and AI-assisted juniors;intergroup differences and augmentation effects were analyzed statistically.Results:Of 50 challenging cases(18 complex,17 rare,and 15 refractory)rated by three experts,DeepSeek R1 achieved scores of 3.95±0.33,3.71±0.53,and 4.26±0.18 for comprehensiveness,specificity,and readability,respectively,positioning it between intermediate(3.68,3.68,3.75)and senior(4.50,4.64,4.53)physicians.GPT-4o and Claude 3.5 reached intermediate physician–level comprehensiveness(3.76±0.39,3.60±0.39)but junior-to-intermediate physician–level specificity(3.39±0.39,3.39±0.49).All LLMs scored higher on rare cases than intermediate physicians but fell below junior physicians in refractory-case specificity.AIassisted junior physicians showed marked gains in rare cases,with comprehensiveness rising from 2.32 to 4.29(84.8%),specificity from 2.24 to 4.26(90.8%),and readability from 2.76 to 4.59(66.0%),while specificity declined by 3.2%(3.17 to 3.07)in refractory cases.Error analysis showed complementary strengths,with physicians demonstrating reasoning stability and LLMs excelling in knowledge updating and risk management.Conclusions:LLMs performed variably in clinical decision-making tasks depending on case type,performing better in rare cases and worse in refractory cases requiring longitudinal reasoning.Complementary strengths between LLMs and physicians support case-and task-tailored human–AI collaboration.展开更多
Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articul...Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.展开更多
Despite having multiple treatment options,the overall outcomes,including the survival rates of non-small cell lung cancer(NSCLC)patients,remain relatively low,indicating the need to explore new approaches to achieve i...Despite having multiple treatment options,the overall outcomes,including the survival rates of non-small cell lung cancer(NSCLC)patients,remain relatively low,indicating the need to explore new approaches to achieve improved therapeutic responses.To that end,repurposed drugs such as metformin have been evaluated against many cancer types,including NSCLC.Metformin,a widely used oral hypoglycemic drug for type 2 diabetes,exhibits anticancer properties and synergy with several standards of care agents.In this review,we provide a comprehensive overview of the role and anticancer mechanisms of metformin-based combination approaches for the treatment of NSCLC.We logically discussed the experimental evidence from the in vitro and in vivo studies utilizing metformin alone,and then its combination with chemotherapeutic agents,targeted therapy,and immunotherapy.We also present clinical trials that underscore the beneficial and adverse outcomes of metformin use in combination with targeted therapy and chemotherapeutic agents,and emphasize the limitations and challenges for the treatment of diabetic and nondiabetic NSCLC patients.It appears that,regardless of the diverse anticancer mechanisms of this biguanide,the benefits may be confined to a specific patient subgroup,which opens new avenues to be explored for NSCLC treatment.展开更多
The published article titled“MicroRNA-138 Inhibits Cell Growth,Invasion,and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop”has been retracted fromOncology Research,Vol.26,No.3,2018,pp.385–400.DOI:10.3...The published article titled“MicroRNA-138 Inhibits Cell Growth,Invasion,and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop”has been retracted fromOncology Research,Vol.26,No.3,2018,pp.385–400.DOI:10.3727/096504017X14973124850905 URL:https://www.techscience.com/or/v26n3/56651 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
Background:Myeloid-derived suppressor cells(MDSCs)are important tumor microenvironment components in small cell lung cancer(SCLC).We successfully identified MDSCs expressing the surface marker CD33 in SCLC;nonetheless...Background:Myeloid-derived suppressor cells(MDSCs)are important tumor microenvironment components in small cell lung cancer(SCLC).We successfully identified MDSCs expressing the surface marker CD33 in SCLC;nonetheless,whether CD33^(+)MDSCs promote SCLC angiogenesis remains unclear.This study aims to explore the angiogenic effect and clinical significance of CD33^(+)MDSCs derived from SCLC.Method:Nineteen patients diagnosed with extensive-stage SCLC at Jilin Cancer Hospital were selected as the research subjects.CD33^(+)MDSCs were isolated from the peripheral blood of patients with SCLC using magnetic bead separation and CD33 expression was detected by flow cytometry.The angiogenic potential of CD33^(+)MDSCs derived from the peripheral blood of patients with SCLC and healthy individuals was assessed using human umbilical vein endothelial cell(HUVEC)angiogenesis assays,and the clinical significance of CD33^(+)MDSCs in promoting angiogenesis in patients with SCLC was analyzed using clinical data.Results:Compared to healthy individuals,the CD33^(+)MDSCs(CD14^(+)CD33^(+))isolated from the peripheral blood of SCLC patients exhibited a greater ability to promote HUVEC tubular growth(average vessel length:57.60 mm[47.78 mm]vs.39.07 mm[15.84 mm],p=0.000;vessel area:371,890 mm^(3)[699,927 mm^(3)]vs.334,652 mm^(3)[219,520 mm^(3)],p<0.000;total number of junctions:141[301]vs.120[94],p<0.005),and their angiogenic ability was associated with older age,female sex,high performance status scores,no systematic treatment,and treatment unresponsiveness(p<0.050).Furthermore,the enhanced angiogenic ability of CD33^(+)MDSCs may represent a risk factor for treatment unresponsiveness(average vessel length:Odds ratio=3.904,95%CI=1.812-8.409,p=0.001;vessel area:Odds ratio=2.501,95%CI=1.187-5.267,p=0.016;total number of junctions:Odds ratio=3.630,95%CI=1.686-7.815,p=0.001)and is associated with a poor SCLC prognosis(average vessel length:Hazard ratio=2.210,95%CI=1.299-3.758,p=0.003;vessel area:Hazard ratio=2.170,95%CI=1.274-3.693,p=0.004;total number of junctions:Hazard ratio=2.267,95%CI=1.333-3.853,p=0.003).Conclusion:CD33^(+)MDSCs derived from the peripheral blood of patients with SCLC promote angiogenesis,which is a risk factor for treatment unresponsiveness and is associated with poor prognosis.展开更多
Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve bette...Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve better efficacy in LS-SCLC patients.Methods:We evaluated 122 LS-SCLC patients who received concurrent chemoradiotherapy(CCRT)or sequential chemoradiotherapy(SCRT)(Group A)and immunotherapy combined with CCRT/SCRT followed by immunotherapy(Group B),to assess the objective response rate(ORR),disease control rate(DCR),and progression-free survival(PFS).Factors affecting prognosis were also explored using Cox analysis.The prognosis of patients with type 2 diabetes and patients with different TNM stages was compared to guide the selection of clinical regimens.Results:The overall ORR was 55.93%.The overall DCR was 98.31%.The DCR was 100%in Group A and 96.61%in Group B.There was no statistical difference in ORR and DCR.The overall median PFS was 9.86 months(95%CI,8.62-11.10),and the difference in median PFS between the two groups was statistically significant(8.94 vs.11.89 months,p=0.03).The Cox regression analysis showed type 2 diabetes was associated with the survival prognosis.Patients with type 2 diabetes tended to choose immunotherapy combined with CCRT/SCRT.Patients in TNM stage IIIB had a significantly worse prognosis than those in stage I+II+IIIA.Conclusion:We suggest that LS-SCLC patients who receive immunotherapy combined with CCRT/SCRT can achieve longer PFS than those with CCRT/SCRT.Type 2 diabetes and TNM stage affect the survival prognosis.Patients with type 2 diabetes may benefit from immunotherapy combination treatments.展开更多
The published article titled“Long Noncoding RNA(lncRNA)HOTAIR Affects Tumorigenesis andMetastasis of Non-Small Cell Lung Cancer by Upregulating miR-613”has been retracted from Oncology Research,Vol.26,No.5,2018,pp....The published article titled“Long Noncoding RNA(lncRNA)HOTAIR Affects Tumorigenesis andMetastasis of Non-Small Cell Lung Cancer by Upregulating miR-613”has been retracted from Oncology Research,Vol.26,No.5,2018,pp.725–734.DOI:10.3727/096504017X15119467381615 URL:https://www.techscience.com/or/v26n5/56685 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
Objectives:Although immune checkpoint inhibitors(ICIs)and targeted therapies have reshaped treatment non-small cell lung cancer(NSCLC)paradigms,prognosis remains poor for many patients due to delayed diagnosis and res...Objectives:Although immune checkpoint inhibitors(ICIs)and targeted therapies have reshaped treatment non-small cell lung cancer(NSCLC)paradigms,prognosis remains poor for many patients due to delayed diagnosis and resistance mechanisms.Liquid biopsy offers a minimally invasive approach to monitoring tumor evolution.Among circulating biomarkers,circulating tumor cells(CTCs)and cancer-associated macrophage-like cells(CAM-Ls)may provide complementary prognostic insights.The study aimed to evaluate the prognostic role of CTC and CAM-Ls dynamic in metastatic NSCLC patients.Methods:We retrospectively analyzed 77 patients with metastatic NSCLC who underwent CTC and CAM-L evaluation via the CellSearch^(■)system at baseline(T0)and after three months of first-line treatment(T1)including chemotherapy,targeted therapy,or ICIs.Survival outcomes were analyzed using Kaplan-Meier and Cox regression analyses.Results:Conversion to CTC-negative status at T1 was associated with improved outcomes,with median overall survival(OS)and progression-free survival(PFS)of 33 and 18 months,respectively,vs.10 and 6 months in persistently positive patients(both p<0.001).CTC negativity at T1 remained an independent prognostic factor for OS(HR:6.68)and PFS(HR:5.91,both p<0.0001).CAM-L positivity at T1 also correlated with longer OS(30 vs.12 months)and PFS(13 vs.6 months,both p<0.0001),particularly among ICI-treated patients.Combined CTC and CAM-L assessment further refined risk stratification.Conclusions:Dynamic monitoring of CTCs and CAM-Ls provides actionable prognostic information in metastatic NSCLC.CTC-negative status predicted longer OS and PFS,while CAM-L positivity at T1 was associated with improved outcomes,particularly in ICI-treated patients.Combined assessment of both biomarkers may directly inform therapeutic decision-making,through early detection of outcomes.展开更多
Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanoca...Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanocatalytic medicine utilizes nanomaterials to generate ROS specifically within tumor sites,enabling efficient and targeted cancer treatment.In this study,hyaluronic acid(HA)-modified copper-N,N-dimethyl-Nphenylsulfonylbisamine(DMSA)-assembled nanoparticles(Cu-DMSA-HA NPs)are developed with tumor-targeting capability and efficiently catalyze ROS production via coordination chemistry.Targeted delivery is facilitated by HA surface modification through recognition of overexpressed cluster of differentiation 44 receptors on cancer cells,which enhances nanoparticle uptake.Once internalized,intracellular glutathione is depleted by the NPs,followed by a Fenton-like reaction that sustains ROS production.Both in vitro and in vivo studies demonstrate that this catalytic strategy effectively inhibits DNA replication,prevents cell cycle progression,downregulates glutathione peroxidase 4 expression,induces ferroptosis,and ultimately suppresses NSCLC progression.Overall,the readily prepared Cu-DMSA-HA NPs exhibit robust catalytic activity and tumor specificity,highlighting their strong potential for clinical translation in nanocatalytic cancer therapy.展开更多
Honeycombing Lung(HCL)is a chronic lung condition marked by advanced fibrosis,resulting in enlarged air spaces with thick fibrotic walls,which are visible on Computed Tomography(CT)scans.Differentiating between normal...Honeycombing Lung(HCL)is a chronic lung condition marked by advanced fibrosis,resulting in enlarged air spaces with thick fibrotic walls,which are visible on Computed Tomography(CT)scans.Differentiating between normal lung tissue,honeycombing lungs,and Ground Glass Opacity(GGO)in CT images is often challenging for radiologists and may lead to misinterpretations.Although earlier studies have proposed models to detect and classify HCL,many faced limitations such as high computational demands,lower accuracy,and difficulty distinguishing between HCL and GGO.CT images are highly effective for lung classification due to their high resolution,3D visualization,and sensitivity to tissue density variations.This study introduces Honeycombing Lungs Network(HCL Net),a novel classification algorithm inspired by ResNet50V2 and enhanced to overcome the shortcomings of previous approaches.HCL Net incorporates additional residual blocks,refined preprocessing techniques,and selective parameter tuning to improve classification performance.The dataset,sourced from the University Malaya Medical Centre(UMMC)and verified by expert radiologists,consists of CT images of normal,honeycombing,and GGO lungs.Experimental evaluations across five assessments demonstrated that HCL Net achieved an outstanding classification accuracy of approximately 99.97%.It also recorded strong performance in other metrics,achieving 93%precision,100%sensitivity,89%specificity,and an AUC-ROC score of 97%.Comparative analysis with baseline feature engineering methods confirmed the superior efficacy of HCL Net.The model significantly reduces misclassification,particularly between honeycombing and GGO lungs,enhancing diagnostic precision and reliability in lung image analysis.展开更多
Colorectal cancer(CRC)with lung oligometastases,particularly in the presence of extrapulmonary disease,poses considerable therapeutic challenges in clinical practice.We have carefully studied the multicenter study by ...Colorectal cancer(CRC)with lung oligometastases,particularly in the presence of extrapulmonary disease,poses considerable therapeutic challenges in clinical practice.We have carefully studied the multicenter study by Hu et al,which evaluated the survival outcomes of patients with metastatic CRC who received image-guided thermal ablation(IGTA).These findings provide valuable clinical evidence supporting IGTA as a feasible,minimally invasive approach and underscore the prognostic significance of metastatic distribution.However,the study by Hu et al has several limitations,including that not all pulmonary lesions were pathologically confirmed,postoperative follow-up mainly relied on dynamic contrast-enhanced computed tomography,no comparative analysis was performed with other local treatments,and the impact of other imaging features on efficacy and prognosis was not evaluated.Future studies should include complete pathological confirmation,integrate functional imaging and radiomics,and use prospective multicenter collaboration to optimize patient selection standards for IGTA treatment,strengthen its clinical evidence base,and ultimately promote individualized decision-making for patients with metastatic CRC.展开更多
Objectives:Combined chemotherapy and photothermal therapy(PTT)represents a promising approach for enhancing cancer treatment efficacy.This study aimed to develop arsenic trioxide(ATO)and poly(cyclopentadithiophene-alt...Objectives:Combined chemotherapy and photothermal therapy(PTT)represents a promising approach for enhancing cancer treatment efficacy.This study aimed to develop arsenic trioxide(ATO)and poly(cyclopentadithiophene-alt-benzothiadiazole)(PCPDTBT)-loaded nanoparticles(ATO/PCPDTBT@NPs)to evaluate their synergistic efficacy in inhibiting lung cancer growth and metastasis.Methods:Nanovesicles were synthesized via a streamlined protocol and subjected to 808 nm NIR irradiation to assess their photothermal conversion capabilities.The therapeutic efficacy was evaluated in vitro using A549 lung carcinoma cells to assess apoptosis,invasion,and migration,and in vivo to monitor tumor volume reduction.Results:The nanoparticles exhibited excellent hemocompatibility and low cytotoxicity while demonstrating robust photothermal conversion,inducing a rapid 20.8℃ temperature rise within five minutes.In vitro,ATO enhanced apoptotic pathways and suppressed metastasis,while the combination therapy significantly reduced cell viability(OD:0.23 vs.0.62 in controls)and migration(13.6%vs.74.9%),outperforming monotherapies.In vivo,the chemo-photothermal treatment reduced tumor volumes by 2.5-and 3-fold compared to ATO or PTT alone,confirming superior antitumor effects.Conclusions:These findings highlight the dual-action ATO/PCPDTBT@NPs nanoplatform as a potential multifaceted strategy for effective tumor suppression and metastasis inhibition.展开更多
Background:Lung adenocarcinoma(LUAD),the most prevalent histological subtype of lung cancer,remains a leading cause of cancer-related mortality due to late diagnosis,metastasis,and therapy resistance.The aim of the st...Background:Lung adenocarcinoma(LUAD),the most prevalent histological subtype of lung cancer,remains a leading cause of cancer-related mortality due to late diagnosis,metastasis,and therapy resistance.The aim of the study is to investigate the role of Kinetochore Scaffold 1(KNL1)in promoting LUAD progression and its underlying molecular regulatory mechanisms.Methods:KNL1 mRNA expression levels across 33 cancer types were analyzed using bioinformatics analysis based on the TCGA database.Immunohistochemistry(IHC)was used to assess KNL1 expression in LUAD and normal tissues.Stable KNL1-knockdown and KNL1-overexpressing LUAD cell lines were established using lentiviral infection.Western blotting(WB)was used to measure epithelial-mesenchymal transition(EMT)markers and ferroptosis-related protein expression.Cell migration was evaluated via scratch wound healing assays.The thiobarbituric acid(TBA)method was employed for the detection of malondialdehyde.a fluorescent probe was utilized to determine ferrous ion content.WB determined the phosphorylation ratios of AMP-activated protein kinase(AMPK)and mammalian target of rapamycin(mTOR)proteins.Results:1.KNL1 was highly expressed in 31 cancer types,including LUAD.Kaplan-Meier curves showed significantly shorter median survival in patients with high KNL1 expression.IHC confirmed upregulated KNL1 expression in LUAD tissues.2.KNL1 overexpression significantly promoted LUAD cell migration and increased mesenchymal marker expression,whereas KNL1 knockdown exerted opposite effects.3.KNL1 overexpression significantly reduced MDA content and Fe^(2+)levels in RSL3-treated LUAD cells while increasing the expression of key ferroptosis defense proteins;conversely,it markedly increased the accumulation of MDA and Fe^(2+)and downregulated these proteins.KNL1 overexpression significantly increased phosphorylated AMPK(p-AMPK)expression but decreased phosphorylated mTOR(p-mTOR)expression in RSL3-treated LUAD cells;conversely,it inhibited p-AMPK expression and activated p-mTOR.Conclusion:KNL1 promotes lung adenocarcinoma progression by suppressing ferroptosis through regulation of the AMPK-mTOR signaling pathway.展开更多
基金Key Science and Technology Program of Shaanxi Province,Grant/Award Number:2024SF2-GJHX-45National Natural Science Foundation of China,Grant/Award Number:82472191The Natural Science Foundation of Shaanxi Province,Grant/Award Number:2024JC-ZDXM-49。
文摘Background:Ex vivo lung perfusion(EVLP)has emerged as a critical technique for lung preservation and evaluation prior to transplantation.While conventional rat EVLP systems utilize closed-loop dual cannulation of pulmonary artery(PA)and vein,the effect of the simplified model using single PA cannulation with passive venous drainage is unknown.Methods:We developed two EVLP models in rats:a semi-closed circuit with PA-only cannulation and left atrial incision for passive venous drainage(SC-EVLP),and a closed circuit employing both arterial and venous cannulation(C-EVLP).Donor lungs were perfused for a defined duration and subsequently orthotopically transplanted.We evaluated pulmonary function parameters,histopathological injury scores,inflammatory cytokine levels,and apoptotic marker expression at the end of perfusion and posttransplantation.Results:Compared to the conventional EVLP,the SC-EVLP group exhibited significantly lower PA pressure and improved dynamic lung compliance throughout perfusion.Although the levels of tumor necrosis factor-αin the perfusate were higher in the SC-EVLP group,other cytokine levels in the perfusate and bronchoalveolar lavage fluid exhibited no significant differences.Pulmonary edema was reduced in the SC-EVLP group,as indicated by a lower lung wet-to-dry ratio.After transplantation,lungs from the SC-EVLP group exhibited lower histological injury scores,reduced apoptosis,and decreased serum cytokine levels,suggesting attenuated inflammation and tissue damage.Conclusions:In a rat model,single PA cannulation with passive venous drainage reduced pulmonary edema during EVLP and reduced lung injury and systemic inflammation after transplantation.
基金National Natural Science Foundation of China,Grant/Award Number:No.82560858Beijing Science and Technology New Star Program Cross-cooperation Project,Grant/Award Number:No.20240484711Jiangxi Provincial Natural Science Foundation,Grant/Award Number:20252BAC200586。
文摘Background:Triptolide(TP)exhibits various pharmacological activities.Our previous studies have confirmed the efficacy of TP against lung adenocarcinoma(LUAD).However,the potent pharmacological activity of TP is underpinned by its complex mechanisms.Exploring its potential mechanisms is of great value for promoting the clinical application of TP and extending its clinical use.Methods:Differentially expressed genes(DEGs)associated with LUAD were analyzed and acquired from the TCGA database,while DEGs related to TP were obtained through RNA sequencing.Hub genes were identified through LASSO and random forest models.The efficacy of TP against LUAD was validated using tumor-bearing mouse models and A549 cells.The validation of hub genes was conducted using RT-qPCR.The regulatory effect of hub genes on TP efficacy was validated through overexpression cell models.Furthermore,the potential mechanisms by which TP improves gemcitabine(GEM)resistance were explored using a GEM-resistant cell line in combination with the overexpression model.Results:This study validated the therapeutic effect of TP against LUAD in vivo and in vitro.Bioinformatics revealed that the mechanism of TP's effect against LUAD might be associated with amino acid-related biological processes.Five hub genes were screened and identified by combining bioinformatics methods and experiments.The overexpression model validated that PSAT1 plays an effective role in the efficacy of TP and in alleviating GEM resistance.Conclusion:This study preliminarily demonstrated that the anti-LUAD effect of TP was associated with the PSAT1-regulated serine biosynthesis pathway,and that TP effectively improves GEM resistance by inhibiting PSAT1 expression.
基金supported by the National Natural Science Foundation of China(No.82574683)the National Natural Science Foundation of Science and Technology Department of Sichuan Province(Nos.2023NSFSC1928 and 2023NSFSC1992)+2 种基金Project of State Administration of Traditional Chinese Medicine of China(No.ZYYCXTD-D-202209)Project of Sichuan Provincial Administration of Traditional Chinese Medicine(No.2022C001)Fundamental Research Funds for the Central Universities(No.YJ201880).
文摘Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent challenges in its clinical management.Neddylation,a novel type of post-translational modification,was overactivated in lung cancer and was closely associated with its occurrence,development,metastasis,and drug resistance.This review systematically summarizes the biological process of neddylation and deeply explores the latest research progress on how neddylation affects lung cancer cell proliferation,metastasis,and drug resistance mechanisms,with a focus on its regulation of key molecules such as Cullin-RING E3 ligases and the SCCRO family.Meanwhile,it concludes the current advances in potential therapeutic agents targeting neddylation-related targets,including small-molecule compounds(such as Pevonedistat)and natural extracts(such as arctigenin).Finally,the review prospectively evaluates the application potential and questions requiring further exploration of neddylation in lung cancer treatment.In conclusion,we aim to systematically summarize the biological process of neddylation,critically explore its roles in lung cancer proliferation,metastasis,and drug resistance,and evaluate the therapeutic potential of neddylation-targeting agents.
基金supported by Key Research and Development Projects of Henan Province in 2023-Key Technologies of Novel Precision Immunotherapy for Refractory Malignant Tumors(No.231111313300)Zhongyuan Qianren Jihua(No.ZYQR201912118)+2 种基金Key Research and Development Projects of Henan Province(No.251111310100)Henan Province Medical Science and Technology Talent Overseas Training Program(HNMOT2024062)The Excellent Young Talent Cultivation Project of Henan Health Science and Technology Innovation Talents(No.YXKC2020046)。
文摘Objective:Chemotherapy-based regimens remain the standard first-and second-line treatment options for patients with driver gene-negative non-small cell lung cancer(NSCLC).However,in real-world settings,certain patients cannot tolerate chemotherapy or opt to decline it.Immune checkpoint inhibitors(ICIs)constitute the preferred chemotherapy-free alternative.To enhance patient prognosis,this study aimed to examine the efficacy of ICIs combined with anlotinib in real-world scenarios.Methods:This prospective,multicenter,real-world study evaluated the efficacy and safety of ICIs combined with anlotinib in patients with advanced NSCLC.Patients undergoing first-or second-line treatment were enrolled.The primary endpoint was progression-free survival(PFS),while the secondary endpoints included overall survival(OS),objective response rate(ORR),disease control rate(DCR),and safety.Results:In total,242 patients were enrolled from 28 centers.The median PFS for the entire cohort was 7.8[95%confidence interval(95%CI),7.0-9.5]months,OS events occurred in 112(46.3%)patients,with a current median OS of 17.0(95%CI,15.1-19.4)months.The ORR and DCR were 36.0%(95%CI,30.2%-42.2%)and97.9%(95%CI,95.3%-99.1%),respectively.The median PFS was 9.8(95%CI,7.4-12.5)months for first-line therapy and 6.9(95%CI,6.0-8.3)months for second-line therapy.Treatment-related adverse events(AEs)occurred in 198(81.8%)patients,with grade 3-4 AEs reported in 22(9.1%)patients.Conclusions:This multicenter,real-world study demonstrates that the anlotinib-ICI combination regimen exhibits clinically meaningful efficacy and tolerability as a chemotherapy-free alternative for advanced NSCLC,offering viable evidence to guide treatment for patients who are unsuitable for conventional chemotherapy.
基金supported by the Henan Provincial Science and Technology Research and Development Plan Joint Fund(Grant No.242103810035).
文摘Lung cancer remains the leading cause of cancer-related mortality worldwide,primarily driven by metabolic reprogramming and immune evasion mechanisms within tumor cells.To adapt to the nutrient-deprived tumor microenvironment(TME),lung cancer cells undergo profound metabolic reprogramming,characterized by enhanced glycolysis(the Warburg effect),increased glutamine dependency(mediated by GLS1),and accelerated lipid synthesis(involving enzymes such as FASN).These metabolic alterations not only remodel the TME but also dampen antitumor immune responses by promoting immunosuppressive cell populations(e.g.,Tregs and M2 macrophages)and inhibiting effector functions of CD8^(+)T cells and natural killer(NK)cells.Critically,a bidirectional crosstalk operates between tumor cell metabolism and the immunosuppressive TME:metabolic reprogramming drives immune suppression through metabolite accumulation,whereas the immunosuppressive TME,in turn,promotes tumor cell adaptability—thus forming a positive feedback loop that reinforces immune evasion and therapy resistance.This review elucidates key molecular pathways governing metabolic reprogramming in lung cancer—spanning glucose,amino acid,and lipid metabolism—and their dynamic crosstalk with immune regulation,including epigenetic modifications and non-coding RNA-mediated mechanisms.Additionally,it evaluates emerging therapeutic strategies targeting the metabolic-immune axis,such as inhibitors of HK2 or GLS1 combined with anti-PD-1/PD-L1 agents,which aim to reverse immunosuppression and improve clinical outcomes.By synthesizing recent advances,this work provides a theoretical framework for precision oncology interventions,highlighting the potential of metabolic immunotherapies and future directions integrating AI and multi-omics data to overcome resistance in lung cancer.
基金supported by the National Science and Technology Major Project for the Prevention and Control of Emerging and Major Infectious Diseases[2025ZD01908702]Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological innovation[BMU2024YFJHP014]supported by Fundamental Research Funds for the Central Universities+1 种基金Key Clinical Projects of Peking University Third Hospital[BYSYZD2022014]Peking University Third Hospital[2025024].
文摘Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This study aimed to assess longitudinal changes in lung function over a 5-year period and to identify predictors of airflow obstruction in a cohort of patients treated for active pulmonary TB.Methods Patients with active pulmonary TB were enrolled in this study and were followed during treatment,at treatment completion and five years post-treatment.Assessments included lung function and chest CT,analyzing longitudinal trends and airflow obstruction risk factors.Results Among 53 patients(mean age 36.9±13.9 years;64.2%male),7 patients(13.2%)exhibited airflow obstruction.At the 5-year follow-up,the mean FEV_(1)/FVC declined significantly(76.27%±12.04%vs.80.23%±11.02%,P<0.001)and 9 patients(17.0%)exhibited airflow obstruction.Seven of these patients predominantly showed air trapping consistent with small airway disease on chest CT,aligning with TB-COPD phenotype.Notably,four young-to-middle-aged patients(<60 years old)had persistent obstruction over the five years.Conclusion The initial test revealed that 13.2%of patients presented with airflow obstruction.By the 5-year follow-up,this proportion had increased to 17.0%,with most cases demonstrating imaging findings aligning with TB-COPD,even among younger,non-smoking individuals.These findings emphasize the importance of long-term follow-up and routine lung function assessments in TB survivors.
基金supported by the Fundamental Research Funds for the Central Universities(226-2022-00035)the National Natural Science Foundation of China(81600986).
文摘Down syndrome(DS)is caused by an extra copy of chromosome 21(Hsa21).Children with DS have an increased frequency of respiratory tract infections,impaired alveolar and vascular development,and pulmonary hypertension.How trisomy 21 causes lung diseases remains poorly understood.In this study,we use the Dp16 mouse model,which contains a segmental chromosomal duplication of the entire Hsa21 syntenic region on mouse chromosome 16,to explore the gene dosage effects on DS-related lung diseases.The Dp16 mice present impaired alveolar development and inflammatory-like pathological changes.Single-cell RNA sequencing(scRNA-seq)analysis highlights increased APP-related interactions among male Dp16 lung cells.Specifically,altered antigen processing and presentation with increased MHC-II signaling are found in Dp16 immune cells.Reduced angiogenesis and altered inflammatory responses of Dp16 endothelial cells are also suggested.Moreover,scRNA-seq indicates hyperplasia of Dp16 vascular smooth muscle cells,which is validated by tissue immunofluorescence assessment.Transthoracic echocardiography further shows the existence of pulmonary hypertension in young Dp16 mice.Independent scRNA-seq analysis of the female lung cells recapitulates the majority of key findings identified in male mice,confirming the reproducibility of the results.Collectively,our results provide important clues for the further development of therapeutic approaches for DS-related lung diseases.
文摘Background:Despite the promise shown by large language models(LLMs)for standardized tasks,their multidimensional performance in real-world oncology decision-making remains unevaluated.This study aims to introduce a framework for evaluating LLMs and physician decisions in challenging lung cancer cases.Methods:We curated 50 challenging lung cancer cases(25 local and 25 published)classified as complex,rare,or refractory.Blinded three-dimensional,five-point Likert evaluations(1–5 for comprehensiveness,specificity,and readability)compared standalone LLMs(DeepSeek R1,Claude 3.5,Gemini 1.5,and GPT-4o),physicians by experience level(junior,intermediate,and senior),and AI-assisted juniors;intergroup differences and augmentation effects were analyzed statistically.Results:Of 50 challenging cases(18 complex,17 rare,and 15 refractory)rated by three experts,DeepSeek R1 achieved scores of 3.95±0.33,3.71±0.53,and 4.26±0.18 for comprehensiveness,specificity,and readability,respectively,positioning it between intermediate(3.68,3.68,3.75)and senior(4.50,4.64,4.53)physicians.GPT-4o and Claude 3.5 reached intermediate physician–level comprehensiveness(3.76±0.39,3.60±0.39)but junior-to-intermediate physician–level specificity(3.39±0.39,3.39±0.49).All LLMs scored higher on rare cases than intermediate physicians but fell below junior physicians in refractory-case specificity.AIassisted junior physicians showed marked gains in rare cases,with comprehensiveness rising from 2.32 to 4.29(84.8%),specificity from 2.24 to 4.26(90.8%),and readability from 2.76 to 4.59(66.0%),while specificity declined by 3.2%(3.17 to 3.07)in refractory cases.Error analysis showed complementary strengths,with physicians demonstrating reasoning stability and LLMs excelling in knowledge updating and risk management.Conclusions:LLMs performed variably in clinical decision-making tasks depending on case type,performing better in rare cases and worse in refractory cases requiring longitudinal reasoning.Complementary strengths between LLMs and physicians support case-and task-tailored human–AI collaboration.
文摘Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.
基金supported by the National Institutes of Health(RPS,R21 ES033806).
文摘Despite having multiple treatment options,the overall outcomes,including the survival rates of non-small cell lung cancer(NSCLC)patients,remain relatively low,indicating the need to explore new approaches to achieve improved therapeutic responses.To that end,repurposed drugs such as metformin have been evaluated against many cancer types,including NSCLC.Metformin,a widely used oral hypoglycemic drug for type 2 diabetes,exhibits anticancer properties and synergy with several standards of care agents.In this review,we provide a comprehensive overview of the role and anticancer mechanisms of metformin-based combination approaches for the treatment of NSCLC.We logically discussed the experimental evidence from the in vitro and in vivo studies utilizing metformin alone,and then its combination with chemotherapeutic agents,targeted therapy,and immunotherapy.We also present clinical trials that underscore the beneficial and adverse outcomes of metformin use in combination with targeted therapy and chemotherapeutic agents,and emphasize the limitations and challenges for the treatment of diabetic and nondiabetic NSCLC patients.It appears that,regardless of the diverse anticancer mechanisms of this biguanide,the benefits may be confined to a specific patient subgroup,which opens new avenues to be explored for NSCLC treatment.
文摘The published article titled“MicroRNA-138 Inhibits Cell Growth,Invasion,and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop”has been retracted fromOncology Research,Vol.26,No.3,2018,pp.385–400.DOI:10.3727/096504017X14973124850905 URL:https://www.techscience.com/or/v26n3/56651 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
基金Science and Technology Agency of Jilin Provincial Project(Grant/Award Number:20230203075SF)Youth Project of Jilin Provincial Health Commission(Grant/Award Number:2024A123)。
文摘Background:Myeloid-derived suppressor cells(MDSCs)are important tumor microenvironment components in small cell lung cancer(SCLC).We successfully identified MDSCs expressing the surface marker CD33 in SCLC;nonetheless,whether CD33^(+)MDSCs promote SCLC angiogenesis remains unclear.This study aims to explore the angiogenic effect and clinical significance of CD33^(+)MDSCs derived from SCLC.Method:Nineteen patients diagnosed with extensive-stage SCLC at Jilin Cancer Hospital were selected as the research subjects.CD33^(+)MDSCs were isolated from the peripheral blood of patients with SCLC using magnetic bead separation and CD33 expression was detected by flow cytometry.The angiogenic potential of CD33^(+)MDSCs derived from the peripheral blood of patients with SCLC and healthy individuals was assessed using human umbilical vein endothelial cell(HUVEC)angiogenesis assays,and the clinical significance of CD33^(+)MDSCs in promoting angiogenesis in patients with SCLC was analyzed using clinical data.Results:Compared to healthy individuals,the CD33^(+)MDSCs(CD14^(+)CD33^(+))isolated from the peripheral blood of SCLC patients exhibited a greater ability to promote HUVEC tubular growth(average vessel length:57.60 mm[47.78 mm]vs.39.07 mm[15.84 mm],p=0.000;vessel area:371,890 mm^(3)[699,927 mm^(3)]vs.334,652 mm^(3)[219,520 mm^(3)],p<0.000;total number of junctions:141[301]vs.120[94],p<0.005),and their angiogenic ability was associated with older age,female sex,high performance status scores,no systematic treatment,and treatment unresponsiveness(p<0.050).Furthermore,the enhanced angiogenic ability of CD33^(+)MDSCs may represent a risk factor for treatment unresponsiveness(average vessel length:Odds ratio=3.904,95%CI=1.812-8.409,p=0.001;vessel area:Odds ratio=2.501,95%CI=1.187-5.267,p=0.016;total number of junctions:Odds ratio=3.630,95%CI=1.686-7.815,p=0.001)and is associated with a poor SCLC prognosis(average vessel length:Hazard ratio=2.210,95%CI=1.299-3.758,p=0.003;vessel area:Hazard ratio=2.170,95%CI=1.274-3.693,p=0.004;total number of junctions:Hazard ratio=2.267,95%CI=1.333-3.853,p=0.003).Conclusion:CD33^(+)MDSCs derived from the peripheral blood of patients with SCLC promote angiogenesis,which is a risk factor for treatment unresponsiveness and is associated with poor prognosis.
基金funded by the National Natural Science Foundation of China(grant no.82273162)the National Natural Science Foundation of China(grant no.82203272)the Science and Technology Development Foundation of Nanjing Medical University(grant NMUB20240119)。
文摘Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve better efficacy in LS-SCLC patients.Methods:We evaluated 122 LS-SCLC patients who received concurrent chemoradiotherapy(CCRT)or sequential chemoradiotherapy(SCRT)(Group A)and immunotherapy combined with CCRT/SCRT followed by immunotherapy(Group B),to assess the objective response rate(ORR),disease control rate(DCR),and progression-free survival(PFS).Factors affecting prognosis were also explored using Cox analysis.The prognosis of patients with type 2 diabetes and patients with different TNM stages was compared to guide the selection of clinical regimens.Results:The overall ORR was 55.93%.The overall DCR was 98.31%.The DCR was 100%in Group A and 96.61%in Group B.There was no statistical difference in ORR and DCR.The overall median PFS was 9.86 months(95%CI,8.62-11.10),and the difference in median PFS between the two groups was statistically significant(8.94 vs.11.89 months,p=0.03).The Cox regression analysis showed type 2 diabetes was associated with the survival prognosis.Patients with type 2 diabetes tended to choose immunotherapy combined with CCRT/SCRT.Patients in TNM stage IIIB had a significantly worse prognosis than those in stage I+II+IIIA.Conclusion:We suggest that LS-SCLC patients who receive immunotherapy combined with CCRT/SCRT can achieve longer PFS than those with CCRT/SCRT.Type 2 diabetes and TNM stage affect the survival prognosis.Patients with type 2 diabetes may benefit from immunotherapy combination treatments.
文摘The published article titled“Long Noncoding RNA(lncRNA)HOTAIR Affects Tumorigenesis andMetastasis of Non-Small Cell Lung Cancer by Upregulating miR-613”has been retracted from Oncology Research,Vol.26,No.5,2018,pp.725–734.DOI:10.3727/096504017X15119467381615 URL:https://www.techscience.com/or/v26n5/56685 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
基金funded by Sapienza University PNRR-RT_SPOKE_1—ROME TECHNOPOLE—Spoke 1—B83C22002820006—ECS00000024 and FO R.O.onlus.
文摘Objectives:Although immune checkpoint inhibitors(ICIs)and targeted therapies have reshaped treatment non-small cell lung cancer(NSCLC)paradigms,prognosis remains poor for many patients due to delayed diagnosis and resistance mechanisms.Liquid biopsy offers a minimally invasive approach to monitoring tumor evolution.Among circulating biomarkers,circulating tumor cells(CTCs)and cancer-associated macrophage-like cells(CAM-Ls)may provide complementary prognostic insights.The study aimed to evaluate the prognostic role of CTC and CAM-Ls dynamic in metastatic NSCLC patients.Methods:We retrospectively analyzed 77 patients with metastatic NSCLC who underwent CTC and CAM-L evaluation via the CellSearch^(■)system at baseline(T0)and after three months of first-line treatment(T1)including chemotherapy,targeted therapy,or ICIs.Survival outcomes were analyzed using Kaplan-Meier and Cox regression analyses.Results:Conversion to CTC-negative status at T1 was associated with improved outcomes,with median overall survival(OS)and progression-free survival(PFS)of 33 and 18 months,respectively,vs.10 and 6 months in persistently positive patients(both p<0.001).CTC negativity at T1 remained an independent prognostic factor for OS(HR:6.68)and PFS(HR:5.91,both p<0.0001).CAM-L positivity at T1 also correlated with longer OS(30 vs.12 months)and PFS(13 vs.6 months,both p<0.0001),particularly among ICI-treated patients.Combined CTC and CAM-L assessment further refined risk stratification.Conclusions:Dynamic monitoring of CTCs and CAM-Ls provides actionable prognostic information in metastatic NSCLC.CTC-negative status predicted longer OS and PFS,while CAM-L positivity at T1 was associated with improved outcomes,particularly in ICI-treated patients.Combined assessment of both biomarkers may directly inform therapeutic decision-making,through early detection of outcomes.
基金supported by National Natural Science Foundation of China (82272943)Shanghai Municipal Science and Technology Commission (21Y11913400)+1 种基金Fundamental Research Funds for the Central UniversitiesNational Key Research and Development Program of China (2022YFC2407405)
文摘Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanocatalytic medicine utilizes nanomaterials to generate ROS specifically within tumor sites,enabling efficient and targeted cancer treatment.In this study,hyaluronic acid(HA)-modified copper-N,N-dimethyl-Nphenylsulfonylbisamine(DMSA)-assembled nanoparticles(Cu-DMSA-HA NPs)are developed with tumor-targeting capability and efficiently catalyze ROS production via coordination chemistry.Targeted delivery is facilitated by HA surface modification through recognition of overexpressed cluster of differentiation 44 receptors on cancer cells,which enhances nanoparticle uptake.Once internalized,intracellular glutathione is depleted by the NPs,followed by a Fenton-like reaction that sustains ROS production.Both in vitro and in vivo studies demonstrate that this catalytic strategy effectively inhibits DNA replication,prevents cell cycle progression,downregulates glutathione peroxidase 4 expression,induces ferroptosis,and ultimately suppresses NSCLC progression.Overall,the readily prepared Cu-DMSA-HA NPs exhibit robust catalytic activity and tumor specificity,highlighting their strong potential for clinical translation in nanocatalytic cancer therapy.
文摘Honeycombing Lung(HCL)is a chronic lung condition marked by advanced fibrosis,resulting in enlarged air spaces with thick fibrotic walls,which are visible on Computed Tomography(CT)scans.Differentiating between normal lung tissue,honeycombing lungs,and Ground Glass Opacity(GGO)in CT images is often challenging for radiologists and may lead to misinterpretations.Although earlier studies have proposed models to detect and classify HCL,many faced limitations such as high computational demands,lower accuracy,and difficulty distinguishing between HCL and GGO.CT images are highly effective for lung classification due to their high resolution,3D visualization,and sensitivity to tissue density variations.This study introduces Honeycombing Lungs Network(HCL Net),a novel classification algorithm inspired by ResNet50V2 and enhanced to overcome the shortcomings of previous approaches.HCL Net incorporates additional residual blocks,refined preprocessing techniques,and selective parameter tuning to improve classification performance.The dataset,sourced from the University Malaya Medical Centre(UMMC)and verified by expert radiologists,consists of CT images of normal,honeycombing,and GGO lungs.Experimental evaluations across five assessments demonstrated that HCL Net achieved an outstanding classification accuracy of approximately 99.97%.It also recorded strong performance in other metrics,achieving 93%precision,100%sensitivity,89%specificity,and an AUC-ROC score of 97%.Comparative analysis with baseline feature engineering methods confirmed the superior efficacy of HCL Net.The model significantly reduces misclassification,particularly between honeycombing and GGO lungs,enhancing diagnostic precision and reliability in lung image analysis.
文摘Colorectal cancer(CRC)with lung oligometastases,particularly in the presence of extrapulmonary disease,poses considerable therapeutic challenges in clinical practice.We have carefully studied the multicenter study by Hu et al,which evaluated the survival outcomes of patients with metastatic CRC who received image-guided thermal ablation(IGTA).These findings provide valuable clinical evidence supporting IGTA as a feasible,minimally invasive approach and underscore the prognostic significance of metastatic distribution.However,the study by Hu et al has several limitations,including that not all pulmonary lesions were pathologically confirmed,postoperative follow-up mainly relied on dynamic contrast-enhanced computed tomography,no comparative analysis was performed with other local treatments,and the impact of other imaging features on efficacy and prognosis was not evaluated.Future studies should include complete pathological confirmation,integrate functional imaging and radiomics,and use prospective multicenter collaboration to optimize patient selection standards for IGTA treatment,strengthen its clinical evidence base,and ultimately promote individualized decision-making for patients with metastatic CRC.
文摘Objectives:Combined chemotherapy and photothermal therapy(PTT)represents a promising approach for enhancing cancer treatment efficacy.This study aimed to develop arsenic trioxide(ATO)and poly(cyclopentadithiophene-alt-benzothiadiazole)(PCPDTBT)-loaded nanoparticles(ATO/PCPDTBT@NPs)to evaluate their synergistic efficacy in inhibiting lung cancer growth and metastasis.Methods:Nanovesicles were synthesized via a streamlined protocol and subjected to 808 nm NIR irradiation to assess their photothermal conversion capabilities.The therapeutic efficacy was evaluated in vitro using A549 lung carcinoma cells to assess apoptosis,invasion,and migration,and in vivo to monitor tumor volume reduction.Results:The nanoparticles exhibited excellent hemocompatibility and low cytotoxicity while demonstrating robust photothermal conversion,inducing a rapid 20.8℃ temperature rise within five minutes.In vitro,ATO enhanced apoptotic pathways and suppressed metastasis,while the combination therapy significantly reduced cell viability(OD:0.23 vs.0.62 in controls)and migration(13.6%vs.74.9%),outperforming monotherapies.In vivo,the chemo-photothermal treatment reduced tumor volumes by 2.5-and 3-fold compared to ATO or PTT alone,confirming superior antitumor effects.Conclusions:These findings highlight the dual-action ATO/PCPDTBT@NPs nanoplatform as a potential multifaceted strategy for effective tumor suppression and metastasis inhibition.
基金supported by grants from Natural Science Foundation of Hunan Province(No.2022JJ50158).
文摘Background:Lung adenocarcinoma(LUAD),the most prevalent histological subtype of lung cancer,remains a leading cause of cancer-related mortality due to late diagnosis,metastasis,and therapy resistance.The aim of the study is to investigate the role of Kinetochore Scaffold 1(KNL1)in promoting LUAD progression and its underlying molecular regulatory mechanisms.Methods:KNL1 mRNA expression levels across 33 cancer types were analyzed using bioinformatics analysis based on the TCGA database.Immunohistochemistry(IHC)was used to assess KNL1 expression in LUAD and normal tissues.Stable KNL1-knockdown and KNL1-overexpressing LUAD cell lines were established using lentiviral infection.Western blotting(WB)was used to measure epithelial-mesenchymal transition(EMT)markers and ferroptosis-related protein expression.Cell migration was evaluated via scratch wound healing assays.The thiobarbituric acid(TBA)method was employed for the detection of malondialdehyde.a fluorescent probe was utilized to determine ferrous ion content.WB determined the phosphorylation ratios of AMP-activated protein kinase(AMPK)and mammalian target of rapamycin(mTOR)proteins.Results:1.KNL1 was highly expressed in 31 cancer types,including LUAD.Kaplan-Meier curves showed significantly shorter median survival in patients with high KNL1 expression.IHC confirmed upregulated KNL1 expression in LUAD tissues.2.KNL1 overexpression significantly promoted LUAD cell migration and increased mesenchymal marker expression,whereas KNL1 knockdown exerted opposite effects.3.KNL1 overexpression significantly reduced MDA content and Fe^(2+)levels in RSL3-treated LUAD cells while increasing the expression of key ferroptosis defense proteins;conversely,it markedly increased the accumulation of MDA and Fe^(2+)and downregulated these proteins.KNL1 overexpression significantly increased phosphorylated AMPK(p-AMPK)expression but decreased phosphorylated mTOR(p-mTOR)expression in RSL3-treated LUAD cells;conversely,it inhibited p-AMPK expression and activated p-mTOR.Conclusion:KNL1 promotes lung adenocarcinoma progression by suppressing ferroptosis through regulation of the AMPK-mTOR signaling pathway.
