Objectives:Non-small cell lung cancer(NSCLC)remains a leading cause of cancer-related mortality,with limited understanding of lncRNA-driven mechanisms in tumor progression.This study aimed to identify differentially e...Objectives:Non-small cell lung cancer(NSCLC)remains a leading cause of cancer-related mortality,with limited understanding of lncRNA-driven mechanisms in tumor progression.This study aimed to identify differentially expressed lncRNAs in NSCLC tissues and elucidate the functional role of the significantly upregulated RP3-340N1.2 in promoting malignancy.Methods:RNA sequencing was used to screen dysregulated lncRNAs.RP3-340N1.2 was functionally characterized via gain/loss-of-function assays in NSCLC cells,assessing proliferation,migration,and macrophage polarization.Mechanisms of interleukin 6(IL-6)regulation were explored using cytokine profiling,Actinomycin D assays,and RNA Immunoprecipitation(RIP)assays to study RP3-340N1.2 interactions with zinc finger CCCH-type containing 12A(ZC3H12A)and IL-6 mRNA.Results:RP3-340N1.2 was upregulated in NSCLC tissues and cells.Functional assays demonstrated that RP3-340N1.2 knockdown suppressed NSCLC cell proliferation/migration and reduced macrophage polarization toward tumor-associated phenotypes.Mechanistically,RP3-340N1.2 knockdown promoted IL-6 mRNA degradation,as supported by reduced IL-6 levels and accelerated mRNA decay.Further RIP assays revealed that RP3-340N1.2 interacts with ZC3H12A,an RNA-binding protein previously reported to degrade IL-6 mRNA,and that RP3-340N1.2 knockdown enhanced ZC3H12A binding to IL-6 mRNA.Consequently,RP3-340N1.2 knockdown in carcinoma cells attenuated IL-6-mediated tumor-promoting effects,including tumor cell proliferation and migration.Importantly,these effectswere observed not only in a direct carcinoma cell culturing system but also when carcinoma cells were exposed to conditioned medium from co-culturing RP3-340N1.2-knockdown tumor cells andmacrophages.Conclusion:RP3-340N1.2 drivesNSCLC malignancy by stabilizing IL-6 mRNA;its inhibition offers a potential therapeutic strategy to disrupt tumor-promoting interactions.展开更多
As the leading cause of cancer-related deaths,lung cancer remains a noteworthy threat to human health.Although immunotherapies,such as immune checkpoint inhibitors(ICIs),have significantly increased the efficacy of lu...As the leading cause of cancer-related deaths,lung cancer remains a noteworthy threat to human health.Although immunotherapies,such as immune checkpoint inhibitors(ICIs),have significantly increased the efficacy of lung cancer treatment,a significant percentage of patients are not sensitive to immunotherapies and patients who initially respond to treatment can quickly develop acquired drug resistance.Bispecific antibodies(bs Abs)bind two different antigens or epitopes simultaneously and have been shown to enhance antitumor efficacy with suitable safety profiles,thus attracting increasing attention as novel antitumor therapies.At present,in addition to the approved bs Ab,amivantamab,three novel bs Abs(KN046,AK112,and SHR-1701)are being evaluated in phase 3 clinical trials and many bs Abs are being evaluated in phase 1/2 clinical trials for patients with non-small cell lung cancer(NSCLC).Herein we present the structure,classification,and mechanism of action underlying bs Abs in NSCLC and introduce related clinical trials.Finally,we discuss challenges,potential solutions,and future prospects in the context of cancer treatment with bsAbs.展开更多
Objective:Patients with homologous recombination deficiency(HRD)demonstrate distinct clinicopathological and prognostic features.However,standardised and clinically validated HRD detection methodologies specifically t...Objective:Patients with homologous recombination deficiency(HRD)demonstrate distinct clinicopathological and prognostic features.However,standardised and clinically validated HRD detection methodologies specifically tailored for non-small cell lung cancer(NSCLC)have yet to be established.Further research is needed to clarify the precise role and clinical implications of HRD in NSCLC.Methods:A cohort of 580 treatment-naive NSCLC patients was retrospectively enrolled.Comprehensive genomic profiling(CGP)was performed for all patients,and HRD status was evaluated using two genomic scar score(GSS)-based algorithms:a machine learning-based GSS(ML-GSS)and a continuous linear regression-based GSS(CLR-GSS).To assess the diagnostic performance(sensitivity and specificity)of the ML-GSS and CLR-GSS algorithms for HRD detection,immunohistochemical(IHC)staining was conducted for two HRD-related biomarkers:Schlafen 11(SLFN11)and RAD51.Survival analysis,including progression-free survival(PFS),along with multivariable Cox proportional hazards models,was performed to compare the prognostic value of the two HRD algorithms.Results:Among all patients,146(25.2%)and 46(7.9%)were classified as HRD-positive(HRD+)by ML-GSS and CLR-GSS,respectively.Using SLFN11 IHC expression as the reference standard,comparative analysis demonstrated that ML-GSS exhibited significantly higher sensitivity but lower specificity than CLR-GSS.This trend was consistently observed in RAD51 staining analysis.Compared to HRD-negative(HRD-)patients,MLGSS-defined HRD+cases displayed distinct clinicopathological and genomic features,including a higher prevalence of homologous recombination(HR)-related genes mutations,BRCA1/2 mutations,TP53 mutations,elevated tumor mutation burden(TMB),and increased copy number variations(CNVs).In contrast,CLR-GSSdefined HRD+patients were only enriched for BRCA1/2 mutations,TP53 mutations,and elevated TMB.Furthermore,ML-GSS-defined HRD+status was associated with significantly worse prognosis following first-line therapy compared to HRD-patients.Univariate and multivariable Cox analyses identified ML-GSS-defined HRD+and TP53 mutations as significant predictors and independent risk factors,respectively.No such associations were observed in the CLR-GSS-defined HRD+cohort.Conclusions:ML-GSS demonstrated superior performance to CLR-GSS in assessing chromosomal instability(CIN)and showed greater clinical utility.We recommend the ML-GSS algorithm as a robust and clinically validated tool for HRD/CIN evaluation in NSCLC.Furthermore,ML-GSS-defined HRD+status was identified as both a significant predictor and an independent risk factor.展开更多
Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSC...Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSCLC)and its molecular mechanism using mice bearing Lewis lung carcinoma cells.LRC significantly suppressed the growth of NSCLC.Besides,RNA sequencing of mice tumors and hematoxylin&eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes,specifically GZMB~+CD8~+T lymphocytes,in tumor tissues.The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways,suggesting that LRC exerted its effects through the PDL1/PD-1 pathway.Further experiments revealed that LRC interacted with PD-L1,blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells.Together,these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.展开更多
Lung cancer is one of the main causes of cancer-related deaths globally,with non-small cell lung cancer(NSCLC)being the most prevalent histological subtype of lung cancer.Glutathione peroxidase 4(GPX4)is a crucial ant...Lung cancer is one of the main causes of cancer-related deaths globally,with non-small cell lung cancer(NSCLC)being the most prevalent histological subtype of lung cancer.Glutathione peroxidase 4(GPX4)is a crucial antioxidant enzyme that plays a role in regulating ferroptosis.It is also involved in a wide variety of biological processes,such as tumor cell growth invasion,migration,and resistance to drugs.This study comprehensively examined the role of GPX4 in NSCLC and investigated the clinical feasibility of targeting GPX4 for NSCLC treatment.We discovered that GPX4 influences the progression of NSCLC by modulating multiple signaling pathways,and that blocking GPX4 can trigger ferroptosis and increase the sensitivity to chemotherapy.As a result,GPX4 represents a prospective therapeutic target for NSCLC.Targeting GPX4 inhibits the development of NSCLC cells and decreases their resistance to treatment.展开更多
Numerous research conducted in recent years has revealed that gut microbial dysbiosis,such as modifications in composition and activity,might influence lung tissue homeostasis through specific pathways,thereby promoti...Numerous research conducted in recent years has revealed that gut microbial dysbiosis,such as modifications in composition and activity,might influence lung tissue homeostasis through specific pathways,thereby promoting susceptibility to lung diseases.The development and progression of lung cancer,as well as the effectiveness of immunotherapy are closely associated with gut flora and metabolites,which influence immunological and inflammatory responses.During abnormal proliferation,non-small cell lung cancer cells acquire more substances and energy by altering their own metabolic pathways.Glucose and amino acid metabolism reprogramming provide tumor cells with abundant ATP,carbon,and nitrogen sources,respectively,providing optimal conditions for tumor cell proliferation,invasion,and immune escape.This article reviews the relationship of immune response with gut flora and metabolic reprogramming in non-small cell lung cancer,and discusses the potential mechanisms by which gut flora and metabolic reprogramming affect the occurrence,development,and immunotherapy of non-small cell lung cancer,in order to provide new ideas for precision treatment of lung cancer patients.展开更多
Background:The mortality rate of non-small cell lung cancer(NSCLC)has continued to rise in recent decades,and the five-year survival rate remains extremely low,despite the accelerated incorporation of a variety of med...Background:The mortality rate of non-small cell lung cancer(NSCLC)has continued to rise in recent decades,and the five-year survival rate remains extremely low,despite the accelerated incorporation of a variety of medical treatments in its treatment and the increasing incidence of lung cancer.Traditional Chinese medicine plays an important role in the prevention and treatment of lung cancer.We used network pharmacology to investigate and predict the targets and associated signaling pathways of Wen-Yang-Hua-Liu Decoction(WYHLD)for the treatment of NSCLC.In addition,we investigated the growth mechanism of WYHLD on NSCLC by observing the effects of WYHLD on the processes of NSCLC proliferation,apoptosis,and ferroptosis.Methods:WYHLD drugs were obtained from the TCMSP database and potential targets from the Swiss Target Prediction and Uniprot databases;NSCLC-related genes were collected from the Genecards database;and the intersection genes of WYHLD and NSCLC were obtained from the Venny2.1 platform and imported into the STRING database.The intersection genes of WYHLD and NSCLC were collected from the Genecards database,imported into the STRING database,constructed into a into a protein-protein interaction network(PPI),visualized by Cytoscape 3.9.1 software,and analysed by GO enrichment and KEGG pathway analysis using the Metascape database to predict the direct targets and signaling pathways of WYHLD in the treatment of NSCLC.The NSCLC cell line A549 was cultured,and CCK-8 and wound healing assays were performed to assess cell proliferation and migration.Apoptosis was detected by Hoechst staining.Reactive oxygen species(ROS)levels were measured using flow cytometry.The microstructure of A549 cells observed by transmission electron microscopy.In addition,Western blot was performed to detect MYC,VEGF,HIF-1α,β-catenin,Cleaved-caspase3,GPX4,and SLC7A11 protein expression.Results:The network pharmacological analysis identified 160 WYHLD compounds,1,444 NSCLC disease-related targets,and 133 overlapping WYHLD and NSCLC targets.MYC,AKT1,JUN,ESR1,FOS,TP53,BCL2,and other proteins with high degree values were ranked as therapeutic targets in the STRING 11.0 database.The enriched pathways were identified as being associated with the cancer pathway,the AGE-RAGE signaling pathway,and NSCLC.In in vitro experiments,we found that WYHLD inhibited the migration and proliferation of NSCLC cells and promoted their apoptosis.Analysis of reactive oxygen species showed that WYHLD could promote cellular production of reactive oxygen species.In addition,WYHLD significantly suppressed the expression of MYC,GPX4,SLC7A11,β-catenin,and VEGF while increasing the expression of Cleaved-caspase3.Conclusion:Our results suggest that WYHLD may act as a novel strategy for the prevention and treatment of lung cancer by targeting the Wnt pathway,thereby inhibiting the growth mechanism of NSCLC.展开更多
This letter addresses Wang and Zhang's investigation into the role of tankyrase 2(TNKS2)as a pivotal driver of malignancy in non-small cell lung cancer(NSCLC)through mechanisms including apoptosis inhibition,enhan...This letter addresses Wang and Zhang's investigation into the role of tankyrase 2(TNKS2)as a pivotal driver of malignancy in non-small cell lung cancer(NSCLC)through mechanisms including apoptosis inhibition,enhanced cellular migration,andβ-catenin pathway activation.Their study in NSCLC cell lines demonstrates that TNKS2 overexpression stabilizesβ-catenin,subsequently triggering onco-genic gene expression and facilitating cellular migration-key attributes of meta-static potential.These insights position TNKS2 as a compelling target for therapy and a potential prognostic marker in NSCLC.Nevertheless,translating these in vitro findings to clinical practice requires validation in in vivo models.Addi-tionally,further research should investigate TNKS2 expression in patient samples and assess its implications in therapy resistance and combination treatment strategies.展开更多
Objective:Patients with stage III non-small cell lung cancer(NSCLC)present with a heterogeneous disease profile and often require multifaceted treatment strategies.This research aimed to investigate the demographic fe...Objective:Patients with stage III non-small cell lung cancer(NSCLC)present with a heterogeneous disease profile and often require multifaceted treatment strategies.This research aimed to investigate the demographic features,therapeutic patterns,and survival outcomes of such patients in Vietnam.Methods:A retrospective descriptive study was conducted on 731 patients diagnosed with stage III NSCLC American Joint Committee on Cancer(AJCC)8th edition,at Nghe An Oncology Hospital from January 2018 to August 2024.Descriptive statistics summarized baseline and treatment characteristics.We calculated progression-free survival(PFS)and overall survival(OS)through the Kaplan–Meier approach and compared survival curves with the log-rank test.Prognostic variables were assessed using Cox regression analysis.Results:Patients had a median age of 64 years,and the majority(84%)were male.Disease stages IIIA,IIIB,and IIICaccounted for 26.0%,49.9%,and 24.1%of cases,respectively.Adenocarcinoma(60.7%)was the most common histological subtype.Initial treatments included surgery(8.5%),concurrent chemoradiotherapy(38.6%),sequential chemoradiotherapy(2.2%),radiotherapy alone(1.4%),systemic therapy(37.3%),and palliative care(12.0%).From 2018 to 2024,the use of systemic therapy declined(88.5%to 21.7%),while concurrent chemoradiotherapy rose significantly(1.1%to 51.5%).Median progression-free survival(mPFS)and median overall survival(mOS)were 8.9 months and 20.5 months,respectively.Patients with stage IIIA had significantly better outcomes(mPFS:12.6 months;mOS:32.4 months;p<0.001).Surgical treatment yielded the longest survival(mPFS:13.5 months;mOS:42.8 months).Favorable prognostic factors included adenocarcinoma subtype,presence of driver mutations,stage IIIA,and good performance status.Conclusion:For stage III NSCLC,concurrent chemoradiotherapy is still considered the standard treatment,whereas surgery can provide the highest survival advantage in carefully selected cases.Histology,molecular profile,and disease stage are key prognostic indicators.展开更多
Background:Sleeve lobectomy(SL)presents an attractive option compared to pneumonectomy(PN)for patients with central or locally advanced non-small cell lung cancer(NSCLC).This study aimed to assess the advantages of SL...Background:Sleeve lobectomy(SL)presents an attractive option compared to pneumonectomy(PN)for patients with central or locally advanced non-small cell lung cancer(NSCLC).This study aimed to assess the advantages of SL over PN for NSCLC via a meta-analysis.Methods:We performed a systematic review and cumulative analysis of comparative studies that reported both postoperative and survival outcomes for SL and PN.This was accomplished through a thorough search of electronic databases,including PubMed,EMBASE,and the Cochrane library,from inception to April 2023.Results:A total of 5727 patients(SL:1945;PN:3782)from thirty-one studies were analyzed.The meta-analysis focused on perioperative mortality,local recurrence,and overall survival.The SL group exhibited a significantly lower rate of perioperative mortality(OR=0.43,95%CI=0.32–0.60,P<0.0001).However,no significant difference was observed in local recurrence rates between SL and PN(OR=1.25;95%CI,0.92 to 1.69;P=0.16).Additionally,the survival rates at 1 year and 5 years in the SL cohort(1-year:0.14,95%CI:0.12 to 0.17,p<0.0001;5-year:2.15,95%CI:1.77 to 2.61,p<0.0001)along with the survival in patients with pN0 or pN1 at 5 years(OR=0.13,95%CI 0.04 to 0.22;P=0.006)were notably superior compared to those undergoing PN.Conclusions:Sleeve lobectomy should be regarded as a viable alternative to pneumonectomy for treating NSCLC.展开更多
BACKGROUND The optimal sequencing of immune checkpoint inhibitor(ICI)and brain radiotherapy in the management of brain metastasis from non-small cell lung cancer(NSCLC)is unclear.AIM To evaluate the survival of concur...BACKGROUND The optimal sequencing of immune checkpoint inhibitor(ICI)and brain radiotherapy in the management of brain metastasis from non-small cell lung cancer(NSCLC)is unclear.AIM To evaluate the survival of concurrent ICI and consolidation ICI in NSCLC patients treated with brain radiotherapy.METHODS We retrospectively analyzed NSCLC patients treated with brain radiotherapy and ICI.Treatment response and survival were estimated.The cox proportional hazards regression model was utilized to investigate the association between overall survival and clinical variables.RESULTS There were 54 patients in concurrent ICI and radiotherapy group,and 62 individuals treated with radiotherapy followed by consolidation ICI.The objective response rates were similar between the two group.The median progression free survival was significantly high in the concurrent ICI group compared with consolidation ICI group(9.56 months vs 8.15 months,P=0.038).In addition,the median overall survival was 22.08 months in the concurrent ICI group,clearly longer than that in the consolidation group(13.24 months,P=0.009).CONCLUSION In NSCLC patients with brain metastases,our analyses suggested that radio therapy concurrent with ICI was associated with significant benefit compared with radiotherapy followed by consolidation ICI.展开更多
[Objectives]To investigate whether Ailanthone(AIL)could reverse cisplatin resistance in non-small cell lung cancer(NSCLC)by modulating autophagy pathways in A549/DDP cells.[Methods]Cisplatin-resistant A549/DDP cells w...[Objectives]To investigate whether Ailanthone(AIL)could reverse cisplatin resistance in non-small cell lung cancer(NSCLC)by modulating autophagy pathways in A549/DDP cells.[Methods]Cisplatin-resistant A549/DDP cells were treated with AIL(0.6μmol/L),cisplatin(50μg/mL),or their combination.Cell proliferation was assessed by MTT,EdU and colony formation assays;migration by Transwell and wound healing assays;autophagy markers(P62,LC3B,Beclin1,ATG5)by Western blot;LC3B puncta by immunofluorescence;with rescue experiments using rapamycin.[Results]The AIL-cisplatin combination synergistically inhibited proliferation and migration,while downregulating P-gp and MVP.AIL significantly increased P62 accumulation while decreasing LC3B-II,Beclin1 and ATG5.Rapamycin reversed these effects,restoring viability and resistance markers.[Conclusions]AIL reverses cisplatin resistance in NSCLC by inhibiting autophagy through P62/LC3B regulation,offering a promising therapeutic strategy for refractory NSCLC.展开更多
BACKGROUND Non-small cell lung cancer(NSCLC)is frequently characterized by poor response to cisplatin(DDP)-based chemotherapy,with increasing evidence suggesting that inflammatory cytokines in the tumor microenvironme...BACKGROUND Non-small cell lung cancer(NSCLC)is frequently characterized by poor response to cisplatin(DDP)-based chemotherapy,with increasing evidence suggesting that inflammatory cytokines in the tumor microenvironment contribute to chemoresistance.AIM To investigate the role of inflammatory cytokines in DDP resistance and to effect of IL-6 inhibition on chemosensitivity in NSCLC.METHODS Twenty NSCLC patients were grouped into DDP-sensitive or DDP-resistant cohorts based on their clinical response.Cytokine levels in tumor tissues and NSCLC cell lines,including DDP-resistant A549/DDP and SK-MES-1/DDP,were quantified using enzyme-linked immunosorbent assay.To verify the effects of interleukin(IL)-6 on DDP resistance,NSCLC and resistant cells were treated with IL-6 inhibitors tocilizumab(TCZ),followed by DDP treatment.Cell viability,apoptosis,migration and invasion were detected via cell counting kit-8,flow cytometry,scratch assay,and transwell,respectively.RESULTS IL-6,IL-8,and tumor necrosis factor-αlevels were significantly elevated in DDP-resistance tissues and cell models compared to sensitive controls(P<0.05).TCZ treatment significantly reduced the half-maximal inhibitory concentration of DDP in resistant cells,induced apoptosis,and hindered migration and invasion(P<0.05).IL-6 and IL-8 were identified as key cytokines associated with DDP resistance.CONCLUSION These findings demonstrated that IL-6 and related cytokines contribute to DDP resistance in NSCLC.IL-6 inhibition restores chemosensitivity and may serve as a promising therapeutic strategy in resistant NSCLC.展开更多
Objectives:Fractionated radiotherapy represents a standardized and widely adopted treatment modality for cancermanagement,with approximately 40% of non-small cell lung cancer(NSCLC)patients receiving it.However,repeat...Objectives:Fractionated radiotherapy represents a standardized and widely adopted treatment modality for cancermanagement,with approximately 40% of non-small cell lung cancer(NSCLC)patients receiving it.However,repeated irradiationmay induce radioresistance in cancer cells,reducing treatment effectiveness and raising recurrence risk.The long noncoding RNA CRYBG3(lncRNA CRYBG3),which is upregulated in lung cancer cells after Xray irradiation,contributes to the radioresistance of NSCLC cells by promoting wild-type p53 protein degradation.This study aims to elucidate the mechanism of fractionated irradiation-induced radioresistance,in which lncRNA CRYBG3 regulates radiation-induced mitochondrial damage and reactive oxygen species(ROS)generation through the p53 downstream signaling pathway.Methods:To investigate the critical roles of lncRNA CRYBG3 in mediating radioresistance induced by fractionated irradiation in NSCLC,we established radioresistant NSCLC cells by irradiating the A549 and H460 cell lines with 60 Gy of X-rays in 12 fractions,and named the radioresistant cells A549R and H460R,respectively.Lentiviral vectors were used to deliver short hairpin RNA(shRNA)into cells to knock down lncRNA CRYBG3,thereby investigating its contribution to adaptive radioresistance in A549R and H460R cells.All cells were irradiated with 4 Gy of X-rays,and subsequent analyses were conducted to evaluate mitochondrial damage,ROS generation,apoptosis,and the expression of oxidative stress-related proteins.Results:Increased expression levels of lncRNA CRYBG3 were positively associated with the acquisition of radioresistance in NSCLC cells.Additionally,suppressing lncRNA CRYBG3 increased mitochondrial damage and promoted radiation-induced apoptosis in radioresistant NSCLC cells.Mechanistically,the downregulation of lncRNA CRYBG3 led to increased p53 levels,resulting in decreased expression of heat shock factor 1(HSF1)and tumor necrosis factor receptor-associated protein 1(TRAP1),as well as enhanced radiation-induced mitochondrial oxidative damage and apoptosis.Conclusion:The results indicate that lncRNA CRYBG3 plays a regulatory role in adaptive radioresistance in NSCLC cells through the p53/HSF1/TRAP1 axis.Therefore,targeting lncRNA CRYBG3 could potentially improve the efficacy of fractionated radiotherapy in NSCLC.展开更多
Chemoresistance remains a major challenge in non-small cell lung cancer,especially for cisplatin(DDP)-based therapies,which are a mainstay of treatment.In their study,Dai et al investigate how inflammatory cytokines w...Chemoresistance remains a major challenge in non-small cell lung cancer,especially for cisplatin(DDP)-based therapies,which are a mainstay of treatment.In their study,Dai et al investigate how inflammatory cytokines within the tumor microenvironment contribute to DDP resistance.By analyzing tumor samples from 20 non-small cell lung cancer patients and two resistant cell lines(A549/DDP and SK-MES-1/DDP),the authors show that increased levels of interleukin(IL)-6,IL-8,and tumor necrosis factor-αare linked to resistance.Logistic regression identifies IL-6 and IL-8 as key risk factors.Functional experiments using tocilizumab,an IL-6 receptor antagonist,demonstrate a reduction in DDP half maximum inhibitory concentration,higher apoptosis rates,and decreased migration and invasion in resistant cells.Although the study has certain limitations,such as the analysis of only five inflammatory cytokines in a small,non-stratified patient cohort;it demonstrates that targeting the IL-6 cytokine axis may help overcome DDP resistance.Overall,the study highlights the inflammatory component of the tumor microenvironment as a modifiable driver of chemoresistance and provide a rationale for integrating cytokine blockade into platinum-based chemotherapy regimens to enhance therapeutic response.展开更多
BACKGROUND Lung cancer is one of the most common and deadly cancers worldwide.As the disease progresses and due to the side effects of treatment,patients’physical activity significantly decreases.AIM To systematicall...BACKGROUND Lung cancer is one of the most common and deadly cancers worldwide.As the disease progresses and due to the side effects of treatment,patients’physical activity significantly decreases.AIM To systematically review and conduct a meta-analysis on the effects of exercise rehabilitation on the physical activity of lung cancer patients and determine the best implementation methods to provide clinical guidance.METHODS Literature was searched through multiple electronic databases.A random effects model was used to combine effect sizes through standardized mean difference(SMD).The Cochrane risk of bias tool was used to assess the quality of the lite-rature,sensitivity analysis was used to ensure the robustness of the results,and Egger’s test was used to detect publication bias and asymmetry.RESULTS A total of 11 studies involving 541 patients were included in this study.The phy-sical endurance,muscle function and cardiopulmonary function of non-small cell lung cancer(NSCLC)patients were evaluated.The overall effect size of the six-minute walk test(6MWT)was not statistically significant.However,subgroup analysis found that endurance significantly improved when exercise duration exceeded 0.5 hours(P≤0.05).In terms of muscle function,the overall effect size was SMD=0.619.Subgroup analysis showed that strength training,respiratory training,and cross-training(XT)significantly improved muscle function.Exercise rehabilitation significantly enhanced cardiopulmonary endurance(SMD=0.856,P=0.002),and the effect was better when the single exercise duration was more than 1 hour,age was over 65 years,and the intervention period was more than 3 months.CONCLUSION Exercise rehabilitation effectively improved muscle function in NSCLC patients,especially strength training,respiratory training,and cross-training.Cardiopulmonary function also showed improvement,particularly when exercise duration exceeded 1 hour,age was≥65 years,and the intervention period was more than 3 months.A single exercise duration of more than 0.5 hours can enhance patients’physical endurance.Appropriately increasing exercise duration and selecting suitable exercise forms can effectively improve the physical activity of NSCLC patients.展开更多
The Wnt/b-catenin signaling pathway is renowned for its contribution to the immunosuppressive microenvironment in non-small cell lung cancer(NSCLC).Consequently,inhibiting this pathway has emerged as a promising strat...The Wnt/b-catenin signaling pathway is renowned for its contribution to the immunosuppressive microenvironment in non-small cell lung cancer(NSCLC).Consequently,inhibiting this pathway has emerged as a promising strategy to enhance immune activation and reinstate T cell responses in cancer treatment.In this study,we initially investigate the metabolic characteristics of Wnt-hyperactivated NSCLC using mass spectroscopic detection in a mouse in-situ model and unveil its significant feature of acid accumulation at tumor sites.Building upon this discovery,we design an acid-sensitive peptidecarnosic acid(CA)supramolecular droplet(Pep1@CA),which leverages the acidic microenvironment characteristic of NSCLC for controlled release.By doing so,we aim to enhance targeting efficiency while minimizing off-target effects.As anticipated,Pep1@CA demonstrates potent tumor-specific inhibition of the Wnt signaling pathway and effectively reactivates T cell immunity in Wnt-hyperactivated NSCLC.Importantly,comprehensive in vivo evaluations reveal significant antitumor efficacy alongside excellent biosafety profiles.Collectively,this study provides a therapeutic strategy with promising clinical translational potential for targeting the Wnt signaling pathway and offers theoretical support for its application in immunotherapy.This innovative approach underscores that targeting pathways beyond traditional immunotherapy can also activate tumor immunity,thereby expanding the potential of cancer immunotherapy.展开更多
Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, ...Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, targeted therapy, immunotherapy or combination therapy is the main treatment for NSCLC, but it is still inevitably faced with the challenges of acquired drug resistance and tumor progression. The birth of antibody conjugator provides a new choice for its treatment. Antibody conjugator is a new type of biotherapeutic drug which is connected by monoclonal antibody via linker and cytotoxic drug. It has the characteristics of precision, high efficiency and low toxicity, etc. In recent years, its research and development and clinical trials have been endless. It shows that this new type of drug has great potential in the field of tumor therapy. In this paper, the structural characteristics, mechanism of action, current application, research achievements, challenges, countermeasures and development of ADC in NSCLC treatment are reviewed.展开更多
Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).Howev...Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Interestingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.展开更多
Over the past 2 decades,remarkable advancements in the screening,diagnosis,and treatment of non-small cell lung cancer(NSCLC)have led to improved patient outcomes.For the treatment of NSCLC with actionable gene mutati...Over the past 2 decades,remarkable advancements in the screening,diagnosis,and treatment of non-small cell lung cancer(NSCLC)have led to improved patient outcomes.For the treatment of NSCLC with actionable gene mutations,tyrosine kinase inhibitors developed against EGFR,ALK,RET,BRAF,ROS1,NTRK,MET,and KRAS,exhibit substantial antitumor activity and have been incorporated into standard treatment regimens.Additionally,numerous novel therapies,including immunotherapy and antibody-drug conjugate therapy,have been found to benefit patients with NSCLC.This review summarizes current advancements in targeted therapy for NSCLC,according to a systematic search of the PubMed database and synthesis of cutting-edge findings presented at the 2024 American Society of Clinical Oncology Annual Meeting and 2024 World Conference on Lung Cancer.展开更多
基金supported by the National Natural Science Foundation of China(No.81702296).
文摘Objectives:Non-small cell lung cancer(NSCLC)remains a leading cause of cancer-related mortality,with limited understanding of lncRNA-driven mechanisms in tumor progression.This study aimed to identify differentially expressed lncRNAs in NSCLC tissues and elucidate the functional role of the significantly upregulated RP3-340N1.2 in promoting malignancy.Methods:RNA sequencing was used to screen dysregulated lncRNAs.RP3-340N1.2 was functionally characterized via gain/loss-of-function assays in NSCLC cells,assessing proliferation,migration,and macrophage polarization.Mechanisms of interleukin 6(IL-6)regulation were explored using cytokine profiling,Actinomycin D assays,and RNA Immunoprecipitation(RIP)assays to study RP3-340N1.2 interactions with zinc finger CCCH-type containing 12A(ZC3H12A)and IL-6 mRNA.Results:RP3-340N1.2 was upregulated in NSCLC tissues and cells.Functional assays demonstrated that RP3-340N1.2 knockdown suppressed NSCLC cell proliferation/migration and reduced macrophage polarization toward tumor-associated phenotypes.Mechanistically,RP3-340N1.2 knockdown promoted IL-6 mRNA degradation,as supported by reduced IL-6 levels and accelerated mRNA decay.Further RIP assays revealed that RP3-340N1.2 interacts with ZC3H12A,an RNA-binding protein previously reported to degrade IL-6 mRNA,and that RP3-340N1.2 knockdown enhanced ZC3H12A binding to IL-6 mRNA.Consequently,RP3-340N1.2 knockdown in carcinoma cells attenuated IL-6-mediated tumor-promoting effects,including tumor cell proliferation and migration.Importantly,these effectswere observed not only in a direct carcinoma cell culturing system but also when carcinoma cells were exposed to conditioned medium from co-culturing RP3-340N1.2-knockdown tumor cells andmacrophages.Conclusion:RP3-340N1.2 drivesNSCLC malignancy by stabilizing IL-6 mRNA;its inhibition offers a potential therapeutic strategy to disrupt tumor-promoting interactions.
基金supported by the National Natural Science Foundation of China(Grant No.82272845)the Natural Science Foundation of Shandong(Grant No.ZR2023LZL001)。
文摘As the leading cause of cancer-related deaths,lung cancer remains a noteworthy threat to human health.Although immunotherapies,such as immune checkpoint inhibitors(ICIs),have significantly increased the efficacy of lung cancer treatment,a significant percentage of patients are not sensitive to immunotherapies and patients who initially respond to treatment can quickly develop acquired drug resistance.Bispecific antibodies(bs Abs)bind two different antigens or epitopes simultaneously and have been shown to enhance antitumor efficacy with suitable safety profiles,thus attracting increasing attention as novel antitumor therapies.At present,in addition to the approved bs Ab,amivantamab,three novel bs Abs(KN046,AK112,and SHR-1701)are being evaluated in phase 3 clinical trials and many bs Abs are being evaluated in phase 1/2 clinical trials for patients with non-small cell lung cancer(NSCLC).Herein we present the structure,classification,and mechanism of action underlying bs Abs in NSCLC and introduce related clinical trials.Finally,we discuss challenges,potential solutions,and future prospects in the context of cancer treatment with bsAbs.
基金supported by the National High Level Hospital Clinical Research Funding(No.BJ-2019-195)the National High Level Hospital Clinical Research Funding(No.BJ-2023-090)。
文摘Objective:Patients with homologous recombination deficiency(HRD)demonstrate distinct clinicopathological and prognostic features.However,standardised and clinically validated HRD detection methodologies specifically tailored for non-small cell lung cancer(NSCLC)have yet to be established.Further research is needed to clarify the precise role and clinical implications of HRD in NSCLC.Methods:A cohort of 580 treatment-naive NSCLC patients was retrospectively enrolled.Comprehensive genomic profiling(CGP)was performed for all patients,and HRD status was evaluated using two genomic scar score(GSS)-based algorithms:a machine learning-based GSS(ML-GSS)and a continuous linear regression-based GSS(CLR-GSS).To assess the diagnostic performance(sensitivity and specificity)of the ML-GSS and CLR-GSS algorithms for HRD detection,immunohistochemical(IHC)staining was conducted for two HRD-related biomarkers:Schlafen 11(SLFN11)and RAD51.Survival analysis,including progression-free survival(PFS),along with multivariable Cox proportional hazards models,was performed to compare the prognostic value of the two HRD algorithms.Results:Among all patients,146(25.2%)and 46(7.9%)were classified as HRD-positive(HRD+)by ML-GSS and CLR-GSS,respectively.Using SLFN11 IHC expression as the reference standard,comparative analysis demonstrated that ML-GSS exhibited significantly higher sensitivity but lower specificity than CLR-GSS.This trend was consistently observed in RAD51 staining analysis.Compared to HRD-negative(HRD-)patients,MLGSS-defined HRD+cases displayed distinct clinicopathological and genomic features,including a higher prevalence of homologous recombination(HR)-related genes mutations,BRCA1/2 mutations,TP53 mutations,elevated tumor mutation burden(TMB),and increased copy number variations(CNVs).In contrast,CLR-GSSdefined HRD+patients were only enriched for BRCA1/2 mutations,TP53 mutations,and elevated TMB.Furthermore,ML-GSS-defined HRD+status was associated with significantly worse prognosis following first-line therapy compared to HRD-patients.Univariate and multivariable Cox analyses identified ML-GSS-defined HRD+and TP53 mutations as significant predictors and independent risk factors,respectively.No such associations were observed in the CLR-GSS-defined HRD+cohort.Conclusions:ML-GSS demonstrated superior performance to CLR-GSS in assessing chromosomal instability(CIN)and showed greater clinical utility.We recommend the ML-GSS algorithm as a robust and clinically validated tool for HRD/CIN evaluation in NSCLC.Furthermore,ML-GSS-defined HRD+status was identified as both a significant predictor and an independent risk factor.
基金supported by Natural Science Foundation of Guangdong Province,China(2022A1515011575)National Natural Science Foundation of China,China(81873154)President Foundation of Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,China(1202103010)。
文摘Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSCLC)and its molecular mechanism using mice bearing Lewis lung carcinoma cells.LRC significantly suppressed the growth of NSCLC.Besides,RNA sequencing of mice tumors and hematoxylin&eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes,specifically GZMB~+CD8~+T lymphocytes,in tumor tissues.The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways,suggesting that LRC exerted its effects through the PDL1/PD-1 pathway.Further experiments revealed that LRC interacted with PD-L1,blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells.Together,these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.
文摘Lung cancer is one of the main causes of cancer-related deaths globally,with non-small cell lung cancer(NSCLC)being the most prevalent histological subtype of lung cancer.Glutathione peroxidase 4(GPX4)is a crucial antioxidant enzyme that plays a role in regulating ferroptosis.It is also involved in a wide variety of biological processes,such as tumor cell growth invasion,migration,and resistance to drugs.This study comprehensively examined the role of GPX4 in NSCLC and investigated the clinical feasibility of targeting GPX4 for NSCLC treatment.We discovered that GPX4 influences the progression of NSCLC by modulating multiple signaling pathways,and that blocking GPX4 can trigger ferroptosis and increase the sensitivity to chemotherapy.As a result,GPX4 represents a prospective therapeutic target for NSCLC.Targeting GPX4 inhibits the development of NSCLC cells and decreases their resistance to treatment.
基金supported by the Scientific Research Fund Project of Education Department of Yunnan Province,China(No.2024Y386).
文摘Numerous research conducted in recent years has revealed that gut microbial dysbiosis,such as modifications in composition and activity,might influence lung tissue homeostasis through specific pathways,thereby promoting susceptibility to lung diseases.The development and progression of lung cancer,as well as the effectiveness of immunotherapy are closely associated with gut flora and metabolites,which influence immunological and inflammatory responses.During abnormal proliferation,non-small cell lung cancer cells acquire more substances and energy by altering their own metabolic pathways.Glucose and amino acid metabolism reprogramming provide tumor cells with abundant ATP,carbon,and nitrogen sources,respectively,providing optimal conditions for tumor cell proliferation,invasion,and immune escape.This article reviews the relationship of immune response with gut flora and metabolic reprogramming in non-small cell lung cancer,and discusses the potential mechanisms by which gut flora and metabolic reprogramming affect the occurrence,development,and immunotherapy of non-small cell lung cancer,in order to provide new ideas for precision treatment of lung cancer patients.
基金Full-time Introduction of Talent Research Start-up Fund(No.RSC-0015)Key project of Jiangxi Science and Technology Department(No.20203BBE52W010)Jiangxi province Traditional Chinese Medicine science and technology plan project(No.2023B0016,No.2024B0217).
文摘Background:The mortality rate of non-small cell lung cancer(NSCLC)has continued to rise in recent decades,and the five-year survival rate remains extremely low,despite the accelerated incorporation of a variety of medical treatments in its treatment and the increasing incidence of lung cancer.Traditional Chinese medicine plays an important role in the prevention and treatment of lung cancer.We used network pharmacology to investigate and predict the targets and associated signaling pathways of Wen-Yang-Hua-Liu Decoction(WYHLD)for the treatment of NSCLC.In addition,we investigated the growth mechanism of WYHLD on NSCLC by observing the effects of WYHLD on the processes of NSCLC proliferation,apoptosis,and ferroptosis.Methods:WYHLD drugs were obtained from the TCMSP database and potential targets from the Swiss Target Prediction and Uniprot databases;NSCLC-related genes were collected from the Genecards database;and the intersection genes of WYHLD and NSCLC were obtained from the Venny2.1 platform and imported into the STRING database.The intersection genes of WYHLD and NSCLC were collected from the Genecards database,imported into the STRING database,constructed into a into a protein-protein interaction network(PPI),visualized by Cytoscape 3.9.1 software,and analysed by GO enrichment and KEGG pathway analysis using the Metascape database to predict the direct targets and signaling pathways of WYHLD in the treatment of NSCLC.The NSCLC cell line A549 was cultured,and CCK-8 and wound healing assays were performed to assess cell proliferation and migration.Apoptosis was detected by Hoechst staining.Reactive oxygen species(ROS)levels were measured using flow cytometry.The microstructure of A549 cells observed by transmission electron microscopy.In addition,Western blot was performed to detect MYC,VEGF,HIF-1α,β-catenin,Cleaved-caspase3,GPX4,and SLC7A11 protein expression.Results:The network pharmacological analysis identified 160 WYHLD compounds,1,444 NSCLC disease-related targets,and 133 overlapping WYHLD and NSCLC targets.MYC,AKT1,JUN,ESR1,FOS,TP53,BCL2,and other proteins with high degree values were ranked as therapeutic targets in the STRING 11.0 database.The enriched pathways were identified as being associated with the cancer pathway,the AGE-RAGE signaling pathway,and NSCLC.In in vitro experiments,we found that WYHLD inhibited the migration and proliferation of NSCLC cells and promoted their apoptosis.Analysis of reactive oxygen species showed that WYHLD could promote cellular production of reactive oxygen species.In addition,WYHLD significantly suppressed the expression of MYC,GPX4,SLC7A11,β-catenin,and VEGF while increasing the expression of Cleaved-caspase3.Conclusion:Our results suggest that WYHLD may act as a novel strategy for the prevention and treatment of lung cancer by targeting the Wnt pathway,thereby inhibiting the growth mechanism of NSCLC.
文摘This letter addresses Wang and Zhang's investigation into the role of tankyrase 2(TNKS2)as a pivotal driver of malignancy in non-small cell lung cancer(NSCLC)through mechanisms including apoptosis inhibition,enhanced cellular migration,andβ-catenin pathway activation.Their study in NSCLC cell lines demonstrates that TNKS2 overexpression stabilizesβ-catenin,subsequently triggering onco-genic gene expression and facilitating cellular migration-key attributes of meta-static potential.These insights position TNKS2 as a compelling target for therapy and a potential prognostic marker in NSCLC.Nevertheless,translating these in vitro findings to clinical practice requires validation in in vivo models.Addi-tionally,further research should investigate TNKS2 expression in patient samples and assess its implications in therapy resistance and combination treatment strategies.
文摘Objective:Patients with stage III non-small cell lung cancer(NSCLC)present with a heterogeneous disease profile and often require multifaceted treatment strategies.This research aimed to investigate the demographic features,therapeutic patterns,and survival outcomes of such patients in Vietnam.Methods:A retrospective descriptive study was conducted on 731 patients diagnosed with stage III NSCLC American Joint Committee on Cancer(AJCC)8th edition,at Nghe An Oncology Hospital from January 2018 to August 2024.Descriptive statistics summarized baseline and treatment characteristics.We calculated progression-free survival(PFS)and overall survival(OS)through the Kaplan–Meier approach and compared survival curves with the log-rank test.Prognostic variables were assessed using Cox regression analysis.Results:Patients had a median age of 64 years,and the majority(84%)were male.Disease stages IIIA,IIIB,and IIICaccounted for 26.0%,49.9%,and 24.1%of cases,respectively.Adenocarcinoma(60.7%)was the most common histological subtype.Initial treatments included surgery(8.5%),concurrent chemoradiotherapy(38.6%),sequential chemoradiotherapy(2.2%),radiotherapy alone(1.4%),systemic therapy(37.3%),and palliative care(12.0%).From 2018 to 2024,the use of systemic therapy declined(88.5%to 21.7%),while concurrent chemoradiotherapy rose significantly(1.1%to 51.5%).Median progression-free survival(mPFS)and median overall survival(mOS)were 8.9 months and 20.5 months,respectively.Patients with stage IIIA had significantly better outcomes(mPFS:12.6 months;mOS:32.4 months;p<0.001).Surgical treatment yielded the longest survival(mPFS:13.5 months;mOS:42.8 months).Favorable prognostic factors included adenocarcinoma subtype,presence of driver mutations,stage IIIA,and good performance status.Conclusion:For stage III NSCLC,concurrent chemoradiotherapy is still considered the standard treatment,whereas surgery can provide the highest survival advantage in carefully selected cases.Histology,molecular profile,and disease stage are key prognostic indicators.
文摘Background:Sleeve lobectomy(SL)presents an attractive option compared to pneumonectomy(PN)for patients with central or locally advanced non-small cell lung cancer(NSCLC).This study aimed to assess the advantages of SL over PN for NSCLC via a meta-analysis.Methods:We performed a systematic review and cumulative analysis of comparative studies that reported both postoperative and survival outcomes for SL and PN.This was accomplished through a thorough search of electronic databases,including PubMed,EMBASE,and the Cochrane library,from inception to April 2023.Results:A total of 5727 patients(SL:1945;PN:3782)from thirty-one studies were analyzed.The meta-analysis focused on perioperative mortality,local recurrence,and overall survival.The SL group exhibited a significantly lower rate of perioperative mortality(OR=0.43,95%CI=0.32–0.60,P<0.0001).However,no significant difference was observed in local recurrence rates between SL and PN(OR=1.25;95%CI,0.92 to 1.69;P=0.16).Additionally,the survival rates at 1 year and 5 years in the SL cohort(1-year:0.14,95%CI:0.12 to 0.17,p<0.0001;5-year:2.15,95%CI:1.77 to 2.61,p<0.0001)along with the survival in patients with pN0 or pN1 at 5 years(OR=0.13,95%CI 0.04 to 0.22;P=0.006)were notably superior compared to those undergoing PN.Conclusions:Sleeve lobectomy should be regarded as a viable alternative to pneumonectomy for treating NSCLC.
文摘BACKGROUND The optimal sequencing of immune checkpoint inhibitor(ICI)and brain radiotherapy in the management of brain metastasis from non-small cell lung cancer(NSCLC)is unclear.AIM To evaluate the survival of concurrent ICI and consolidation ICI in NSCLC patients treated with brain radiotherapy.METHODS We retrospectively analyzed NSCLC patients treated with brain radiotherapy and ICI.Treatment response and survival were estimated.The cox proportional hazards regression model was utilized to investigate the association between overall survival and clinical variables.RESULTS There were 54 patients in concurrent ICI and radiotherapy group,and 62 individuals treated with radiotherapy followed by consolidation ICI.The objective response rates were similar between the two group.The median progression free survival was significantly high in the concurrent ICI group compared with consolidation ICI group(9.56 months vs 8.15 months,P=0.038).In addition,the median overall survival was 22.08 months in the concurrent ICI group,clearly longer than that in the consolidation group(13.24 months,P=0.009).CONCLUSION In NSCLC patients with brain metastases,our analyses suggested that radio therapy concurrent with ICI was associated with significant benefit compared with radiotherapy followed by consolidation ICI.
基金Supported by National Natural Science Foundation of China(81703001)Key R&D Project of Hebei Province(19277783D)+1 种基金Natural Science Foundation of Hebei Province(H2021406021)Chengde Medical University Discipline Construction Funds.
文摘[Objectives]To investigate whether Ailanthone(AIL)could reverse cisplatin resistance in non-small cell lung cancer(NSCLC)by modulating autophagy pathways in A549/DDP cells.[Methods]Cisplatin-resistant A549/DDP cells were treated with AIL(0.6μmol/L),cisplatin(50μg/mL),or their combination.Cell proliferation was assessed by MTT,EdU and colony formation assays;migration by Transwell and wound healing assays;autophagy markers(P62,LC3B,Beclin1,ATG5)by Western blot;LC3B puncta by immunofluorescence;with rescue experiments using rapamycin.[Results]The AIL-cisplatin combination synergistically inhibited proliferation and migration,while downregulating P-gp and MVP.AIL significantly increased P62 accumulation while decreasing LC3B-II,Beclin1 and ATG5.Rapamycin reversed these effects,restoring viability and resistance markers.[Conclusions]AIL reverses cisplatin resistance in NSCLC by inhibiting autophagy through P62/LC3B regulation,offering a promising therapeutic strategy for refractory NSCLC.
文摘BACKGROUND Non-small cell lung cancer(NSCLC)is frequently characterized by poor response to cisplatin(DDP)-based chemotherapy,with increasing evidence suggesting that inflammatory cytokines in the tumor microenvironment contribute to chemoresistance.AIM To investigate the role of inflammatory cytokines in DDP resistance and to effect of IL-6 inhibition on chemosensitivity in NSCLC.METHODS Twenty NSCLC patients were grouped into DDP-sensitive or DDP-resistant cohorts based on their clinical response.Cytokine levels in tumor tissues and NSCLC cell lines,including DDP-resistant A549/DDP and SK-MES-1/DDP,were quantified using enzyme-linked immunosorbent assay.To verify the effects of interleukin(IL)-6 on DDP resistance,NSCLC and resistant cells were treated with IL-6 inhibitors tocilizumab(TCZ),followed by DDP treatment.Cell viability,apoptosis,migration and invasion were detected via cell counting kit-8,flow cytometry,scratch assay,and transwell,respectively.RESULTS IL-6,IL-8,and tumor necrosis factor-αlevels were significantly elevated in DDP-resistance tissues and cell models compared to sensitive controls(P<0.05).TCZ treatment significantly reduced the half-maximal inhibitory concentration of DDP in resistant cells,induced apoptosis,and hindered migration and invasion(P<0.05).IL-6 and IL-8 were identified as key cytokines associated with DDP resistance.CONCLUSION These findings demonstrated that IL-6 and related cytokines contribute to DDP resistance in NSCLC.IL-6 inhibition restores chemosensitivity and may serve as a promising therapeutic strategy in resistant NSCLC.
基金supported by the National Natural Science Foundation of China(No.12205215)Suzhou Fundamental Research Project(No.SJC2023001)+2 种基金Basic Research Program of Nantong Science and Technology Bureau(No.JC12022103)College Student Innovation Training Program Project of Soochow University(No.202410285101Z)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘Objectives:Fractionated radiotherapy represents a standardized and widely adopted treatment modality for cancermanagement,with approximately 40% of non-small cell lung cancer(NSCLC)patients receiving it.However,repeated irradiationmay induce radioresistance in cancer cells,reducing treatment effectiveness and raising recurrence risk.The long noncoding RNA CRYBG3(lncRNA CRYBG3),which is upregulated in lung cancer cells after Xray irradiation,contributes to the radioresistance of NSCLC cells by promoting wild-type p53 protein degradation.This study aims to elucidate the mechanism of fractionated irradiation-induced radioresistance,in which lncRNA CRYBG3 regulates radiation-induced mitochondrial damage and reactive oxygen species(ROS)generation through the p53 downstream signaling pathway.Methods:To investigate the critical roles of lncRNA CRYBG3 in mediating radioresistance induced by fractionated irradiation in NSCLC,we established radioresistant NSCLC cells by irradiating the A549 and H460 cell lines with 60 Gy of X-rays in 12 fractions,and named the radioresistant cells A549R and H460R,respectively.Lentiviral vectors were used to deliver short hairpin RNA(shRNA)into cells to knock down lncRNA CRYBG3,thereby investigating its contribution to adaptive radioresistance in A549R and H460R cells.All cells were irradiated with 4 Gy of X-rays,and subsequent analyses were conducted to evaluate mitochondrial damage,ROS generation,apoptosis,and the expression of oxidative stress-related proteins.Results:Increased expression levels of lncRNA CRYBG3 were positively associated with the acquisition of radioresistance in NSCLC cells.Additionally,suppressing lncRNA CRYBG3 increased mitochondrial damage and promoted radiation-induced apoptosis in radioresistant NSCLC cells.Mechanistically,the downregulation of lncRNA CRYBG3 led to increased p53 levels,resulting in decreased expression of heat shock factor 1(HSF1)and tumor necrosis factor receptor-associated protein 1(TRAP1),as well as enhanced radiation-induced mitochondrial oxidative damage and apoptosis.Conclusion:The results indicate that lncRNA CRYBG3 plays a regulatory role in adaptive radioresistance in NSCLC cells through the p53/HSF1/TRAP1 axis.Therefore,targeting lncRNA CRYBG3 could potentially improve the efficacy of fractionated radiotherapy in NSCLC.
文摘Chemoresistance remains a major challenge in non-small cell lung cancer,especially for cisplatin(DDP)-based therapies,which are a mainstay of treatment.In their study,Dai et al investigate how inflammatory cytokines within the tumor microenvironment contribute to DDP resistance.By analyzing tumor samples from 20 non-small cell lung cancer patients and two resistant cell lines(A549/DDP and SK-MES-1/DDP),the authors show that increased levels of interleukin(IL)-6,IL-8,and tumor necrosis factor-αare linked to resistance.Logistic regression identifies IL-6 and IL-8 as key risk factors.Functional experiments using tocilizumab,an IL-6 receptor antagonist,demonstrate a reduction in DDP half maximum inhibitory concentration,higher apoptosis rates,and decreased migration and invasion in resistant cells.Although the study has certain limitations,such as the analysis of only five inflammatory cytokines in a small,non-stratified patient cohort;it demonstrates that targeting the IL-6 cytokine axis may help overcome DDP resistance.Overall,the study highlights the inflammatory component of the tumor microenvironment as a modifiable driver of chemoresistance and provide a rationale for integrating cytokine blockade into platinum-based chemotherapy regimens to enhance therapeutic response.
基金Supported by the Youth Doctor Support Project of the Education Department of Gansu Province,No.2024QB-100.
文摘BACKGROUND Lung cancer is one of the most common and deadly cancers worldwide.As the disease progresses and due to the side effects of treatment,patients’physical activity significantly decreases.AIM To systematically review and conduct a meta-analysis on the effects of exercise rehabilitation on the physical activity of lung cancer patients and determine the best implementation methods to provide clinical guidance.METHODS Literature was searched through multiple electronic databases.A random effects model was used to combine effect sizes through standardized mean difference(SMD).The Cochrane risk of bias tool was used to assess the quality of the lite-rature,sensitivity analysis was used to ensure the robustness of the results,and Egger’s test was used to detect publication bias and asymmetry.RESULTS A total of 11 studies involving 541 patients were included in this study.The phy-sical endurance,muscle function and cardiopulmonary function of non-small cell lung cancer(NSCLC)patients were evaluated.The overall effect size of the six-minute walk test(6MWT)was not statistically significant.However,subgroup analysis found that endurance significantly improved when exercise duration exceeded 0.5 hours(P≤0.05).In terms of muscle function,the overall effect size was SMD=0.619.Subgroup analysis showed that strength training,respiratory training,and cross-training(XT)significantly improved muscle function.Exercise rehabilitation significantly enhanced cardiopulmonary endurance(SMD=0.856,P=0.002),and the effect was better when the single exercise duration was more than 1 hour,age was over 65 years,and the intervention period was more than 3 months.CONCLUSION Exercise rehabilitation effectively improved muscle function in NSCLC patients,especially strength training,respiratory training,and cross-training.Cardiopulmonary function also showed improvement,particularly when exercise duration exceeded 1 hour,age was≥65 years,and the intervention period was more than 3 months.A single exercise duration of more than 0.5 hours can enhance patients’physical endurance.Appropriately increasing exercise duration and selecting suitable exercise forms can effectively improve the physical activity of NSCLC patients.
基金supported by the National Natural Science Foundation of China(Grant No.:82141126)the Key Research and Development Program of Shaanxi Province(Program No.:2020GXLH-Y-020)+4 种基金the Innovation Capability Support Program of Shaanxi(Program No.:2021TD-44)the Key Research and Development Program of Shaanxi(Program No.:2023-GHZD-18)the Natural Science Basic Research Program of Shaanxi(Program No.:2023-JC-QN-0828)the Elite talent program of Shaanxi Provincial People's Hospital(Grant No.:2022JY-43)the Beijing Xisike Clinical Oncology Research Foundation(Grant No.:Y-HH202101-0234).
文摘The Wnt/b-catenin signaling pathway is renowned for its contribution to the immunosuppressive microenvironment in non-small cell lung cancer(NSCLC).Consequently,inhibiting this pathway has emerged as a promising strategy to enhance immune activation and reinstate T cell responses in cancer treatment.In this study,we initially investigate the metabolic characteristics of Wnt-hyperactivated NSCLC using mass spectroscopic detection in a mouse in-situ model and unveil its significant feature of acid accumulation at tumor sites.Building upon this discovery,we design an acid-sensitive peptidecarnosic acid(CA)supramolecular droplet(Pep1@CA),which leverages the acidic microenvironment characteristic of NSCLC for controlled release.By doing so,we aim to enhance targeting efficiency while minimizing off-target effects.As anticipated,Pep1@CA demonstrates potent tumor-specific inhibition of the Wnt signaling pathway and effectively reactivates T cell immunity in Wnt-hyperactivated NSCLC.Importantly,comprehensive in vivo evaluations reveal significant antitumor efficacy alongside excellent biosafety profiles.Collectively,this study provides a therapeutic strategy with promising clinical translational potential for targeting the Wnt signaling pathway and offers theoretical support for its application in immunotherapy.This innovative approach underscores that targeting pathways beyond traditional immunotherapy can also activate tumor immunity,thereby expanding the potential of cancer immunotherapy.
文摘Lung cancer is one of the malignant tumor diseases with high morbidity and high mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, chemotherapy, targeted therapy, immunotherapy or combination therapy is the main treatment for NSCLC, but it is still inevitably faced with the challenges of acquired drug resistance and tumor progression. The birth of antibody conjugator provides a new choice for its treatment. Antibody conjugator is a new type of biotherapeutic drug which is connected by monoclonal antibody via linker and cytotoxic drug. It has the characteristics of precision, high efficiency and low toxicity, etc. In recent years, its research and development and clinical trials have been endless. It shows that this new type of drug has great potential in the field of tumor therapy. In this paper, the structural characteristics, mechanism of action, current application, research achievements, challenges, countermeasures and development of ADC in NSCLC treatment are reviewed.
基金supported by the National Natural Science Foundation of China(Grant No.:82225048)the Dalian Science and Technology Leading Talents Project,China(Grant No.:2019RD15)Sanming Project of Medicine in Shenzhen,China(Grant No.:SZZYSM202106004).
文摘Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Interestingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.
基金funded by the National Natural Science Foundation of China(Grant no.82172776)Tianjin Health Research Project(Grant no.TJWJ2023XK005)Tianjin Science and Technology Plan Project(Grant no.24ZXGZSY00010).
文摘Over the past 2 decades,remarkable advancements in the screening,diagnosis,and treatment of non-small cell lung cancer(NSCLC)have led to improved patient outcomes.For the treatment of NSCLC with actionable gene mutations,tyrosine kinase inhibitors developed against EGFR,ALK,RET,BRAF,ROS1,NTRK,MET,and KRAS,exhibit substantial antitumor activity and have been incorporated into standard treatment regimens.Additionally,numerous novel therapies,including immunotherapy and antibody-drug conjugate therapy,have been found to benefit patients with NSCLC.This review summarizes current advancements in targeted therapy for NSCLC,according to a systematic search of the PubMed database and synthesis of cutting-edge findings presented at the 2024 American Society of Clinical Oncology Annual Meeting and 2024 World Conference on Lung Cancer.
