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
Lung cancer is among the most prevalent cancers and has the highest mortality rate globally.The diagnosis,pathohistological classification,and molecular testing of lung cancer primarily rely on tissue biopsy or surgic...Lung cancer is among the most prevalent cancers and has the highest mortality rate globally.The diagnosis,pathohistological classification,and molecular testing of lung cancer primarily rely on tissue biopsy or surgical resection.These methods are invasive and associated with limitations,including sample quantity and quality,as well as patient tolerance.Radiomics,an emerging technology,enables the extraction of high-throughput quantitative information from medical images,providing radiomic features applicable to clinical diagnosis and treatment.Significant advancements have been made in the application of radiomics to the diagnosis,molecular detection,efficacy prediction,and prognosis of lung cancer.This review examines the progress in radiomics for individualized and precise diagnosis and treatment of lung cancer in recent years.展开更多
Lung cancer, the leading cause of cancer deaths worldwide and in China, has a 19.7% five-year survival rate due to terminal-stage diagnosis^([1-3]).Although low-dose computed tomography(CT) screening can reduce mortal...Lung cancer, the leading cause of cancer deaths worldwide and in China, has a 19.7% five-year survival rate due to terminal-stage diagnosis^([1-3]).Although low-dose computed tomography(CT) screening can reduce mortality, high false positive rates can create economic and psychological burdens.展开更多
Dear Editor,Lung cancer is a major global health concern,with 2.2 million patients diagnosed in 2020.Non-small cell lung cancer(NSCLC)accounts for 80%of these cases,primarily comprising two subtypes:lung adenocarcinom...Dear Editor,Lung cancer is a major global health concern,with 2.2 million patients diagnosed in 2020.Non-small cell lung cancer(NSCLC)accounts for 80%of these cases,primarily comprising two subtypes:lung adenocarcinoma(LUAD)and squamous cell carcinoma(LUSC)[1].Researchers use immunohisto-chemistry,next-generation sequencing,and single-cell RNA sequencing to study genetic alterations,tumor heterogeneity,and tumor microenvironments,aiming to identify potential therapeutic options for specific NSCLC subtypes[2].展开更多
Introduction Small cell lung cancer(SCLC)is a highly aggressive malignancy with limited treatment options.Despite advances in immunotherapy,response rates remain low,and the efficacy of current molecular subtyping1,2 ...Introduction Small cell lung cancer(SCLC)is a highly aggressive malignancy with limited treatment options.Despite advances in immunotherapy,response rates remain low,and the efficacy of current molecular subtyping1,2 is insufficient to predict therapeutic outcomes3,4.A recently identified vulnerability in SCLC involves the dysregulation of nuclear-cytoplasmic transport,particularly through exportin 1(XPO1)5-7.展开更多
Lung cancer has one of the highest rates of incidence and mortality worldwide,mak-ing research on its mechanisms and treatments crucial.Animal models are essential in lung cancer research as they accurately replicate ...Lung cancer has one of the highest rates of incidence and mortality worldwide,mak-ing research on its mechanisms and treatments crucial.Animal models are essential in lung cancer research as they accurately replicate the biological characteristics and treatment outcomes seen in human diseases.Currently,various lung cancer models have been established,including chemical induction models,orthotopic transplan-tation models,ectopic transplantation models,metastasis models,and gene editing mouse models.Additionally,lung cancer grafts can be categorized into two types:tissue-based and cell-based grafts.This paper summarizes the phenotypes,advan-tages,and disadvantages of various induction methods based on their modeling tech-niques.The goal is to enhance the simulation of clinical lung cancer characteristics and to establish a solid foundation for future clinical research.展开更多
This article summarizes recent domestic literature on the use of Huangqin(Scutellaria baicalensis)in the treatment of lung cancer.It reviews the mechanism of action of Huangqin in treating lung cancer from six aspects...This article summarizes recent domestic literature on the use of Huangqin(Scutellaria baicalensis)in the treatment of lung cancer.It reviews the mechanism of action of Huangqin in treating lung cancer from six aspects:inhibiting the growth of lung cancer cells,inducing apoptosis of lung cancer cells,inducing autophagy of lung cancer cells,inhibiting the migration of lung cancer cells,promoting the differentiation of lung cancer cells,and improving immune function.The aim is to provide a reference for the material basis and further research on the anti-inflammatory and anti-tumor efficacy of Huangqin.展开更多
This corrigendum clarifies information in the article"PI3K/Akt/mTOR signaling orchestrates the phenotypic transition and chemo-resistance of small cell lung cancer"by Li et al.(2021).The authors regret that ...This corrigendum clarifies information in the article"PI3K/Akt/mTOR signaling orchestrates the phenotypic transition and chemo-resistance of small cell lung cancer"by Li et al.(2021).The authors regret that the image of H526 cells in the schematic illustration in Fig.4A displayed on the Webpage is wrong.The correct image for H526cells inthe schematic illustration is listed below。展开更多
Lung cancer continues to be a leading cause of cancer-related deaths worldwide,emphasizing the critical need for improved diagnostic techniques.Early detection of lung tumors significantly increases the chances of suc...Lung cancer continues to be a leading cause of cancer-related deaths worldwide,emphasizing the critical need for improved diagnostic techniques.Early detection of lung tumors significantly increases the chances of successful treatment and survival.However,current diagnostic methods often fail to detect tumors at an early stage or to accurately pinpoint their location within the lung tissue.Single-model deep learning technologies for lung cancer detection,while beneficial,cannot capture the full range of features present in medical imaging data,leading to incomplete or inaccurate detection.Furthermore,it may not be robust enough to handle the wide variability in medical images due to different imaging conditions,patient anatomy,and tumor characteristics.To overcome these disadvantages,dual-model or multi-model approaches can be employed.This research focuses on enhancing the detection of lung cancer by utilizing a combination of two learning models:a Convolutional Neural Network(CNN)for categorization and the You Only Look Once(YOLOv8)architecture for real-time identification and pinpointing of tumors.CNNs automatically learn to extract hierarchical features from raw image data,capturing patterns such as edges,textures,and complex structures that are crucial for identifying lung cancer.YOLOv8 incorporates multiscale feature extraction,enabling the detection of tumors of varying sizes and scales within a single image.This is particularly beneficial for identifying small or irregularly shaped tumors that may be challenging to detect.Furthermore,through the utilization of cutting-edge data augmentation methods,such as Deep Convolutional Generative Adversarial Networks(DCGAN),the suggested approach can handle the issue of limited data and boost the models’ability to learn from diverse and comprehensive datasets.The combined method not only improved accuracy and localization but also ensured efficient real-time processing,which is crucial for practical clinical applications.The CNN achieved an accuracy of 97.67%in classifying lung tissues into healthy and cancerous categories.The YOLOv8 model achieved an Intersection over Union(IoU)score of 0.85 for tumor localization,reflecting high precision in detecting and marking tumor boundaries within the images.Finally,the incorporation of synthetic images generated by DCGAN led to a 10%improvement in both the CNN classification accuracy and YOLOv8 detection performance.展开更多
Lung carcinoma is associated with a high mortality worldwide,being the leading cause of cancer death.It is mainly classified into squamous non-small cell lung cancer(NSCLC),non-squamous NSCLC,and small cell lung cance...Lung carcinoma is associated with a high mortality worldwide,being the leading cause of cancer death.It is mainly classified into squamous non-small cell lung cancer(NSCLC),non-squamous NSCLC,and small cell lung cancer.However,such malignancy has been increasingly subdivided into histological and molecular subtypes to guide treatment.Therapies can be used in adjuvant and palliative settings.Regarding immunotherapy,it has been widely tested in both first or subsequent palliative lines.In this sense,drugs such as pembrolizumab,nivolumab,atezolizumab,ipilimumab,avelumab,and durvalumab have been assessed in large studies.Some of these trials have also studied these medicines in adjuvant and in maintenance therapy.In recent years,advances in immunotherapy have raised the hope that the unfavorable prognosis observed in several affected individuals can be changed.Immunotherapy has increased the overall survival in squamous NSCLC,non-squamous NSCLC,and small cell lung cancer.However,it has added to the oncology practice some side effects that are unusual in standard chemotherapy and require special clinical support.In order to show how immunotherapy is being applied in the treatment of lung carcinoma,we reviewed the main studies in adjuvant and palliative scenarios.What is the better scheme?What is the better combination?What is the better dose?When should we use immunotherapy?Does programmed cell death ligand 1 expression significantly interfere in immunotherapy efficiency?Some of these questions have already been answered,while others require more investigations.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
Lung cancer is the most frequent cause of cancer-related mortality worldwide.Nitric oxide(NO),prostaglandins(PGs),thromboxanes(TXs),and endothelins(ETs)participate in numerous physiological processes.These agents play...Lung cancer is the most frequent cause of cancer-related mortality worldwide.Nitric oxide(NO),prostaglandins(PGs),thromboxanes(TXs),and endothelins(ETs)participate in numerous physiological processes.These agents play an important role in lung carcinogenesis by regulating cancer cell proliferation,apoptosis,invasion,and angiogenesis.NO is a gaseous free radical with tumo-ricidal and tumorigenic activities in lung cancer.Arachidonic acid-derived PGs,including PGD2,PGE2,8-iso-PGF2α,and PGI2,are related to the development of lung cancer.PGD2 and PGI2 act as tumor suppressors,while PGE2 and 8-iso-PGF2αpromote tumor progression.TXA2 catalyzed by cyclooxygenase induces prolif-eration as well as angiogenesis.Elevated levels of TXB2,an inactive metabolite of TXA2,are positively correlated with lung carcinoma stages.ET-1 and ET-2 are 21 amino acid polypeptides;their silencing hinders lung cancer cell proliferation and invasion.ET-2 depletion also triggers apoptotic death.This chapter review aims to provide a comprehensive overview of the role of NO,PGs,TXs,and ETs in lung cancer.展开更多
BACKGROUND Lung cancer(LC)is one of the most prevalent cancers globally,with a high incidence among the elderly population.Elderly patients,particularly those with diabetes mellitus,are at an increased risk of postope...BACKGROUND Lung cancer(LC)is one of the most prevalent cancers globally,with a high incidence among the elderly population.Elderly patients,particularly those with diabetes mellitus,are at an increased risk of postoperative complications,in-cluding pulmonary infections,due to weakened immune function and metabolic abnormalities.Postoperative pulmonary infection(PPI)is a predominant com-plication after thoracoscopic radical resection of LC,significantly affecting patient outcomes and increasing healthcare burdens.Determining risk factors for PPI in this vulnerable population is crucial for improving surgical outcomes and redu-cing infection rates.AIM To develop and validate a predictive model for PPI in elderly patients with dia-betes undergoing thoracoscopic radical resection for LC and to assess its reliability and validity.METHODS This retrospective study included 212 patients with LC who received treatment at our hospital from March 2015 to March 2022.General clinical information,sur-gical treatment details,and laboratory test results were collected and analyzed.Patients were grouped according to infection occurrence during the postoperative hospitalization period.Risk factors for PPIs were determined through logistic regression analysis,and a nomogram prediction model was established using R software to assess its predictive accuracy and performance.RESULTS Among the 212 patients[median age:72 years(interquartile range:60-82 years)],41 developed PPI(19.34%),with Gram-negative bacteria being the predominant pathogens(64.14%).Factors,such as age of≥70 years,presence of respiratory diseases,maximum tumor diameter of≥4 cm,stages II-III,receiving neoadjuvant chemotherapy of≥2 times preoperatively,surgery duration of≥3 hours,chest drainage tube placement duration of≥3.5 days,preoperative fasting blood glucose levels,hemoglobin A1c(HbA1c)levels,and multi-leaf resection,were markedly higher in the infection group than in the non-infection group.Conversely,forced expiratory volume in 1 second(FEV1)of≥80%and albumin(Alb)levels were lower in the infection group.Multivariate logistic regression analysis revealed that receiving neoadjuvant chemotherapy of≥2 times[odds ratio(OR)=2.987;P=0.036],maximum tumor diameter of≥4 cm(OR=3.959;P=0.013),multi-leaf resection(OR=3.18;P=0.036),preoperative FEV1 of≤80%(OR=3.305;P=0.029),and high HbA1c levels(OR=2.39;P=0.003)as key risk factors for PPI,whereas high Alb levels(OR=0.507;P<0.001)was protective.The nomogram model demonstrated excellent diagnostic ability(area under the curve=0.901,0.915),and calibration curves and decision curve analysis revealed good predictive performance and clinical applicability of the model.CONCLUSION The primary pathogens of PPI in elderly patients with diabetes and LC undergoing thoracoscopic radical resection are Gram-negative bacteria.The nomogram model,based on preoperative neoadjuvant chemotherapy cycles,maximum tumor diameter,range of resection,and preoperative FEV1,Alb,and HbA1c levels,shows high clinical value in predicting the risk of PPI in this patient population.展开更多
Objective:Erianin has potential anticancer activities,especially against lung cancer.The specific mechanisms underlying the anticancer effects,including the molecular targets and signaling pathways in lung cancer,rema...Objective:Erianin has potential anticancer activities,especially against lung cancer.The specific mechanisms underlying the anticancer effects,including the molecular targets and signaling pathways in lung cancer,remain poorly understood and necessitate further investigation.Methods:Lung cancer cell viability was evaluated using the CCK-8 assay.Flow cytometry was used to examine the effects of erianin on apoptosis and cell cycle progression.m RNA sequencing and metabolomics analysis were utilized to explore erianin-induced biological changes.Potential targets were identified and validated through molecular docking and Western blot analysis.The roles of mammalian target of rapamycin(m TOR)and carbamoyl-phosphate synthetase/aspartate transcarbamylase/dihydroorotase(CAD)in erianin-induced growth inhibition were studied using gene overexpression/knockdown techniques with uridine and aspartate supplementation confirming pyrimidine metabolism involvement.Additionally,lung cancer-bearing nude mouse models were established to evaluate the anti-lung cancer effects of erianin in vivo.Results:Erianin significantly inhibits the proliferation of lung cancer cells,induces apoptosis,and causes G2/M phase cell cycle arrest.Integrative analysis of m RNA sequencing and metabolomics data demonstrated that erianin disrupts pyrimidine metabolism in lung cancer cells.Notably,uridine supplementation mitigated the inhibitory effects of erianin,establishing a connection between pyrimidine metabolism and anticancer activity.Network pharmacology analyses identified m TOR as a key target of erianin.Erianin inhibited m TOR phosphorylation,thereby blocking downstream effectors(S6K and CAD),which are essential regulators of pyrimidine metabolism.Conclusions:Erianin is a promising therapeutic candidate for lung cancer.Erianin likely inhibits lung cancer cell growth by disrupting pyrimidine metabolism by suppressing m TOR activation.展开更多
In the present study,we aimed to investigate whether anlotinib reverses osimertinib resistance by inhibiting the formation of epithelial-mesenchymal transition(EMT)and angiogenesis.In a clinical case,anlotinib reverse...In the present study,we aimed to investigate whether anlotinib reverses osimertinib resistance by inhibiting the formation of epithelial-mesenchymal transition(EMT)and angiogenesis.In a clinical case,anlotinib reversed osimertinib resistance in non-small cell lung cancer(NSCLC).Therefore,we performed immunohistochemical analyses on tumor tissues from three NSCLC patients with osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A(VEGFA)before and after the development of osimertinib resistance.The results revealed the downregulation of E-cadherin,coupled with the upregulation of vimentin and VEGFA in tumor tissues of patients exhibiting osimertinib resistance,compared with those in tissues from patients before receiving osimertinib.Subsequently,we established osimertinib-resistant(Osi-R)cell lines and found that the Osi-R cells acquired EMT features.Next,we analyzed the synergistic effects of the combination therapy to verify whether anlotinib could reverse osimertinib resistance by inhibiting EMT.The expression levels of VEGFA and tube formation were analyzed in the combination group in vitro.Finally,we determined the reversal of osimertinib resistance by the combination of osimertinib and anlotinib in vivo using 20 nude mice.The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of Osi-R cells,inhibited tumor growth,exerted antitumor activity,and ultimately reversed osimertinib resistance in mice.The co-administration of osimertinib and anlotinib demonstrated synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients,ultimately reversing osimertinib resistance.展开更多
Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NS...Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NSCLC.Nonethe-less,it is unclear whether SAL can decrease the resistance of NSCLC to PTX.Methods PTX-resistant NSCLC cells(H1299/PTX and A549/PTX)were generated.Cell Counting Kit-8(CCK-8)assay was used to detect cell viability.Colony formation assay and flow cytometry were utilized to assess cell proliferation and apop-tosis,respectively.Immunofluorescence staining and TOP/FOP flash luciferase assay were employed to estimateβ-catenin activation.Western blotting was implemented to estimate the protein levels of apoptosis-,proliferation-,and Wnt/β-catenin signaling-associated markers.A xenograft mouse model was established to investigate the impact of SAL on PTX resist-ance in vivo.Results SAL increased PTX-induced suppression of proliferation and promoted apoptosis in PTX-resistant NSCLC cells.SAL blocked the Wnt/β-catenin signaling in A549/PTX cells and in tumor-bearing mice.Activating Wnt/β-catenin signaling reversed the SAL-mediated increase in the sensitivity of NSCLC cells to PTX.SAL attenuated PTX resistance in NSCLC in the xenograft mouse model.Conclusion SAL enhances the sensitivity of NSCLC cells to PTX by blocking the Wnt/β-catenin signal transduction.展开更多
Herein,porous poly(lactic-co-glycolic acid)(PLGA)microspheres were prepared to load icariin andmiR-23b for the treatment of metastatic lung cancer.The microspheres exhibited desirable aerodynamic diameter,high drug lo...Herein,porous poly(lactic-co-glycolic acid)(PLGA)microspheres were prepared to load icariin andmiR-23b for the treatment of metastatic lung cancer.The microspheres exhibited desirable aerodynamic diameter,high drug loading and encapsulation efficiency,as well as a favorable drug release profile,which was beneficial for the deposition and exposure of drugs in the lung tissues.The release solution from microspheres exhibited a favorable anti-proliferative effect by inducting cell apoptosis and arresting the cell cycle at G1 phase,and meanwhile inhibited the migration and invasion of cancer cells.More importantly,the microspheres could be effectively inhaled and accumulated in the lung tissues to trigger the in situ apoptosis of tumor cells and suppress metastasis,using mice bearing melanoma-metastatic lung cancer as a model.Furthermore,inhalation of themicrospheres showed favorable biocompatibility,barely causing tissue damage.Overall,porous PLGA microspheres provide a promising platform for the inhalable co-delivery of drugs and genes to obtain ideal therapeutic efficacy in lung cancer and other pulmonary diseases.展开更多
The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the ...The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the influence of different TRT timing strategies(consolidative vs.salvage)on survival rates.We retrospectively analyzed a total of 54 patients with ES-SCLC treated between January 2019 and July 2022.Patients receiving consolidative TRT(cTRT)within three months after completion of first-line treatment were compared with those receiving salvage TRT(sTRT)after disease progression.The primary endpoints were overall survival(OS),progression-free survival(PFS),locoregional-free survival(LRFS),and distant metastasis-free survival(DMFS);the secondary endpoint included safety.The cTRT group(n=41)showed significantly longer median OS(26.6 vs.14.8 months,P=0.048),PFS(12.9 vs.3.5 months,P<0.0001),and DMFS(10.7 vs.3.4 months,P=0.0044)than the sTRT group(n=13).Multivariate analysis revealed that cTRT was an independent,favorable prognostic factor.No significant differences in OS or LRFS were observed between high-dose(≥50 Gy)and low-dose(<50 Gy)TRT.Hematologic and respiratory toxicities were the most frequently reported adverse events,with acceptable tolerability.In conclusion,cTRT after chemoimmunotherapy significantly improves survival outcomes for ES-SCLC patients,and low-dose TRT may be a suitable option.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
BACKGROUND Uncertainty in illness(UI)and fear of progression(FoP)are significant psycho-logical challenges for lung cancer patients.Coping styles and social support are critical mediators,influencing patients'abil...BACKGROUND Uncertainty in illness(UI)and fear of progression(FoP)are significant psycho-logical challenges for lung cancer patients.Coping styles and social support are critical mediators,influencing patients'ability to manage the emotional and psy-chological burden of UI and FoP.However,limited research has explored the chain mediation effect of these factors on the relationship between UI and FoP,particularly among Chinese lung cancer patients.Convenience sampling was used to recruit inpatients diagnosed with lung cancer at a tertiary hospital in Changde City between November and December 2023.A total of 320 participants completed the Mishel Uncertainty in Illness Scale,Simp-lified Coping Style Questionnaire,Mandarin Chinese Version of the Medical Outcomes Study Social Support Survey,and Fear of Progression Questionnaire-Short Form.The chain mediation analysis was performed using the PROCESS macro to examine the relationships between the variables.RESULTS The results revealed that UI had a significant direct effect on FoP(effect=0.224,95%CI:0.136-0.408).Additionally,three indirect pathways were identified:(1)Social support(effect=0.128,95%CI:0.045-0.153);(2)Coping style(effect=0.115,95%CI:0.048-0.157);and(3)Chain mediators involving social support and coping style(effect=0.072,95%CI:0.045-0.120).The total indirect effect of the three mediation paths is 31.5%.These results confirm that social support and coping style significantly mediate the relationship between UI and FoP.CONCLUSION Based on cross-sectional data and a chain mediation model,this study explored the mechanisms between UI,social support,coping style,and FOP.Patients with lung cancer have higher levels of FOP,and the results of this study revealed a correlation between these four factors.Social support and coping style partially mediated the effects of UI on FOP,and there was a chain-mediating effect between UI and FOP.Programs designed to strengthen social support networks should also incorporate training to develop adaptive coping strategies,ultimately reducing FOP and improving overall quality of life.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.
文摘Lung cancer is among the most prevalent cancers and has the highest mortality rate globally.The diagnosis,pathohistological classification,and molecular testing of lung cancer primarily rely on tissue biopsy or surgical resection.These methods are invasive and associated with limitations,including sample quantity and quality,as well as patient tolerance.Radiomics,an emerging technology,enables the extraction of high-throughput quantitative information from medical images,providing radiomic features applicable to clinical diagnosis and treatment.Significant advancements have been made in the application of radiomics to the diagnosis,molecular detection,efficacy prediction,and prognosis of lung cancer.This review examines the progress in radiomics for individualized and precise diagnosis and treatment of lung cancer in recent years.
基金supported by the National Natural Science Foundation of China(grant numbers 82204127 and 72204172)。
文摘Lung cancer, the leading cause of cancer deaths worldwide and in China, has a 19.7% five-year survival rate due to terminal-stage diagnosis^([1-3]).Although low-dose computed tomography(CT) screening can reduce mortality, high false positive rates can create economic and psychological burdens.
基金support through Manipal University Jaipur for the Enhanced Seed Grant under the Endowment Fund(Grant No.E3/2023-24/QE-04-05).
文摘Dear Editor,Lung cancer is a major global health concern,with 2.2 million patients diagnosed in 2020.Non-small cell lung cancer(NSCLC)accounts for 80%of these cases,primarily comprising two subtypes:lung adenocarcinoma(LUAD)and squamous cell carcinoma(LUSC)[1].Researchers use immunohisto-chemistry,next-generation sequencing,and single-cell RNA sequencing to study genetic alterations,tumor heterogeneity,and tumor microenvironments,aiming to identify potential therapeutic options for specific NSCLC subtypes[2].
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82172635,82272686,and 82203628)Natural Science Foundation of Tianjin(Grant No.23JCZDJC00200)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-010A).
文摘Introduction Small cell lung cancer(SCLC)is a highly aggressive malignancy with limited treatment options.Despite advances in immunotherapy,response rates remain low,and the efficacy of current molecular subtyping1,2 is insufficient to predict therapeutic outcomes3,4.A recently identified vulnerability in SCLC involves the dysregulation of nuclear-cytoplasmic transport,particularly through exportin 1(XPO1)5-7.
基金Sichuan Provincial Administration of Traditional Chinese Medicine,Grant/Award Number:2023MS564National Natural Science Foundation of China,Grant/Award Number:82474436。
文摘Lung cancer has one of the highest rates of incidence and mortality worldwide,mak-ing research on its mechanisms and treatments crucial.Animal models are essential in lung cancer research as they accurately replicate the biological characteristics and treatment outcomes seen in human diseases.Currently,various lung cancer models have been established,including chemical induction models,orthotopic transplan-tation models,ectopic transplantation models,metastasis models,and gene editing mouse models.Additionally,lung cancer grafts can be categorized into two types:tissue-based and cell-based grafts.This paper summarizes the phenotypes,advan-tages,and disadvantages of various induction methods based on their modeling tech-niques.The goal is to enhance the simulation of clinical lung cancer characteristics and to establish a solid foundation for future clinical research.
文摘This article summarizes recent domestic literature on the use of Huangqin(Scutellaria baicalensis)in the treatment of lung cancer.It reviews the mechanism of action of Huangqin in treating lung cancer from six aspects:inhibiting the growth of lung cancer cells,inducing apoptosis of lung cancer cells,inducing autophagy of lung cancer cells,inhibiting the migration of lung cancer cells,promoting the differentiation of lung cancer cells,and improving immune function.The aim is to provide a reference for the material basis and further research on the anti-inflammatory and anti-tumor efficacy of Huangqin.
文摘This corrigendum clarifies information in the article"PI3K/Akt/mTOR signaling orchestrates the phenotypic transition and chemo-resistance of small cell lung cancer"by Li et al.(2021).The authors regret that the image of H526 cells in the schematic illustration in Fig.4A displayed on the Webpage is wrong.The correct image for H526cells inthe schematic illustration is listed below。
文摘Lung cancer continues to be a leading cause of cancer-related deaths worldwide,emphasizing the critical need for improved diagnostic techniques.Early detection of lung tumors significantly increases the chances of successful treatment and survival.However,current diagnostic methods often fail to detect tumors at an early stage or to accurately pinpoint their location within the lung tissue.Single-model deep learning technologies for lung cancer detection,while beneficial,cannot capture the full range of features present in medical imaging data,leading to incomplete or inaccurate detection.Furthermore,it may not be robust enough to handle the wide variability in medical images due to different imaging conditions,patient anatomy,and tumor characteristics.To overcome these disadvantages,dual-model or multi-model approaches can be employed.This research focuses on enhancing the detection of lung cancer by utilizing a combination of two learning models:a Convolutional Neural Network(CNN)for categorization and the You Only Look Once(YOLOv8)architecture for real-time identification and pinpointing of tumors.CNNs automatically learn to extract hierarchical features from raw image data,capturing patterns such as edges,textures,and complex structures that are crucial for identifying lung cancer.YOLOv8 incorporates multiscale feature extraction,enabling the detection of tumors of varying sizes and scales within a single image.This is particularly beneficial for identifying small or irregularly shaped tumors that may be challenging to detect.Furthermore,through the utilization of cutting-edge data augmentation methods,such as Deep Convolutional Generative Adversarial Networks(DCGAN),the suggested approach can handle the issue of limited data and boost the models’ability to learn from diverse and comprehensive datasets.The combined method not only improved accuracy and localization but also ensured efficient real-time processing,which is crucial for practical clinical applications.The CNN achieved an accuracy of 97.67%in classifying lung tissues into healthy and cancerous categories.The YOLOv8 model achieved an Intersection over Union(IoU)score of 0.85 for tumor localization,reflecting high precision in detecting and marking tumor boundaries within the images.Finally,the incorporation of synthetic images generated by DCGAN led to a 10%improvement in both the CNN classification accuracy and YOLOv8 detection performance.
文摘Lung carcinoma is associated with a high mortality worldwide,being the leading cause of cancer death.It is mainly classified into squamous non-small cell lung cancer(NSCLC),non-squamous NSCLC,and small cell lung cancer.However,such malignancy has been increasingly subdivided into histological and molecular subtypes to guide treatment.Therapies can be used in adjuvant and palliative settings.Regarding immunotherapy,it has been widely tested in both first or subsequent palliative lines.In this sense,drugs such as pembrolizumab,nivolumab,atezolizumab,ipilimumab,avelumab,and durvalumab have been assessed in large studies.Some of these trials have also studied these medicines in adjuvant and in maintenance therapy.In recent years,advances in immunotherapy have raised the hope that the unfavorable prognosis observed in several affected individuals can be changed.Immunotherapy has increased the overall survival in squamous NSCLC,non-squamous NSCLC,and small cell lung cancer.However,it has added to the oncology practice some side effects that are unusual in standard chemotherapy and require special clinical support.In order to show how immunotherapy is being applied in the treatment of lung carcinoma,we reviewed the main studies in adjuvant and palliative scenarios.What is the better scheme?What is the better combination?What is the better dose?When should we use immunotherapy?Does programmed cell death ligand 1 expression significantly interfere in immunotherapy efficiency?Some of these questions have already been answered,while others require more investigations.
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.
文摘Lung cancer is the most frequent cause of cancer-related mortality worldwide.Nitric oxide(NO),prostaglandins(PGs),thromboxanes(TXs),and endothelins(ETs)participate in numerous physiological processes.These agents play an important role in lung carcinogenesis by regulating cancer cell proliferation,apoptosis,invasion,and angiogenesis.NO is a gaseous free radical with tumo-ricidal and tumorigenic activities in lung cancer.Arachidonic acid-derived PGs,including PGD2,PGE2,8-iso-PGF2α,and PGI2,are related to the development of lung cancer.PGD2 and PGI2 act as tumor suppressors,while PGE2 and 8-iso-PGF2αpromote tumor progression.TXA2 catalyzed by cyclooxygenase induces prolif-eration as well as angiogenesis.Elevated levels of TXB2,an inactive metabolite of TXA2,are positively correlated with lung carcinoma stages.ET-1 and ET-2 are 21 amino acid polypeptides;their silencing hinders lung cancer cell proliferation and invasion.ET-2 depletion also triggers apoptotic death.This chapter review aims to provide a comprehensive overview of the role of NO,PGs,TXs,and ETs in lung cancer.
文摘BACKGROUND Lung cancer(LC)is one of the most prevalent cancers globally,with a high incidence among the elderly population.Elderly patients,particularly those with diabetes mellitus,are at an increased risk of postoperative complications,in-cluding pulmonary infections,due to weakened immune function and metabolic abnormalities.Postoperative pulmonary infection(PPI)is a predominant com-plication after thoracoscopic radical resection of LC,significantly affecting patient outcomes and increasing healthcare burdens.Determining risk factors for PPI in this vulnerable population is crucial for improving surgical outcomes and redu-cing infection rates.AIM To develop and validate a predictive model for PPI in elderly patients with dia-betes undergoing thoracoscopic radical resection for LC and to assess its reliability and validity.METHODS This retrospective study included 212 patients with LC who received treatment at our hospital from March 2015 to March 2022.General clinical information,sur-gical treatment details,and laboratory test results were collected and analyzed.Patients were grouped according to infection occurrence during the postoperative hospitalization period.Risk factors for PPIs were determined through logistic regression analysis,and a nomogram prediction model was established using R software to assess its predictive accuracy and performance.RESULTS Among the 212 patients[median age:72 years(interquartile range:60-82 years)],41 developed PPI(19.34%),with Gram-negative bacteria being the predominant pathogens(64.14%).Factors,such as age of≥70 years,presence of respiratory diseases,maximum tumor diameter of≥4 cm,stages II-III,receiving neoadjuvant chemotherapy of≥2 times preoperatively,surgery duration of≥3 hours,chest drainage tube placement duration of≥3.5 days,preoperative fasting blood glucose levels,hemoglobin A1c(HbA1c)levels,and multi-leaf resection,were markedly higher in the infection group than in the non-infection group.Conversely,forced expiratory volume in 1 second(FEV1)of≥80%and albumin(Alb)levels were lower in the infection group.Multivariate logistic regression analysis revealed that receiving neoadjuvant chemotherapy of≥2 times[odds ratio(OR)=2.987;P=0.036],maximum tumor diameter of≥4 cm(OR=3.959;P=0.013),multi-leaf resection(OR=3.18;P=0.036),preoperative FEV1 of≤80%(OR=3.305;P=0.029),and high HbA1c levels(OR=2.39;P=0.003)as key risk factors for PPI,whereas high Alb levels(OR=0.507;P<0.001)was protective.The nomogram model demonstrated excellent diagnostic ability(area under the curve=0.901,0.915),and calibration curves and decision curve analysis revealed good predictive performance and clinical applicability of the model.CONCLUSION The primary pathogens of PPI in elderly patients with diabetes and LC undergoing thoracoscopic radical resection are Gram-negative bacteria.The nomogram model,based on preoperative neoadjuvant chemotherapy cycles,maximum tumor diameter,range of resection,and preoperative FEV1,Alb,and HbA1c levels,shows high clinical value in predicting the risk of PPI in this patient population.
基金supported by the National Natural Science Foundation of China(82104207)Natural Science Foundation of Zhejiang Province(LQ22H280001)。
文摘Objective:Erianin has potential anticancer activities,especially against lung cancer.The specific mechanisms underlying the anticancer effects,including the molecular targets and signaling pathways in lung cancer,remain poorly understood and necessitate further investigation.Methods:Lung cancer cell viability was evaluated using the CCK-8 assay.Flow cytometry was used to examine the effects of erianin on apoptosis and cell cycle progression.m RNA sequencing and metabolomics analysis were utilized to explore erianin-induced biological changes.Potential targets were identified and validated through molecular docking and Western blot analysis.The roles of mammalian target of rapamycin(m TOR)and carbamoyl-phosphate synthetase/aspartate transcarbamylase/dihydroorotase(CAD)in erianin-induced growth inhibition were studied using gene overexpression/knockdown techniques with uridine and aspartate supplementation confirming pyrimidine metabolism involvement.Additionally,lung cancer-bearing nude mouse models were established to evaluate the anti-lung cancer effects of erianin in vivo.Results:Erianin significantly inhibits the proliferation of lung cancer cells,induces apoptosis,and causes G2/M phase cell cycle arrest.Integrative analysis of m RNA sequencing and metabolomics data demonstrated that erianin disrupts pyrimidine metabolism in lung cancer cells.Notably,uridine supplementation mitigated the inhibitory effects of erianin,establishing a connection between pyrimidine metabolism and anticancer activity.Network pharmacology analyses identified m TOR as a key target of erianin.Erianin inhibited m TOR phosphorylation,thereby blocking downstream effectors(S6K and CAD),which are essential regulators of pyrimidine metabolism.Conclusions:Erianin is a promising therapeutic candidate for lung cancer.Erianin likely inhibits lung cancer cell growth by disrupting pyrimidine metabolism by suppressing m TOR activation.
基金supported by the National Natural Science Foundation of China(Grant Nos.82172728,82370096).
文摘In the present study,we aimed to investigate whether anlotinib reverses osimertinib resistance by inhibiting the formation of epithelial-mesenchymal transition(EMT)and angiogenesis.In a clinical case,anlotinib reversed osimertinib resistance in non-small cell lung cancer(NSCLC).Therefore,we performed immunohistochemical analyses on tumor tissues from three NSCLC patients with osimertinib resistance to analyze alterations in the expression levels of EMT markers and vascular endothelial growth factor A(VEGFA)before and after the development of osimertinib resistance.The results revealed the downregulation of E-cadherin,coupled with the upregulation of vimentin and VEGFA in tumor tissues of patients exhibiting osimertinib resistance,compared with those in tissues from patients before receiving osimertinib.Subsequently,we established osimertinib-resistant(Osi-R)cell lines and found that the Osi-R cells acquired EMT features.Next,we analyzed the synergistic effects of the combination therapy to verify whether anlotinib could reverse osimertinib resistance by inhibiting EMT.The expression levels of VEGFA and tube formation were analyzed in the combination group in vitro.Finally,we determined the reversal of osimertinib resistance by the combination of osimertinib and anlotinib in vivo using 20 nude mice.The combined treatment of osimertinib and anlotinib effectively prevented the metastasis of Osi-R cells,inhibited tumor growth,exerted antitumor activity,and ultimately reversed osimertinib resistance in mice.The co-administration of osimertinib and anlotinib demonstrated synergistic efficacy in inhibiting EMT and angiogenesis in three NSCLC patients,ultimately reversing osimertinib resistance.
基金supported by the Scientific Research Project of Hubei Cancer Hospital(No.2024HBCHYN08)the Natural Science Foundation of Hubei Province(No.2023AFB988)+1 种基金the Scientific Research Project in the Field of Oncology(No.FB2024025225)the Talent Project of Hubei Cancer Hospital(No.2025HBCHHHRC007).
文摘Objective Chemoresistance,such as paclitaxel(PTX)resistance,has become a great obstacle in non-small cell lung cancer(NSCLC)treatment.The natural agent salidroside(SAL)has been shown to exert an antitumor effect on NSCLC.Nonethe-less,it is unclear whether SAL can decrease the resistance of NSCLC to PTX.Methods PTX-resistant NSCLC cells(H1299/PTX and A549/PTX)were generated.Cell Counting Kit-8(CCK-8)assay was used to detect cell viability.Colony formation assay and flow cytometry were utilized to assess cell proliferation and apop-tosis,respectively.Immunofluorescence staining and TOP/FOP flash luciferase assay were employed to estimateβ-catenin activation.Western blotting was implemented to estimate the protein levels of apoptosis-,proliferation-,and Wnt/β-catenin signaling-associated markers.A xenograft mouse model was established to investigate the impact of SAL on PTX resist-ance in vivo.Results SAL increased PTX-induced suppression of proliferation and promoted apoptosis in PTX-resistant NSCLC cells.SAL blocked the Wnt/β-catenin signaling in A549/PTX cells and in tumor-bearing mice.Activating Wnt/β-catenin signaling reversed the SAL-mediated increase in the sensitivity of NSCLC cells to PTX.SAL attenuated PTX resistance in NSCLC in the xenograft mouse model.Conclusion SAL enhances the sensitivity of NSCLC cells to PTX by blocking the Wnt/β-catenin signal transduction.
基金the National Natural Science Foundation of China(32271319 and 32071267)the Science and Technology Department of Jilin Province(YDZJ202301ZYTS537 and 20240402035GH)+1 种基金the Development and Reform Commission of Jilin Province(2023C015)the“Medicine+X”cross-innovation team of Bethune Medical Department of Jilin University“Leading the Charge with Open Competition”construction project(2022JBGS04).
文摘Herein,porous poly(lactic-co-glycolic acid)(PLGA)microspheres were prepared to load icariin andmiR-23b for the treatment of metastatic lung cancer.The microspheres exhibited desirable aerodynamic diameter,high drug loading and encapsulation efficiency,as well as a favorable drug release profile,which was beneficial for the deposition and exposure of drugs in the lung tissues.The release solution from microspheres exhibited a favorable anti-proliferative effect by inducting cell apoptosis and arresting the cell cycle at G1 phase,and meanwhile inhibited the migration and invasion of cancer cells.More importantly,the microspheres could be effectively inhaled and accumulated in the lung tissues to trigger the in situ apoptosis of tumor cells and suppress metastasis,using mice bearing melanoma-metastatic lung cancer as a model.Furthermore,inhalation of themicrospheres showed favorable biocompatibility,barely causing tissue damage.Overall,porous PLGA microspheres provide a promising platform for the inhalable co-delivery of drugs and genes to obtain ideal therapeutic efficacy in lung cancer and other pulmonary diseases.
基金supported by the Young Talents Program of Jiangsu Cancer Hospital(Grant No.QL201802)the Science and Technology Development Fund of Jiangsu Cancer Hospital(Grant No.ZL202105).
文摘The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the influence of different TRT timing strategies(consolidative vs.salvage)on survival rates.We retrospectively analyzed a total of 54 patients with ES-SCLC treated between January 2019 and July 2022.Patients receiving consolidative TRT(cTRT)within three months after completion of first-line treatment were compared with those receiving salvage TRT(sTRT)after disease progression.The primary endpoints were overall survival(OS),progression-free survival(PFS),locoregional-free survival(LRFS),and distant metastasis-free survival(DMFS);the secondary endpoint included safety.The cTRT group(n=41)showed significantly longer median OS(26.6 vs.14.8 months,P=0.048),PFS(12.9 vs.3.5 months,P<0.0001),and DMFS(10.7 vs.3.4 months,P=0.0044)than the sTRT group(n=13).Multivariate analysis revealed that cTRT was an independent,favorable prognostic factor.No significant differences in OS or LRFS were observed between high-dose(≥50 Gy)and low-dose(<50 Gy)TRT.Hematologic and respiratory toxicities were the most frequently reported adverse events,with acceptable tolerability.In conclusion,cTRT after chemoimmunotherapy significantly improves survival outcomes for ES-SCLC patients,and low-dose TRT may be a suitable option.
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 Hunan Provincial Natural Science Foundation of China,No.2024JJ9579 and No.2025JJ80410The Science and Technology Innovation Program of Changde City,No.2023YD23.
文摘BACKGROUND Uncertainty in illness(UI)and fear of progression(FoP)are significant psycho-logical challenges for lung cancer patients.Coping styles and social support are critical mediators,influencing patients'ability to manage the emotional and psy-chological burden of UI and FoP.However,limited research has explored the chain mediation effect of these factors on the relationship between UI and FoP,particularly among Chinese lung cancer patients.Convenience sampling was used to recruit inpatients diagnosed with lung cancer at a tertiary hospital in Changde City between November and December 2023.A total of 320 participants completed the Mishel Uncertainty in Illness Scale,Simp-lified Coping Style Questionnaire,Mandarin Chinese Version of the Medical Outcomes Study Social Support Survey,and Fear of Progression Questionnaire-Short Form.The chain mediation analysis was performed using the PROCESS macro to examine the relationships between the variables.RESULTS The results revealed that UI had a significant direct effect on FoP(effect=0.224,95%CI:0.136-0.408).Additionally,three indirect pathways were identified:(1)Social support(effect=0.128,95%CI:0.045-0.153);(2)Coping style(effect=0.115,95%CI:0.048-0.157);and(3)Chain mediators involving social support and coping style(effect=0.072,95%CI:0.045-0.120).The total indirect effect of the three mediation paths is 31.5%.These results confirm that social support and coping style significantly mediate the relationship between UI and FoP.CONCLUSION Based on cross-sectional data and a chain mediation model,this study explored the mechanisms between UI,social support,coping style,and FOP.Patients with lung cancer have higher levels of FOP,and the results of this study revealed a correlation between these four factors.Social support and coping style partially mediated the effects of UI on FOP,and there was a chain-mediating effect between UI and FOP.Programs designed to strengthen social support networks should also incorporate training to develop adaptive coping strategies,ultimately reducing FOP and improving overall quality of life.
