Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent...Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent challenges in its clinical management.Neddylation,a novel type of post-translational modification,was overactivated in lung cancer and was closely associated with its occurrence,development,metastasis,and drug resistance.This review systematically summarizes the biological process of neddylation and deeply explores the latest research progress on how neddylation affects lung cancer cell proliferation,metastasis,and drug resistance mechanisms,with a focus on its regulation of key molecules such as Cullin-RING E3 ligases and the SCCRO family.Meanwhile,it concludes the current advances in potential therapeutic agents targeting neddylation-related targets,including small-molecule compounds(such as Pevonedistat)and natural extracts(such as arctigenin).Finally,the review prospectively evaluates the application potential and questions requiring further exploration of neddylation in lung cancer treatment.In conclusion,we aim to systematically summarize the biological process of neddylation,critically explore its roles in lung cancer proliferation,metastasis,and drug resistance,and evaluate the therapeutic potential of neddylation-targeting agents.展开更多
Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanoca...Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanocatalytic medicine utilizes nanomaterials to generate ROS specifically within tumor sites,enabling efficient and targeted cancer treatment.In this study,hyaluronic acid(HA)-modified copper-N,N-dimethyl-Nphenylsulfonylbisamine(DMSA)-assembled nanoparticles(Cu-DMSA-HA NPs)are developed with tumor-targeting capability and efficiently catalyze ROS production via coordination chemistry.Targeted delivery is facilitated by HA surface modification through recognition of overexpressed cluster of differentiation 44 receptors on cancer cells,which enhances nanoparticle uptake.Once internalized,intracellular glutathione is depleted by the NPs,followed by a Fenton-like reaction that sustains ROS production.Both in vitro and in vivo studies demonstrate that this catalytic strategy effectively inhibits DNA replication,prevents cell cycle progression,downregulates glutathione peroxidase 4 expression,induces ferroptosis,and ultimately suppresses NSCLC progression.Overall,the readily prepared Cu-DMSA-HA NPs exhibit robust catalytic activity and tumor specificity,highlighting their strong potential for clinical translation in nanocatalytic cancer therapy.展开更多
Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve bette...Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve better efficacy in LS-SCLC patients.Methods:We evaluated 122 LS-SCLC patients who received concurrent chemoradiotherapy(CCRT)or sequential chemoradiotherapy(SCRT)(Group A)and immunotherapy combined with CCRT/SCRT followed by immunotherapy(Group B),to assess the objective response rate(ORR),disease control rate(DCR),and progression-free survival(PFS).Factors affecting prognosis were also explored using Cox analysis.The prognosis of patients with type 2 diabetes and patients with different TNM stages was compared to guide the selection of clinical regimens.Results:The overall ORR was 55.93%.The overall DCR was 98.31%.The DCR was 100%in Group A and 96.61%in Group B.There was no statistical difference in ORR and DCR.The overall median PFS was 9.86 months(95%CI,8.62-11.10),and the difference in median PFS between the two groups was statistically significant(8.94 vs.11.89 months,p=0.03).The Cox regression analysis showed type 2 diabetes was associated with the survival prognosis.Patients with type 2 diabetes tended to choose immunotherapy combined with CCRT/SCRT.Patients in TNM stage IIIB had a significantly worse prognosis than those in stage I+II+IIIA.Conclusion:We suggest that LS-SCLC patients who receive immunotherapy combined with CCRT/SCRT can achieve longer PFS than those with CCRT/SCRT.Type 2 diabetes and TNM stage affect the survival prognosis.Patients with type 2 diabetes may benefit from immunotherapy combination treatments.展开更多
The published article titled“MicroRNA-138 Inhibits Cell Growth,Invasion,and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop”has been retracted fromOncology Research,Vol.26,No.3,2018,pp.385–400.DOI:10.3...The published article titled“MicroRNA-138 Inhibits Cell Growth,Invasion,and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop”has been retracted fromOncology Research,Vol.26,No.3,2018,pp.385–400.DOI:10.3727/096504017X14973124850905 URL:https://www.techscience.com/or/v26n3/56651 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
The published article titled“Long Noncoding RNA(lncRNA)HOTAIR Affects Tumorigenesis andMetastasis of Non-Small Cell Lung Cancer by Upregulating miR-613”has been retracted from Oncology Research,Vol.26,No.5,2018,pp....The published article titled“Long Noncoding RNA(lncRNA)HOTAIR Affects Tumorigenesis andMetastasis of Non-Small Cell Lung Cancer by Upregulating miR-613”has been retracted from Oncology Research,Vol.26,No.5,2018,pp.725–734.DOI:10.3727/096504017X15119467381615 URL:https://www.techscience.com/or/v26n5/56685 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
Colorectal cancer(CRC)with lung oligometastases,particularly in the presence of extrapulmonary disease,poses considerable therapeutic challenges in clinical practice.We have carefully studied the multicenter study by ...Colorectal cancer(CRC)with lung oligometastases,particularly in the presence of extrapulmonary disease,poses considerable therapeutic challenges in clinical practice.We have carefully studied the multicenter study by Hu et al,which evaluated the survival outcomes of patients with metastatic CRC who received image-guided thermal ablation(IGTA).These findings provide valuable clinical evidence supporting IGTA as a feasible,minimally invasive approach and underscore the prognostic significance of metastatic distribution.However,the study by Hu et al has several limitations,including that not all pulmonary lesions were pathologically confirmed,postoperative follow-up mainly relied on dynamic contrast-enhanced computed tomography,no comparative analysis was performed with other local treatments,and the impact of other imaging features on efficacy and prognosis was not evaluated.Future studies should include complete pathological confirmation,integrate functional imaging and radiomics,and use prospective multicenter collaboration to optimize patient selection standards for IGTA treatment,strengthen its clinical evidence base,and ultimately promote individualized decision-making for patients with metastatic CRC.展开更多
Objectives:Although immune checkpoint inhibitors(ICIs)and targeted therapies have reshaped treatment non-small cell lung cancer(NSCLC)paradigms,prognosis remains poor for many patients due to delayed diagnosis and res...Objectives:Although immune checkpoint inhibitors(ICIs)and targeted therapies have reshaped treatment non-small cell lung cancer(NSCLC)paradigms,prognosis remains poor for many patients due to delayed diagnosis and resistance mechanisms.Liquid biopsy offers a minimally invasive approach to monitoring tumor evolution.Among circulating biomarkers,circulating tumor cells(CTCs)and cancer-associated macrophage-like cells(CAM-Ls)may provide complementary prognostic insights.The study aimed to evaluate the prognostic role of CTC and CAM-Ls dynamic in metastatic NSCLC patients.Methods:We retrospectively analyzed 77 patients with metastatic NSCLC who underwent CTC and CAM-L evaluation via the CellSearch^(R)system at baseline(T0)and after three months of first-line treatment(T1)including chemotherapy,targeted therapy,or ICIs.Survival outcomes were analyzed using Kaplan-Meier and Cox regression analyses.Results:Conversion to CTC-negative status at T1 was associated with improved outcomes,with median overall survival(OS)and progression-free survival(PFS)of 33 and 18 months,respectively,vs.10 and 6 months in persistently positive patients(both p<0.001).CTC negativity at T1 remained an independent prognostic factor for OS(HR:6.68)and PFS(HR:5.91,both p<0.0001).CAM-L positivity at T1 also correlated with longer OS(30 vs.12 months)and PFS(13 vs.6 months,both p<0.0001),particularly among ICI-treated patients.Combined CTC and CAM-L assessment further refined risk stratification.Conclusions:Dynamic monitoring of CTCs and CAM-Ls provides actionable prognostic information in metastatic NSCLC.CTC-negative status predicted longer OS and PFS,while CAM-L positivity at T1 was associated with improved outcomes,particularly in ICI-treated patients.Combined assessment of both biomarkers may directly inform therapeutic decision-making,through early detection of outcomes.展开更多
Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 tr...Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.展开更多
Objectives:Acquired resistance to paclitaxel represents a critical barrier to the effective chemotherapy of non-small cell lung cancer(NSCLC).The present study aimed to elucidate the molecular and pharmacological mech...Objectives:Acquired resistance to paclitaxel represents a critical barrier to the effective chemotherapy of non-small cell lung cancer(NSCLC).The present study aimed to elucidate the molecular and pharmacological mechanisms promoting paclitaxel resistance in NSCLC and to explore potential strategies for overcoming this resistance.Methods:Here,we report an integrated pharmacological and analytical approach to quantify paclitaxel disposition and overcome resistance in a A549/TAX cell model(paclitaxel-resistant A549 cells).Results:Cell counting kit-8(CCK-8)assay,colony formation,and apoptosis assays confirmed that A549/TAX cells exhibited marked resistance to paclitaxel relative to parental A549 cells.Based on transcriptome profiling by RNA sequencing analysis and validation by western blotting assay,we found that the expression of the ATP-binding cassette subfamily B member 1(ABCB1)(the encoded protein is termed P-glycoprotein)was significantly upregulated in resistant cells.By using ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),we demonstrated that ABCB1 overexpression promotes enhanced efflux of intracellular paclitaxel,thereby lowering its cytotoxic accumulation.Genetic silencing of ABCB1 or pharmacological inhibition with the specific P-glycoprotein modulator elacridar or tariquidar restored intracellular paclitaxel levels,as determined by UPLC-MS/MS,and synergistically decreased cell viability as observed in CCK-8 assay.Conclusion:These findings reveal that the ABCB1-mediated drug efflux is a crucial mechanism underlying paclitaxel resistance in NSCLC cells,with UPLC-MS/MS serving as a sensitive analytical method to detect paclitaxel concentration.Inhibition of ABCB1 is a promising therapeutic strategy to resensitize resistant tumor cells to paclitaxel.展开更多
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 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
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
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
Non-small cell lung cancer (NSCLC), as the leading cause of cancer-related deaths, poses a serious health issue worldwide1,according to the Global Cancer Statistics 2022. Approximately 30% of NSCLC patients are diagno...Non-small cell lung cancer (NSCLC), as the leading cause of cancer-related deaths, poses a serious health issue worldwide1,according to the Global Cancer Statistics 2022. Approximately 30% of NSCLC patients are diagnosed at an advanced or metastatic stage with a 5-year overall survival (OS) rate ranging from 7%-18%^(2). Unlike localized NSCLC, which can be treated with curative intent, patients with metastatic NSCLC typically undergo systemic treatment to delay progression and prolong survival.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
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
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
Lung cancer exhibits the highest incidence and mortality rates among cancers globally,with a five-year overall survival rate alarmingly below 20%.Targeting autophagy,though a controversial therapeutic strategy,is exte...Lung cancer exhibits the highest incidence and mortality rates among cancers globally,with a five-year overall survival rate alarmingly below 20%.Targeting autophagy,though a controversial therapeutic strategy,is extensively employed in clinical practice.Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy.Nevertheless,the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention.This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer.It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells.Notably,most autophagy-targeting drugs,primarily natural small molecules,have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer,as opposed to inhibiting protective autophagy.These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies,offering promising approaches to combat this disease.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
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
基金supported by the National Natural Science Foundation of China(No.82574683)the National Natural Science Foundation of Science and Technology Department of Sichuan Province(Nos.2023NSFSC1928 and 2023NSFSC1992)+2 种基金Project of State Administration of Traditional Chinese Medicine of China(No.ZYYCXTD-D-202209)Project of Sichuan Provincial Administration of Traditional Chinese Medicine(No.2022C001)Fundamental Research Funds for the Central Universities(No.YJ201880).
文摘Lung cancer is the most common but fatal malignant tumor worldwide.Patients with lung cancer experienced a relatively low 5-year overall survival rate,and issues such as metastasis and drug resistance remain prominent challenges in its clinical management.Neddylation,a novel type of post-translational modification,was overactivated in lung cancer and was closely associated with its occurrence,development,metastasis,and drug resistance.This review systematically summarizes the biological process of neddylation and deeply explores the latest research progress on how neddylation affects lung cancer cell proliferation,metastasis,and drug resistance mechanisms,with a focus on its regulation of key molecules such as Cullin-RING E3 ligases and the SCCRO family.Meanwhile,it concludes the current advances in potential therapeutic agents targeting neddylation-related targets,including small-molecule compounds(such as Pevonedistat)and natural extracts(such as arctigenin).Finally,the review prospectively evaluates the application potential and questions requiring further exploration of neddylation in lung cancer treatment.In conclusion,we aim to systematically summarize the biological process of neddylation,critically explore its roles in lung cancer proliferation,metastasis,and drug resistance,and evaluate the therapeutic potential of neddylation-targeting agents.
基金supported by National Natural Science Foundation of China (82272943)Shanghai Municipal Science and Technology Commission (21Y11913400)+1 种基金Fundamental Research Funds for the Central UniversitiesNational Key Research and Development Program of China (2022YFC2407405)
文摘Conventional treatments for non-small cell lung cancer(NSCLC)suffer from low remission rates,high drug resistance,and severe adverse effects.To leverage the therapeutic potential of reactive oxygen species(ROS),nanocatalytic medicine utilizes nanomaterials to generate ROS specifically within tumor sites,enabling efficient and targeted cancer treatment.In this study,hyaluronic acid(HA)-modified copper-N,N-dimethyl-Nphenylsulfonylbisamine(DMSA)-assembled nanoparticles(Cu-DMSA-HA NPs)are developed with tumor-targeting capability and efficiently catalyze ROS production via coordination chemistry.Targeted delivery is facilitated by HA surface modification through recognition of overexpressed cluster of differentiation 44 receptors on cancer cells,which enhances nanoparticle uptake.Once internalized,intracellular glutathione is depleted by the NPs,followed by a Fenton-like reaction that sustains ROS production.Both in vitro and in vivo studies demonstrate that this catalytic strategy effectively inhibits DNA replication,prevents cell cycle progression,downregulates glutathione peroxidase 4 expression,induces ferroptosis,and ultimately suppresses NSCLC progression.Overall,the readily prepared Cu-DMSA-HA NPs exhibit robust catalytic activity and tumor specificity,highlighting their strong potential for clinical translation in nanocatalytic cancer therapy.
基金funded by the National Natural Science Foundation of China(grant no.82273162)the National Natural Science Foundation of China(grant no.82203272)the Science and Technology Development Foundation of Nanjing Medical University(grant NMUB20240119)。
文摘Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve better efficacy in LS-SCLC patients.Methods:We evaluated 122 LS-SCLC patients who received concurrent chemoradiotherapy(CCRT)or sequential chemoradiotherapy(SCRT)(Group A)and immunotherapy combined with CCRT/SCRT followed by immunotherapy(Group B),to assess the objective response rate(ORR),disease control rate(DCR),and progression-free survival(PFS).Factors affecting prognosis were also explored using Cox analysis.The prognosis of patients with type 2 diabetes and patients with different TNM stages was compared to guide the selection of clinical regimens.Results:The overall ORR was 55.93%.The overall DCR was 98.31%.The DCR was 100%in Group A and 96.61%in Group B.There was no statistical difference in ORR and DCR.The overall median PFS was 9.86 months(95%CI,8.62-11.10),and the difference in median PFS between the two groups was statistically significant(8.94 vs.11.89 months,p=0.03).The Cox regression analysis showed type 2 diabetes was associated with the survival prognosis.Patients with type 2 diabetes tended to choose immunotherapy combined with CCRT/SCRT.Patients in TNM stage IIIB had a significantly worse prognosis than those in stage I+II+IIIA.Conclusion:We suggest that LS-SCLC patients who receive immunotherapy combined with CCRT/SCRT can achieve longer PFS than those with CCRT/SCRT.Type 2 diabetes and TNM stage affect the survival prognosis.Patients with type 2 diabetes may benefit from immunotherapy combination treatments.
文摘The published article titled“MicroRNA-138 Inhibits Cell Growth,Invasion,and EMT of Non-Small Cell Lung Cancer via SOX4/p53 Feedback Loop”has been retracted fromOncology Research,Vol.26,No.3,2018,pp.385–400.DOI:10.3727/096504017X14973124850905 URL:https://www.techscience.com/or/v26n3/56651 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
文摘The published article titled“Long Noncoding RNA(lncRNA)HOTAIR Affects Tumorigenesis andMetastasis of Non-Small Cell Lung Cancer by Upregulating miR-613”has been retracted from Oncology Research,Vol.26,No.5,2018,pp.725–734.DOI:10.3727/096504017X15119467381615 URL:https://www.techscience.com/or/v26n5/56685 Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
文摘Colorectal cancer(CRC)with lung oligometastases,particularly in the presence of extrapulmonary disease,poses considerable therapeutic challenges in clinical practice.We have carefully studied the multicenter study by Hu et al,which evaluated the survival outcomes of patients with metastatic CRC who received image-guided thermal ablation(IGTA).These findings provide valuable clinical evidence supporting IGTA as a feasible,minimally invasive approach and underscore the prognostic significance of metastatic distribution.However,the study by Hu et al has several limitations,including that not all pulmonary lesions were pathologically confirmed,postoperative follow-up mainly relied on dynamic contrast-enhanced computed tomography,no comparative analysis was performed with other local treatments,and the impact of other imaging features on efficacy and prognosis was not evaluated.Future studies should include complete pathological confirmation,integrate functional imaging and radiomics,and use prospective multicenter collaboration to optimize patient selection standards for IGTA treatment,strengthen its clinical evidence base,and ultimately promote individualized decision-making for patients with metastatic CRC.
基金funded by Sapienza University PNRR-RT_SPOKE_1—ROME TECHNOPOLE—Spoke 1—B83C22002820006—ECS00000024 and FO R.O.onlus.
文摘Objectives:Although immune checkpoint inhibitors(ICIs)and targeted therapies have reshaped treatment non-small cell lung cancer(NSCLC)paradigms,prognosis remains poor for many patients due to delayed diagnosis and resistance mechanisms.Liquid biopsy offers a minimally invasive approach to monitoring tumor evolution.Among circulating biomarkers,circulating tumor cells(CTCs)and cancer-associated macrophage-like cells(CAM-Ls)may provide complementary prognostic insights.The study aimed to evaluate the prognostic role of CTC and CAM-Ls dynamic in metastatic NSCLC patients.Methods:We retrospectively analyzed 77 patients with metastatic NSCLC who underwent CTC and CAM-L evaluation via the CellSearch^(R)system at baseline(T0)and after three months of first-line treatment(T1)including chemotherapy,targeted therapy,or ICIs.Survival outcomes were analyzed using Kaplan-Meier and Cox regression analyses.Results:Conversion to CTC-negative status at T1 was associated with improved outcomes,with median overall survival(OS)and progression-free survival(PFS)of 33 and 18 months,respectively,vs.10 and 6 months in persistently positive patients(both p<0.001).CTC negativity at T1 remained an independent prognostic factor for OS(HR:6.68)and PFS(HR:5.91,both p<0.0001).CAM-L positivity at T1 also correlated with longer OS(30 vs.12 months)and PFS(13 vs.6 months,both p<0.0001),particularly among ICI-treated patients.Combined CTC and CAM-L assessment further refined risk stratification.Conclusions:Dynamic monitoring of CTCs and CAM-Ls provides actionable prognostic information in metastatic NSCLC.CTC-negative status predicted longer OS and PFS,while CAM-L positivity at T1 was associated with improved outcomes,particularly in ICI-treated patients.Combined assessment of both biomarkers may directly inform therapeutic decision-making,through early detection of outcomes.
基金the National Institute for Health and Care Research(NHR)Manchester Biomedical Research Centre(BRC)(NIHR203308,NIHR-BRC-1215-20007)Astra-Zeneca(ESR-14-10711)+2 种基金CRUK RadNet(C19941/A27801)TMI and CFF are the recipient of an NIHR Senior Investigator Award(NIHR205054 and NIHR205061)CTH is supported by the NIHR University College London Hospitals NHS Foundation Trust BRC,the City of London CRUK RadNet and the CRUK Lung Cancer Centre of Excellence.
文摘Objectives:The PACIFIC trial established the benefit of durvalumab following chemo-radiotherapy for stage III non-small cell lung cancer(NSCLC).However,the concurrent use of radiotherapy(RT)and durvalumab(PACIFIC-2 trial)showed no additional advantage.The PD-RAD study was set up to understand the immunological effects of RT on the tumor microenvironment(TME)to aid in optimizing sequencing of combination therapies.Methods:The PD-RAD trial(ClinicalTrials.gov identifier:NCT03258788)aimed to enroll thirty NSCLC patients receiving radical-intent RT.Tumor biopsies and blood samples were collected pre-RT and at week 2 during RT and analyzed using multiplex immunohistochemistry(mIHC)and high-dimensional mass cytometry(CyTOF),respectively.Results:Paired biopsies were collected from only three patients(Pts 1,3&4)and blood from four patients(Pts 1-4)before the study was closed early during the COVID-19 pandemic.Programmed Death-Ligand 1(PD-L1)expression in the TME was raised in Patient 1,who responded well to treatment,and unaltered in two patients with progressive disease.CyTOF analysis revealed elevated circulating classical monocytes,highest in the patient with a good response.Conclusions:This study underscores the challenges of integrating advanced immune monitoring during RT delivery and did not meet its primary endpoint.The hypothesis-generating findings highlight PD-L1+macrophages in the TME and classical monocytes in the blood as potential immune biomarkers of RT response,but larger studies are needed to validate these observations and characterize the immune changes following curative-intent RT in patients with NSCLC.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82172840)Gusu Health Talents Project of Suzhou Municipal Health Commission(Grant Nos.GSWS2023007 and GSWS2022062)+2 种基金Suzhou Science and Technology Development Plan Project(Grant No.SYW2024005)Chinese Pharmaceutical Association Hospital Pharmacy Department(Grant No.CPA-Z05-ZC-2024002)Jiangsu Research Hospital Association for Precision Medication(Grant No.JY202202).
文摘Objectives:Acquired resistance to paclitaxel represents a critical barrier to the effective chemotherapy of non-small cell lung cancer(NSCLC).The present study aimed to elucidate the molecular and pharmacological mechanisms promoting paclitaxel resistance in NSCLC and to explore potential strategies for overcoming this resistance.Methods:Here,we report an integrated pharmacological and analytical approach to quantify paclitaxel disposition and overcome resistance in a A549/TAX cell model(paclitaxel-resistant A549 cells).Results:Cell counting kit-8(CCK-8)assay,colony formation,and apoptosis assays confirmed that A549/TAX cells exhibited marked resistance to paclitaxel relative to parental A549 cells.Based on transcriptome profiling by RNA sequencing analysis and validation by western blotting assay,we found that the expression of the ATP-binding cassette subfamily B member 1(ABCB1)(the encoded protein is termed P-glycoprotein)was significantly upregulated in resistant cells.By using ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),we demonstrated that ABCB1 overexpression promotes enhanced efflux of intracellular paclitaxel,thereby lowering its cytotoxic accumulation.Genetic silencing of ABCB1 or pharmacological inhibition with the specific P-glycoprotein modulator elacridar or tariquidar restored intracellular paclitaxel levels,as determined by UPLC-MS/MS,and synergistically decreased cell viability as observed in CCK-8 assay.Conclusion:These findings reveal that the ABCB1-mediated drug efflux is a crucial mechanism underlying paclitaxel resistance in NSCLC cells,with UPLC-MS/MS serving as a sensitive analytical method to detect paclitaxel concentration.Inhibition of ABCB1 is a promising therapeutic strategy to resensitize resistant tumor cells to paclitaxel.
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 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.
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 Noncommunicable Chronic Diseases-National Science and Technology Major Project (Grant No. 2023ZD0501700)the National Natural Science Foundation of China (Grant No. 82373349)the MOE Changjiang Distinguished Professor Supporting Project (Grant No. KY0120240205)。
文摘Non-small cell lung cancer (NSCLC), as the leading cause of cancer-related deaths, poses a serious health issue worldwide1,according to the Global Cancer Statistics 2022. Approximately 30% of NSCLC patients are diagnosed at an advanced or metastatic stage with a 5-year overall survival (OS) rate ranging from 7%-18%^(2). Unlike localized NSCLC, which can be treated with curative intent, patients with metastatic NSCLC typically undergo systemic treatment to delay progression and prolong survival.
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.
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.:81503272,81630101,and 81891012)the Application Foundation Research Project of Sichuan Provincial Department of Science and Technology,China(Grant No.:2017JY0187)+4 种基金the Xinglin Scholar Research Premotion Project of Chengdu University of Traditional Chinese Medicine,China(Grant No.:2018016)the Regional Joint Fund of the National Natural Science Foundation of China(Grant No.:U19A2010)the National Interdisciplinary Innovation Team of Traditional Chinese Medicine,China(Grant No.:ZYYCXTD-D-202209)the Sichuan Traditional Chinese Medicine Technology Industry Innovation Team,China(Grant No.:2022C001)the Sichuan Provincial Administration of Traditional Chinese Medicine Project,China(Grant Nos.:2020JC0031 and 2024ZD02).
文摘Lung cancer exhibits the highest incidence and mortality rates among cancers globally,with a five-year overall survival rate alarmingly below 20%.Targeting autophagy,though a controversial therapeutic strategy,is extensively employed in clinical practice.Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy.Nevertheless,the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention.This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer.It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells.Notably,most autophagy-targeting drugs,primarily natural small molecules,have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer,as opposed to inhibiting protective autophagy.These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies,offering promising approaches to combat this disease.
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.
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.
