Ubiquitin-specific protease 1 facilitates tumor immune escape from natural killer cells and predicts the prognosis in small cell lung cancer

Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with SCLC.In the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were elucidated.Methods:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in SCLC.The functional role of the key gene identified in SCLC was determined both in vitro and in vivo.Results:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell proportion.Furthermore,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in SCLC.Bioinformatics analysis revealed that USP1 is upregulated in SCLC.In addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune responses.By co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological inhibition.Furthermore,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated markers.Conclusions:Our study findings highlight the importance of NK cells in regulating SCLC.USP1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.

Small cell lung cancer with peripheral neuropathy as the first symptom:Two case reports

BACKGROUND Small cell lung cancer(SCLC)is the most malignant type of lung cancer.Even in the latent period and early stage of the tumor,SCLC is prone to produce distant metastases with complex and diverse clinical manifestations.SCLC is most closely related to paraneoplastic syndrome,and some cases present as paraneoplastic peripheral neuropathy(PPN).PPN in SCLC appears early,lacks specificity,and often occurs before diagnosis of the primary tumor.It is easy to be misdiagnosed as a primary disease of the nervous system,leading to missed diagnosis and delayed diagnosis and treatment.CASE SUMMARY This paper reports two cases of SCLC with limb weakness as the first symptom.The first symptoms of one patient were rash,limb weakness,and abnormal electromyography.The patient was repeatedly referred to the hospital for limb weakness and rash for>1 year,during which time,treatment with hormones and immunosuppressants did not lead to significant improvement,and the condition gradually aggravated.The patient was later diagnosed with SCLC,and the dyskinesia did not worsen as the dermatomyositis improved after antineoplastic and hormone therapy.The second case presented with limb numbness and weakness as the first symptom,but the patient did not pay attention to it.Later,the patient was diagnosed with SCLC after facial edema caused by tumor thrombus invading the vein.However,he was diagnosed with extensive SCLC and died 1 year after diagnosis.CONCLUSION The two cases had PPN and abnormal electromyography,highlighting its correlation with early clinical indicators of SCLC.

Tankyrase 2 as a therapeutic target in non-small cell lung cancer: Implications for apoptosis and migration

This letter addresses Wang and Zhang's investigation into the role of tankyrase 2(TNKS2)as a pivotal driver of malignancy in non-small cell lung cancer(NSCLC)through mechanisms including apoptosis inhibition,enhanced cellular migration,andβ-catenin pathway activation.Their study in NSCLC cell lines demonstrates that TNKS2 overexpression stabilizesβ-catenin,subsequently triggering onco-genic gene expression and facilitating cellular migration-key attributes of meta-static potential.These insights position TNKS2 as a compelling target for therapy and a potential prognostic marker in NSCLC.Nevertheless,translating these in vitro findings to clinical practice requires validation in in vivo models.Addi-tionally,further research should investigate TNKS2 expression in patient samples and assess its implications in therapy resistance and combination treatment strategies.

Exercise rehabilitation on patients with non-small cell lung cancer: A meta-analysis of randomized controlled trials

BACKGROUND Lung cancer is one of the most common and deadly cancers worldwide.As the disease progresses and due to the side effects of treatment,patients’physical activity significantly decreases.AIM To systematically review and conduct a meta-analysis on the effects of exercise rehabilitation on the physical activity of lung cancer patients and determine the best implementation methods to provide clinical guidance.METHODS Literature was searched through multiple electronic databases.A random effects model was used to combine effect sizes through standardized mean difference(SMD).The Cochrane risk of bias tool was used to assess the quality of the lite-rature,sensitivity analysis was used to ensure the robustness of the results,and Egger’s test was used to detect publication bias and asymmetry.RESULTS A total of 11 studies involving 541 patients were included in this study.The phy-sical endurance,muscle function and cardiopulmonary function of non-small cell lung cancer(NSCLC)patients were evaluated.The overall effect size of the six-minute walk test(6MWT)was not statistically significant.However,subgroup analysis found that endurance significantly improved when exercise duration exceeded 0.5 hours(P≤0.05).In terms of muscle function,the overall effect size was SMD=0.619.Subgroup analysis showed that strength training,respiratory training,and cross-training(XT)significantly improved muscle function.Exercise rehabilitation significantly enhanced cardiopulmonary endurance(SMD=0.856,P=0.002),and the effect was better when the single exercise duration was more than 1 hour,age was over 65 years,and the intervention period was more than 3 months.CONCLUSION Exercise rehabilitation effectively improved muscle function in NSCLC patients,especially strength training,respiratory training,and cross-training.Cardiopulmonary function also showed improvement,particularly when exercise duration exceeded 1 hour,age was≥65 years,and the intervention period was more than 3 months.A single exercise duration of more than 0.5 hours can enhance patients’physical endurance.Appropriately increasing exercise duration and selecting suitable exercise forms can effectively improve the physical activity of NSCLC patients.

Enhanced recovery after surgery in elderly patients with non-small cell lung cancer who underwent video-assisted thoracic surgery

BACKGROUND This study was designed to investigate the clinical outcomes of enhanced recovery after surgery(ERAS)in the perioperative period in elderly patients with nonsmall cell lung cancer(NSCLC).AIM To investigate the potential enhancement of video-assisted thoracic surgery(VATS)in postoperative recovery in elderly patients with NSCLC.METHODS We retrospectively analysed the clinical data of 85 elderly NSCLC patients who underwent ERAS(the ERAS group)and 327 elderly NSCLC patients who received routine care(the control group)after VATS at the Department of Thoracic Surgery of Peking University Shenzhen Hospital between May 2015 and April 2017.After propensity score matching of baseline data,we analysed the postoperative stay,total hospital expenses,postoperative 48-h pain score,and postoperative complication rate for the 2 groups of patients who underwent lobectomy or sublobar resection.RESULTS After propensity score matching,ERAS significantly reduced the postoperative hospital stay(6.96±4.16 vs 8.48±4.18 d,P=0.001)and total hospital expenses(48875.27±18437.5 vs 55497.64±21168.63 CNY,P=0.014)and improved the satisfaction score(79.8±7.55 vs 77.35±7.72,P=0.029)relative to those for routine care.No significant between-group difference was observed in postoperative 48-h pain score(4.68±1.69 vs 5.28±2.1,P=0.090)or postoperative complication rate(21.2%vs 27.1%,P=0.371).Subgroup analysis showed that ERAS significantly reduced the postoperative hospital stay and total hospital expenses and increased the satisfaction score of patients who underwent lobectomy but not of patients who underwent sublobar resection.CONCLUSION ERAS effectively reduced the postoperative hospital stay and total hospital expenses and improved the satisfaction score in the perioperative period for elderly NSCLC patients who underwent lobectomy but not for patients who underwent sublobar resection.

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation:A multicenter,case-series study in China

Objective:To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor(EGFR)21L858R mutant non-small cell lung cancer(NSCLC)patients in China and to explore the factors influencing the efficacy and safety.Methods:A longitudinal,consecutive case-series,multicenter study with mixed prospective and retrospective data was conducted.The primary endpoint was progression-free survival(PFS),and the secondary endpoints included duration of treatment(DOT),overall survival(OS),objective response rate(ORR),disease control rate(DCR)and safety.Results:A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included.The median follow-up time for these patients was 20.4 months.Among 134 patients with evaluable lesions,the ORR was 70.9%and the DCR was 96.3%.The median PFS was 16.3[95%confidence interval(95%CI),13.7−18.9]months.Multivariate Cox regression analysis suggested that the baseline brain metastasis(BM)status[with vs.without BM:hazard ratio(HR),1.331;95%CI,0.720−2.458;P=0.361]and initial doses(45 mg vs.30 mg:HR,0.837;95%CI,0.427−1.641;P=0.604)did not significantly affect the median PFS.The median DOT was 21.0(95%CI,17.5−24.6)months and the median OS was not reached.Genetic tests were performed in 64 patients after progression,among whom 29(45.3%)patients developed the EGFR 20T790M mutation.In addition,among the 46 patients who discontinued dacomitinib treatment after progression,31(67.4%)patients received subsequent third-generation EGFR-tyrosine kinase inhibitors.The most common grade 3−4 adverse events were rash(10.4%),diarrhea(9.1%),stomatitis(7.1%)and paronychia(4.5%).The incidence of grade 3−4 rash was significantly higher in the 45 mg group than that in the 30 mg group(21.9%vs.7.5%,P=0.042).Conclusions:First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

Objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully investigated.This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care.Methods:A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled.HRD status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered HRD-positive.Genomic,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were analyzed.Results:Of the patients,25.1%(89/355)were HRD-positive.Compared to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(P<0.001),and fewer driver gene mutations(P<0.001).Furthermore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC.HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity.HRD-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T cells.HRD-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens.Conclusions:Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC.Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC.This study highlights potential actionable alterations in HRD-positive NSCLC,suggesting possible combinational therapeutic strategies for these patients.

IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

Employing a Backpropagation Neural Network for Predicting Fear of Cancer Recurrence among Non-Small Cell Lung Cancer Patients

Objective:Non-small cell lung cancer(NSCLC)patients often experience significant fear of recurrence.To facilitate precise identification and appropriate management of this fear,this study aimed to compare the efficacy and accuracy of a Backpropagation Neural Network(BPNN)against logistic regression in modeling fear of cancer recurrence prediction.Methods:Data from 596 NSCLC patients,collected between September 2023 and December 2023 at the Cancer Hospital of the Chinese Academy of Medical Sciences,were analyzed.Nine clinically and statistically significant variables,identified via univariate logistic regression,were inputted into both BPNN and logistic regression models developed on a training set(N=427)and validated on an independent set(N=169).Model performances were assessed using Area Under the Receiver Operating Characteristic(ROC)Curve and Decision Curve Analysis(DCA)in both sets.Results:The BPNN model,incorporating nine selected variables,demonstrated superior performance over logistic regression in the training set(AUC=0.842 vs.0.711,p<0.001)and validation set(0.7 vs.0.675,p<0.001).Conclusion:The BPNN model outperforms logistic regression in accurately predicting fear of cancer recurrence in NSCLC patients,offering an advanced approach for fear assessment.

Piperlongumine in combination with EGFR tyrosine kinase inhibitors for the treatment of lung cancer cells

Objectives:EGFR tyrosine kinase inhibitor(EGFR-TKI)therapies such as erlotinib and gefitinib are approved for the treatment of non-small cell lung cancer(NSCLC).However,the high incidence of acquired resistance to these EGFR-TKIs may preclude their effectiveness.Piperlongumine(PPL),an extract from the long pepper fruit(Piper longum),has been shown to possess anticancer properties.The purpose of the study was to investigate piperlongumine as an anticancer agent and to study a combination treatment approach with EGFR-TKIs against lung cancer cells.Methods:Anticancer efficacy of PPL,erlotinib(ERL),gefitinib(GEF),and cisplatin(CIS)were investigated in H1299 and H1975 cell lines.Cells were treated with PPL,ERL,GEF,and CIS alone,and in combination,cell viability was determined after 72 h.The mechanism of PPL-induced cytotoxicity was investigated via reactive oxygen species(ROS)induction,and apoptosis induction using acridine orange/ethidium bromide staining and flow cytometry.The effect of treatment on EGFR-mediated oncogenic signaling was investigated by immunoblotting for mitogenic and apoptotic markers.Results:PPL exhibited a potent cytotoxic effect in H1299 and H1975 cells compared to ERL,GEF,and CIS.Combination treatments of PPL with GEF and ERL showed significant reductions in cancer cells compared to control in both cell lines,which were associated with apoptotic induction,but without significant ROS induction.Compared to control,PPL with GEF significantly increased apoptotic cell death in H1975as confirmed with flow cytometry.Treatment with PPL alone and in combination induced anti-mitogenic and apoptotic responses at the molecular level.Conclusion:PPL sensitized lung cancer cells to EGFR-TKI and induced potent cytotoxic effects at low concentrations.

Machine learning based on metabolomics unveils neutrophil extracellular trap-related metabolic signatures in non-small cell lung cancer patients undergoing chemoimmunotherapy

BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However,the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies.Consequently,it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments.AIM To identify the metabolic signatures associated with neutrophil extracellular traps(NETs)and chemoimmunotherapy efficacy in NSCLC patients.METHODS In total,159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled.We first investigated the characteristics influencing clinical efficacy.Circulating levels of NETs and cytokines were measured by commercial kits.Liquid chromatography tandem mass spectrometry quantified plasma metabolites,and differential metabolites were identified.Least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest algorithms were employed.By using plasma metabolic profiles and machine learning algorithms,predictive metabolic signatures were established.RESULTS First,the levels of circulating interleukin-8,neutrophil-to-lymphocyte ratio,and NETs were closely related to poor efficacy of first-line chemoimmunotherapy.Patients were classed into a low NET group or a high NET group.A total of 54 differential plasma metabolites were identified.These metabolites were primarily involved in arachidonic acid and purine metabolism.Three key metabolites were identified as crucial variables,including 8,9-epoxyeicosatrienoic acid,L-malate,and bis(monoacylglycerol)phosphate(18:1/16:0).Using metabolomic sequencing data and machine learning methods,key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy.CONCLUSION The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.

Network Structure and Variability of Recurrence Fear in Early-Stage Non-Small Cell Lung Cancer:A Symptom Network Analysis

Background:Lung cancer,one of the most prevalent and deadly malignancies worldwide,not only poses a significant physical burden but also a profound psychological challenge to patients.Among these psychological challenges,the fear of recurrence stands out as a particularly distressing issue.This fear,often rooted in the patients’past experiences with the disease and its treatment,can significantly impact their quality of life,mental health,and even compliance with follow-up care.Moreover,this fear can be exacerbated by the lack of understanding and support from healthcare professionals and family members,further isolating patients and compounding their psychological burden.Therefore,understanding and addressing the fear of recurrence in lung cancer patients is crucial for improving their overall well-being and outcomes.Aims:This study aims to develop a symptom network model for fear of recurrence in early-stage lung cancer patients,analyzing symptom correlations to enhance healthcare providers’understanding and management of these symptoms,thereby improving patient outcomes and quality of life.Design:A cross-sectional study design was used.Method:We employed convenience sampling to recruit 551 lung cancer patients from the Thoracic Surgery Department of a tertiary hospital in Beijing between January 2023 and December 2023.A cross-sectional study was conducted using the General Information Questionnaire,Fear of Disease Progression Scale,and Level of Hope Scale.Network analysis was performed with JASP 0.18.3.0 using the EBICglasso method,and centrality metrics including Betweenness,Closeness,Degree centrality,and Expected influence were calculated.Results:Symptom network analysis identified fear of family impact and future work disruption as central to recurrence fear in these patients.Gender-based analysis revealed‘fear of being unable to continue work’as central in males,while‘fear of affecting family members’was central in females.Among adolescents,concerns about future work,medication side effects,and family impact showed the highest expected influence.In contrast,older patients predominantly feared major treatment implications.One-way ANOVA indicated that older age correlated with reduced recurrence fear,and higher hope levels significantly mitigated this fear.Conclusion:This study broadens understanding of fear of recurrence across demographic variables like gender and age,elucidating symptom interrelations and impacts.Future strategies should focus on patient-specific differences in recurrence fear to formulate targeted interventions.Relevance to Clinical Practice:Through in-depth analysis of the symptom network,healthcare professionals can more comprehensively understand the psychological responses of lung cancer patients when they face the risk of recurrence,and then formulate more precise and personalized treatment plans.At the same time,doctors and nurses can adjust treatment strategies in a timely manner according to the changes in the patient’s symptom network and provide more comprehensive psychological support,thus enhancing the patient’s treatment adherence and outcome.Patient Contribution:People who were invited to participate voluntarily completed a range of questionnaires.

Research progress on dynamic monitoring of ctDNA and drug resistance related concomitant mutations in non-small cell lung cancer

Owing to significantly prolonged survival,targeted therapy has become standardized recommendation for advanced non-small cell lung cancer patients with mutated driver genes.However,the genetic status of lung cancer patients is dynamic.By dynamically monitoring the evolution of genes status,differential genes and concomitant genes related to progressive disease could be confirmed early,so as to achieve a more accurate and comprehensive insight of the whole process management of targeted therapy for lung cancer patients.Under the guidance of accurate genetic testing results,it is helpful to provide patients with more effective,long-term,and stable individualized targeted therapy.

Stage Ⅳ non-small cell lung cancer with multiple metastases to the small intestine leading to intussusception: A case report

BACKGROUND Gastrointestinal tract metastasis from lung cancer is rare and compared to small cell lung cancer(SCLC),non-SCLC(NSCLC)is even less likely to metastasize in this manner.Additionally,small intestinal tumors can also present with diverse complications,some of which require urgent intervention.CASE SUMMARY In this report,we detail a unique case of stage IV lung cancer,where the presence of small intestine tumors led to intussusception.Subsequent to a small intestine resection,pathology confirmed that all three tumors within the small intestine were metastases from adenocarcinoma of the lung.The postoperative follow-up period extended beyond 14 mo.CONCLUSION In patients with stage IV NSCLC,local tumor control can be achieved with various treatments.However,if small intestinal metastasis occurs,surgical intervention remains necessary,as it may improve survival.

Correlation between pre-anesthesia anxiety and emergence agitation in non-small cell lung cancer surgery patients

BACKGROUND Preoperative anxiety is a common emotional problem during the perioperative period and may adversely affect postoperative recovery.Emergence agitation(EA)is a common complication of general anesthesia that may increase patient discomfort and hospital stay and may be associated with the development of postoperative complications.Pre-anesthetic anxiety may be associated with the development of EA,but studies in this area are lacking.AIM To determine the relationship between pre-anesthetic anxiety and EA after radical surgery in patients with non-small cell lung cancer(NSCLC).METHODS Eighty patients with NSCLC undergoing surgical treatment between June 2020 and June 2023 were conveniently sampled.We used the Hospital Anxiety and Depression Scale’s(HADS)anxiety subscale(HADS-A)to determine patients’anxiety at four time points(T1-T4):Patients’preoperative visit,waiting period in the surgical waiting room,after entering the operating room,and before anesthesia induction,respectively.The Riker Sedation-Agitation Scale(RSAS)examined EA after surgery.Scatter plots of HADS-A and RSAS scores assessed the correlation between patients’pre-anesthesia anxiety status and EA.We performed a partial correlation analysis of HADS-A scores with RSAS scores.RESULTS NSCLC patients’HADS-A scores gradually increased at the four time points:7.33±2.03 at T1,7.99±2.22 at T2,8.05±2.81 at T3,and 8.36±4.17 at T4.The patients’postoperative RSAS score was 4.49±1.18,and 27 patients scored≥5,indicating that 33.75%patients had EA.HADS-A scores at T3 and T4 were significantly higher in patients with EA(9.67±3.02 vs 7.23±2.31,12.56±4.10 vs 6.23±2.05,P<0.001).Scatter plots showed the highest correlation between HADS-A and RSAS scores at T3 and T4.Partial correlation analysis showed a strong positive correlation between HADS-A and RSAS scores at T3 and T4(r=0.296,0.314,P<0.01).CONCLUSION Agitation during anesthesia recovery in patients undergoing radical resection for NSCLC correlated with anxiety at the time of entering the operating room and before anesthesia induction.

Transformation of lung adenocarcinoma into small cell lung cancer after treatment with epidermal growth factor receptor tyrosine kinase inhibitors

Epidermal growth factor receptor tyrosine kinase inhibitors effectively improve the prognosis of patients with epidermal growth factor receptor–mutant lung adenocarcinoma.However,acquired resistance inevitably develops with small cell lung cancer transformation emerging as a rare but increasingly frequent mechanism of tyrosine kinase inhibitor resistance.This transformation poses significant chal-lenges to the health of patients with lung cancer and complicates their clinical management.This article comprehensively reviews the di-agnostic,predictive,mechanistic,and therapeutic aspects of small cell lung cancer transformation to enhance our understanding and clin-ical awareness of this phenomenon.

Celecoxib enhances the response of tumor cells to cisplatin through upregulating PUMA in non–small cell lung cancer carrying wild-type p53

Celecoxib,a cyclooxygenase-2 inhibitor,can enhance the efficacy of chemotherapy;however,its effect seems inconsistent.In this study,we investigated whether celecoxib would increase the antiproliferative effects of cisplatin in human lung cancer cells.Our data demonstrated the synergistic effects of celecoxib with cisplatin in wild-type p53 cells and their antagonistic effects inmutated or deleted p53 cells.Combination indices of 0.82 to 0.93 reflected a synergistic effect between celecoxib and cisplatin in lung cancer cells with wild-type p53.Combination indices of 1.63 to 3.00 reflected antagonism between celecoxib and cisplatin in lung cancer cells with mutated or deleted p53.Compared with that in cells with mutated or deleted p53,apoptosis significantly increased with the addition of celecoxib and cisplatin in wild-type p53 cells(P<0.05).Moreover,the results in vivo were similar to those in vitro:celecoxib combinedwith cisplatin slowed tumor growth in wild-type p53 groups and not in mutated or deleted p53 groups.In addition,celecoxib promoted p53 translocation into the nucleus and upregulated active p53 expression in wild-type p53 cells.Celecoxib combined with cisplatin upregulated PUMA(PUMA is a downstream gene of p53)after active p53 increased in wild-type p53 cells.In summary,the combination of celecoxib and cisplatin demonstrates clear synergistic effects in wild-type p53 cells and antagonistic effects inmutated or deleted p53 cells.The synergistic effect was achieved by apoptosis,induced by upregulating PUMA.Our results will provide a new treatment strategy for patients carrying wild-type p53,insensitive to cisplatin.