Introduction Small cell lung cancer(SCLC)is a highly aggressive malignancy with limited treatment options.Despite advances in immunotherapy,response rates remain low,and the efficacy of current molecular subtyping1,2 ...Introduction Small cell lung cancer(SCLC)is a highly aggressive malignancy with limited treatment options.Despite advances in immunotherapy,response rates remain low,and the efficacy of current molecular subtyping1,2 is insufficient to predict therapeutic outcomes3,4.A recently identified vulnerability in SCLC involves the dysregulation of nuclear-cytoplasmic transport,particularly through exportin 1(XPO1)5-7.展开更多
Objective:This study aimed at exploring the effects of the epigenetic regulator,chidamide,on reprogramming the immunosuppressive tumor microenvironment in small cell lung cancer(SCLC),particularly the roles in macroph...Objective:This study aimed at exploring the effects of the epigenetic regulator,chidamide,on reprogramming the immunosuppressive tumor microenvironment in small cell lung cancer(SCLC),particularly the roles in macrophage polarization and angiogenesis.The therapeutic efficacy of combining chidamide with the anti-angiogenic agent,anlotinib,for refractory SCLC was also evaluated.Methods:RNA sequencing and functional validation were performed to assess chidamide’s effects on macrophages.Signal transducer and activator of transcription 4(STAT4)-mediated transcriptional activation of CCL2 was confirmed with ChIP-qPCR.The synergistic efficacy of chidamide in combination with anlotinib was tested in preclinical models.Results:Chidamide enhanced macrophage infiltration and induced macrophage polarization toward the anti-tumor M1 phenotype.Mechanistically,chidamide upregulated CCL2 via STAT4 transcriptional activation,thereby reshaping the tumor immune microenvironment(TIME).Combining chidamide with anlotinib synergistically suppressed tumor growth and remodeled the immunosuppressive TME in SCLC in vivo.Conclusions:Chidamide reshaped the SCLC TIME by activating STAT4/CCL2,thus driving M1 macrophage polarization and enhancing anti-tumor immunity.Our findings highlight coordinated TIME-targeted therapy as a translatable strategy to overcome therapeutic resistance in SCLC and provide a rationale for clinical trials examining epigenetic and anti-angiogenic therapeutics combinations.展开更多
Objective:Cancer-associated inflammation and coagulation cascades play vital roles in cancer progression and survival.In this study,we investigated the significance of the combination of preoperative fibrinogen and th...Objective:Cancer-associated inflammation and coagulation cascades play vital roles in cancer progression and survival.In this study,we investigated the significance of the combination of preoperative fibrinogen and the neutrophil-to-lymphocyte ratio(NLR)in predicting the survival of patients with non-small cell lung cancer(NSCLC).Methods:We retrospectively enrolled 589 patients with NSCLC who underwent surgery.The univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators,including the combination of fibrinogen and NLR(F-NLR).The cut-off values for fibrinogen,NLR,and clinical laboratory variables were defined by the receiver operating characteristic(ROC)curve analysis.According to the ROC curve,the recommended cut-off values for fibrinogen and the NLR were 3.48 g/L and 2.30,respectively.Patients with both a high NLR(≥2.30)and hyperfibrinogenemia(≥3.48 g/L)were given a score of 2,whereas those with one or neither were scored as 1 or 0,respectively.Results:Our results showed that F-NLR was an independent prognostic indicator for disease-free survival(DFS)[hazard ratio(HR),1.466;95%confidence interval(CI),1.243–1.730;P<0.001]and overall survival(OS)(HR,1.512;95%CI,1.283–1.783;P<0.001).The five-year OS rates were 66.1%,53.5%,and 33.3%for the F-NLR=0,F-NLR=1,and F-NLR=2,respectively(P<0.001).Correspondingly,their five-year DFS rates were 62.2%,50.3%,and 30.4%,respectively(P<0.001).In the subgroup analyses of the pathological stages,the F-NLR level was significantly correlated with DFS and OS in stage I and IIIA cancers.Conclusions:Preoperative F-NLR score can be used as a valuable prognostic marker for patients with resectable early-stage NSCLC.展开更多
Objective： Increasing numbers of cancer patients are using Chinese herbs （CHs）. However, differences among prior studies make it difficult to draw firm conclusions about the clinical usefulness of any specific CH f...Objective： Increasing numbers of cancer patients are using Chinese herbs （CHs）. However, differences among prior studies make it difficult to draw firm conclusions about the clinical usefulness of any specific CH formula. The primary objective of this study was to establish the acceptability of taking a standardized CH formula for patients with advanced lung cancer. The secondary objective was to identify any toxicities attributable to this CH formula and to measure changes in quality of life. Methods： A single-arm, prospective study of a 6-week intervention with a selected CH formula in 15 patients with stage 4 nonsmall-cell lung cancer （NSCLC, Seventh American Joint Committee on Cancer TNM staging system）. Results： Patients with advanced lung cancer were interested in using the CH formula. Completion （93%） and adherence （98%） levels were very high and most patients perceived the CH treatment as easy to take and were willing to take the CHs used in the study again if it was available. About half of the patients reported adverse events, all of which were mild （Grade 1 or 2） and only a small minority （8%） were poten- tially related to CHs. No biochemical or hematological evidence of toxicity was observed. Overall, there were improvement in quality of life, and reduced feelings of tiredness and sleepiness. Conclusion： This study provides preliminary evidence that short-term use of a carefully selected and pre- pared CH formula in patients with stage 4 NSCLC is acceptable and safe.展开更多
Objective: Chemotherapy is the standard treatment for small-cell lung cancer (SCLC), and leukopenia is a common side effect. This study assesses whether chemotherapy-induced leukopenia is a predictor of efficacy and w...Objective: Chemotherapy is the standard treatment for small-cell lung cancer (SCLC), and leukopenia is a common side effect. This study assesses whether chemotherapy-induced leukopenia is a predictor of efficacy and whether it is associated with the survival of SCLC patients. Methods: A retrospective analysis was conducted on data from 445 patients with SCLC who received standard chemotherapy for 4 to 10 cycles. The World Health Organization grading system classifies leukopenia during chemotherapy as follows: absent (grade 0), mild (grades 1 and 2), or severe (grades 3 and 4). The primary endpoint is overall survival (OS). Results: The association between chemotherapy-induced leukopenia and OS was assessed. According to a multivariate Cox model with time-varying covariates, the hazard ratio of death was significantly lower among patients with mild leukopenia than among patients with severe leukopenia at 0.687 (0.506 to 0.943) and 1.414 (1.147 to 1.744), respectively. The median survival was 13 months (95% CI: 11 to 15 months) for patients who did not experience leukopenia, 17 months (95% CI: 14 to 18 months) for those with mild leukopenia, and 14 months (95% CI: 13 to 16 months) for those with severe leukopenia (absent vs. mild vs. severe leukopenia, P=0.047). Conclusion: Leukopenia during chemotherapy is associated with the survival of SCLC patients. Mild leukopenia is strongly associated with longer survival time.展开更多
A 65-year-old man with right central type of lung squamous carcinoma was admitted to our department.Bronchoscopy displayed complete obstruction of right upper lobe bronchus and infiltration of the bronchus intermedius...A 65-year-old man with right central type of lung squamous carcinoma was admitted to our department.Bronchoscopy displayed complete obstruction of right upper lobe bronchus and infiltration of the bronchus intermedius with tumor.Chest contrast computed tomography revealed the tumor invaded right pulmonary artery,superior vena cava,and the persistant left superior vena cava flowed into the coronary sinus.The tumor was successfully removed by means of bronchial and pulmonary artery sleeve resection of the right upper and middle lobes combined with resection and reconstruction of superior vena cava(SVC)utilizing ringed polytetrafluoroethylene graft.To the best of our knowledge,this was the first report of complete resection of locally advanced lung cancer involving superior vena cava,right pulmonary artery trunk and main bronchus with persistant left superior vena cava.展开更多
Genome-wide association studies revealed that allelic variation in the α5-α3-β4 nicotine acetylcholine receptor(n ACh R) cluster on chromosome 15q24-15q25.1 was associated with lung cancer risk. n ACh Rs are membra...Genome-wide association studies revealed that allelic variation in the α5-α3-β4 nicotine acetylcholine receptor(n ACh R) cluster on chromosome 15q24-15q25.1 was associated with lung cancer risk. n ACh Rs are membrane ligand-gated cation channels whose activation is triggered by the binding of the endogenous neurotransmitter acetylcholine(ACh) or other biologic compounds including nicotine. n ACh Rs have been found on lung cancer cells, underscoring the idea that the non-neuronal n ACh R pathway has important implications for lung cancer. Several studies focusing on the treatment with n ACh R antagonists with improved selectivity might trigger novel strategies for the intervention and prevention of lung cancer. Here we review the genetic risk factors for lung cancer in the n ACh R gene cluster, the roles of nicotine receptors, and the molecular mechanisms of acetylcholine receptor pathways to lead to more opportunities for intervention and prevention of lung cancer.展开更多
Objective:Dysfunction in fibroblast growth factor receptor(FGFR)signaling has been reported in diverse cancer types,including non-small cell lung cancer(NSCLC).The frequency of FGFR aberrations in Chinese NSCLC patien...Objective:Dysfunction in fibroblast growth factor receptor(FGFR)signaling has been reported in diverse cancer types,including non-small cell lung cancer(NSCLC).The frequency of FGFR aberrations in Chinese NSCLC patients is therefore of great clinical significance.Methods:A total of 10,966 NSCLC patients whose tumor specimen and/or circulating cell-free DNA(cf DNA)underwent hybridization capture-based next-generation sequencing were reviewed.Patients'clinical characteristics and treatment histories were also evaluated.Results:FGFR aberrations,including mutations,fusions,and gene amplifications,were detected in 1.9%(210/10,966)of the population.FGFR abnormalities were more frequently observed in lung squamous cell carcinomas(6.8%,65/954)than lung adenocarcinomas(1.3%,128/9,596).FGFR oncogenic mutations were identified in 19 patients(~0.17%),of which,68%were male lung squamous cell carcinoma patients.Eleven out of the 19 patients(58%)had concurrent altered PI3 K signaling,thus highlighting a potential combination therapeutic strategy of dual-targeting FGFR and PI3 K signaling in such patients.Furthermore,FGFR fusions retaining the intact kinase domain were identified in 12 patients(0.11%),including 9 FGFR3-TACC3,1 FGFR2-INA,1 novel FGFR4-RAPGEFL1,and 1 novel fusion between the FGFR1 and SLC20 A25′-untranslated regions,which may have caused FGFR1 overexpressions.Concomitant EGFR mutations or amplifications were observed in 6 patients,and 4 patients received anti-EGFR inhibitors,in whom FGFR fusions may have mediated resistance to anti-EGFR therapies.FGFR amplification was detected in 24 patients,with the majority being FGFR1 amplifications.Importantly,FGFR oncogenic mutations,fusions,and gene amplifications were almost always mutually exclusive events.Conclusions:We report the prevalence of FGFR anomalies in a large NSCLC population,including mutations,gene amplifications,and novel FGFR fusions.展开更多
Objective: To identify clinical and pathologic factors that were associated with the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients. Methods: A retrospective study of 147 subjects who had ...Objective: To identify clinical and pathologic factors that were associated with the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients. Methods: A retrospective study of 147 subjects who had undergone curative resection for stage IB upper lobe NSCLC was performed. Patients who had received any adjuvant or neo-adjuvant chemotherapy were excluded. Survival function curves were estimated using the Kaplan-Meier procedure. Crude and adjusted hazard ratios (HRs) of potential prognostic factors were estimated using Cox proportional hazards models. Results: Five factors, including age, tumor size, histologic grade of differentiation, number of removed superior mediastinal lymph node stations and presence of visceral pleura invasion, were significantly and independently associated with mortality risk. Adjusted HRs were 2.6 [95% confidence interval (95% CI): 1.1?6.5] and 4.6 (95% CI: 1.9?11) for those aged 58?68 years and those >68 years, respectively, relative to those aged <58 years. HRs for those with poorly and moderately differentiated tumors were 6.4 (95% CI: 2.3?18) and 1.4 (95% CI: 0.7?2.8), respectively. HRs for those with tumor size 3.1?5 cm and >5 cm (vs ?3.0 cm) were 2.3 (95% CI: 1.1?4.9) and 4.3 (95% CI: 1.9?10), respectively. The presence of visceral pleura invasion also increased the risk of mortality (HR=4.0, 95% CI: 1.3?12). Conclusion: Advanced age, larger tumor size, poorly differentiated histology, smaller number of removed superior mediastinal lymph node stations, and presence of visceral pleura invasion were associated with poor survival of surgically treated stage IB upper lobe NSCLC patients.展开更多
Background:Baoyuan decoction is used clinically as an adjuvant treatment for lung cancer.However,the underlying mechanism remains unclear.Therefore,this study aimed to explore the mechanism of action of Baoyuan decoct...Background:Baoyuan decoction is used clinically as an adjuvant treatment for lung cancer.However,the underlying mechanism remains unclear.Therefore,this study aimed to explore the mechanism of action of Baoyuan decoction in lung cancer treatment using network pharmacology and molecular docking technology.Methods:The Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction databases were used to screen the active ingredients of Baoyuan decoction and their relevant targets.Lung cancer-related targets were obtained from the GeneCards,Online Mendelian Inheritance in Man,and DrugBank databases.Protein-protein interaction network of the common targets was constructed using the STRING database and analyzed using Cytoscape software 3.10.1.Furthermore,Gene Ontology enrichment,Kyoto Encyclopedia of Genes and Genomes pathway analyses and visualization of common genes were performed using the R software.Finally,molecular docking of the selected key ingredients and targets was performed,and the results were verified using AutoDock Vina software.Results:We identified 142 potential active ingredients,3624 potential lung cancer-related targets,and 341 common drug targets.A total of 72 core targets were identified,of which AKT1,TP53,interleukin-6,epithelial growth factor receptor,and signal transducer and activator of transcription 3 were key.A total of 4116 items were obtained via Gene Ontology enrichment analyses.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 189 related signaling pathways,including the PI3K-Akt,AGE-RAGE signaling pathways in diabetic complications,FOXO,and TH signaling pathways,which are involved in cell proliferation,autophagy,metastasis,invasion,radiation resistance,and chemotherapy resistance in the lung cancer microenvironment.The molecular docking results suggested that the key ingredients had a strong affinity for key targets.Conclusion:This study demonstrates that Baoyuan decoction plays a key therapeutic role in a complex manner involving multiple ingredients,targets,and pathways in lung cancer.Our findings are anticipated to provide new ideas for follow-up experimental research and clinical application.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
BACKGROUND Life-threatening hypoxia can occur in patients with lung cancer due to bronchial obstruction.Extracorporeal membrane oxygenation(ECMO)can be used as a bridge therapy for patients with severe hypoxia not rel...BACKGROUND Life-threatening hypoxia can occur in patients with lung cancer due to bronchial obstruction.Extracorporeal membrane oxygenation(ECMO)can be used as a bridge therapy for patients with severe hypoxia not relieved by conventional mechanical treatment.However,the usefulness of chemotherapy in patients with lung cancer receiving ECMO therapy is not well known.CASE SUMMARY A 53-year-old man visited the emergency room with worsening dyspnea for 1 mo.A series of imaging and diagnostic tests were performed,and stageⅢB(cT4N2M0)lung cancer was eventually diagnosed.On hospital day 3,he experienced dyspnea and hypoxia that was not relieved with oxygen support via a high-flow nasal cannula.ECMO was initiated because his respiratory condition did not improve even with mechanical ventilation.The patient then underwent gemcitabine/cisplatin chemotherapy without dose reduction while on ECMO.After two cycles of chemotherapy,there was a decrease in the size of the primary tumor in the right main bronchus.After the completion of concurrent chemoradiotherapy,a computed tomography scan revealed further improvement in the right main bronchus narrowing.Eight months after a lung cancer diagnosis,the patient did well without any dyspnea.CONCLUSION ECMO is a potential bridge therapy for respiratory failure in patients with central airway obstruction secondary to lung cancer.展开更多
As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-small cell lung cancer(NSCLC) and has proven effective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal anti...As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-small cell lung cancer(NSCLC) and has proven effective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal antibody targeting angiogenesis, is the only antiangiogenic agent approved for use in combination with first-line chemotherapy for non-squamous NSCLC. Small-molecule inhibitors targeting the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced NSCLC. However, unlike bevacizumab, not all other antiangiogenic agents show significant benefits when combined with chemotherapy. As for the failures of most other combinations, the combination schedule may be an important reason that has so far been overlooked in clinical trials. This article reviews the combination of angiogenic agents with chemotherapy in the treatment of NSCLC.展开更多
OBJECTIVE To investigate whether CXCL12 and its receptor, CXCR7, play a role in lung cancer invasion and metastasis. METHODS Western blot and immunocytochemistry were used to detect CXCR7 protein expression in 8 lung ...OBJECTIVE To investigate whether CXCL12 and its receptor, CXCR7, play a role in lung cancer invasion and metastasis. METHODS Western blot and immunocytochemistry were used to detect CXCR7 protein expression in 8 lung cancer cell lines, EKVX, HOP62, HOP92, NCI-H23, NCI-H226, NCI- H322M, NCI-H446, and A549, and cell migration experiment was conducted to observe mobility of the lung cancer cells. The concentration of intracellular calcium in cytoplasm was measured under the fluorescence microscopy. RESULTS CXCR7 protein was positively expressed in the 8 lung cancer cell lines EKVX, HOP62, HOP92, NCI-H23, NCI-H226, NCI- H322M, NCI-H446, and A549. Following CXCL12 stimulation, obvious pseudopodia of lung cancer cells was observed under the microscope. The cell migration experiment showed that after incubation with CXCL12, the number of EKVX cells, which passed through the polycarbonate microporous filter membranes increased to a great extent. This phenomenon can be reversed by CXCR7-siRNA. After CXCL12 incubation, the intracellular Ca2＋ level in the EKVX cells was increased to a great extent. CONCLUSION Chemokine CXCL12 facilitates the migration of lung cancer cells by changing the concentration of intracellular Ca2＋. The CXCL12-CXCR7 axis may play an important role in lung cancer invasion and metastasis. It could be a potential target for lung cancer therapy and an effective way to prevent recurrence and metastasis of lung cancer.展开更多
Patients with stage Ⅲ N2 non-small cell lung cancer （NSCLC） are more than one third of all NSCLC patients. The 5-year survival rate of them is approximately 15%. From therapeutic views, stage ⅢA N2 of 97 Internati...Patients with stage Ⅲ N2 non-small cell lung cancer （NSCLC） are more than one third of all NSCLC patients. The 5-year survival rate of them is approximately 15%. From therapeutic views, stage ⅢA N2 of 97 International Lung Cancer Staging System is an obvious hetero-combination, which includes mediastinal lymph node metastasis based on microscope after postoperative examination and N2 of single station or N2 of multiple stations based on computerized tomographic scanning and N2 of mediastinal lymph node mixed together. The different status of stage N2 lead to different prognosis. Andre et al reported the results of continuous surgery in 702 patients with NSCLC, which showed that N2 of single station based on microscope, 5-year survival rate was 34% （244 cases）, N2 of multiple stations based on microscope, 5-year survival rate was 11% （788 cases）, N2 of single station based on radiograph, 5-year survival rate was 8% （118 cases）,展开更多
Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer.Notably,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic types1.Precision therapy for lung cance...Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer.Notably,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic types1.Precision therapy for lung cancer has progressed rapidly and immune checkpoint inhibitors(ICIs)have become a leading research topic.Indeed,ICI therapy has been shown to improve the prognosis of lung cancer patients.展开更多
Backgroud and Objective At present, lung cancer has become the most frenquent malignant tumor in China and in the world which its mortality and morbidity is increasing fastest.
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...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.展开更多
AIM To assess the validity and reliability of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer 29 (EORTC QLQ-CR29) in Chinese patients with colorectal canc...AIM To assess the validity and reliability of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer 29 (EORTC QLQ-CR29) in Chinese patients with colorectal cancer (CRC). METHODS From March 2014 to January 2015, 356 patients with CRC from four different hospitals in China were enrolled in the study, and all patients self-administered the EORTC QLQ-CR29 and the quality of life core questionnaire (EORTC QLQ-C30). Evaluation of the scores was based on the Karnofsky Performance Scale (KPS). The reliability and validity of the questionnaires were assessed by Cronbach's proportional to coefficient, the Spearman correlation test and Wilcoxon rank sum test. RESULTS The EORTC QLQ-CR29 showed satisfactory reliability (proportional to > 0.7), although the urinary frequency and blood and mucus in stool dimensions had only moderate reliability (proportional to = 0.608). The multitrait scaling analyses showed good convergent (r > 0.4) and discriminant validity. Significant differences were obtained for each item in the different KPS subgroups (KPS <= 80; KPS > 80). Body image and most single- item dimensions showed statistically significant differences in patients with a stoma compared with the rest of the patients. CONCLUSION The EORTC QLQ-CR29 exhibits high validity and reliability in Chinese patients with CRC, and can therefore be recommended as a valuable tool for the assessment of quality of life in these patients.展开更多
Background:The aberrant intraellular expression of a mitochondrial aspartyl tRNA synthetase 2(DARS2)has been reported in human cancers.Nevertheless its critical role and detailed mechanism in lung adenocarcinoma(LUAD)...Background:The aberrant intraellular expression of a mitochondrial aspartyl tRNA synthetase 2(DARS2)has been reported in human cancers.Nevertheless its critical role and detailed mechanism in lung adenocarcinoma(LUAD)remain unexplored.Methods:Initially,The Cancer Genome Atlas(TCGA)based Gene Expression Profiling Interactive Analysis(GEPIA)database (http:/gepia.cancer-pku.cn/)was used to analyze the prognostic relevance of DARS2 expression in LUAD.Further,cell counting kit(CCK)8,immunostaining,and transwell invasion assays in LUAD cell lines in vitro,as well as DARS2 silence on LUAD by tumorigenicity experiments in wivo in nude mice,were performed.Besides,we analyzed the expression levels of p-PI3K(phosphorylated Phosphotylinosital3 kinase),PI3K,AKT(Protein Kinase B),p-AKT(phosphorylated Protein Kinase B),PCNA(proliferating cell nudear antigen),cleaved-caspase 3,E cadherin,and N-cadherin proteins using the Westem blot analysis.Results:LUAD tissues showed higher DARS2 expression compared to normal tissues.Upregulation of DARS2 could be related to Tumor-Node-Metastasis(TNM)stage,high lymph node metastasis,and inferior prognosis.DARS2 silence decreased the proliferation,migration,and invasion abilities of LUAD cells.In addition,the DARS2 downregulation decreased the PCNA and N-cadherin expression and increased cleaved:caspase 3 and E cadherin expressions in LUAD cells,coupled with the inactivation of the PI3K/AKT signaling pathway.Moreover,DARS2 silence impaired the tumonigenicity of LUAD in vivo.Interestingly,let:7b-5p could recognize DARS2 through a complementary sequence.Mechanistically,the increased let 7b 5p expression attenuated the promo oncogenic action of DARS2 during LUAD progression,which were inversely correlated to each other in the LUAD tssues Conclusion:In summary,let 7b-5p,downregulated DARS2 expression,regulating the progression of LUAD cells by the PI3K/AKT signaling pathway.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82172635,82272686,and 82203628)Natural Science Foundation of Tianjin(Grant No.23JCZDJC00200)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-010A).
文摘Introduction Small cell lung cancer(SCLC)is a highly aggressive malignancy with limited treatment options.Despite advances in immunotherapy,response rates remain low,and the efficacy of current molecular subtyping1,2 is insufficient to predict therapeutic outcomes3,4.A recently identified vulnerability in SCLC involves the dysregulation of nuclear-cytoplasmic transport,particularly through exportin 1(XPO1)5-7.
基金supported in part by grants from National Natural Science Foundation of China(Grant Nos.82172635,82272686,and 82203628)the Natural Science Foundation of Tianjin(Grant Nos.23JCZDJC00200 and 21JCYBJC01000)the Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-010A).
文摘Objective:This study aimed at exploring the effects of the epigenetic regulator,chidamide,on reprogramming the immunosuppressive tumor microenvironment in small cell lung cancer(SCLC),particularly the roles in macrophage polarization and angiogenesis.The therapeutic efficacy of combining chidamide with the anti-angiogenic agent,anlotinib,for refractory SCLC was also evaluated.Methods:RNA sequencing and functional validation were performed to assess chidamide’s effects on macrophages.Signal transducer and activator of transcription 4(STAT4)-mediated transcriptional activation of CCL2 was confirmed with ChIP-qPCR.The synergistic efficacy of chidamide in combination with anlotinib was tested in preclinical models.Results:Chidamide enhanced macrophage infiltration and induced macrophage polarization toward the anti-tumor M1 phenotype.Mechanistically,chidamide upregulated CCL2 via STAT4 transcriptional activation,thereby reshaping the tumor immune microenvironment(TIME).Combining chidamide with anlotinib synergistically suppressed tumor growth and remodeled the immunosuppressive TME in SCLC in vivo.Conclusions:Chidamide reshaped the SCLC TIME by activating STAT4/CCL2,thus driving M1 macrophage polarization and enhancing anti-tumor immunity.Our findings highlight coordinated TIME-targeted therapy as a translatable strategy to overcome therapeutic resistance in SCLC and provide a rationale for clinical trials examining epigenetic and anti-angiogenic therapeutics combinations.
基金supported by grants from National Key R&D Program of China (Grant No. 2016YFC0905501)the Tianjin Science and Technology Major Project, China (Grant No. 12ZCDZSY15400)
文摘Objective:Cancer-associated inflammation and coagulation cascades play vital roles in cancer progression and survival.In this study,we investigated the significance of the combination of preoperative fibrinogen and the neutrophil-to-lymphocyte ratio(NLR)in predicting the survival of patients with non-small cell lung cancer(NSCLC).Methods:We retrospectively enrolled 589 patients with NSCLC who underwent surgery.The univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators,including the combination of fibrinogen and NLR(F-NLR).The cut-off values for fibrinogen,NLR,and clinical laboratory variables were defined by the receiver operating characteristic(ROC)curve analysis.According to the ROC curve,the recommended cut-off values for fibrinogen and the NLR were 3.48 g/L and 2.30,respectively.Patients with both a high NLR(≥2.30)and hyperfibrinogenemia(≥3.48 g/L)were given a score of 2,whereas those with one or neither were scored as 1 or 0,respectively.Results:Our results showed that F-NLR was an independent prognostic indicator for disease-free survival(DFS)[hazard ratio(HR),1.466;95%confidence interval(CI),1.243–1.730;P<0.001]and overall survival(OS)(HR,1.512;95%CI,1.283–1.783;P<0.001).The five-year OS rates were 66.1%,53.5%,and 33.3%for the F-NLR=0,F-NLR=1,and F-NLR=2,respectively(P<0.001).Correspondingly,their five-year DFS rates were 62.2%,50.3%,and 30.4%,respectively(P<0.001).In the subgroup analyses of the pathological stages,the F-NLR level was significantly correlated with DFS and OS in stage I and IIIA cancers.Conclusions:Preoperative F-NLR score can be used as a valuable prognostic marker for patients with resectable early-stage NSCLC.
文摘Objective： Increasing numbers of cancer patients are using Chinese herbs （CHs）. However, differences among prior studies make it difficult to draw firm conclusions about the clinical usefulness of any specific CH formula. The primary objective of this study was to establish the acceptability of taking a standardized CH formula for patients with advanced lung cancer. The secondary objective was to identify any toxicities attributable to this CH formula and to measure changes in quality of life. Methods： A single-arm, prospective study of a 6-week intervention with a selected CH formula in 15 patients with stage 4 nonsmall-cell lung cancer （NSCLC, Seventh American Joint Committee on Cancer TNM staging system）. Results： Patients with advanced lung cancer were interested in using the CH formula. Completion （93%） and adherence （98%） levels were very high and most patients perceived the CH treatment as easy to take and were willing to take the CHs used in the study again if it was available. About half of the patients reported adverse events, all of which were mild （Grade 1 or 2） and only a small minority （8%） were poten- tially related to CHs. No biochemical or hematological evidence of toxicity was observed. Overall, there were improvement in quality of life, and reduced feelings of tiredness and sleepiness. Conclusion： This study provides preliminary evidence that short-term use of a carefully selected and pre- pared CH formula in patients with stage 4 NSCLC is acceptable and safe.
基金supported by the Key Problem Tackling Project for Cancer Therapy, China (Grant No. 12ZCDZSY15600)
文摘Objective: Chemotherapy is the standard treatment for small-cell lung cancer (SCLC), and leukopenia is a common side effect. This study assesses whether chemotherapy-induced leukopenia is a predictor of efficacy and whether it is associated with the survival of SCLC patients. Methods: A retrospective analysis was conducted on data from 445 patients with SCLC who received standard chemotherapy for 4 to 10 cycles. The World Health Organization grading system classifies leukopenia during chemotherapy as follows: absent (grade 0), mild (grades 1 and 2), or severe (grades 3 and 4). The primary endpoint is overall survival (OS). Results: The association between chemotherapy-induced leukopenia and OS was assessed. According to a multivariate Cox model with time-varying covariates, the hazard ratio of death was significantly lower among patients with mild leukopenia than among patients with severe leukopenia at 0.687 (0.506 to 0.943) and 1.414 (1.147 to 1.744), respectively. The median survival was 13 months (95% CI: 11 to 15 months) for patients who did not experience leukopenia, 17 months (95% CI: 14 to 18 months) for those with mild leukopenia, and 14 months (95% CI: 13 to 16 months) for those with severe leukopenia (absent vs. mild vs. severe leukopenia, P=0.047). Conclusion: Leukopenia during chemotherapy is associated with the survival of SCLC patients. Mild leukopenia is strongly associated with longer survival time.
文摘A 65-year-old man with right central type of lung squamous carcinoma was admitted to our department.Bronchoscopy displayed complete obstruction of right upper lobe bronchus and infiltration of the bronchus intermedius with tumor.Chest contrast computed tomography revealed the tumor invaded right pulmonary artery,superior vena cava,and the persistant left superior vena cava flowed into the coronary sinus.The tumor was successfully removed by means of bronchial and pulmonary artery sleeve resection of the right upper and middle lobes combined with resection and reconstruction of superior vena cava(SVC)utilizing ringed polytetrafluoroethylene graft.To the best of our knowledge,this was the first report of complete resection of locally advanced lung cancer involving superior vena cava,right pulmonary artery trunk and main bronchus with persistant left superior vena cava.
基金Supported by Youth Foundation of Shanghai Municipal Public Health Bureau,No.20124Y114Shanghai Chest Hospital"1050 Talents Project",ChinaProject of Shanghai Chest Hospital,No.YZ13-16
文摘Genome-wide association studies revealed that allelic variation in the α5-α3-β4 nicotine acetylcholine receptor(n ACh R) cluster on chromosome 15q24-15q25.1 was associated with lung cancer risk. n ACh Rs are membrane ligand-gated cation channels whose activation is triggered by the binding of the endogenous neurotransmitter acetylcholine(ACh) or other biologic compounds including nicotine. n ACh Rs have been found on lung cancer cells, underscoring the idea that the non-neuronal n ACh R pathway has important implications for lung cancer. Several studies focusing on the treatment with n ACh R antagonists with improved selectivity might trigger novel strategies for the intervention and prevention of lung cancer. Here we review the genetic risk factors for lung cancer in the n ACh R gene cluster, the roles of nicotine receptors, and the molecular mechanisms of acetylcholine receptor pathways to lead to more opportunities for intervention and prevention of lung cancer.
基金supported by the National Key R&D Program of China(Grant No.2016YFC1303800)。
文摘Objective:Dysfunction in fibroblast growth factor receptor(FGFR)signaling has been reported in diverse cancer types,including non-small cell lung cancer(NSCLC).The frequency of FGFR aberrations in Chinese NSCLC patients is therefore of great clinical significance.Methods:A total of 10,966 NSCLC patients whose tumor specimen and/or circulating cell-free DNA(cf DNA)underwent hybridization capture-based next-generation sequencing were reviewed.Patients'clinical characteristics and treatment histories were also evaluated.Results:FGFR aberrations,including mutations,fusions,and gene amplifications,were detected in 1.9%(210/10,966)of the population.FGFR abnormalities were more frequently observed in lung squamous cell carcinomas(6.8%,65/954)than lung adenocarcinomas(1.3%,128/9,596).FGFR oncogenic mutations were identified in 19 patients(~0.17%),of which,68%were male lung squamous cell carcinoma patients.Eleven out of the 19 patients(58%)had concurrent altered PI3 K signaling,thus highlighting a potential combination therapeutic strategy of dual-targeting FGFR and PI3 K signaling in such patients.Furthermore,FGFR fusions retaining the intact kinase domain were identified in 12 patients(0.11%),including 9 FGFR3-TACC3,1 FGFR2-INA,1 novel FGFR4-RAPGEFL1,and 1 novel fusion between the FGFR1 and SLC20 A25′-untranslated regions,which may have caused FGFR1 overexpressions.Concomitant EGFR mutations or amplifications were observed in 6 patients,and 4 patients received anti-EGFR inhibitors,in whom FGFR fusions may have mediated resistance to anti-EGFR therapies.FGFR amplification was detected in 24 patients,with the majority being FGFR1 amplifications.Importantly,FGFR oncogenic mutations,fusions,and gene amplifications were almost always mutually exclusive events.Conclusions:We report the prevalence of FGFR anomalies in a large NSCLC population,including mutations,gene amplifications,and novel FGFR fusions.
文摘Objective: To identify clinical and pathologic factors that were associated with the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients. Methods: A retrospective study of 147 subjects who had undergone curative resection for stage IB upper lobe NSCLC was performed. Patients who had received any adjuvant or neo-adjuvant chemotherapy were excluded. Survival function curves were estimated using the Kaplan-Meier procedure. Crude and adjusted hazard ratios (HRs) of potential prognostic factors were estimated using Cox proportional hazards models. Results: Five factors, including age, tumor size, histologic grade of differentiation, number of removed superior mediastinal lymph node stations and presence of visceral pleura invasion, were significantly and independently associated with mortality risk. Adjusted HRs were 2.6 [95% confidence interval (95% CI): 1.1?6.5] and 4.6 (95% CI: 1.9?11) for those aged 58?68 years and those >68 years, respectively, relative to those aged <58 years. HRs for those with poorly and moderately differentiated tumors were 6.4 (95% CI: 2.3?18) and 1.4 (95% CI: 0.7?2.8), respectively. HRs for those with tumor size 3.1?5 cm and >5 cm (vs ?3.0 cm) were 2.3 (95% CI: 1.1?4.9) and 4.3 (95% CI: 1.9?10), respectively. The presence of visceral pleura invasion also increased the risk of mortality (HR=4.0, 95% CI: 1.3?12). Conclusion: Advanced age, larger tumor size, poorly differentiated histology, smaller number of removed superior mediastinal lymph node stations, and presence of visceral pleura invasion were associated with poor survival of surgically treated stage IB upper lobe NSCLC patients.
文摘Background:Baoyuan decoction is used clinically as an adjuvant treatment for lung cancer.However,the underlying mechanism remains unclear.Therefore,this study aimed to explore the mechanism of action of Baoyuan decoction in lung cancer treatment using network pharmacology and molecular docking technology.Methods:The Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction databases were used to screen the active ingredients of Baoyuan decoction and their relevant targets.Lung cancer-related targets were obtained from the GeneCards,Online Mendelian Inheritance in Man,and DrugBank databases.Protein-protein interaction network of the common targets was constructed using the STRING database and analyzed using Cytoscape software 3.10.1.Furthermore,Gene Ontology enrichment,Kyoto Encyclopedia of Genes and Genomes pathway analyses and visualization of common genes were performed using the R software.Finally,molecular docking of the selected key ingredients and targets was performed,and the results were verified using AutoDock Vina software.Results:We identified 142 potential active ingredients,3624 potential lung cancer-related targets,and 341 common drug targets.A total of 72 core targets were identified,of which AKT1,TP53,interleukin-6,epithelial growth factor receptor,and signal transducer and activator of transcription 3 were key.A total of 4116 items were obtained via Gene Ontology enrichment analyses.Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 189 related signaling pathways,including the PI3K-Akt,AGE-RAGE signaling pathways in diabetic complications,FOXO,and TH signaling pathways,which are involved in cell proliferation,autophagy,metastasis,invasion,radiation resistance,and chemotherapy resistance in the lung cancer microenvironment.The molecular docking results suggested that the key ingredients had a strong affinity for key targets.Conclusion:This study demonstrates that Baoyuan decoction plays a key therapeutic role in a complex manner involving multiple ingredients,targets,and pathways in lung cancer.Our findings are anticipated to provide new ideas for follow-up experimental research and clinical application.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
文摘BACKGROUND Life-threatening hypoxia can occur in patients with lung cancer due to bronchial obstruction.Extracorporeal membrane oxygenation(ECMO)can be used as a bridge therapy for patients with severe hypoxia not relieved by conventional mechanical treatment.However,the usefulness of chemotherapy in patients with lung cancer receiving ECMO therapy is not well known.CASE SUMMARY A 53-year-old man visited the emergency room with worsening dyspnea for 1 mo.A series of imaging and diagnostic tests were performed,and stageⅢB(cT4N2M0)lung cancer was eventually diagnosed.On hospital day 3,he experienced dyspnea and hypoxia that was not relieved with oxygen support via a high-flow nasal cannula.ECMO was initiated because his respiratory condition did not improve even with mechanical ventilation.The patient then underwent gemcitabine/cisplatin chemotherapy without dose reduction while on ECMO.After two cycles of chemotherapy,there was a decrease in the size of the primary tumor in the right main bronchus.After the completion of concurrent chemoradiotherapy,a computed tomography scan revealed further improvement in the right main bronchus narrowing.Eight months after a lung cancer diagnosis,the patient did well without any dyspnea.CONCLUSION ECMO is a potential bridge therapy for respiratory failure in patients with central airway obstruction secondary to lung cancer.
文摘As a targeted therapy, antiangiogenic treatment has been increasingly studied for advanced non-small cell lung cancer(NSCLC) and has proven effective for the treatment of advanced NSCLC. Bevacizumab, a monoclonal antibody targeting angiogenesis, is the only antiangiogenic agent approved for use in combination with first-line chemotherapy for non-squamous NSCLC. Small-molecule inhibitors targeting the tyrosine kinase receptor have also shown promise when combined with standard chemotherapeutic agents in patients with advanced NSCLC. However, unlike bevacizumab, not all other antiangiogenic agents show significant benefits when combined with chemotherapy. As for the failures of most other combinations, the combination schedule may be an important reason that has so far been overlooked in clinical trials. This article reviews the combination of angiogenic agents with chemotherapy in the treatment of NSCLC.
文摘OBJECTIVE To investigate whether CXCL12 and its receptor, CXCR7, play a role in lung cancer invasion and metastasis. METHODS Western blot and immunocytochemistry were used to detect CXCR7 protein expression in 8 lung cancer cell lines, EKVX, HOP62, HOP92, NCI-H23, NCI-H226, NCI- H322M, NCI-H446, and A549, and cell migration experiment was conducted to observe mobility of the lung cancer cells. The concentration of intracellular calcium in cytoplasm was measured under the fluorescence microscopy. RESULTS CXCR7 protein was positively expressed in the 8 lung cancer cell lines EKVX, HOP62, HOP92, NCI-H23, NCI-H226, NCI- H322M, NCI-H446, and A549. Following CXCL12 stimulation, obvious pseudopodia of lung cancer cells was observed under the microscope. The cell migration experiment showed that after incubation with CXCL12, the number of EKVX cells, which passed through the polycarbonate microporous filter membranes increased to a great extent. This phenomenon can be reversed by CXCR7-siRNA. After CXCL12 incubation, the intracellular Ca2＋ level in the EKVX cells was increased to a great extent. CONCLUSION Chemokine CXCL12 facilitates the migration of lung cancer cells by changing the concentration of intracellular Ca2＋. The CXCL12-CXCR7 axis may play an important role in lung cancer invasion and metastasis. It could be a potential target for lung cancer therapy and an effective way to prevent recurrence and metastasis of lung cancer.
文摘Patients with stage Ⅲ N2 non-small cell lung cancer （NSCLC） are more than one third of all NSCLC patients. The 5-year survival rate of them is approximately 15%. From therapeutic views, stage ⅢA N2 of 97 International Lung Cancer Staging System is an obvious hetero-combination, which includes mediastinal lymph node metastasis based on microscope after postoperative examination and N2 of single station or N2 of multiple stations based on computerized tomographic scanning and N2 of mediastinal lymph node mixed together. The different status of stage N2 lead to different prognosis. Andre et al reported the results of continuous surgery in 702 patients with NSCLC, which showed that N2 of single station based on microscope, 5-year survival rate was 34% （244 cases）, N2 of multiple stations based on microscope, 5-year survival rate was 11% （788 cases）, N2 of single station based on radiograph, 5-year survival rate was 8% （118 cases）,
基金the Hunan Lung Cancer Clinical Medical Research Center(Grant No.2023SK4024 to LW)the Hunan Science and Technology Innovation Program(Grant No.2021SK51121 to LW)the Hunan Cancer Hospital Climb plan(Grant No.ZX2020005-5 to LW)。
文摘Global Cancer Statistics 2022 reported the prevalence and high mortality rate of lung cancer.Notably,non-small cell lung cancer(NSCLC)accounts for the majority of the histologic types1.Precision therapy for lung cancer has progressed rapidly and immune checkpoint inhibitors(ICIs)have become a leading research topic.Indeed,ICI therapy has been shown to improve the prognosis of lung cancer patients.
基金supported by the Key Project of National Natural Sciences Fundation of China (to Qinghua ZHOU) (No. 30430300)grant from the National Natural Science Foundation of China. ( to Qinghua ZHOU)(No.3007033 )
文摘Backgroud and Objective At present, lung cancer has become the most frenquent malignant tumor in China and in the world which its mortality and morbidity is increasing fastest.
基金funded by F. Hoffmann-La Roche Ltd. F. Hoffmann-La Roche Ltd sponsored the IMpower210 study。
文摘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.
基金Supported by Science&Technology Innovation Commission of Shenzhen(to Lin JB)No.201404113000346 and No.JCYJ20140411150916744+1 种基金the Science &Technology Project of Shenzhen Longgang District,No.201406063001007 and No.YLWS20140606101914846the Science &Technology Project of Shenzhen Longgang District,No.20160607153104624(to Zhang YF)
文摘AIM To assess the validity and reliability of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer 29 (EORTC QLQ-CR29) in Chinese patients with colorectal cancer (CRC). METHODS From March 2014 to January 2015, 356 patients with CRC from four different hospitals in China were enrolled in the study, and all patients self-administered the EORTC QLQ-CR29 and the quality of life core questionnaire (EORTC QLQ-C30). Evaluation of the scores was based on the Karnofsky Performance Scale (KPS). The reliability and validity of the questionnaires were assessed by Cronbach's proportional to coefficient, the Spearman correlation test and Wilcoxon rank sum test. RESULTS The EORTC QLQ-CR29 showed satisfactory reliability (proportional to > 0.7), although the urinary frequency and blood and mucus in stool dimensions had only moderate reliability (proportional to = 0.608). The multitrait scaling analyses showed good convergent (r > 0.4) and discriminant validity. Significant differences were obtained for each item in the different KPS subgroups (KPS <= 80; KPS > 80). Body image and most single- item dimensions showed statistically significant differences in patients with a stoma compared with the rest of the patients. CONCLUSION The EORTC QLQ-CR29 exhibits high validity and reliability in Chinese patients with CRC, and can therefore be recommended as a valuable tool for the assessment of quality of life in these patients.
文摘Background:The aberrant intraellular expression of a mitochondrial aspartyl tRNA synthetase 2(DARS2)has been reported in human cancers.Nevertheless its critical role and detailed mechanism in lung adenocarcinoma(LUAD)remain unexplored.Methods:Initially,The Cancer Genome Atlas(TCGA)based Gene Expression Profiling Interactive Analysis(GEPIA)database (http:/gepia.cancer-pku.cn/)was used to analyze the prognostic relevance of DARS2 expression in LUAD.Further,cell counting kit(CCK)8,immunostaining,and transwell invasion assays in LUAD cell lines in vitro,as well as DARS2 silence on LUAD by tumorigenicity experiments in wivo in nude mice,were performed.Besides,we analyzed the expression levels of p-PI3K(phosphorylated Phosphotylinosital3 kinase),PI3K,AKT(Protein Kinase B),p-AKT(phosphorylated Protein Kinase B),PCNA(proliferating cell nudear antigen),cleaved-caspase 3,E cadherin,and N-cadherin proteins using the Westem blot analysis.Results:LUAD tissues showed higher DARS2 expression compared to normal tissues.Upregulation of DARS2 could be related to Tumor-Node-Metastasis(TNM)stage,high lymph node metastasis,and inferior prognosis.DARS2 silence decreased the proliferation,migration,and invasion abilities of LUAD cells.In addition,the DARS2 downregulation decreased the PCNA and N-cadherin expression and increased cleaved:caspase 3 and E cadherin expressions in LUAD cells,coupled with the inactivation of the PI3K/AKT signaling pathway.Moreover,DARS2 silence impaired the tumonigenicity of LUAD in vivo.Interestingly,let:7b-5p could recognize DARS2 through a complementary sequence.Mechanistically,the increased let 7b 5p expression attenuated the promo oncogenic action of DARS2 during LUAD progression,which were inversely correlated to each other in the LUAD tssues Conclusion:In summary,let 7b-5p,downregulated DARS2 expression,regulating the progression of LUAD cells by the PI3K/AKT signaling pathway.
