In China,lung cancer is a primary cancer type with high incidence and mortality.Risk factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung diseases.Most early-...In China,lung cancer is a primary cancer type with high incidence and mortality.Risk factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung diseases.Most early-stage non-small cell lung cancer(NSCLC)patients miss the optimal timing for treatment due to the lack of clinical presentations.Population-based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in China.The understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC,thus prolonging survival in patients with positive drivers.In the exploration of immune escape mechanisms,programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1)inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in China.In the Chinese Society of Clinical Oncology’s guidelines for NSCLC,maintenance immunotherapy is recommended for locally advanced NSCLC after chemoradiotherapy.Adjuvant immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable NSCLC.In this review,we summarized recent advances in NSCLC in China in terms of epidemiology,biology,molecular pathology,pathogenesis,screening,diagnosis,targeted therapy,and immunotherapy。展开更多
The successes achieved by chimeric antigen receptor-modified T （CAR-T） cells in hematological malignancies raised the pos- sibility of their use in non-small lung cancer （NSCLC）. In this phase I clinical study （N...The successes achieved by chimeric antigen receptor-modified T （CAR-T） cells in hematological malignancies raised the pos- sibility of their use in non-small lung cancer （NSCLC）. In this phase I clinical study （NCT01869166）, patients with epidermal growth factor receptor （EGFR）-positive （〉50% expression）, relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECISTI.1 and im- mune-related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR＋ T cells was 0.97x 10^7 cells kg J （interquar- tile range （IQR）, 0.45 to 1.09x 10^7 cells kg 1）. Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced re- lapsed/refractory NSCLC.展开更多
Studies have shown cell-free microRNA(miRNA) circulating in the serum and plasma with specific expression in cancer,indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy.This study wa...Studies have shown cell-free microRNA(miRNA) circulating in the serum and plasma with specific expression in cancer,indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy.This study was to investigate whether plasma miRNA-21(miR-21) can be used as a biomarker for the early detection of non-small cell lung cancer(NSCLC) and to explore its association with clinicopathologic features and sensitivity to platinum-based chemotherapy.We used real-time RT-PCR to investigate the expression of miR-21 in the plasma of 63 NSCLC patients and 30 healthy controls and correlated the findings with early diagnosis,pathologic parameters,and treatment.Thirty-five patients(stages IIIB and IV) were evaluable for chemotherapeutic responses:11 had partial response(PR);24 had stable and progressive disease(SD+PD).Plasma miR-21 was significantly higher in NSCLC patients than in age-and sex-matched controls(P<0.001).miR-21 was related to TNM stage(P<0.001),but not related to age,sex,smoking status,histological classification,lymph node status,and metastasis(all P>0.05).This marker yielded a receiver operating characteristic(ROC) curve area of 0.775(95% CI:0.681-0.868) with 76.2% sensitivity and 70.0% specificity.Importantly,miR-21 plasma levels in PR samples were several folds lower than that in SD plus PD samples(P=0.049),and were close to that in healthy controls(P=0.130).Plasma miR-21 can serve as a circulating tumor biomarker for the early diagnosis of NSCLC and is related to the sensitivity to platinum-base chemotherapy.展开更多
OBJECTIVE: To investigate the effect of thorascopic administration of ginseng polysaccharides(GPS)plus dendritic cells(DC) on T helper cell type 1/T helper cell type 2(Th1/Th2) balance in patients with non-small cell ...OBJECTIVE: To investigate the effect of thorascopic administration of ginseng polysaccharides(GPS)plus dendritic cells(DC) on T helper cell type 1/T helper cell type 2(Th1/Th2) balance in patients with non-small cell lung cancer(NSCLC).METHODS: A total of 96 NSCLC patients were divided evenly into two groups. The control group was treated with DCs alone and the treatment group was treated with DCs plus GPS. After DCs and GPS were administered thoracoscopically, once a week,4 times for 30 days, the patients' quality of life was measured with the Functional Assessment of Can-cer Treatment-Lung(FACT-L) questionnaire before and after treatment. Serum interferon-γ(INF-γ), interleukin-4(IL-4), IL-2 and IL-5 were examined before and after treatments.RESULTS: The level of Th1 cytokines(INF-γ, IL-2)and the ratio of Th1/Th2 cytokines(INF-γ/IL-4, IL-2/IL-5) increased in both treatment groups, while Th2cytokines(IL-4, IL-5) and FACT-L scores decreased(P<0.01). Furthermore, after treatment Th1 cytokines(INF-γ, IL-2) and the ratio of Th1/Th2 cytokines(INF-γ/IL-4, IL-2/IL-5) were higher in the DCs +GPS group than in the control group(P<0.05). Conversely, FACT-L scores and Th2 cytokines(IL-4, IL-5)were higher in the control group than in the DCs +GPS group(P<0.05).CONCLUSION: The treatment regime of DCs plus GPS had a greater effect on NSCLC patients' immune function as compared with DCs alone. This was evident by increased expression of Th1 cytokines(INF-γ, IL-2) and the ratio of Th1/Th2(INF-γ/IL-4, IL-2/IL-5), as well as by decreased FACT-L scores and the expression of Th2 cytokines(IL-4,IL-5).展开更多
Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung ca...Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung can-cer(NSCLC)who have progressed after treatment with two or more lines of prior systemic chemotherapy.Main body of the abstract:China NMPA reviewed and inspected a regional double-blinded,placebo-controlled,Phase III trial comparing the overall survival(OS)of NSCLC patients between the anlotinib and placebo arms.A total of 437 patients were randomized(2:1)to receive either anlotinib(n=294)or placebo(n=143)once daily on a 2-week on and 1-week off schedule.Patients with epidermal growth factor receptor(EGFR)or activating anaplastic lymphoma kinase(ALK)genomic tumor aberrations should have disease progression on NMPA-approved therapy.Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China.The approval was based on a statistically and clinically significant improvement in median OS with anlotinib(9.46 months)compared with placebo[6.37 months;hazard ratio(HR])=0.70,95%confidence interval(CI)=0.55-0.89;two-sided log-rank P=0.002].The confirmed objective response rate(ORR)was 9.2%in the anlotinib arm and 0.7%in the placebo arm.The median duration of response(DoR)was 4.83 months,with a 95%CI of 3.31-6.97 months.The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors.Common adverse drug reactions(ADRs)in anlotinib-treated patients included hypertension(67.4%),hand-foot syndrome(43.9%),hemoptysis(14.0%),thyroid stimulating hormone(TSH)elevation(46.6%),and corrected QT interval(QTc)prolongation(26.2%).Short conclusion:Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.展开更多
Immune checkpoint inhibitors(ICIs)are new and promising therapeutic agents for non-small cell lung cancer(NSCLC).However,along with demonstrating remarkable efficacy,ICIs can also trigger immune-related adverse events...Immune checkpoint inhibitors(ICIs)are new and promising therapeutic agents for non-small cell lung cancer(NSCLC).However,along with demonstrating remarkable efficacy,ICIs can also trigger immune-related adverse events.Checkpoint inhibitor pneumonitis(CIP)has been reported to have a morbidity rate of 3%to 5%and a mortality rate of 10%to 17%.Moreover,the incidence of CIP in NSCLC is higher than that in other tumor types,reaching 7%to 13%.With the increased use of ICIs in NSCLC,CIP has drawn extensive attention from oncologists and cancer researchers.Identifying high risk factors for CIP and the potential mechanism of CIP are key points in preventing and monitoring serious adverse events.In this review,the results of our analysis and summary of previous studies suggested that the risk factors for CIP may include previous lung disease,prior thoracic irradiation,and combinations with other drugs.Our review also explored potential mechanisms closely related toCIP,including increasedT cell activity against associated antigens in tumor and normal tissues,preexisting autoantibodies,and inflammatory cytokines.展开更多
OBJECTIVE: To observe effect of compound Kushen injection on T-cell subgroups and NK cells in patients with locally advanced non-small-cell lung cancer(NSCLC) treated with concomitant radiochemotherapy.METHODS: We ran...OBJECTIVE: To observe effect of compound Kushen injection on T-cell subgroups and NK cells in patients with locally advanced non-small-cell lung cancer(NSCLC) treated with concomitant radiochemotherapy.METHODS: We randomly divided 60 patients with locally advanced NSCLC who were treated at our hospital between May 2011 and May 2013 into a treatment group and a control group by drawing.The treatment group(n = 30) received concomitant radiochemotherapy plus compound Keshen injection, and the control group(n = 30) received only radiochemotherapy.RESULTS: After treatment, levels of CD3+, CD4+,CD4 +/CD8 + and CD16 +/CD56 + cells had significantly increased, and CD8 + cells had significantly decreased, in the treatment group compared with both their pretreatment levels and with levels in the control group. In the control group, post-treatment levels of CD3 +, CD4 +, CD4 +/CD8 + and CD16+/CD56+ cells were not significantly changed from pretreatment levels. The two groups did not significantly differ in their rates of toxicity reactions(P > 0.05).CONCLUSION: Compound Kushen injections can increase immunologic function in patients with locally advanced non-small cell lung cancer who receive concomitant radiochemotherapy.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
Lung cancer mortality has decreased over the past decade and can be partly attributed to advances in targeted therapy and immunotherapy.Immune checkpoint inhibitors(ICIs)have rapidly evolved from investigational drugs...Lung cancer mortality has decreased over the past decade and can be partly attributed to advances in targeted therapy and immunotherapy.Immune checkpoint inhibitors(ICIs)have rapidly evolved from investigational drugs to standard of care for the treatment ofmetastatic non-small cell lung cancer(NSCLC).In particular,antibodies that block inhibitory immune checkpoints,such as programmed cell death protein 1(PD-1)and programmed cell death 1 ligand 1(PD-L1),have revolutionized the treatment of advanced NSCLC,when administered alone or in combination with chemotherapy.Immunotherapy is associated with higher response rates,improved overall survival(OS),and increased tolerability compared with conventional cytotoxic chemotherapy.These benefits may increase the utility of immunotherapy and its combinational use with chemotherapy in the neoadjuvant treatment of patients with NSCLC.Early findings from various ongoing clinical trials suggest that neoadjuvant ICIs alone or combined with chemotherapy may significantly reduce systemic recurrence and improve long-term OS or cure rates in resectable NSCLC.Here we further summarize the safety and efficacy of various neoadjuvant treatment regimens including immunotherapy from ongoing clinical trials and elaborate the role of neoadjuvant immunotherapy in patients with resectable NSCLC.In addition,we discuss several unresolved challenges,including the evaluations to assess neoadjuvant immunotherapy response,the role of adjuvant treatment after neoadjuvant immunotherapy,the efficacy of treatment for oncogenic-addicted tumors,and predictive biomarkers.We also provide our perspective on ways to overcome current obstacles and establish neoadjuvant immunotherapy as a standard of care.展开更多
As a leading cause of cancer deaths worldwide, lung cancer is a collection of diseases with diverse etiologies which can be broadly classified into small-cell lung cancer （SCLC） and non-small-cell lung cancer （NSCL...As a leading cause of cancer deaths worldwide, lung cancer is a collection of diseases with diverse etiologies which can be broadly classified into small-cell lung cancer （SCLC） and non-small-cell lung cancer （NSCLC）. Lung cancer is characterized by genomic and epigenomic alterations; however, mechanisms underlying lung tumorigenesis remain to be elucidated. Long noncoding RNAs （lncRNAs） are a group of non-coding RNAs that consist of ≥ 200 nucleotides but possess low or no protein-coding potential. Accumulating evidence indicates that abnormal expression of lncRNAs is associated with tumorigenesis of various cancers, including lung cancer, through multiple biological mechanisms involving epigenetic, transcriptional, and post-transcriptional alterations. In this review, we highlight the expression and roles of lncRNAs in NSCLC and discuss their potential clinical applications as diagnostic or prognostic biomarkers, as well as therapeutic targets.展开更多
背景与目的:维甲酸/干扰素联合应用诱导细胞凋亡相关的基因(gene associated with retinoid-interferon-induced mortality-19,GRIM-19)是死亡相关基因中的一员,它的过高表达可以抑制肿瘤细胞的增殖,促进细胞的凋亡。本研究检测非小细...背景与目的:维甲酸/干扰素联合应用诱导细胞凋亡相关的基因(gene associated with retinoid-interferon-induced mortality-19,GRIM-19)是死亡相关基因中的一员,它的过高表达可以抑制肿瘤细胞的增殖,促进细胞的凋亡。本研究检测非小细胞肺癌和正常肺组织中GRIM-19蛋白的表达和定位,探讨其在非小细胞肺癌组织中表达的临床意义。方法:应用免疫组化ABC法检测49例非小细胞肺癌组织及相应癌旁正常组织中GRIM-19蛋白的表达情况,并用光密度(A)值定量描述其表达水平;同时用激光共聚焦扫描技术检测GRIM-19蛋白在细胞内的定位。结果:正常肺组织中GRIM-19主要定位于细胞浆中;而肿瘤组织主要位于细胞核中。激光共聚焦扫描技术检测验证了这种结果。GRIM-19蛋白在正常肺组织中阳性率为93.8%(46/49),而在非小细胞肺癌中阳性率为55.1%(27/49),两者之间的差异有统计学意义(P<0.01)。肿瘤组织中GRIM-19蛋白的平均表达水平(A值为0.22±0.01)比正常组织(A值为0.29±0.02)下降24.3%(P<0.01)。GRIM-19蛋白阳性率在Ⅰ、Ⅱ、Ⅲ+Ⅳ期非小细胞肺癌组织中分别是78.6%、48.1%、12.5%,其差异有统计学意义(rs=-0.428,P<0.05)。结论:肺癌组织中GRIM-19蛋白表达随肿瘤恶性程度升高而显著下降甚至缺失,分布由胞浆转入细胞核;GRIM-19蛋白表达可能与肺癌的发生发展相关。展开更多
Objective： In the present study, we have examined the safety and efficacy of recombinant adenovirus encoding human p53 tumor suppressor gene （rAd-p53） injection in patients with advanced non-small-cell lung cancer ...Objective： In the present study, we have examined the safety and efficacy of recombinant adenovirus encoding human p53 tumor suppressor gene （rAd-p53） injection in patients with advanced non-small-cell lung cancer （NSCLC） in the combination with the therapy of bronchial arterial infusion （BAI）. Methods： A total of 58 patients with advanced NSCLC were enrolled in a non-randomized, two-armed clinical trial. Of which, 19 received a combination treatment of BAI and rAd-p53 （the combo group）, while the remaining 39 were treated with only BAI （the control group）. Patients were followed up for 12 months, with safety and local response evaluated by the National Cancer lnstitute＇s Common Toxicity Criteria and response evaluation criteria in solid tumor （RECIST）, respectively. Time to progression （TTP） and survival rates were also analyzed by Kaplan-Meier method. Results In the combo group, 19 patients received a total of 49 injections ofrAd-p53 and 46 times of BAI, respectively, while 39 patients in the control group received a total of 113 times of BAI. The combination treatment was found to have less adverse events such as anorexia, nausea and emesis, pain, and leucopenia （P〈0.05） but more arthralgia, fever, influenza-like symptom, and myalgia （P〈0.05）, compared with the control group. The overall response rates （complete response （CR）＋partial response （PR）） were 47.3% and 38.4% for the combo group and the control group, respectively （P〉0.05）. Patients in the combo group had a longer TTP than those in the control group （a median 7.75 vs 5.5 months, P-0.018）. However, the combination treatment did not lead to better survival, with survival rates at 3, 6, and 12 months in the combo group being 94.74%, 89.47%, and 52.63%, respectively, com- pared with 92.31%, 69.23%, and 38.83% in the control group （P=0.224）. Conclusion： Our results show that the combination of rAd-p53 and BAI was well tolerated in patients with NSCLC and may have improved the qual展开更多
Background The outcome of surgical treatment of non-small-cell lung cancer （NSCLC） remains poor. In many patients the biological behavior of NSCLC does not follow a definite pattern, and can not be accurately predic...Background The outcome of surgical treatment of non-small-cell lung cancer （NSCLC） remains poor. In many patients the biological behavior of NSCLC does not follow a definite pattern, and can not be accurately predicted before treatment. ^18F-fluoro-2-deoxy-glucose （^18F-FDG） uptake on positron-emission tomography （PET） is associated with the aggressiveness of NSCLC. The present study focused on the role of ^18F-FDG uptake in predicting the outcome of surgically treated patients with NSCLC. Methods A retrospective analysis was made of 82 patients who underwent complete resection and preoperative FDG PET. The maximum standardized uptake value （SUVmax）, in addition to five clinicopathological factors and three biomolecular factors, which could possibly influence survival, was compared for possible association with patients＇ recurrence and survival, by the Log-rank test in univariate analysis and the Cox proportional hazards model in multivariate analysis. The association between SUVmax and other factors was also analyzed. Results Patients with SUVmax more than 11 had a disease-free survival and overall survival shorter than patients with SUVmax less than 11 in univariate analyses （P〈0.001, P=0.002）. In the multivariate analysis, SUVmax （dichotomized by 11） was the only significant predictor for tumor recurrence. TNM stage and SUVmax （dichotomized by 11） were independent predictors for the overall survival. Associations of SUVmax with p53 overexpression, proliferating cell nuclear antigen （PCNA） labeling index and microvascular density of the tumor were significant in the entire group. Conclusions ^18F-FDG uptake on PET may be used to noninvasively assess biological aggressiveness of NSCLC in vivo, identifying the surgically-treated patients with poor prognosis who could benefit from additional therapy.展开更多
基金National Natural Science Foundation of China,Grant/Award Number:81871865Collaborative Innovation Program of Shanghai Municipal Health Commission,Grant/Award Number:2020CXJQ02Science and Technology Innovation Action Plan Project of Shanghai Municipal Science and Technology Commission,Grant/Award Numbers:19411950300,19411950301。
文摘In China,lung cancer is a primary cancer type with high incidence and mortality.Risk factors for lung cancer include tobacco use,family history,radiation exposure,and the presence of chronic lung diseases.Most early-stage non-small cell lung cancer(NSCLC)patients miss the optimal timing for treatment due to the lack of clinical presentations.Population-based nationwide screening programs are of significant help in increasing the early detection and survival rates of NSCLC in China.The understanding of molecular carcinogenesis and the identification of oncogenic drivers dramatically facilitate the development of targeted therapy for NSCLC,thus prolonging survival in patients with positive drivers.In the exploration of immune escape mechanisms,programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1)inhibitor monotherapy and PD-1/PD-L1 inhibitor plus chemotherapy have become a standard of care for advanced NSCLC in China.In the Chinese Society of Clinical Oncology’s guidelines for NSCLC,maintenance immunotherapy is recommended for locally advanced NSCLC after chemoradiotherapy.Adjuvant immunotherapy and neoadjuvant chemoimmunotherapy will be approved for resectable NSCLC.In this review,we summarized recent advances in NSCLC in China in terms of epidemiology,biology,molecular pathology,pathogenesis,screening,diagnosis,targeted therapy,and immunotherapy。
基金supported by the Science and Technology Planning Project of Beijing City (Z151100003915076)the National Natural Science Foundation of China (31270820, 81230061, 81472612, 81402566)+1 种基金the National Basic Science and Development Programme of China (2013BAI01B04)the Nursery Innovation Fund (15KMM50)
文摘The successes achieved by chimeric antigen receptor-modified T （CAR-T） cells in hematological malignancies raised the pos- sibility of their use in non-small lung cancer （NSCLC）. In this phase I clinical study （NCT01869166）, patients with epidermal growth factor receptor （EGFR）-positive （〉50% expression）, relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECISTI.1 and im- mune-related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR＋ T cells was 0.97x 10^7 cells kg J （interquar- tile range （IQR）, 0.45 to 1.09x 10^7 cells kg 1）. Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced re- lapsed/refractory NSCLC.
基金supported by grants from the National Natural Science Foundation of China(No.30772549)the Medical Sci-Tech Development Foundation from Health Department of Jiangsu Province(No.P200965)
文摘Studies have shown cell-free microRNA(miRNA) circulating in the serum and plasma with specific expression in cancer,indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy.This study was to investigate whether plasma miRNA-21(miR-21) can be used as a biomarker for the early detection of non-small cell lung cancer(NSCLC) and to explore its association with clinicopathologic features and sensitivity to platinum-based chemotherapy.We used real-time RT-PCR to investigate the expression of miR-21 in the plasma of 63 NSCLC patients and 30 healthy controls and correlated the findings with early diagnosis,pathologic parameters,and treatment.Thirty-five patients(stages IIIB and IV) were evaluable for chemotherapeutic responses:11 had partial response(PR);24 had stable and progressive disease(SD+PD).Plasma miR-21 was significantly higher in NSCLC patients than in age-and sex-matched controls(P<0.001).miR-21 was related to TNM stage(P<0.001),but not related to age,sex,smoking status,histological classification,lymph node status,and metastasis(all P>0.05).This marker yielded a receiver operating characteristic(ROC) curve area of 0.775(95% CI:0.681-0.868) with 76.2% sensitivity and 70.0% specificity.Importantly,miR-21 plasma levels in PR samples were several folds lower than that in SD plus PD samples(P=0.049),and were close to that in healthy controls(P=0.130).Plasma miR-21 can serve as a circulating tumor biomarker for the early diagnosis of NSCLC and is related to the sensitivity to platinum-base chemotherapy.
基金2011 National Key Specialty Construction of Clinical Projects of ChinaThe National Natural Science Foundation of China(No.81273639)Science and Technology Projects of Traditional Chinese Medicine Bureau in Jiangsu Province of China(No.LB13042)
文摘OBJECTIVE: To investigate the effect of thorascopic administration of ginseng polysaccharides(GPS)plus dendritic cells(DC) on T helper cell type 1/T helper cell type 2(Th1/Th2) balance in patients with non-small cell lung cancer(NSCLC).METHODS: A total of 96 NSCLC patients were divided evenly into two groups. The control group was treated with DCs alone and the treatment group was treated with DCs plus GPS. After DCs and GPS were administered thoracoscopically, once a week,4 times for 30 days, the patients' quality of life was measured with the Functional Assessment of Can-cer Treatment-Lung(FACT-L) questionnaire before and after treatment. Serum interferon-γ(INF-γ), interleukin-4(IL-4), IL-2 and IL-5 were examined before and after treatments.RESULTS: The level of Th1 cytokines(INF-γ, IL-2)and the ratio of Th1/Th2 cytokines(INF-γ/IL-4, IL-2/IL-5) increased in both treatment groups, while Th2cytokines(IL-4, IL-5) and FACT-L scores decreased(P<0.01). Furthermore, after treatment Th1 cytokines(INF-γ, IL-2) and the ratio of Th1/Th2 cytokines(INF-γ/IL-4, IL-2/IL-5) were higher in the DCs +GPS group than in the control group(P<0.05). Conversely, FACT-L scores and Th2 cytokines(IL-4, IL-5)were higher in the control group than in the DCs +GPS group(P<0.05).CONCLUSION: The treatment regime of DCs plus GPS had a greater effect on NSCLC patients' immune function as compared with DCs alone. This was evident by increased expression of Th1 cytokines(INF-γ, IL-2) and the ratio of Th1/Th2(INF-γ/IL-4, IL-2/IL-5), as well as by decreased FACT-L scores and the expression of Th2 cytokines(IL-4,IL-5).
基金This work was supported by the Grant from Chinese National Major Project for New Drug Innovation(Grant No.2017ZX09304015)
文摘Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung can-cer(NSCLC)who have progressed after treatment with two or more lines of prior systemic chemotherapy.Main body of the abstract:China NMPA reviewed and inspected a regional double-blinded,placebo-controlled,Phase III trial comparing the overall survival(OS)of NSCLC patients between the anlotinib and placebo arms.A total of 437 patients were randomized(2:1)to receive either anlotinib(n=294)or placebo(n=143)once daily on a 2-week on and 1-week off schedule.Patients with epidermal growth factor receptor(EGFR)or activating anaplastic lymphoma kinase(ALK)genomic tumor aberrations should have disease progression on NMPA-approved therapy.Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China.The approval was based on a statistically and clinically significant improvement in median OS with anlotinib(9.46 months)compared with placebo[6.37 months;hazard ratio(HR])=0.70,95%confidence interval(CI)=0.55-0.89;two-sided log-rank P=0.002].The confirmed objective response rate(ORR)was 9.2%in the anlotinib arm and 0.7%in the placebo arm.The median duration of response(DoR)was 4.83 months,with a 95%CI of 3.31-6.97 months.The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors.Common adverse drug reactions(ADRs)in anlotinib-treated patients included hypertension(67.4%),hand-foot syndrome(43.9%),hemoptysis(14.0%),thyroid stimulating hormone(TSH)elevation(46.6%),and corrected QT interval(QTc)prolongation(26.2%).Short conclusion:Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy.
基金This work was supported by a grant from the Wu Jieping Medical Foundation(Grant No.320675018288).
文摘Immune checkpoint inhibitors(ICIs)are new and promising therapeutic agents for non-small cell lung cancer(NSCLC).However,along with demonstrating remarkable efficacy,ICIs can also trigger immune-related adverse events.Checkpoint inhibitor pneumonitis(CIP)has been reported to have a morbidity rate of 3%to 5%and a mortality rate of 10%to 17%.Moreover,the incidence of CIP in NSCLC is higher than that in other tumor types,reaching 7%to 13%.With the increased use of ICIs in NSCLC,CIP has drawn extensive attention from oncologists and cancer researchers.Identifying high risk factors for CIP and the potential mechanism of CIP are key points in preventing and monitoring serious adverse events.In this review,the results of our analysis and summary of previous studies suggested that the risk factors for CIP may include previous lung disease,prior thoracic irradiation,and combinations with other drugs.Our review also explored potential mechanisms closely related toCIP,including increasedT cell activity against associated antigens in tumor and normal tissues,preexisting autoantibodies,and inflammatory cytokines.
文摘OBJECTIVE: To observe effect of compound Kushen injection on T-cell subgroups and NK cells in patients with locally advanced non-small-cell lung cancer(NSCLC) treated with concomitant radiochemotherapy.METHODS: We randomly divided 60 patients with locally advanced NSCLC who were treated at our hospital between May 2011 and May 2013 into a treatment group and a control group by drawing.The treatment group(n = 30) received concomitant radiochemotherapy plus compound Keshen injection, and the control group(n = 30) received only radiochemotherapy.RESULTS: After treatment, levels of CD3+, CD4+,CD4 +/CD8 + and CD16 +/CD56 + cells had significantly increased, and CD8 + cells had significantly decreased, in the treatment group compared with both their pretreatment levels and with levels in the control group. In the control group, post-treatment levels of CD3 +, CD4 +, CD4 +/CD8 + and CD16+/CD56+ cells were not significantly changed from pretreatment levels. The two groups did not significantly differ in their rates of toxicity reactions(P > 0.05).CONCLUSION: Compound Kushen injections can increase immunologic function in patients with locally advanced non-small cell lung cancer who receive concomitant radiochemotherapy.
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.
基金supported by the High-Level Hospital Construction Project(grant No.Dfjh201801)the National Natural Science Foundation of China(grant No.81872510 and 81802266)+2 种基金the Guangdong Provincial People’s Hospital Young Talent Project(grant No.Gdpphytp201902)the Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine(grant No.2017b030314120)the Guangdong Basic and Applied Basic Research Foundation(grant No.2019b1515130002).
文摘Lung cancer mortality has decreased over the past decade and can be partly attributed to advances in targeted therapy and immunotherapy.Immune checkpoint inhibitors(ICIs)have rapidly evolved from investigational drugs to standard of care for the treatment ofmetastatic non-small cell lung cancer(NSCLC).In particular,antibodies that block inhibitory immune checkpoints,such as programmed cell death protein 1(PD-1)and programmed cell death 1 ligand 1(PD-L1),have revolutionized the treatment of advanced NSCLC,when administered alone or in combination with chemotherapy.Immunotherapy is associated with higher response rates,improved overall survival(OS),and increased tolerability compared with conventional cytotoxic chemotherapy.These benefits may increase the utility of immunotherapy and its combinational use with chemotherapy in the neoadjuvant treatment of patients with NSCLC.Early findings from various ongoing clinical trials suggest that neoadjuvant ICIs alone or combined with chemotherapy may significantly reduce systemic recurrence and improve long-term OS or cure rates in resectable NSCLC.Here we further summarize the safety and efficacy of various neoadjuvant treatment regimens including immunotherapy from ongoing clinical trials and elaborate the role of neoadjuvant immunotherapy in patients with resectable NSCLC.In addition,we discuss several unresolved challenges,including the evaluations to assess neoadjuvant immunotherapy response,the role of adjuvant treatment after neoadjuvant immunotherapy,the efficacy of treatment for oncogenic-addicted tumors,and predictive biomarkers.We also provide our perspective on ways to overcome current obstacles and establish neoadjuvant immunotherapy as a standard of care.
基金supported by the National Natural Science Funds for Distinguished Young Scholar(Grant No.81425025)the National Basic Research Program of China(Grant No.2012CB910800)
文摘As a leading cause of cancer deaths worldwide, lung cancer is a collection of diseases with diverse etiologies which can be broadly classified into small-cell lung cancer （SCLC） and non-small-cell lung cancer （NSCLC）. Lung cancer is characterized by genomic and epigenomic alterations; however, mechanisms underlying lung tumorigenesis remain to be elucidated. Long noncoding RNAs （lncRNAs） are a group of non-coding RNAs that consist of ≥ 200 nucleotides but possess low or no protein-coding potential. Accumulating evidence indicates that abnormal expression of lncRNAs is associated with tumorigenesis of various cancers, including lung cancer, through multiple biological mechanisms involving epigenetic, transcriptional, and post-transcriptional alterations. In this review, we highlight the expression and roles of lncRNAs in NSCLC and discuss their potential clinical applications as diagnostic or prognostic biomarkers, as well as therapeutic targets.
文摘背景与目的:维甲酸/干扰素联合应用诱导细胞凋亡相关的基因(gene associated with retinoid-interferon-induced mortality-19,GRIM-19)是死亡相关基因中的一员,它的过高表达可以抑制肿瘤细胞的增殖,促进细胞的凋亡。本研究检测非小细胞肺癌和正常肺组织中GRIM-19蛋白的表达和定位,探讨其在非小细胞肺癌组织中表达的临床意义。方法:应用免疫组化ABC法检测49例非小细胞肺癌组织及相应癌旁正常组织中GRIM-19蛋白的表达情况,并用光密度(A)值定量描述其表达水平;同时用激光共聚焦扫描技术检测GRIM-19蛋白在细胞内的定位。结果:正常肺组织中GRIM-19主要定位于细胞浆中;而肿瘤组织主要位于细胞核中。激光共聚焦扫描技术检测验证了这种结果。GRIM-19蛋白在正常肺组织中阳性率为93.8%(46/49),而在非小细胞肺癌中阳性率为55.1%(27/49),两者之间的差异有统计学意义(P<0.01)。肿瘤组织中GRIM-19蛋白的平均表达水平(A值为0.22±0.01)比正常组织(A值为0.29±0.02)下降24.3%(P<0.01)。GRIM-19蛋白阳性率在Ⅰ、Ⅱ、Ⅲ+Ⅳ期非小细胞肺癌组织中分别是78.6%、48.1%、12.5%,其差异有统计学意义(rs=-0.428,P<0.05)。结论:肺癌组织中GRIM-19蛋白表达随肿瘤恶性程度升高而显著下降甚至缺失,分布由胞浆转入细胞核;GRIM-19蛋白表达可能与肺癌的发生发展相关。
文摘Objective： In the present study, we have examined the safety and efficacy of recombinant adenovirus encoding human p53 tumor suppressor gene （rAd-p53） injection in patients with advanced non-small-cell lung cancer （NSCLC） in the combination with the therapy of bronchial arterial infusion （BAI）. Methods： A total of 58 patients with advanced NSCLC were enrolled in a non-randomized, two-armed clinical trial. Of which, 19 received a combination treatment of BAI and rAd-p53 （the combo group）, while the remaining 39 were treated with only BAI （the control group）. Patients were followed up for 12 months, with safety and local response evaluated by the National Cancer lnstitute＇s Common Toxicity Criteria and response evaluation criteria in solid tumor （RECIST）, respectively. Time to progression （TTP） and survival rates were also analyzed by Kaplan-Meier method. Results In the combo group, 19 patients received a total of 49 injections ofrAd-p53 and 46 times of BAI, respectively, while 39 patients in the control group received a total of 113 times of BAI. The combination treatment was found to have less adverse events such as anorexia, nausea and emesis, pain, and leucopenia （P〈0.05） but more arthralgia, fever, influenza-like symptom, and myalgia （P〈0.05）, compared with the control group. The overall response rates （complete response （CR）＋partial response （PR）） were 47.3% and 38.4% for the combo group and the control group, respectively （P〉0.05）. Patients in the combo group had a longer TTP than those in the control group （a median 7.75 vs 5.5 months, P-0.018）. However, the combination treatment did not lead to better survival, with survival rates at 3, 6, and 12 months in the combo group being 94.74%, 89.47%, and 52.63%, respectively, com- pared with 92.31%, 69.23%, and 38.83% in the control group （P=0.224）. Conclusion： Our results show that the combination of rAd-p53 and BAI was well tolerated in patients with NSCLC and may have improved the qual
文摘Background The outcome of surgical treatment of non-small-cell lung cancer （NSCLC） remains poor. In many patients the biological behavior of NSCLC does not follow a definite pattern, and can not be accurately predicted before treatment. ^18F-fluoro-2-deoxy-glucose （^18F-FDG） uptake on positron-emission tomography （PET） is associated with the aggressiveness of NSCLC. The present study focused on the role of ^18F-FDG uptake in predicting the outcome of surgically treated patients with NSCLC. Methods A retrospective analysis was made of 82 patients who underwent complete resection and preoperative FDG PET. The maximum standardized uptake value （SUVmax）, in addition to five clinicopathological factors and three biomolecular factors, which could possibly influence survival, was compared for possible association with patients＇ recurrence and survival, by the Log-rank test in univariate analysis and the Cox proportional hazards model in multivariate analysis. The association between SUVmax and other factors was also analyzed. Results Patients with SUVmax more than 11 had a disease-free survival and overall survival shorter than patients with SUVmax less than 11 in univariate analyses （P〈0.001, P=0.002）. In the multivariate analysis, SUVmax （dichotomized by 11） was the only significant predictor for tumor recurrence. TNM stage and SUVmax （dichotomized by 11） were independent predictors for the overall survival. Associations of SUVmax with p53 overexpression, proliferating cell nuclear antigen （PCNA） labeling index and microvascular density of the tumor were significant in the entire group. Conclusions ^18F-FDG uptake on PET may be used to noninvasively assess biological aggressiveness of NSCLC in vivo, identifying the surgically-treated patients with poor prognosis who could benefit from additional therapy.
