Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and...Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and c-MET;therefore,it exhibits both antitumor and anti-angiogenetic activities.A phase III trial has shown that anlotinib improved progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small cell lung cancer(NSCLC),who presented with progressive disease or intolerance after standard chemotherapy.This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods:Data were collected from March 2015 to January 2017 from a randomized,double-blind,placebo-controlled,multicenter,phase III trial of anlotinib(ALTER0303).A total of 437 patients were enrolled and randomly allocated(2:1)to the anlotinib and placebo groups.Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS.Cox proportional hazards model was adopted for multivariate prognostic analysis.Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS.Meanwhile,elevated thyroid-stimulating hormone,blood glucose,and triglyceride levels;hypertension;and hand–foot syndrome were independent protective factors of PFS.High posttherapeutic peripheral blood granulocyte/lymphocyte ratio,an Eastern Cooperative Oncology Group(ECOG)score≥2,and the sum of the maximal target lesion length at baseline were independent risk factors of OS,and hypertriglyceridemia was an independent protective factor of OS.Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC,and the baseline characteristics of the therapeutically dominant populations were then identified.展开更多
Objective: To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 89 patients with stage ⅢB or IV NSCLC received icotinib at a ...Objective: To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 89 patients with stage ⅢB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. Results: A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate (RR) was 36.0% (32/89), and the disease control rate (DCR) was 69.7% (62/89). RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (P<0.05). The symptom improvement rate was 57.3% (51/89), and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 (33.7%)] and diarrhea [15/89 (16.9%)]. The level of toxicity was typically low. Conclusions: The use of icotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.展开更多
Objective:This phase 3 study aimed to test equivalence in efficacy and safety for QL1101,a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer(NSCLC).Method...Objective:This phase 3 study aimed to test equivalence in efficacy and safety for QL1101,a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer(NSCLC).Methods:Eligible patients were randomly assigned 1:1 to receive carboplatin and paclitaxel in combination with either QL1101 or bevacizumab,15 mg/kg every 3-week for 6 cycles.This was followed by maintenance treatment with single agent QL1101 every 3-week.The primary end-point was objective response rate(ORR),with secondary end-points being progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and adverse events(AEs).Results:Of 675 patients,535 eligible patients were randomized to the QL1101 group(n=269)and bevacizumab group(n=266).ORRs were 52.8%and 56.8%,respectively,for the QL1101 and bevacizumab groups,with an ORR hazard ratio 0.93(95%confidence interval:0.8-0131.1).The PFS,OS,DCR,and AEs were comparable between the 2 groups,which remained the same after stratification according to epidermal growth factor receptor mutation or smoking history.Conclusions:QL1101 showed similar efficacy and safety profiles as compared to bevacizumab among Chinese patients with untreated locally advanced non-squamous NSCLC.展开更多
Objective: Anti-vascular endothelial growth factor(VEGF) monoclonal antibodies are an effective means of treating non-small cell lung cancer(NSCLC). Here, we aim to update the equivalent efficacy assessment between QL...Objective: Anti-vascular endothelial growth factor(VEGF) monoclonal antibodies are an effective means of treating non-small cell lung cancer(NSCLC). Here, we aim to update the equivalent efficacy assessment between QL1101 and bevacizumab based on two-year follow-up data.Methods: In total, 535 eligible NSCLC patients were enrolled in this randomized controlled trial. Patients were randomly assigned 1:1 to the QL1101 group and the bevacizumab group. The full end time of this study was defined as 24 months after the last enrolled patient was randomized. The primary endpoint was the objective response rate(ORR);equivalence was confirmed if the two-sided 90% confidence interval(90% CI) of the relative risk was within the range of 0.75-1.33. The secondary endpoints were progression-free survival(PFS) and overall survival(OS).Results: The two-year updated data showed similar ORR(QL1101 vs. bevacizumab: 53.1% vs. 54.3%;relative risk=0.977;90% CI: 0.838-1.144), PFS(235 d vs. 254 d, log-rank P=0.311), and OS(577 d vs. 641 d, log-rank P=0.099) results between the QL1101 group and the bevacizumab group. The mean shrinkage ratio of targeted lesions was also similar between the QL1101 group and the bevacizumab group(22.5% vs. 23.5%). For patients who received QL1101 maintenance therapy, similar results were shown between the QL1101 group(n=157) and the bevacizumab group(n=148)(PFS: 253 d vs. 272 d, log-rank P=0.387;OS: 673 d vs. 790 d, log-rank P=0.101;mean tumor shrinkage rate: 26.6% vs. 27.5%).Conclusions: This study reported that QL1101 had similar efficacy in treating nonsquamous NSCLC in terms of ORR, PFS and OS based on two-year updated data, providing a basis for the clinical application of QL1101.展开更多
With the advances in surgery, chemotherapy, and radiotherapy over the last decades, the treatment strategies of lung cancer has been largely changed. In this review, we summarize recent advances in lung cancer and tre...With the advances in surgery, chemotherapy, and radiotherapy over the last decades, the treatment strategies of lung cancer has been largely changed. In this review, we summarize recent advances in lung cancer and treatment research. We discuss current clinical management, highlight stage-specific therapy approaches, chemotherapy options for advanced-stage of non-small-cell lung cancer (NSCLC) patients, along with new agents such as epidermal growth factor receptor (EGFR)-targeting tyrosine kinase inhibitors erlotinib and gefitinib, and the anaplastic lymphoma kinase (ALK) inhibitor crizotinib. We also give an outlook into NSCLC disease biology, focuse on the importance of EGFR activating mutations and the role of the tumor-microenvironment. Finally we summarize the new recommendations in treating small-cell-lung cancer (SCLC).展开更多
Objective: To investigate the expressions and the clinical significance of P53, C-erbB-2 and vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC). Methods: 121 specimens of NSCLC were examin...Objective: To investigate the expressions and the clinical significance of P53, C-erbB-2 and vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC). Methods: 121 specimens of NSCLC were examined for P53, C-erbB-2 and VEGF by immunohistochemical staining. Results: The positive rates of P53, C-erbB-2 and VEGF in the carci- nomatous tissue were 43%, 39% and 31% respectively. P53 gene protein expression in lung cancer was significantly related to histological type and P-TNM staging of lung cancer patients (P < 0.05), and was not associated with the sex, age, the size of primary cancer, lymph node metastasis and cell differentiation (P > 0.05). C-erbB-2 gene protein expression in lung cancer was closely related to histological type and cell differentiation (P < 0.05), and was not associated with the sex, age, the size of primary cancer, lymph node metastasis and P-TNM staging of lung cancer patients (P > 0.05). VEGF in lung cancer was only closely related to cell differentiation (P < 0.05), and was not associated with the sex, age, the size of primary cancer, lymph node metastasis, histological type and P-TNM staging of lung cancer patients (P > 0.05). Conclusion: It is possible for P53, C-erbB-2 and VEGF to play an important role in the oncogenesis and development of non-small cell lung cancer.展开更多
Early detection of lung cancer (LC) is vital for reducing LC-related mortality. However, noninvasive diagnostic tools remain a great challenge. We aim to identify blood-based biomarkers for the early detection of LC. ...Early detection of lung cancer (LC) is vital for reducing LC-related mortality. However, noninvasive diagnostic tools remain a great challenge. We aim to identify blood-based biomarkers for the early detection of LC. Here, LC-associated hypomethylation in alpha-1,3-fucosyltransferase VII (FUT7) is identified via the Illumina 850K array in a discovery study and validated by mass spectrometry in two independent casecontrol studies with blood samples from 1720 LC patients (86.8% LC at stage I, blood is collected before surgery and treatment) and 3143 healthy controls. Compared to the controls, blood-based FUT7 hypomethylation is identified in LC patients at stage I, and even in LC patients with malignant nodules ≤1 cm and in patients with adenocarcinoma in situ. Gender plays a role in the LC-associated FUT7 hypomethylation in blood, which is more significant in males than in females. We also reveal that FUT7 hypomethylation in LC could be enhanced by the advanced stage of cancer, involvement of lymph nodes, and larger tumor size. Based on a large sample size and semi-quantitative methods, our study reveals a strong association between blood-based FUT7 hypomethylation and LC, suggesting that methylation signatures in blood may be a group of potential biomarkers for detection of early-stage LC.展开更多
Background:The prognosis of patients with small cell lung cancer(SCLC)and brain metastases(BM)was poor.This study aimed to explore the efficacy and safety of anlotinib as third-line or above treatment in SCLC with BM....Background:The prognosis of patients with small cell lung cancer(SCLC)and brain metastases(BM)was poor.This study aimed to explore the efficacy and safety of anlotinib as third-line or above treatment in SCLC with BM.Methods:This was a subgroup analysis of the ALTER1202 trial,which was a randomized,placebo-controlled trial aimed to evaluate the role of anlotinib as third-line treatment or above in patients with SCLC.This study included patients with BM at baseline.The efficacy and safety outcomes included progression-free survival(PFS),overall survival(OS),central nervous system(CNS),objective response rate(ORR),CNS disease control rate(DCR),time to CNS progression,and adverse events(AEs).Results:Twenty-one and nine patients with BM were included in the anlotinib and placebo groups,respectively.The median PFS and OS were 3.8 months(95%confidence interval[CI]:1.8-6.1)and 6.1 months(95%CI:4.1-8.0)in the anlotinib group.Anlotinib was associated with a significant improvement in PFS(hazard ratio[HR]=0.15,95%CI:0.04-0.51,p=0.0005)and OS(HR=0.26,95%CI:0.09-0.73,p=0.0061)than placebo.Anlotinib significantly prolonged the time to CNS progression(p<0.0001).The anlotinib group had a higher CNS DCR than placebo(95.2%vs.22.2%,p=0.0001).The most common grade 3 or higher AEs were increased lipase(19.0%),hypertension(14.3%),and hyponatremia(14.3%)in the anlotinib group.Conclusions:Anlotinib proved to have potential CNS activity and a manageable toxicity profile in patients with SCLC and BM,significantly delaying CNS progression.展开更多
Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy.Due to their HLA-independent mode of action,allogeneic Vγ9Vδ2 T cells can be considered for clinical application.To apply allogeneic Vγ9Vδ...Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy.Due to their HLA-independent mode of action,allogeneic Vγ9Vδ2 T cells can be considered for clinical application.To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy,the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized,and clinical safety and efficacy also need to be proven.Therefore,we developed a novel formula to improve the expansion of peripheralγδT cells from healthy donors.Then,we used a humanized mouse model to validate the therapeutic efficacy of expandedγδT cells in vivo;furthermore,the expandedγδT cells were adoptively transferred into late-stage liver and lung cancer patients.We found that the expanded cells possessed significantly improved immune effector functions,including proliferation,differentiation,and cancer cell killing,both in vitro and in the humanized mouse model.Furthermore,a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T cells.Among these 132 patients,8 liver cancer patients and 10 lung cancer patients who received≥5 cell infusions showed greatly prolonged survival,which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell therapy.Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy,which will inspire further clinical investigations and eventually benefit cancer patients.展开更多
Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients...Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ≥ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gamma-glutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.展开更多
Background:Thymic carcinomas(TCs)and thymic neuroendocrine neoplasms(TNENs)are two aggressive subtypes of thymic malignancy.Traditional therapy for advanced TCs and TNENs has limited outcome.New genomic profiling of T...Background:Thymic carcinomas(TCs)and thymic neuroendocrine neoplasms(TNENs)are two aggressive subtypes of thymic malignancy.Traditional therapy for advanced TCs and TNENs has limited outcome.New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches.Methods:We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017.Patient samples were sequenced using a 324-gene platform with licensed technologies.In this study,we focused on clinically relevant genomic alterations(CRGAs),which are previously proven to be pathogenic alterations,to identify the pathology-specific mutational patterns,prognostic signatures of TCs and TNENs.Results:The mutational profiles between TCs and TNENs were diverse.The genetic alterations that ranked highest in TCs were in CDKN2A,TP53,ASXL1,CDKN2B,PIK3C2G,PTCH1,and ROS1,while those in TNENs were in MEN1,MLL2,APC,RB1,and TSC2.Prognostic analysis showed that mutations of ROS1,CDKN2A,CDKN2B,BRAF,and BAP1 were significantly associated with worse outcomes in TC patients,and that mutation of ERBB2 indicated shortened disease-free survival(DFS)and overall survival(OS)in TNEN patients.Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control,chromatin remodeling/DNA methylation,phosphoinositide 3-kinases(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR),and receptor tyrosine kinase(RTK)/RAS/mitogen-activated protein kinase(MAPK)signaling.Conclusion:We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors,and identified the pathology-specific mutational patterns,prognostic signatures,and potential therapeutic targets for TCs and TNENs.展开更多
文摘Objective:Anlotinib hydrochloride is a multitarget tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor,fibroblast growth factor receptor,platelet-derived growth factor receptor,c-Kit,and c-MET;therefore,it exhibits both antitumor and anti-angiogenetic activities.A phase III trial has shown that anlotinib improved progression-free survival(PFS)and overall survival(OS)in patients with advanced non-small cell lung cancer(NSCLC),who presented with progressive disease or intolerance after standard chemotherapy.This study aimed to analyze the characteristics of patients receiving anlotinib treatment to determine the dominant populations who are fit for the treatment.Methods:Data were collected from March 2015 to January 2017 from a randomized,double-blind,placebo-controlled,multicenter,phase III trial of anlotinib(ALTER0303).A total of 437 patients were enrolled and randomly allocated(2:1)to the anlotinib and placebo groups.Kaplan–Meier analysis and log-rank test were performed to compare PFS and OS.Cox proportional hazards model was adopted for multivariate prognostic analysis.Results:Multivariate analysis indicated that high post-therapeutic peripheral blood granulocyte/lymphocyte ratio and elevated alkaline phosphatase levels were independent risk factors for PFS.Meanwhile,elevated thyroid-stimulating hormone,blood glucose,and triglyceride levels;hypertension;and hand–foot syndrome were independent protective factors of PFS.High posttherapeutic peripheral blood granulocyte/lymphocyte ratio,an Eastern Cooperative Oncology Group(ECOG)score≥2,and the sum of the maximal target lesion length at baseline were independent risk factors of OS,and hypertriglyceridemia was an independent protective factor of OS.Conclusions:This study preliminarily explored the possible factors that affected PFS and OS after anlotinib treatment in patients with advanced refractory NSCLC,and the baseline characteristics of the therapeutically dominant populations were then identified.
文摘Objective: To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 89 patients with stage ⅢB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. Results: A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate (RR) was 36.0% (32/89), and the disease control rate (DCR) was 69.7% (62/89). RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma (P<0.05). The symptom improvement rate was 57.3% (51/89), and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 (33.7%)] and diarrhea [15/89 (16.9%)]. The level of toxicity was typically low. Conclusions: The use of icotinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.
文摘Objective:This phase 3 study aimed to test equivalence in efficacy and safety for QL1101,a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer(NSCLC).Methods:Eligible patients were randomly assigned 1:1 to receive carboplatin and paclitaxel in combination with either QL1101 or bevacizumab,15 mg/kg every 3-week for 6 cycles.This was followed by maintenance treatment with single agent QL1101 every 3-week.The primary end-point was objective response rate(ORR),with secondary end-points being progression-free survival(PFS),overall survival(OS),disease control rate(DCR),and adverse events(AEs).Results:Of 675 patients,535 eligible patients were randomized to the QL1101 group(n=269)and bevacizumab group(n=266).ORRs were 52.8%and 56.8%,respectively,for the QL1101 and bevacizumab groups,with an ORR hazard ratio 0.93(95%confidence interval:0.8-0131.1).The PFS,OS,DCR,and AEs were comparable between the 2 groups,which remained the same after stratification according to epidermal growth factor receptor mutation or smoking history.Conclusions:QL1101 showed similar efficacy and safety profiles as compared to bevacizumab among Chinese patients with untreated locally advanced non-squamous NSCLC.
基金supported by Shanghai Xuhui District municipal health commission [grant number XHLHGG201806]Shanghai Shenkang three-year project [grant number SHDC2020CR4017]。
基金supported by the foundation of Chinese Society of Clinical Oncology (No. Y-2019AZZD-0355 & Y-QL2019-0125)the foundation of Shanghai Chest Hospital (No. 2019YNJCM11)the program of system biomedicine innovation center from Shanghai Jiao Tong University (No. YG2021QN121)
文摘Objective: Anti-vascular endothelial growth factor(VEGF) monoclonal antibodies are an effective means of treating non-small cell lung cancer(NSCLC). Here, we aim to update the equivalent efficacy assessment between QL1101 and bevacizumab based on two-year follow-up data.Methods: In total, 535 eligible NSCLC patients were enrolled in this randomized controlled trial. Patients were randomly assigned 1:1 to the QL1101 group and the bevacizumab group. The full end time of this study was defined as 24 months after the last enrolled patient was randomized. The primary endpoint was the objective response rate(ORR);equivalence was confirmed if the two-sided 90% confidence interval(90% CI) of the relative risk was within the range of 0.75-1.33. The secondary endpoints were progression-free survival(PFS) and overall survival(OS).Results: The two-year updated data showed similar ORR(QL1101 vs. bevacizumab: 53.1% vs. 54.3%;relative risk=0.977;90% CI: 0.838-1.144), PFS(235 d vs. 254 d, log-rank P=0.311), and OS(577 d vs. 641 d, log-rank P=0.099) results between the QL1101 group and the bevacizumab group. The mean shrinkage ratio of targeted lesions was also similar between the QL1101 group and the bevacizumab group(22.5% vs. 23.5%). For patients who received QL1101 maintenance therapy, similar results were shown between the QL1101 group(n=157) and the bevacizumab group(n=148)(PFS: 253 d vs. 272 d, log-rank P=0.387;OS: 673 d vs. 790 d, log-rank P=0.101;mean tumor shrinkage rate: 26.6% vs. 27.5%).Conclusions: This study reported that QL1101 had similar efficacy in treating nonsquamous NSCLC in terms of ORR, PFS and OS based on two-year updated data, providing a basis for the clinical application of QL1101.
文摘With the advances in surgery, chemotherapy, and radiotherapy over the last decades, the treatment strategies of lung cancer has been largely changed. In this review, we summarize recent advances in lung cancer and treatment research. We discuss current clinical management, highlight stage-specific therapy approaches, chemotherapy options for advanced-stage of non-small-cell lung cancer (NSCLC) patients, along with new agents such as epidermal growth factor receptor (EGFR)-targeting tyrosine kinase inhibitors erlotinib and gefitinib, and the anaplastic lymphoma kinase (ALK) inhibitor crizotinib. We also give an outlook into NSCLC disease biology, focuse on the importance of EGFR activating mutations and the role of the tumor-microenvironment. Finally we summarize the new recommendations in treating small-cell-lung cancer (SCLC).
文摘Objective: To investigate the expressions and the clinical significance of P53, C-erbB-2 and vascular endothelial growth factor (VEGF) in non-small cell lung cancer (NSCLC). Methods: 121 specimens of NSCLC were examined for P53, C-erbB-2 and VEGF by immunohistochemical staining. Results: The positive rates of P53, C-erbB-2 and VEGF in the carci- nomatous tissue were 43%, 39% and 31% respectively. P53 gene protein expression in lung cancer was significantly related to histological type and P-TNM staging of lung cancer patients (P < 0.05), and was not associated with the sex, age, the size of primary cancer, lymph node metastasis and cell differentiation (P > 0.05). C-erbB-2 gene protein expression in lung cancer was closely related to histological type and cell differentiation (P < 0.05), and was not associated with the sex, age, the size of primary cancer, lymph node metastasis and P-TNM staging of lung cancer patients (P > 0.05). VEGF in lung cancer was only closely related to cell differentiation (P < 0.05), and was not associated with the sex, age, the size of primary cancer, lymph node metastasis, histological type and P-TNM staging of lung cancer patients (P > 0.05). Conclusion: It is possible for P53, C-erbB-2 and VEGF to play an important role in the oncogenesis and development of non-small cell lung cancer.
基金supported by the Nanjing Social Supporting Department and Social Supporting Ministry of Jiangsu Province granted from 2018 to 2020,and the Nanjing TANTICA Co.Ltd(grant no.2018LC01.1).
文摘Early detection of lung cancer (LC) is vital for reducing LC-related mortality. However, noninvasive diagnostic tools remain a great challenge. We aim to identify blood-based biomarkers for the early detection of LC. Here, LC-associated hypomethylation in alpha-1,3-fucosyltransferase VII (FUT7) is identified via the Illumina 850K array in a discovery study and validated by mass spectrometry in two independent casecontrol studies with blood samples from 1720 LC patients (86.8% LC at stage I, blood is collected before surgery and treatment) and 3143 healthy controls. Compared to the controls, blood-based FUT7 hypomethylation is identified in LC patients at stage I, and even in LC patients with malignant nodules ≤1 cm and in patients with adenocarcinoma in situ. Gender plays a role in the LC-associated FUT7 hypomethylation in blood, which is more significant in males than in females. We also reveal that FUT7 hypomethylation in LC could be enhanced by the advanced stage of cancer, involvement of lymph nodes, and larger tumor size. Based on a large sample size and semi-quantitative methods, our study reveals a strong association between blood-based FUT7 hypomethylation and LC, suggesting that methylation signatures in blood may be a group of potential biomarkers for detection of early-stage LC.
基金Province Development and Reform Commission,Grant/Award Numbers:2021C042-7,2021C043-1Chia-tai Tianqing 264 Pharmaceutical Group Co.,LtdProvincial Health and Family Planning。
文摘Background:The prognosis of patients with small cell lung cancer(SCLC)and brain metastases(BM)was poor.This study aimed to explore the efficacy and safety of anlotinib as third-line or above treatment in SCLC with BM.Methods:This was a subgroup analysis of the ALTER1202 trial,which was a randomized,placebo-controlled trial aimed to evaluate the role of anlotinib as third-line treatment or above in patients with SCLC.This study included patients with BM at baseline.The efficacy and safety outcomes included progression-free survival(PFS),overall survival(OS),central nervous system(CNS),objective response rate(ORR),CNS disease control rate(DCR),time to CNS progression,and adverse events(AEs).Results:Twenty-one and nine patients with BM were included in the anlotinib and placebo groups,respectively.The median PFS and OS were 3.8 months(95%confidence interval[CI]:1.8-6.1)and 6.1 months(95%CI:4.1-8.0)in the anlotinib group.Anlotinib was associated with a significant improvement in PFS(hazard ratio[HR]=0.15,95%CI:0.04-0.51,p=0.0005)and OS(HR=0.26,95%CI:0.09-0.73,p=0.0061)than placebo.Anlotinib significantly prolonged the time to CNS progression(p<0.0001).The anlotinib group had a higher CNS DCR than placebo(95.2%vs.22.2%,p=0.0001).The most common grade 3 or higher AEs were increased lipase(19.0%),hypertension(14.3%),and hyponatremia(14.3%)in the anlotinib group.Conclusions:Anlotinib proved to have potential CNS activity and a manageable toxicity profile in patients with SCLC and BM,significantly delaying CNS progression.
基金This work was supported by the Key Program of the National Natural Science Foundation of China(31830021)Major International Joint Research Program of China(31420103901)+12 种基金“111 project”(B16021)Scientific and Technological Plan of Guangdong Province(201704KW010)(Z.Y.)Fundamental Research Funds for the Central Universities,Natural Science Foundation of Guangdong Province,China(2020A1515010132)(Y.W.)General Research Fund,Research Grants Council of Hong Kong(17122519,17121214,17115015,and 17126317)(W.T.)Hong Kong SAR,ChinaThis work was also partially supported by the National Natural Science Foundation of China(31570898)the Natural Science Foundation of Guangdong Province,China(2016A030313112)(Z.X.)grant Ka 502/19-1 from the German Research Council(Deutsche Forschungsgemeinschaft)the Cluster of Excellence ExC 306“Inflammation-at-Interfaces”(Deutsche Forschungsgemeinschaft)(D.K.)Y.H.was supported by the China Postdoctoral Science Foundation(2017M622898)Y.X.was supported by the Postdoctoral Fund of the First Affiliated Hospital of Jinan University(809008)L.K.was supported by a long-term fellowship from the German Academic Exchange Service(DAAD)C.P.is the recipient of a grant from the Erich und Gertrud Roggenbruck Foundation.
文摘Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy.Due to their HLA-independent mode of action,allogeneic Vγ9Vδ2 T cells can be considered for clinical application.To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy,the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized,and clinical safety and efficacy also need to be proven.Therefore,we developed a novel formula to improve the expansion of peripheralγδT cells from healthy donors.Then,we used a humanized mouse model to validate the therapeutic efficacy of expandedγδT cells in vivo;furthermore,the expandedγδT cells were adoptively transferred into late-stage liver and lung cancer patients.We found that the expanded cells possessed significantly improved immune effector functions,including proliferation,differentiation,and cancer cell killing,both in vitro and in the humanized mouse model.Furthermore,a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T cells.Among these 132 patients,8 liver cancer patients and 10 lung cancer patients who received≥5 cell infusions showed greatly prolonged survival,which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell therapy.Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy,which will inspire further clinical investigations and eventually benefit cancer patients.
基金This study was supported by the Jilin Provincial Healthand Family Planning Commission (No.2019J077)the Science and Technology Agency of Jilin Provincial Project (No.20200201518JC)。
文摘Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ≥ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gamma-glutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.
基金supported by grants from the National Natural Science Foundation of China(No.82272913)National Multi-disciplinary Treatment Project for Major Disease(No.2020NMDTP)+2 种基金Shanghai Sailing Program of Science and Technology Commission of Shanghai Municipality(No.20YF1428100)Interdisciplinary Program of Shanghai Jiao Tong University(No.YG2021QN126)Shanghai Chest Hospital(No.2020YNJCM10)
文摘Background:Thymic carcinomas(TCs)and thymic neuroendocrine neoplasms(TNENs)are two aggressive subtypes of thymic malignancy.Traditional therapy for advanced TCs and TNENs has limited outcome.New genomic profiling of TCs and TNENs might provide insights that contribute to the development of new treatment approaches.Methods:We used gene panel sequencing technologies to investigate the genetic aberrations of 32 TC patients and 15 TNEN patients who underwent surgery at Shanghai Chest Hospital between 2015 and 2017.Patient samples were sequenced using a 324-gene platform with licensed technologies.In this study,we focused on clinically relevant genomic alterations(CRGAs),which are previously proven to be pathogenic alterations,to identify the pathology-specific mutational patterns,prognostic signatures of TCs and TNENs.Results:The mutational profiles between TCs and TNENs were diverse.The genetic alterations that ranked highest in TCs were in CDKN2A,TP53,ASXL1,CDKN2B,PIK3C2G,PTCH1,and ROS1,while those in TNENs were in MEN1,MLL2,APC,RB1,and TSC2.Prognostic analysis showed that mutations of ROS1,CDKN2A,CDKN2B,BRAF,and BAP1 were significantly associated with worse outcomes in TC patients,and that mutation of ERBB2 indicated shortened disease-free survival(DFS)and overall survival(OS)in TNEN patients.Further investigation found that the prognosis-related genes were focused on signal pathways of cell cycle control,chromatin remodeling/DNA methylation,phosphoinositide 3-kinases(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR),and receptor tyrosine kinase(RTK)/RAS/mitogen-activated protein kinase(MAPK)signaling.Conclusion:We profiled the mutational features of 47 Chinese patients with thymic malignancy of diverse pathologic phenotypes to uncover the integrated genomic landscape of these rare tumors,and identified the pathology-specific mutational patterns,prognostic signatures,and potential therapeutic targets for TCs and TNENs.