Croton crassifolius(CC)is a kind of traditional Chinese medicine rich in terpenoids,with among which diterpene species are the most.CC had biological activities in the treatment of cancer,inflammation,ulcerative colit...Croton crassifolius(CC)is a kind of traditional Chinese medicine rich in terpenoids,with among which diterpene species are the most.CC had biological activities in the treatment of cancer,inflammation,ulcerative colitis,osteoporosis and Alzheimer’s disease.This study reviews the chemical compositions and pharmacological activities of CC to provide reference for further research.展开更多
Lonicera japonica,also known as honeysuckle,is an evergreen shrub in the family of Syzygium.By consulting Sciencedirect databases and Web of Science databases,79 related articles were found,of which 22 were related to...Lonicera japonica,also known as honeysuckle,is an evergreen shrub in the family of Syzygium.By consulting Sciencedirect databases and Web of Science databases,79 related articles were found,of which 22 were related to chemical composition and pharmacological activity.These articles show that L.japonica has a wide range of pharmacological activities,including antiviral,anti-tumor,and antioxidant effects.These activities have important applications in the pharmaceutical,food,and fragrance industries.This review focuses on the chemical composition and pharmacological effects of L.japonicae,which is of great significance to the development of new drugs and therapeutic methods.展开更多
Artemisiae argyi(A.argyi)is a traditional medical plant,with medicinal and economic value.It has been used to treat diseases for more than 2000 years,and its application has been expanded in recent years with the in-d...Artemisiae argyi(A.argyi)is a traditional medical plant,with medicinal and economic value.It has been used to treat diseases for more than 2000 years,and its application has been expanded in recent years with the in-depth research on the chemical composition and pharmacology.It is mainly used clinically for the treatment of“cold pain in the abdomen,cold clotting in the menstrual channels,cold infertility in the uterus,fetal movement,vomiting blood,epistaxis,pus and blood dysentery,and external treatment of itchy skin”and other symptoms.This paper reviews the research on the biological activity and chemical composition of A.argyi by scholars in recent decades.展开更多
Portulaca oleracea(P.oleracea)is a traditional Chinese herbal that has the effects of soothing the liver and clearing collaterals,strengthening the spleen and stomach,moistening the intestines and detoxifying.With the...Portulaca oleracea(P.oleracea)is a traditional Chinese herbal that has the effects of soothing the liver and clearing collaterals,strengthening the spleen and stomach,moistening the intestines and detoxifying.With the development of the pharmaceutical industry,the medicinal value of P.oleracea is becoming increasingly prominent.It is commonly used in clinical practice for clearing heat and detoxifying,inhibiting bacteria,preventing and treating diseases such as hypertension,coronary heart disease,and cerebral infarction,indicating its broad application prospects.This study reviews the chemical components and pharmacological activities of P.oleracea in recent decades.展开更多
Background:Bone metastases are common in patients with advanced cancer.Bisphosphonates(BPs) could prevent or delay the development of skeleton-related events(SREs).The present study aimed to identify the clinical feat...Background:Bone metastases are common in patients with advanced cancer.Bisphosphonates(BPs) could prevent or delay the development of skeleton-related events(SREs).The present study aimed to identify the clinical features of and treatment strategies for Chinese patients with bone metastases.Methods:Consecutive cancer patients who had bone metastases and received BP treatment were enrolled.A questionnaire was developed to collect the patients' clinical data,as well as information on the diagnosis and management of bone metastases.Physicians' awareness of the guidelines and knowledge of the application of BP were also assessed.Results:A total of 3223 patients with lung cancer(36.5%),breast cancer(30.9%),prostate cancer(8.5%),and gastrointestinal cancer(5.7%) were included in this study.The sites of bone metastases were the thoracic spine(56.0%),lumbar spine(47.1%),ribs(32.6%),and pelvis(23.2%).The SRE frequency was the highest in patients with multiple myeloma(36.6%),followed by those with lung cancer(25.9%),breast cancer(20.2%),prostate cancer(18.2%),and gastrointestinal cancer(17.3%).Irradiation to the bone was the most frequent SRE(58%in lung cancer patients,45%in breast cancer patients,and 48%in prostate cancer patients).Our survey also showed that 45.5%of patients received BP within 3 months after their diagnosis of bone metastases,whereas the remaining 54.5%of patients did not receive BP treatment until at least 3 months after their diagnosis of bone metastases.The SRE frequency in the former group was significantly lower than that in the latter group(4.0%vs.42.3%,P < 0.05).In patients with more than 6 months of continuous BP treatment,the mean time to the first SRE was significantly longer than that in patients with less than 6 months of continuous BP treatment(7.2 vs.3.4 months,P < 0.05).In addition,12.2%of the physicians were not aware of the efficacy of BP in preventing and delaying SRE.Only half(52.3%) of the physicians agreed that the BP treatment should persist for at least 6 months unless it was intolerable.Conclusions:Our study suggested that prompt and persistent BP treatment was associated with a reduced risk of SREs.However,our survey also revealed that the proper application of BP was not as common as expected in China.展开更多
To implant radioactive seeds through a needle precisely and safely, a novel multi-DOF surgical robotic system is presented in this paper for percutaneous prostate intervention through the patient's perineum under ...To implant radioactive seeds through a needle precisely and safely, a novel multi-DOF surgical robotic system is presented in this paper for percutaneous prostate intervention through the patient's perineum under real-time ultrasound image guidance. The proposed robot, which is designed with 9-DOF, consists of a 3-DOF automatic location platform for position adjustment, 2-DOF for automatic ultrasonic probe adjustment mounted with electromagnetic trackers, and 4-DOF for manually adjusting the guided template. Meanwhile, a new registration method based on the quaternion algorithm and least square method is developed, and the needle insertion is performed under the realtime guidance of a navigation system. Furthermore, the robot system has undergone some preliminary experiments with a laser tracker to evaluate the repeatability and accuracy of the robot system. The location error of the puncture needle tip can be controlled under 0.7 mm in air for the whole robotic system. The acquired results endorse the precision of the robot system for prostate seed implantation brachytherapy.展开更多
Dear Editor,Camrelizumab(SHR-1210)is a humanized monoclonal antibody(mAb)that binds to programmed cell death protein 1(PD-1).1 Since May 2019,camrelizumab has been successfully approved for the therapy of patients wit...Dear Editor,Camrelizumab(SHR-1210)is a humanized monoclonal antibody(mAb)that binds to programmed cell death protein 1(PD-1).1 Since May 2019,camrelizumab has been successfully approved for the therapy of patients with various malignancies.2 However,only a few studies have focused on the pharmacokinetics(PK).展开更多
Anaplastic lymphoma kinase(ALK)rearrangements are present in about 5–6%of non-small cell lung cancer(NSCLC)cases and associated with increased risks of central nervous system(CNS)involvement.Envonalkib,a novel ALK in...Anaplastic lymphoma kinase(ALK)rearrangements are present in about 5–6%of non-small cell lung cancer(NSCLC)cases and associated with increased risks of central nervous system(CNS)involvement.Envonalkib,a novel ALK inhibitor,demonstrated promising anti-tumor activity and safety in advanced ALK-positive NSCLC in the first-in-human phase I study.This phase III trial(ClinicalTrials.gov NCT04009317)investigated the efficacy and safety of first-line envonalkib in advanced ALK-positive NSCLC cases.Totally 264 participants were randomized 1:1 to receive envonalkib(n=131)or crizotinib(n=133).Median independent review committee(IRC)-assessed progression-free survival(PFS)times were 24.87(95%confidence interval[CI]:15.64–30.36)and 11.60(95%CI:8.28–13.73)months in the envonalkib and crizotinib groups,respectively(hazard ratio[HR]=0.47,95%CI:0.34–0.64,p<0.0001).IRC-assessed confirmed objective response rate(ORR)was higher(81.68%vs.70.68%,p=0.056)and duration of response was longer(median,25.79[95%CI,16.53–29.47]vs.11.14[95%CI,9.23–16.59]months,p=0.0003)in the envonalkib group compared with the crizotinib group.In participants with baseline brain target lesions,IRC-assessed CNS-ORR was improved with envonalkib compared with crizotinib(78.95%vs.23.81%).Overall survival(OS)data were immature,and median OS was not reached in either group(HR=0.84,95%CI:0.48–1.47,p=0.5741).The 12-month OS rates were 90.6%(95%CI,84.0%–94.5%)and 89.4%(95%CI,82.8%–93.6%)in the envonalkib and crizotinib groups,respectively.Grade≥3 treatment-related adverse events were observed in 55.73%and 42.86%of participants in the envonalkib and crizotinib groups,respectively.Envonalkib significantly improved PFS and delayed brain metastasis progression in advanced ALK-positive NSCLC.展开更多
Background:Gefitinib,as the first epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)approved for the treatment of advanced non-small cell lung cancer(NSCLC),has been proved to significantly improve ...Background:Gefitinib,as the first epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)approved for the treatment of advanced non-small cell lung cancer(NSCLC),has been proved to significantly improve the progression-free survival(PFS)in the first-line setting but suffers from resistance 7-10 months after treatment initia-tion.Apatinib(YN968D1),a potent vascular endothelial growth factor receptor(VEGFR)2-TKI,specifically binds to VEGFR2 and leads to anti-angiogenetic and anti-neoplastic effect.Concurrent inhibition of VEGFR and EGFR path-ways represents a rational approach to improve treatment responses and delay the onset of treatment resistance in EGFR-mutant NSCLC.This ACTIVE study aims to assess the combination of apatinib and gefitinib as a new treatment approach for EGFR-mutant NSCLC as a first-line setting.Methods:This multicenter,randomized,double-blind,placebo-controlled phase III study(NCT02824458)has been designed to assess the efficacy and safety of apatinib or placebo combined with gefitinib as a first-line treatment for patients with EGFR-mutant advanced NSCLC.A total of 310 patients with EGFR-mutation(19del or 21L858R),pathological stage IIIB to IV non-squamous NSCLC were to be enrolled.The primary endpoint is investigator assessment of PFS,and the secondary endpoints include independent radiological central(IRC)-confirmed PFS,overall survival(OS),objective response rate(ORR),disease control rate(DCR),time to progressive disease(TTPD),duration of response(DoR),quality of life(QoL)and safety.The patients are randomized in a 1:1 ratio to receive gefitinib(250 mg,p.o.q.d.)plus apatinib(500 mg,p.o.q.d.)or gefitinib plus placebo,given until disease progression or intolerable adverse events.Exploratory biomarker analysis will be performed.This study is being conducted across China and comprises of 30 participating centers.Enrollment commenced in August 2017 and finished in December 2018,most of the patients are in the follow-up period.Anticipated outcomes and significance:The present study will be the first to evaluate the efficacy and safety profile of the combination of apatinib plus gefitinib as a first-line therapy for patients with EGFR-positive advanced non-squamous NSCLC.Importantly,this trial will provide comprehensive evidence on the treatment of EGFR-TKIs combined with antiangiogenic therapy.展开更多
Hepatotoxicity is a common side effect for patients treated with gefitinib,but the related pathogenesis is unclear and lacks effective predictor and management strategies.A multi-omics approach integrating pharmacomet...Hepatotoxicity is a common side effect for patients treated with gefitinib,but the related pathogenesis is unclear and lacks effective predictor and management strategies.A multi-omics approach integrating pharmacometabolomics,pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution.Here,we found that patients with rs4946935 AA,located in Forkhead Box O3(FOXO3)which is a well-known autophagic regulator,had a higher risk of hepatotoxicity than those with the GA or GG variant(OR=18.020,95%CI=2.473 to 459.1784,P=0.018)in a gefitinib-concentration dependent pattern.Furthermore,functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity,increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury.In contrast,erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3.This study reveals that FOXO3 mutation,leading to autophagic imbalance,plays important role in gefitinib-induced hepatotoxicity,especially for patients with high concentration of gefitinib.In conclusion,FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA.展开更多
Over the past 2000 years,a high-resolution pollen record from the Yushenkule Peat(46°45′-46°57′N,90°46′-90°61′E,2374 m a.s.l.)in the south-eastern Altai Mountains of northwestern China has been...Over the past 2000 years,a high-resolution pollen record from the Yushenkule Peat(46°45′-46°57′N,90°46′-90°61′E,2374 m a.s.l.)in the south-eastern Altai Mountains of northwestern China has been used to explore the changes in vegetation and climate.The regional vegetation has been dominated by alpine meadows revealed from pollen diagrams over the past 2000 years.The pollen-based climate was warm and wet during the Roman Warm Period(0-520 AD),cold and wet during the Dark Age Cold Period(520-900 AD),warm and wet during the Medieval Warm Period(900-1300 AD),and cold and dry during the Little Ice Age(1300-1850 AD).Combined with other pollen data from the Altai Mountains,we found that the percentage of arboreal pollen showed a reduced trend along the NW-SE gradient with decreasing moisture and increasing climatic continentality of the Altai Mountains over the past 2000 years;this is consistent with modern distributions of taiga forests.We also found that the taiga(Pinus forest)have spread slightly,while the steppe(Artemisia,Poaceae and Chenopodiaceae)have recovered significantly in the Altai Mountains over the past 2000 years.In addition,the relatively warm-wet climate may promote high grassland productivity and southward expansion of steppe,which favors the formation of Mongol political and military power.展开更多
Dear editor,Lung cancer is the leading cause of cancer-related death worldwide,with the predominant pathological type being non-small cell lung cancer(NSCLC)[1,2].Next-gener-ation sequencing(NGS)analysis is increasing...Dear editor,Lung cancer is the leading cause of cancer-related death worldwide,with the predominant pathological type being non-small cell lung cancer(NSCLC)[1,2].Next-gener-ation sequencing(NGS)analysis is increasingly used to help clinicians select appropriate target therapies,such as epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)for EGFR-mutant patients[3].Both pericarcinomatous tissues and peripheral blood lymphocytes are widely used as normal control for NGS analysis.However,whether pericarcinomatous tissue is suitable for background filtering in mutation analysis remains controversial.According to the whole-genome sequencing data from The Cancer Genome Atlas(TCGA)database,there were some genomic variations in peri-carcinomatous tissue from NSCLC patients,but no driver gene mutation was detected[4,5].Therefore,deep sequencing of pericarcinomatous and tumor tissues is necessary to confirm whether pericarcinomatous tissue harbors low-frequency mutations.展开更多
First-line chemoimmunotherapy(with or without bevacizumab)has improved outcomes in advanced non-small cell lung cancer(NSCLC).Here,this open-label,multi-cohort phase II study(NCT05329025)was done to investigate the sa...First-line chemoimmunotherapy(with or without bevacizumab)has improved outcomes in advanced non-small cell lung cancer(NSCLC).Here,this open-label,multi-cohort phase II study(NCT05329025)was done to investigate the safety and efficacy of QL1706(a single bifunctional MabPair product against PD-1 and CTLA-4)and chemotherapy with or without bevacizumab in this population.Patients were enrolled into five different cohorts based on genotype(cohorts 1-4,epidermal growth factor receptor[EGFR]wild-type;cohort 5,EGFR-mutant and progressed on EGFR-tyrosine kinase inhibitors[TKIs]).Between June 11,2021 and December 29,2021,91 patients were enrolled.Most frequent treatment-related adverse events(TRAEs)included decreased appetite(60[65.9%]),anemia(60[65.9%]),infusion-related reactions(48[52.7%]),and pruritus(44[48.4%]).Grade≥3 TRAEs occurred in 30(33.0%)patients.Twenty-seven(45%)patients with wild-type EGFR achieved partial response(PR)(objective response rate[ORR]=45%)and had a median progression-free survival(mPFS)of 6.8 months(95%CI:5.2-9.7).For 31 patients harboring mutated EGFR,17(54.8%)achieved PR(ORR=54.8%),with an mPFS of 8.5 months(95%CI:5.72-not evaluable).Overall,QL1706 plus chemotherapy,regardless of having bevacizumab,was generally tolerable and had promising antitumor activity for EGFR wild-type advanced NSCLC in first-line setting.Moreover,QL1706 plus chemotherapy and bevacizumab showed favorable antitumor activity for patients who had EGFR mutated NSCLC but failed in TKI therapy,demonstrating a potential for treating this population.展开更多
基金supported by National Nature Science Foundation of China (81973284)Scientific Research Foundation of the Education Department of Liaoning Province (LJKZ0944).
文摘Croton crassifolius(CC)is a kind of traditional Chinese medicine rich in terpenoids,with among which diterpene species are the most.CC had biological activities in the treatment of cancer,inflammation,ulcerative colitis,osteoporosis and Alzheimer’s disease.This study reviews the chemical compositions and pharmacological activities of CC to provide reference for further research.
基金supported by National Nature Science Foundation of China (81973284)Scientific Research Foundation of the Education Department of Liaoning Province (LJKZ0944)Jiangsu Province Capability Improvement Project through Science,Technology and Education (ZDXYS202207).
文摘Lonicera japonica,also known as honeysuckle,is an evergreen shrub in the family of Syzygium.By consulting Sciencedirect databases and Web of Science databases,79 related articles were found,of which 22 were related to chemical composition and pharmacological activity.These articles show that L.japonica has a wide range of pharmacological activities,including antiviral,anti-tumor,and antioxidant effects.These activities have important applications in the pharmaceutical,food,and fragrance industries.This review focuses on the chemical composition and pharmacological effects of L.japonicae,which is of great significance to the development of new drugs and therapeutic methods.
基金This work was financially supported by National Nature Science Foundation of China(81973284)Scientific Research Foundation of the Education Department of Liaoning Province(LJKZ0944).
文摘Artemisiae argyi(A.argyi)is a traditional medical plant,with medicinal and economic value.It has been used to treat diseases for more than 2000 years,and its application has been expanded in recent years with the in-depth research on the chemical composition and pharmacology.It is mainly used clinically for the treatment of“cold pain in the abdomen,cold clotting in the menstrual channels,cold infertility in the uterus,fetal movement,vomiting blood,epistaxis,pus and blood dysentery,and external treatment of itchy skin”and other symptoms.This paper reviews the research on the biological activity and chemical composition of A.argyi by scholars in recent decades.
基金This work was financially supported by National Nature Science Foundation of China(81973284)Scientific Research Foundation of the Education Department of Liaoning Province(LJKZ0944).
文摘Portulaca oleracea(P.oleracea)is a traditional Chinese herbal that has the effects of soothing the liver and clearing collaterals,strengthening the spleen and stomach,moistening the intestines and detoxifying.With the development of the pharmaceutical industry,the medicinal value of P.oleracea is becoming increasingly prominent.It is commonly used in clinical practice for clearing heat and detoxifying,inhibiting bacteria,preventing and treating diseases such as hypertension,coronary heart disease,and cerebral infarction,indicating its broad application prospects.This study reviews the chemical components and pharmacological activities of P.oleracea in recent decades.
文摘Background:Bone metastases are common in patients with advanced cancer.Bisphosphonates(BPs) could prevent or delay the development of skeleton-related events(SREs).The present study aimed to identify the clinical features of and treatment strategies for Chinese patients with bone metastases.Methods:Consecutive cancer patients who had bone metastases and received BP treatment were enrolled.A questionnaire was developed to collect the patients' clinical data,as well as information on the diagnosis and management of bone metastases.Physicians' awareness of the guidelines and knowledge of the application of BP were also assessed.Results:A total of 3223 patients with lung cancer(36.5%),breast cancer(30.9%),prostate cancer(8.5%),and gastrointestinal cancer(5.7%) were included in this study.The sites of bone metastases were the thoracic spine(56.0%),lumbar spine(47.1%),ribs(32.6%),and pelvis(23.2%).The SRE frequency was the highest in patients with multiple myeloma(36.6%),followed by those with lung cancer(25.9%),breast cancer(20.2%),prostate cancer(18.2%),and gastrointestinal cancer(17.3%).Irradiation to the bone was the most frequent SRE(58%in lung cancer patients,45%in breast cancer patients,and 48%in prostate cancer patients).Our survey also showed that 45.5%of patients received BP within 3 months after their diagnosis of bone metastases,whereas the remaining 54.5%of patients did not receive BP treatment until at least 3 months after their diagnosis of bone metastases.The SRE frequency in the former group was significantly lower than that in the latter group(4.0%vs.42.3%,P < 0.05).In patients with more than 6 months of continuous BP treatment,the mean time to the first SRE was significantly longer than that in patients with less than 6 months of continuous BP treatment(7.2 vs.3.4 months,P < 0.05).In addition,12.2%of the physicians were not aware of the efficacy of BP in preventing and delaying SRE.Only half(52.3%) of the physicians agreed that the BP treatment should persist for at least 6 months unless it was intolerable.Conclusions:Our study suggested that prompt and persistent BP treatment was associated with a reduced risk of SREs.However,our survey also revealed that the proper application of BP was not as common as expected in China.
基金supported by the Key Technology and Development Program of the Tianjin Municipal and Technology Commission (No. 14ZCDZGX00490)
文摘To implant radioactive seeds through a needle precisely and safely, a novel multi-DOF surgical robotic system is presented in this paper for percutaneous prostate intervention through the patient's perineum under real-time ultrasound image guidance. The proposed robot, which is designed with 9-DOF, consists of a 3-DOF automatic location platform for position adjustment, 2-DOF for automatic ultrasonic probe adjustment mounted with electromagnetic trackers, and 4-DOF for manually adjusting the guided template. Meanwhile, a new registration method based on the quaternion algorithm and least square method is developed, and the needle insertion is performed under the realtime guidance of a navigation system. Furthermore, the robot system has undergone some preliminary experiments with a laser tracker to evaluate the repeatability and accuracy of the robot system. The location error of the puncture needle tip can be controlled under 0.7 mm in air for the whole robotic system. The acquired results endorse the precision of the robot system for prostate seed implantation brachytherapy.
基金We thank all the patients for participating in this study.This research was supported by the Guangdong Basic and Applied Basic Research Foundation[2020A1515010020 for Y.M.,2018A0303130243 and 2020A1515011464 for H.Z.]the National Nature Science Foundation of China[82002409 for Y.M.,81872201 and 82073396 for H.Z.,81872499 for L.Z.,and 82072558 for Y.Y.].
文摘Dear Editor,Camrelizumab(SHR-1210)is a humanized monoclonal antibody(mAb)that binds to programmed cell death protein 1(PD-1).1 Since May 2019,camrelizumab has been successfully approved for the therapy of patients with various malignancies.2 However,only a few studies have focused on the pharmacokinetics(PK).
基金This study was funded by the National Natural Science Foundation Project of China(Grant No.82072558).
文摘Anaplastic lymphoma kinase(ALK)rearrangements are present in about 5–6%of non-small cell lung cancer(NSCLC)cases and associated with increased risks of central nervous system(CNS)involvement.Envonalkib,a novel ALK inhibitor,demonstrated promising anti-tumor activity and safety in advanced ALK-positive NSCLC in the first-in-human phase I study.This phase III trial(ClinicalTrials.gov NCT04009317)investigated the efficacy and safety of first-line envonalkib in advanced ALK-positive NSCLC cases.Totally 264 participants were randomized 1:1 to receive envonalkib(n=131)or crizotinib(n=133).Median independent review committee(IRC)-assessed progression-free survival(PFS)times were 24.87(95%confidence interval[CI]:15.64–30.36)and 11.60(95%CI:8.28–13.73)months in the envonalkib and crizotinib groups,respectively(hazard ratio[HR]=0.47,95%CI:0.34–0.64,p<0.0001).IRC-assessed confirmed objective response rate(ORR)was higher(81.68%vs.70.68%,p=0.056)and duration of response was longer(median,25.79[95%CI,16.53–29.47]vs.11.14[95%CI,9.23–16.59]months,p=0.0003)in the envonalkib group compared with the crizotinib group.In participants with baseline brain target lesions,IRC-assessed CNS-ORR was improved with envonalkib compared with crizotinib(78.95%vs.23.81%).Overall survival(OS)data were immature,and median OS was not reached in either group(HR=0.84,95%CI:0.48–1.47,p=0.5741).The 12-month OS rates were 90.6%(95%CI,84.0%–94.5%)and 89.4%(95%CI,82.8%–93.6%)in the envonalkib and crizotinib groups,respectively.Grade≥3 treatment-related adverse events were observed in 55.73%and 42.86%of participants in the envonalkib and crizotinib groups,respectively.Envonalkib significantly improved PFS and delayed brain metastasis progression in advanced ALK-positive NSCLC.
基金国家重点研发计划(No.2017YFD0201400)国家自然科学基金(No.21676026)资助National Key Research and Development Program of China(No.2017YFD0201400)National Natural Science Foundation of China(No.21676026)
基金This study was funded by the National Key R&D Program of China(Grant Numbers:2016YFC0905500,2016YFC0905503)the 5010 Clinical Research Foundation of Sun Yat-sen University(Grant Number:2016001)and Hengrui Medicine Co.Ltd
文摘Background:Gefitinib,as the first epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)approved for the treatment of advanced non-small cell lung cancer(NSCLC),has been proved to significantly improve the progression-free survival(PFS)in the first-line setting but suffers from resistance 7-10 months after treatment initia-tion.Apatinib(YN968D1),a potent vascular endothelial growth factor receptor(VEGFR)2-TKI,specifically binds to VEGFR2 and leads to anti-angiogenetic and anti-neoplastic effect.Concurrent inhibition of VEGFR and EGFR path-ways represents a rational approach to improve treatment responses and delay the onset of treatment resistance in EGFR-mutant NSCLC.This ACTIVE study aims to assess the combination of apatinib and gefitinib as a new treatment approach for EGFR-mutant NSCLC as a first-line setting.Methods:This multicenter,randomized,double-blind,placebo-controlled phase III study(NCT02824458)has been designed to assess the efficacy and safety of apatinib or placebo combined with gefitinib as a first-line treatment for patients with EGFR-mutant advanced NSCLC.A total of 310 patients with EGFR-mutation(19del or 21L858R),pathological stage IIIB to IV non-squamous NSCLC were to be enrolled.The primary endpoint is investigator assessment of PFS,and the secondary endpoints include independent radiological central(IRC)-confirmed PFS,overall survival(OS),objective response rate(ORR),disease control rate(DCR),time to progressive disease(TTPD),duration of response(DoR),quality of life(QoL)and safety.The patients are randomized in a 1:1 ratio to receive gefitinib(250 mg,p.o.q.d.)plus apatinib(500 mg,p.o.q.d.)or gefitinib plus placebo,given until disease progression or intolerable adverse events.Exploratory biomarker analysis will be performed.This study is being conducted across China and comprises of 30 participating centers.Enrollment commenced in August 2017 and finished in December 2018,most of the patients are in the follow-up period.Anticipated outcomes and significance:The present study will be the first to evaluate the efficacy and safety profile of the combination of apatinib plus gefitinib as a first-line therapy for patients with EGFR-positive advanced non-squamous NSCLC.Importantly,this trial will provide comprehensive evidence on the treatment of EGFR-TKIs combined with antiangiogenic therapy.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81973398, 81473283, 81730103, 81573507 and 82020108031)The National Key Research and Development Program (Grant Nos. 2017YFC0909300 and 2016YFC0905000, China)+4 种基金Guangdong Provincial Key Laboratory of Construction Foundation (Grant No. 2017B030314030, China)Science and Technology Program of Guangzhou (201607020031, China)National Engineering and Technology Research Center for New drug Druggability Evaluation (Seed Program of Guangdong Province (No. 2017B090903004, China)the 111 project (Grant: B16047, China)China Postdoctoral Science Foundation (Grant Nos. 2019M66324, 2020M683140 and 2020M683139)
文摘Hepatotoxicity is a common side effect for patients treated with gefitinib,but the related pathogenesis is unclear and lacks effective predictor and management strategies.A multi-omics approach integrating pharmacometabolomics,pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution.Here,we found that patients with rs4946935 AA,located in Forkhead Box O3(FOXO3)which is a well-known autophagic regulator,had a higher risk of hepatotoxicity than those with the GA or GG variant(OR=18.020,95%CI=2.473 to 459.1784,P=0.018)in a gefitinib-concentration dependent pattern.Furthermore,functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity,increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury.In contrast,erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3.This study reveals that FOXO3 mutation,leading to autophagic imbalance,plays important role in gefitinib-induced hepatotoxicity,especially for patients with high concentration of gefitinib.In conclusion,FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA.
基金This research was financially supported by Western Young Scholar Program-B of Chinese Academy of Sciences(No.2018-XBQNXZ-B-020)National Natural Science Foundation of China(Grant Nos.41771234 and 41803024)Open Fund of State Key Laboratory of Loess and Quaternary Geology(No.SKLLQG2011).
文摘Over the past 2000 years,a high-resolution pollen record from the Yushenkule Peat(46°45′-46°57′N,90°46′-90°61′E,2374 m a.s.l.)in the south-eastern Altai Mountains of northwestern China has been used to explore the changes in vegetation and climate.The regional vegetation has been dominated by alpine meadows revealed from pollen diagrams over the past 2000 years.The pollen-based climate was warm and wet during the Roman Warm Period(0-520 AD),cold and wet during the Dark Age Cold Period(520-900 AD),warm and wet during the Medieval Warm Period(900-1300 AD),and cold and dry during the Little Ice Age(1300-1850 AD).Combined with other pollen data from the Altai Mountains,we found that the percentage of arboreal pollen showed a reduced trend along the NW-SE gradient with decreasing moisture and increasing climatic continentality of the Altai Mountains over the past 2000 years;this is consistent with modern distributions of taiga forests.We also found that the taiga(Pinus forest)have spread slightly,while the steppe(Artemisia,Poaceae and Chenopodiaceae)have recovered significantly in the Altai Mountains over the past 2000 years.In addition,the relatively warm-wet climate may promote high grassland productivity and southward expansion of steppe,which favors the formation of Mongol political and military power.
基金This work was supported by the National Key R&D Program of China(Grant No.2016YFC0905500,2016YFC0905503)Science and Technology Program of Guangdong(Grant No.2017B020227001,2016A020215084)+3 种基金Science and Technology Program of Guangzhou(Grant No.201607020031,201400000001-2)Chinese National Natural Science Foundation Project(Grant No.81772476,81572659,81602011)Pearl River Nova Program of Guangzhou(Grant No.201610010048)National Natural Science Funds for Young Scholars of China(Grant No.81502355).
文摘Dear editor,Lung cancer is the leading cause of cancer-related death worldwide,with the predominant pathological type being non-small cell lung cancer(NSCLC)[1,2].Next-gener-ation sequencing(NGS)analysis is increasingly used to help clinicians select appropriate target therapies,such as epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)for EGFR-mutant patients[3].Both pericarcinomatous tissues and peripheral blood lymphocytes are widely used as normal control for NGS analysis.However,whether pericarcinomatous tissue is suitable for background filtering in mutation analysis remains controversial.According to the whole-genome sequencing data from The Cancer Genome Atlas(TCGA)database,there were some genomic variations in peri-carcinomatous tissue from NSCLC patients,but no driver gene mutation was detected[4,5].Therefore,deep sequencing of pericarcinomatous and tumor tissues is necessary to confirm whether pericarcinomatous tissue harbors low-frequency mutations.
基金sponsored by Qilu Pharmaceutical Co.Ltd.The study was partly funded by the Chinese National Natural Science Foundation Project(Grant No.82241232,82272789,82173101 and 82373262).
文摘First-line chemoimmunotherapy(with or without bevacizumab)has improved outcomes in advanced non-small cell lung cancer(NSCLC).Here,this open-label,multi-cohort phase II study(NCT05329025)was done to investigate the safety and efficacy of QL1706(a single bifunctional MabPair product against PD-1 and CTLA-4)and chemotherapy with or without bevacizumab in this population.Patients were enrolled into five different cohorts based on genotype(cohorts 1-4,epidermal growth factor receptor[EGFR]wild-type;cohort 5,EGFR-mutant and progressed on EGFR-tyrosine kinase inhibitors[TKIs]).Between June 11,2021 and December 29,2021,91 patients were enrolled.Most frequent treatment-related adverse events(TRAEs)included decreased appetite(60[65.9%]),anemia(60[65.9%]),infusion-related reactions(48[52.7%]),and pruritus(44[48.4%]).Grade≥3 TRAEs occurred in 30(33.0%)patients.Twenty-seven(45%)patients with wild-type EGFR achieved partial response(PR)(objective response rate[ORR]=45%)and had a median progression-free survival(mPFS)of 6.8 months(95%CI:5.2-9.7).For 31 patients harboring mutated EGFR,17(54.8%)achieved PR(ORR=54.8%),with an mPFS of 8.5 months(95%CI:5.72-not evaluable).Overall,QL1706 plus chemotherapy,regardless of having bevacizumab,was generally tolerable and had promising antitumor activity for EGFR wild-type advanced NSCLC in first-line setting.Moreover,QL1706 plus chemotherapy and bevacizumab showed favorable antitumor activity for patients who had EGFR mutated NSCLC but failed in TKI therapy,demonstrating a potential for treating this population.
