BACKGROUND Patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus(RGAVCT)have a poor prognosis,with a 5-year survival rate ranging from 18.42%-53.57%.These patients need a reasonable p...BACKGROUND Patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus(RGAVCT)have a poor prognosis,with a 5-year survival rate ranging from 18.42%-53.57%.These patients need a reasonable postoperative treatment plan to improve their prognosis.AIM To determine the most effective postoperative chemotherapy regimen for patients with RGAVCT.METHODS We retrospectively collected the clinicopathological data of 530 patients who un-derwent radical resection for gastric cancer between January 2017 and January 2022 and who were pathologically diagnosed with gastric adenocarcinoma with a choroidal cancer embolus.Fur-thermore,we identified the high-risk variables that can influence the prognosis of patients with RGAVCT by asse-ssing the clinical and pathological features of the patients who met the inclusion criteria.We also assessed the significance of survival outcomes using Mantel-Cox univariate and multivariate analyses.The subgroups of pa-tients with stages Ⅰ,Ⅱ,and Ⅲ disease who received single-,dual-,or triple-drug regimens following surgery were analyzed using SPSS 25.0 and the ggplot2 package in R 4.3.0.RESULTS In all,530 eligible individuals with RGAVCT were enrolled in this study.The median overall survival(OS)of patients with RGAVCT was 24 months,and the survival rates were 80.2%,62.5%,and 42.3%at 12,24,and 59 months,respectively.Preoperative complications,tumor size,T stage,and postoperative chemotherapy were identified as independent factors that influenced OS in patients with RGAVCT according to the Cox multivariate analysis model.A Kaplan-Meier analysis revealed that chemotherapy had no effect on OS of patients with stage Ⅰ or Ⅱ RGAVCT;however,chemotherapy did have an effect on OS of stage Ⅲ patients.Stage Ⅲ patients who were treated with chemotherapy consisting of dual-or triple-agent regimens had better survival than those treated with single-agent regimens,and no significant difference was observed in the survival of patients treated with chemo-therapy consisting of dual-or triple-agent regimens.CONCLUSION For patients with stage Ⅲ RGAVCT,a dual-agent regimen of postoperative chemotherapy should be recom-mended rather than a triple-agent treatment,as the latter is associated with increased frequency of adverse events.展开更多
Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods ...Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.展开更多
BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal t...BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.展开更多
Lung cancer is the leading cause of cancer-related deaths worldwide.Bone is a common metastatic site of lung cancer,about 50%of bone metastatic patients will experience skeletal related events(SREs).SREs not only seri...Lung cancer is the leading cause of cancer-related deaths worldwide.Bone is a common metastatic site of lung cancer,about 50%of bone metastatic patients will experience skeletal related events(SREs).SREs not only seriously impact the quality of life of patients,but also shorten their survival time.The treatment of bone metastasis requires multi-disciplinary therapy(MDT)and development of individualized treatment plan.In order to standardize the diagnosis and treatment of bone metastasis in lung cancer,the expert group of the MDT Committee of the Chinese Medical Doctor Association has developed the expert consensus on the diagnosis and treatment of lung cancer bone metastasis.展开更多
Esophageal cancer(EC)is one of the most common aggressive malignant tumors in the digestive system with a severe epidemiological situation and poor prognosis.The early diagnostic rate of EC is low,and most EC patients...Esophageal cancer(EC)is one of the most common aggressive malignant tumors in the digestive system with a severe epidemiological situation and poor prognosis.The early diagnostic rate of EC is low,and most EC patients are diagnosed at an advanced stage.Multiple multimodality treatments have gradually evolved into the main treatment for advanced EC,including surgery,chemotherapy,radiotherapy,targeted therapy,and immunotherapy.And the emergence of targeted therapy and immunotherapy has greatly improved the survival of EC patients.This review highlights the latest advances in targeted therapy and immunotherapy for EC,discusses the efficacy and safety of relevant drugs,summarizes related important clinical trials,and tries to provide references for therapeutic strategy of EC.展开更多
Fluorescence-guided surgery(FGS)with tumor-targeted imaging agents,particularly those using the near-infrared wavelength,has emerged as a real-time technique to highlight the tumor location and margins during a surgic...Fluorescence-guided surgery(FGS)with tumor-targeted imaging agents,particularly those using the near-infrared wavelength,has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure.For accurate visualization of prostate cancer(PCa)boundary and lymphatic metastasis,we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe,Cy-KUE-OA,with dual PCa-membrane affinity.Cy-KUE-OA specifically targeted the prostate-specific membrane antigen(PSMA),anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect.This dual–membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models.Furthermore,the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues,PCa,and lymph node metastases.Taken together,our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.展开更多
BACKGROUND The advent of molecular targeted agents and immune checkpoint inhibitors has greatly improved the treatment of advanced renal cell carcinoma(RCC), thus significantly improving patient survival. The incidenc...BACKGROUND The advent of molecular targeted agents and immune checkpoint inhibitors has greatly improved the treatment of advanced renal cell carcinoma(RCC), thus significantly improving patient survival. The incidence of rare drug-related adverse events has gained increased attention.CASE SUMMARY We report a patient with advanced RCC treated with multiple lines of molecular targeted agents and immune checkpoint inhibitors, who developed a pulmonary infection after treatment with everolimus in combination with lenvatinib. Determining the pathogenic organism was difficult, but it was eventually identified as Pneumocystis jirovecii by next-generation sequencing(NGS) of bronchoscopic alveolar lavage fluid(BALF) and successfully treated with trimethoprim-sulfamethoxazole.CONCLUSION Rare pulmonary infections caused by molecular targeted agents are not uncommon in clinical practice, but their diagnosis is difficult. Evaluating BALF with NGS is a good method for rapid diagnosis of such infections.展开更多
Objective To compare the short-term efficacy indicators of laparoscopic technique and open surgery in patients with rectal cancer surgery,and to further evaluate the safety and efficacy of laparoscopic rectal cancer s...Objective To compare the short-term efficacy indicators of laparoscopic technique and open surgery in patients with rectal cancer surgery,and to further evaluate the safety and efficacy of laparoscopic rectal cancer surgery.Methods This study adopted a prospective multicenter,open-label,non-randomized concurrent control method to analyze patients who received rectal cancer surgery from 10 colorectal tumor centers across the country from January 2017 to December 2018.The two groups of patients received laparoscopic-assisted surgery and conventional open surgery respectively.All surgeons were selected according to relevant standards and participated in the two groups of operations at the same time.Comprehensive evaluation and analysis of the operation and postoperative recovery,postoperative pathological results,survival information,postoperative related functional scores and other indicators.Results In the open surgery group,the proportion of tumors with a maximum diameter of more than 5 cm was higher(χ^(2)=0.089,P=0.018),and the proportion of T4 was higher(χ^(2)=0.478,P<0.001).In the laparoscopic group,the proportion of more than 12 harvested lymph nodes was higher(χ^(2)=0.248,P<0.001).There were no significant differences in the length of postoperative hospital stay,intraoperative blood loss,time to first flatus after operation,time to first out of bed,time to first liquid diet,and preservation rate of anal sphincter between the two groups,but in the laparoscopic surgery group the operation time was shorter(t=6.750,P<0.001)and postoperative pain was less(t=0.896,0.63,0.964,and 0.989 on postoperative days 1,2,and 3,respectively,all P<0.001).The incidence of grade 2–4 adverse complication in the two groups was 12.5%and 14.6%,respectively,with no statistical difference(χ2=0.061,P=0.105),but the incidence of incision infection was lower in the laparoscopy group(χ^(2)=0.19,P<0.001).There was no significant difference in 3-year disease-free survival between the two groups(HR=1.089,95%CI=0.962–1.232,P=0.170).Multivariate analysis suggested that intraoperative blood loss,T stage,N stage,nerve invasion,and postoperative sepsis were independent prognostic factors for disease-free survival.Wexner score,IPSS score and LARS score were not statistically different between the two groups.Conclusion The pathological results and short-term outcomes of laparoscopic surgery for rectal cancer are comparable to those of conventional open surgery,and laparoscopic surgery is safe and feasible for rectal cancer patients.展开更多
Background:The mortality of castration-resistant prostate cancer(CRPC)is high due to lack of an effective treatment.Chimeric antigen receptor(CAR)-based therapy is a promising immunotherapeutic strategy.Here,we aimed ...Background:The mortality of castration-resistant prostate cancer(CRPC)is high due to lack of an effective treatment.Chimeric antigen receptor(CAR)-based therapy is a promising immunotherapeutic strategy.Here,we aimed to design a novel CAR-natural killer(NK)cells with a clinically significant tumoricidal effect on CRPC.Methods:We constructed novel CAR-NK92MI cells with a CD244-based recombinant lentiviral vector.Different intracellular segments(CD244,NKG2D,or CD3ζ)were screened to identify the best candidate according to cell lysis assay and CD107a expression levels.To enhance the affinity of the CAR to the tumor antigen,we compared an antibody specific for prostate-specific membrane antigen(anti-PSMA)with PSMA-targeted polypeptide(p-PSMA),which was screened by phage display combinatorial library.Then,CAR-NK92MI cells with both a high affinity for PSMA and a strong tumoricidal capacity were generated.In addition,we verified their tumor-killing effect in vitro and in vivo.The release of cytokine by NK92MI cells was compared with that by CAR-NK92MI cells through flow cytometry and enzyme-linked immunosorbent assay.Moreover,ferroptosis-related cell death was explored as a possible underlying mechanism.Results:Three different CAR intracellular regions CAR1(CD244),CAR2(CD244,NKG2D)and CAR3(CD244,NKG2D,and CD3ζ)were constructed.CAR2 was chosen to confer a stronger tumoricidal ability on CAR-NK92MI cells.Compared with anti-PSMA,p-PSMA exhibited enhanced affinity for the tumor antigen.Thus,p-PSMA-CAR-NK92MI cells,which expressed CAR with a polypeptide-based antigen-binding region,an intracellular CD244 and a NKG2D costimulatory domain,were generated.They could selectively and successfully kill PSMA+target cells and exhibited specific lysis rate of 73.19%for PSMA-positive C4-2 cells and 33.04%for PSMA-negative PC3 cells.Additionally,p-PSMA-CAR-NK92MI cells had significantly higher concentrations of IFN-γ,TNF-αand granzyme B than NK92MI cells.In a CRPC cancer xenograft model,p-PSMA-CAR-NK92MI cells significantly inhibited tumor growth and exerted a more consistent killing effect than NK92MI cells.Moreover,ferroptosis is a potential mechanism through which CAR-NK92MI cells attack cancer cells,and is triggered by IFN-γ.Conclusions:p-PSMA-CAR-NK92MI cells can effectively kill CRPCPSMA+cells in vitro and in vivo.This strategy may provide additional treatment options for patients with CRPC.展开更多
Objectives:To investigate the health-related quality of life(HRQL)of long-term survivors of inoperable esophageal squamous cell carcinoma(ESCC)treated with definitive radiation therapy,the real-world trends in the use...Objectives:To investigate the health-related quality of life(HRQL)of long-term survivors of inoperable esophageal squamous cell carcinoma(ESCC)treated with definitive radiation therapy,the real-world trends in the use of advanced radiation techniques,and their impact on the survival outcomes of ESCC patients.Methods:In this multicenter retrospective observational study,the medical records related to demographics and treatment of ESCC patients who were treated with definitive radiation therapy at 14 provincial hospitals in China from 1 January 2015 to 31 December 2016 were analyzed.A HRQL questionnaire was completed by survivors and collected by doctors at the final follow-up.The difference in quality of life between patients with or without recurrence was compared using the Wilcoxon-Mann-Whitney test.Overall survival(OS)was estimated using the Kaplan-Meier method and the group differences were assessed by unstratified log-rank test.The Cox proportional hazards model with Efron’s method of tie handling was used to calculate the risk factors for OS.Results:The data of a total of 3,308 patients were collected for this study,248 were excluded because of missing data,and a final of 3,060 patients were included in the analysis.Most patients(2,901;94.8%)received intensity-modulated radiotherapy(IMRT)/volumetric-modulated arc therapy(VMAT)/tomotherapy(TOMO).The 5-year OS rate was 30%.Patients who received either two-dimensional radiotherapy(2DRT;HR,2.43[95%CI,1.70-3.47];P<0.001)or three-dimensional radiotherapy(3DRT;HR,1.45[95%CI,1.14-1.84];P=0.003)had a significantly increased risk of death compared to those who received IMRT/VMAT/TOMO.Of the 716(23.4%)long-term survivors who completed the HRQL questionnaire,nearly 70%patients were still able to swallow normally or almost normally,and>80%patients did not experience weight loss.Nearly 80%patients found life very enjoyable or were fairly enjoying life.Conclusions:This large,multicenter retrospective study on ESCC patients who received definitive radiation ther-apy found that most ESCC survivors are satisfied with their quality of life.Most patients received advanced radiation technology.Patients who received either 2DRT or 3DRT had a significantly increased risk of death compared to those who received advanced radiation technology.展开更多
基金Supported by Shanxi Provincial Health Commission,No.20222025Four“Batches”Innovation Project of Invigorating Medical Cause through Science and Technology of Shanxi Province,No.2023XM024.
文摘BACKGROUND Patients with resectable gastric adenocarcinoma accompanied by vascular cancer thrombus(RGAVCT)have a poor prognosis,with a 5-year survival rate ranging from 18.42%-53.57%.These patients need a reasonable postoperative treatment plan to improve their prognosis.AIM To determine the most effective postoperative chemotherapy regimen for patients with RGAVCT.METHODS We retrospectively collected the clinicopathological data of 530 patients who un-derwent radical resection for gastric cancer between January 2017 and January 2022 and who were pathologically diagnosed with gastric adenocarcinoma with a choroidal cancer embolus.Fur-thermore,we identified the high-risk variables that can influence the prognosis of patients with RGAVCT by asse-ssing the clinical and pathological features of the patients who met the inclusion criteria.We also assessed the significance of survival outcomes using Mantel-Cox univariate and multivariate analyses.The subgroups of pa-tients with stages Ⅰ,Ⅱ,and Ⅲ disease who received single-,dual-,or triple-drug regimens following surgery were analyzed using SPSS 25.0 and the ggplot2 package in R 4.3.0.RESULTS In all,530 eligible individuals with RGAVCT were enrolled in this study.The median overall survival(OS)of patients with RGAVCT was 24 months,and the survival rates were 80.2%,62.5%,and 42.3%at 12,24,and 59 months,respectively.Preoperative complications,tumor size,T stage,and postoperative chemotherapy were identified as independent factors that influenced OS in patients with RGAVCT according to the Cox multivariate analysis model.A Kaplan-Meier analysis revealed that chemotherapy had no effect on OS of patients with stage Ⅰ or Ⅱ RGAVCT;however,chemotherapy did have an effect on OS of stage Ⅲ patients.Stage Ⅲ patients who were treated with chemotherapy consisting of dual-or triple-agent regimens had better survival than those treated with single-agent regimens,and no significant difference was observed in the survival of patients treated with chemo-therapy consisting of dual-or triple-agent regimens.CONCLUSION For patients with stage Ⅲ RGAVCT,a dual-agent regimen of postoperative chemotherapy should be recom-mended rather than a triple-agent treatment,as the latter is associated with increased frequency of adverse events.
基金supported by Natural Science Foundation of Shandong ProvinceChina[ZR2022MH115]the National Natural Science Foundation of China[81301479,82202593]。
文摘Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.
文摘BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.
文摘Lung cancer is the leading cause of cancer-related deaths worldwide.Bone is a common metastatic site of lung cancer,about 50%of bone metastatic patients will experience skeletal related events(SREs).SREs not only seriously impact the quality of life of patients,but also shorten their survival time.The treatment of bone metastasis requires multi-disciplinary therapy(MDT)and development of individualized treatment plan.In order to standardize the diagnosis and treatment of bone metastasis in lung cancer,the expert group of the MDT Committee of the Chinese Medical Doctor Association has developed the expert consensus on the diagnosis and treatment of lung cancer bone metastasis.
基金supported by grants from the National Natural Science Foundation of China(No.82002619)the Key Medical Research Projects of Shanxi Province(No.2020XM55)+2 种基金the Talent Introduction Scientific Research Start-up Fund of Shanxi Bethune Hospital(No.2020RC006)the special fund for Science and Technology Innovation Teams of Shanxi Province(No.202204051001031)Fundamental Research Program of Shanxi Province(No.202203021222349)
文摘Esophageal cancer(EC)is one of the most common aggressive malignant tumors in the digestive system with a severe epidemiological situation and poor prognosis.The early diagnostic rate of EC is low,and most EC patients are diagnosed at an advanced stage.Multiple multimodality treatments have gradually evolved into the main treatment for advanced EC,including surgery,chemotherapy,radiotherapy,targeted therapy,and immunotherapy.And the emergence of targeted therapy and immunotherapy has greatly improved the survival of EC patients.This review highlights the latest advances in targeted therapy and immunotherapy for EC,discusses the efficacy and safety of relevant drugs,summarizes related important clinical trials,and tries to provide references for therapeutic strategy of EC.
基金supported by the National Natural Science Foundation of China(NSFC)projects(22122705,22077139 and 81972400)CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-054 and 2021-I2M-1-015)Beijing Outstanding Young Scientist Program(BJJWZYJH01201910023028,China).
文摘Fluorescence-guided surgery(FGS)with tumor-targeted imaging agents,particularly those using the near-infrared wavelength,has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure.For accurate visualization of prostate cancer(PCa)boundary and lymphatic metastasis,we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe,Cy-KUE-OA,with dual PCa-membrane affinity.Cy-KUE-OA specifically targeted the prostate-specific membrane antigen(PSMA),anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect.This dual–membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models.Furthermore,the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues,PCa,and lymph node metastases.Taken together,our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.
文摘BACKGROUND The advent of molecular targeted agents and immune checkpoint inhibitors has greatly improved the treatment of advanced renal cell carcinoma(RCC), thus significantly improving patient survival. The incidence of rare drug-related adverse events has gained increased attention.CASE SUMMARY We report a patient with advanced RCC treated with multiple lines of molecular targeted agents and immune checkpoint inhibitors, who developed a pulmonary infection after treatment with everolimus in combination with lenvatinib. Determining the pathogenic organism was difficult, but it was eventually identified as Pneumocystis jirovecii by next-generation sequencing(NGS) of bronchoscopic alveolar lavage fluid(BALF) and successfully treated with trimethoprim-sulfamethoxazole.CONCLUSION Rare pulmonary infections caused by molecular targeted agents are not uncommon in clinical practice, but their diagnosis is difficult. Evaluating BALF with NGS is a good method for rapid diagnosis of such infections.
基金supported by Beijing Science and Technology Program[D17110002617004]Beijing Hope Run Special Fund of Cancer Foundation of China[LC2019B14 and LC2021A13].
文摘Objective To compare the short-term efficacy indicators of laparoscopic technique and open surgery in patients with rectal cancer surgery,and to further evaluate the safety and efficacy of laparoscopic rectal cancer surgery.Methods This study adopted a prospective multicenter,open-label,non-randomized concurrent control method to analyze patients who received rectal cancer surgery from 10 colorectal tumor centers across the country from January 2017 to December 2018.The two groups of patients received laparoscopic-assisted surgery and conventional open surgery respectively.All surgeons were selected according to relevant standards and participated in the two groups of operations at the same time.Comprehensive evaluation and analysis of the operation and postoperative recovery,postoperative pathological results,survival information,postoperative related functional scores and other indicators.Results In the open surgery group,the proportion of tumors with a maximum diameter of more than 5 cm was higher(χ^(2)=0.089,P=0.018),and the proportion of T4 was higher(χ^(2)=0.478,P<0.001).In the laparoscopic group,the proportion of more than 12 harvested lymph nodes was higher(χ^(2)=0.248,P<0.001).There were no significant differences in the length of postoperative hospital stay,intraoperative blood loss,time to first flatus after operation,time to first out of bed,time to first liquid diet,and preservation rate of anal sphincter between the two groups,but in the laparoscopic surgery group the operation time was shorter(t=6.750,P<0.001)and postoperative pain was less(t=0.896,0.63,0.964,and 0.989 on postoperative days 1,2,and 3,respectively,all P<0.001).The incidence of grade 2–4 adverse complication in the two groups was 12.5%and 14.6%,respectively,with no statistical difference(χ2=0.061,P=0.105),but the incidence of incision infection was lower in the laparoscopy group(χ^(2)=0.19,P<0.001).There was no significant difference in 3-year disease-free survival between the two groups(HR=1.089,95%CI=0.962–1.232,P=0.170).Multivariate analysis suggested that intraoperative blood loss,T stage,N stage,nerve invasion,and postoperative sepsis were independent prognostic factors for disease-free survival.Wexner score,IPSS score and LARS score were not statistically different between the two groups.Conclusion The pathological results and short-term outcomes of laparoscopic surgery for rectal cancer are comparable to those of conventional open surgery,and laparoscopic surgery is safe and feasible for rectal cancer patients.
基金Capital Science and Technology LeadingTalent Project, Grant/Award Number:Z181100006318007National NaturalScience Foundation of China,Grant/Award Numbers: 81972400,32100631+2 种基金Beijing Excellent TalentsProgram-Youth Backbone Project,Grant/Award Number:2018000032600G393Young EliteScientists Sponsorship Program by ChinaAssociation for Science and Technology,Grant/Award Number: YESS20210056Beijing Hope Run Special Fund of CancerFoundation of China, Grant/AwardNumber: LC2019B02。
文摘Background:The mortality of castration-resistant prostate cancer(CRPC)is high due to lack of an effective treatment.Chimeric antigen receptor(CAR)-based therapy is a promising immunotherapeutic strategy.Here,we aimed to design a novel CAR-natural killer(NK)cells with a clinically significant tumoricidal effect on CRPC.Methods:We constructed novel CAR-NK92MI cells with a CD244-based recombinant lentiviral vector.Different intracellular segments(CD244,NKG2D,or CD3ζ)were screened to identify the best candidate according to cell lysis assay and CD107a expression levels.To enhance the affinity of the CAR to the tumor antigen,we compared an antibody specific for prostate-specific membrane antigen(anti-PSMA)with PSMA-targeted polypeptide(p-PSMA),which was screened by phage display combinatorial library.Then,CAR-NK92MI cells with both a high affinity for PSMA and a strong tumoricidal capacity were generated.In addition,we verified their tumor-killing effect in vitro and in vivo.The release of cytokine by NK92MI cells was compared with that by CAR-NK92MI cells through flow cytometry and enzyme-linked immunosorbent assay.Moreover,ferroptosis-related cell death was explored as a possible underlying mechanism.Results:Three different CAR intracellular regions CAR1(CD244),CAR2(CD244,NKG2D)and CAR3(CD244,NKG2D,and CD3ζ)were constructed.CAR2 was chosen to confer a stronger tumoricidal ability on CAR-NK92MI cells.Compared with anti-PSMA,p-PSMA exhibited enhanced affinity for the tumor antigen.Thus,p-PSMA-CAR-NK92MI cells,which expressed CAR with a polypeptide-based antigen-binding region,an intracellular CD244 and a NKG2D costimulatory domain,were generated.They could selectively and successfully kill PSMA+target cells and exhibited specific lysis rate of 73.19%for PSMA-positive C4-2 cells and 33.04%for PSMA-negative PC3 cells.Additionally,p-PSMA-CAR-NK92MI cells had significantly higher concentrations of IFN-γ,TNF-αand granzyme B than NK92MI cells.In a CRPC cancer xenograft model,p-PSMA-CAR-NK92MI cells significantly inhibited tumor growth and exerted a more consistent killing effect than NK92MI cells.Moreover,ferroptosis is a potential mechanism through which CAR-NK92MI cells attack cancer cells,and is triggered by IFN-γ.Conclusions:p-PSMA-CAR-NK92MI cells can effectively kill CRPCPSMA+cells in vitro and in vivo.This strategy may provide additional treatment options for patients with CRPC.
基金supported by the Sanming Project of Medicine in Shenzhen(grant num-ber:SZSM201612063)National Natural Science Foundation of China Research(grant numbers:U22A20326,81872454,21441010)the Beijing Xisike Clinical Oncology Research Foundation(grant number:Y-MSD2020-0324).
文摘Objectives:To investigate the health-related quality of life(HRQL)of long-term survivors of inoperable esophageal squamous cell carcinoma(ESCC)treated with definitive radiation therapy,the real-world trends in the use of advanced radiation techniques,and their impact on the survival outcomes of ESCC patients.Methods:In this multicenter retrospective observational study,the medical records related to demographics and treatment of ESCC patients who were treated with definitive radiation therapy at 14 provincial hospitals in China from 1 January 2015 to 31 December 2016 were analyzed.A HRQL questionnaire was completed by survivors and collected by doctors at the final follow-up.The difference in quality of life between patients with or without recurrence was compared using the Wilcoxon-Mann-Whitney test.Overall survival(OS)was estimated using the Kaplan-Meier method and the group differences were assessed by unstratified log-rank test.The Cox proportional hazards model with Efron’s method of tie handling was used to calculate the risk factors for OS.Results:The data of a total of 3,308 patients were collected for this study,248 were excluded because of missing data,and a final of 3,060 patients were included in the analysis.Most patients(2,901;94.8%)received intensity-modulated radiotherapy(IMRT)/volumetric-modulated arc therapy(VMAT)/tomotherapy(TOMO).The 5-year OS rate was 30%.Patients who received either two-dimensional radiotherapy(2DRT;HR,2.43[95%CI,1.70-3.47];P<0.001)or three-dimensional radiotherapy(3DRT;HR,1.45[95%CI,1.14-1.84];P=0.003)had a significantly increased risk of death compared to those who received IMRT/VMAT/TOMO.Of the 716(23.4%)long-term survivors who completed the HRQL questionnaire,nearly 70%patients were still able to swallow normally or almost normally,and>80%patients did not experience weight loss.Nearly 80%patients found life very enjoyable or were fairly enjoying life.Conclusions:This large,multicenter retrospective study on ESCC patients who received definitive radiation ther-apy found that most ESCC survivors are satisfied with their quality of life.Most patients received advanced radiation technology.Patients who received either 2DRT or 3DRT had a significantly increased risk of death compared to those who received advanced radiation technology.
