Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell p...Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line- CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/ M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMPI. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.展开更多
BACKGROUND Bone metastasis has various negative impacts.Activities of daily living(ADL)and quality of life(QOL)can be significantly decreased,survival may be impacted,and medical expenses may increase.It is estimated ...BACKGROUND Bone metastasis has various negative impacts.Activities of daily living(ADL)and quality of life(QOL)can be significantly decreased,survival may be impacted,and medical expenses may increase.It is estimated that at least 5%cancer patients might be suffering from bone metastases.In 2016,we published the Comprehensive Guidelines for the Diagnosis and Treatment of Bone Metastasis.Since then,the therapeutic outcomes for patients have gradually improved.As life expectancy is a major determinant of surgical intervention,the strategy should be modified if the prolongation of survival is to be achieved.AIM To monitor how bone metastasis treatment has changed before and after launch of our guidelines for bone metastasis.METHODS For advanced cancer patients with bone metastasis who visited the Department of Clinical Oncology at Akita University hospital between 2012 and 2023,parameters including the site and number of bone metastases,laboratory data,and survival time,were extracted from electronic medical records and the Katagiri score was calculated.The association with survival was determined for each factor.RESULTS Data from 136 patients were obtained.The 1-year survival rate for the poor prognosis group with a higher Katagiri score was 20.0%in this study,which was 6%and an apparent improvement from 2014 when the scoring system was developed.Other factors significantly affecting survival included five or more bone metastases than less(P=0.0080),and treatment with chemotherapy(P<0.001),bone modifying agents(P=0.0175)and immune checkpoint inhibitors(P=0.0128).In recent years,advances in various treatment methods have extended the survival period for patients with advanced cancer.It is necessary not only to simply extend survival time,but also to maintain ADL and improve QOL.CONCLUSION Various therapeutic interventions including surgical approach for bone metastasis,which is a disorder of locomotor organs,are increasingly required.Guidelines and scoring system for prognosis need to be revised promptly.展开更多
Dostarlimab,a programmed death receptor-1(PD-1)-blocking IgG4 humanized monoclonal antibody,gained accelerated approval from the US Food and Drug Administration(FDA)in April 2021,and received a full approval in Februa...Dostarlimab,a programmed death receptor-1(PD-1)-blocking IgG4 humanized monoclonal antibody,gained accelerated approval from the US Food and Drug Administration(FDA)in April 2021,and received a full approval in February 2023.Dostarlimab was approved for treating adult patients with mismatch repair deficient(dMMR)recurrent or advanced endometrial cancer(EC)that progressed during or after prior treatment who have no other suitable treatment options.Herein,we review the structure-based mechanism of action of dostarlimab and the results of a clinical study(GARNET;NCT02715284)to comprehensively clarify the efficacy and toxicity of the drug.The efficacy and safety of dostarlimab as monotherapy was assessed in a non-randomized,multicenter,open-label,multi-cohort trial that included 209 patients with dMMR recurrent or advanced solid tumors after receiving systemic therapy.Patients received 500 mg of dostarlimab intravenously every three weeks until they were given four doses.Then,patients received 1000 mg dostarlimab intravenously every six weeks until disease progression or unacceptable toxicity.The overall response rate,as determined by shrinkage in tumor size,was 41.6%(95%confidence interval[CI];34.9,48.6),with 34.7 months as the median response duration.In conclusion,dostarlimab is an immunotherapy-based drug that has shown promising results in adult patients with recurrent or advanced dMMR EC.However,its efficacy in other cancer subtypes,the development of resistance to monotherapy,and efficacy and safety in combination with other immunotherapeutic drugs have not yet been studied.展开更多
基金National Nature Science Foundation for Distinguished Young Scholar of China (No.39525022)National Basic Research Program(No.2004CB518703) National Nature Science Foundation of China (No.30570085).
文摘Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line- CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/ M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMPI. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.
文摘BACKGROUND Bone metastasis has various negative impacts.Activities of daily living(ADL)and quality of life(QOL)can be significantly decreased,survival may be impacted,and medical expenses may increase.It is estimated that at least 5%cancer patients might be suffering from bone metastases.In 2016,we published the Comprehensive Guidelines for the Diagnosis and Treatment of Bone Metastasis.Since then,the therapeutic outcomes for patients have gradually improved.As life expectancy is a major determinant of surgical intervention,the strategy should be modified if the prolongation of survival is to be achieved.AIM To monitor how bone metastasis treatment has changed before and after launch of our guidelines for bone metastasis.METHODS For advanced cancer patients with bone metastasis who visited the Department of Clinical Oncology at Akita University hospital between 2012 and 2023,parameters including the site and number of bone metastases,laboratory data,and survival time,were extracted from electronic medical records and the Katagiri score was calculated.The association with survival was determined for each factor.RESULTS Data from 136 patients were obtained.The 1-year survival rate for the poor prognosis group with a higher Katagiri score was 20.0%in this study,which was 6%and an apparent improvement from 2014 when the scoring system was developed.Other factors significantly affecting survival included five or more bone metastases than less(P=0.0080),and treatment with chemotherapy(P<0.001),bone modifying agents(P=0.0175)and immune checkpoint inhibitors(P=0.0128).In recent years,advances in various treatment methods have extended the survival period for patients with advanced cancer.It is necessary not only to simply extend survival time,but also to maintain ADL and improve QOL.CONCLUSION Various therapeutic interventions including surgical approach for bone metastasis,which is a disorder of locomotor organs,are increasingly required.Guidelines and scoring system for prognosis need to be revised promptly.
文摘Dostarlimab,a programmed death receptor-1(PD-1)-blocking IgG4 humanized monoclonal antibody,gained accelerated approval from the US Food and Drug Administration(FDA)in April 2021,and received a full approval in February 2023.Dostarlimab was approved for treating adult patients with mismatch repair deficient(dMMR)recurrent or advanced endometrial cancer(EC)that progressed during or after prior treatment who have no other suitable treatment options.Herein,we review the structure-based mechanism of action of dostarlimab and the results of a clinical study(GARNET;NCT02715284)to comprehensively clarify the efficacy and toxicity of the drug.The efficacy and safety of dostarlimab as monotherapy was assessed in a non-randomized,multicenter,open-label,multi-cohort trial that included 209 patients with dMMR recurrent or advanced solid tumors after receiving systemic therapy.Patients received 500 mg of dostarlimab intravenously every three weeks until they were given four doses.Then,patients received 1000 mg dostarlimab intravenously every six weeks until disease progression or unacceptable toxicity.The overall response rate,as determined by shrinkage in tumor size,was 41.6%(95%confidence interval[CI];34.9,48.6),with 34.7 months as the median response duration.In conclusion,dostarlimab is an immunotherapy-based drug that has shown promising results in adult patients with recurrent or advanced dMMR EC.However,its efficacy in other cancer subtypes,the development of resistance to monotherapy,and efficacy and safety in combination with other immunotherapeutic drugs have not yet been studied.
