BACKGROUND Recently, more and more studies have demonstrated the pivotal role of programmed death 1/programmed death ligand 1(PD-1/PD-L1) pathway in the immune evasion of tumors from the host immune system. However, t...BACKGROUND Recently, more and more studies have demonstrated the pivotal role of programmed death 1/programmed death ligand 1(PD-1/PD-L1) pathway in the immune evasion of tumors from the host immune system. However, the role of PD-1/PD-L1 pathway in gastric neuroendocrine carcinomas(G-NECs) remains unknown.AIM To investigate the expression of PD-1/PD-L1 and role of PD-1/PD-L1 pathway in G-NECs, which occur rarely but are highly malignant and clinically defiant.METHODS We investigated the expression of PD-L1 on tumor cells and PD-1^+, CD8^+, and FOXP3^+ T cell infiltration by immunohistochemistry in 43 resected G-NEC tissue specimens. The copy number alterations of PD-L1 were assessed by qRT-PCR.RESULTS Most of the G-NECs tumor cells exhibited a near-uniform expression pattern of PD-L1, while some showed a tumor-stromal interface enhanced pattern. Of the 43G-NECs, 21(48.8%) were classified as a high PD-L1 expression group, and the high expression of PD-L1 was associated with poor overall survival(OS). The high expression of PD-L1 was correlated with abundant PD-1^+ tumor infiltrating lymphocytes(TILs) instead of CD8^+ TILs and FOXP3^+ regulatory T cells(Tregs).Our analysis also suggested that the infiltration of CD8^+ TILs tended to be a favorable factor for OS, although the difference did not reach the statistical significance(P = 0.065). Meanwhile, PD-L1 was significantly overexpressed in cases with copy number gain as compared with those without.CONCLUSION Our data demonstrated for the first time that high expression of PD-L1 in GNECs is associated with a poor prognosis, while the high expression may be due to the copy number variation of PD-L1 gene or stimulation of TILs. These results provide a basis for the immunotherapy targeting PD-1/PD-L1 pathway in GNECs.展开更多
Background:Nasopharyngeal carcinoma is a malignant tumor,well known as a cancer type characterized by regional specificity,especially in Southern China.The network pharmacology is an emerging discipline developed in r...Background:Nasopharyngeal carcinoma is a malignant tumor,well known as a cancer type characterized by regional specificity,especially in Southern China.The network pharmacology is an emerging discipline developed in recent years,which has been effectively used to predict the potential therapeutic compounds against disease focusing on the possible therapeutic targets and mechanisms.Sanguinarine,a traditional natural plant-derived phenanthridine alkaloid,has been reported to have a wide variety of pharmacological activities for decades.Methods:In the current study,using the comprehensive network pharmacological method,the potential drug targets of sanguinarine against nasopharyngeal carcinoma were successfully predicted,and verified by molecular docking.The underlying pharmacological mechanism was initially unraveled.Results:Totally,38 potential common targets were confirmed from these potential nasopharyngeal carcinoma therapeutic targets and pharmacological targets of sanguinarine.Their enrichment analyses of GO functions show that protein serine/threonine kinase activity,histone kinase activity,integrin binding,protein tyrosine kinase activity,and cell adhesion molecule binding were top listed.KEGG functional enrichment analysis indicates that the potential pathways are mainly involved into PI3K-Akt signaling pathway.The"drug-target-disease-pathway"network model diagram points out the key genes containing MAPK10,MAPK14,JAK2,BRAF,GSK3B,MET,HSP90AA1,SRC,et al..According to the results of molecular docking,it was further verified that sanguinarine has strong binding ability with MAPK10 and MAPK14.Conclusion:Taken together,this study would provide a clarified theoretical basis for the subsequent wet laboratory research focusing on sanguinarine against nasopharyngeal carcinoma.展开更多
This paper is concerned with optimal harvesting control of a first order partial differential equation system representing a nonlinear n-dimensional competitive population model with age-structure. By the Ekeland＇s v...This paper is concerned with optimal harvesting control of a first order partial differential equation system representing a nonlinear n-dimensional competitive population model with age-structure. By the Ekeland＇s variational principle, the existence and unique char- acterization of the optimal control strategy are established. The optimality conditions for the control problem are obtained by the concept of the normal cone.展开更多
基金Supported by Municipal Commission of Health and Family Planning of Shanghai,China(No.20174Y0243 to Liu DJ,No.20154Y0163 to Chen XJ)Cultivating Funds of Renji Hospital,School of Medicine,Shanghai Jiao Tong University,China(No.PYXJS 16-002 to Liu W)
文摘BACKGROUND Recently, more and more studies have demonstrated the pivotal role of programmed death 1/programmed death ligand 1(PD-1/PD-L1) pathway in the immune evasion of tumors from the host immune system. However, the role of PD-1/PD-L1 pathway in gastric neuroendocrine carcinomas(G-NECs) remains unknown.AIM To investigate the expression of PD-1/PD-L1 and role of PD-1/PD-L1 pathway in G-NECs, which occur rarely but are highly malignant and clinically defiant.METHODS We investigated the expression of PD-L1 on tumor cells and PD-1^+, CD8^+, and FOXP3^+ T cell infiltration by immunohistochemistry in 43 resected G-NEC tissue specimens. The copy number alterations of PD-L1 were assessed by qRT-PCR.RESULTS Most of the G-NECs tumor cells exhibited a near-uniform expression pattern of PD-L1, while some showed a tumor-stromal interface enhanced pattern. Of the 43G-NECs, 21(48.8%) were classified as a high PD-L1 expression group, and the high expression of PD-L1 was associated with poor overall survival(OS). The high expression of PD-L1 was correlated with abundant PD-1^+ tumor infiltrating lymphocytes(TILs) instead of CD8^+ TILs and FOXP3^+ regulatory T cells(Tregs).Our analysis also suggested that the infiltration of CD8^+ TILs tended to be a favorable factor for OS, although the difference did not reach the statistical significance(P = 0.065). Meanwhile, PD-L1 was significantly overexpressed in cases with copy number gain as compared with those without.CONCLUSION Our data demonstrated for the first time that high expression of PD-L1 in GNECs is associated with a poor prognosis, while the high expression may be due to the copy number variation of PD-L1 gene or stimulation of TILs. These results provide a basis for the immunotherapy targeting PD-1/PD-L1 pathway in GNECs.
基金This research was funded by the Project for Department of Science and Technology of Guangxi Zhuang Autonomous Region,China,grant number Guike AB19110052the Natural Science Foundation of Guangxi,China,grant number 2015GXNSFAA139215the National Natural Science Foundation of China,grant number 81260405.
文摘Background:Nasopharyngeal carcinoma is a malignant tumor,well known as a cancer type characterized by regional specificity,especially in Southern China.The network pharmacology is an emerging discipline developed in recent years,which has been effectively used to predict the potential therapeutic compounds against disease focusing on the possible therapeutic targets and mechanisms.Sanguinarine,a traditional natural plant-derived phenanthridine alkaloid,has been reported to have a wide variety of pharmacological activities for decades.Methods:In the current study,using the comprehensive network pharmacological method,the potential drug targets of sanguinarine against nasopharyngeal carcinoma were successfully predicted,and verified by molecular docking.The underlying pharmacological mechanism was initially unraveled.Results:Totally,38 potential common targets were confirmed from these potential nasopharyngeal carcinoma therapeutic targets and pharmacological targets of sanguinarine.Their enrichment analyses of GO functions show that protein serine/threonine kinase activity,histone kinase activity,integrin binding,protein tyrosine kinase activity,and cell adhesion molecule binding were top listed.KEGG functional enrichment analysis indicates that the potential pathways are mainly involved into PI3K-Akt signaling pathway.The"drug-target-disease-pathway"network model diagram points out the key genes containing MAPK10,MAPK14,JAK2,BRAF,GSK3B,MET,HSP90AA1,SRC,et al..According to the results of molecular docking,it was further verified that sanguinarine has strong binding ability with MAPK10 and MAPK14.Conclusion:Taken together,this study would provide a clarified theoretical basis for the subsequent wet laboratory research focusing on sanguinarine against nasopharyngeal carcinoma.
文摘This paper is concerned with optimal harvesting control of a first order partial differential equation system representing a nonlinear n-dimensional competitive population model with age-structure. By the Ekeland＇s variational principle, the existence and unique char- acterization of the optimal control strategy are established. The optimality conditions for the control problem are obtained by the concept of the normal cone.
