AIM： To investigate how a complex network of CC chemokine ligands （eeLs） and their receptors influence the progression of tumor and metastasis.METHODS： In the present study, we used immunohistochemistry to examine...AIM： To investigate how a complex network of CC chemokine ligands （eeLs） and their receptors influence the progression of tumor and metastasis.METHODS： In the present study, we used immunohistochemistry to examine the expression of CCL7, CCL8 and CCL21 in 194 gastric cancer samples and adjacent normal tissues. We analyzed their correlation with tumor metastasis, clinicopathologic parameters and clinical outcome.RESULTS： We found that the higher expression of CCL7 and CCL21 in cancer tissues than in normal tissues was significantly correlated with advanced depth of wall invasion, lymph node metastasis and higher tumornode metastasis stage. Moreover, Kaplan-Meier survival analysis revealed that CCL7 and CCL21 overexpression in cancer tissues was correlated with poor prognosis.CONCLUSION： These results suggest that overexpression of these two CC chemokine ligands is associ- ated with tumor metastasis and serves as a prognostic factor in patients with gastric cancer.展开更多
Objective： To obtain recombinant human CCL21 with biological activity from eukary0tic expression system for further use in cancer gene therapy. Methods： A fragment of human CCL21 gene was obtained from pSK-hCCL21 pl...Objective： To obtain recombinant human CCL21 with biological activity from eukary0tic expression system for further use in cancer gene therapy. Methods： A fragment of human CCL21 gene was obtained from pSK-hCCL21 plasmid digested by Xho I and BamH I, inserted into the responding sites of eukaryotic expression vector pVAX1, and then transfected into COS-7 cells by electroporation method. The expression of hCCL21 protein was detected by western blotting analysis. The in vitro chemotaxis assay was used to test the chemotactic function of the expression product to lymphocytes. Results： Human CCL21 protein was expressed by transfected COS-7 cells with recombinant plasmid containing hCCL21 gene, and was verified by western blotting. The in vitro chemotaxis assay demonstrated that human CCL21 protein had a potent chemotactic function to lymphocytes. Conclusion： Human CCL21 was successfully and transiently expressed in eukaryotic cells, which lays some foundation for the study of CCL21 gene therapy in murine tumor models.展开更多
Background:The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma(DLBCL)has been reported previously.However,the detailed mechanisms of CCR7 in DLBCL,particularly regarding its int...Background:The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma(DLBCL)has been reported previously.However,the detailed mechanisms of CCR7 in DLBCL,particularly regarding its interaction with lenalidomide treatment,are not fully understood.Methods:Our study utilized bioinformatics approaches to identify hub genes in SU-DHL-2 cell lines treated with lenalidomide compared to control groups.Immunohistochemical data and clinical information from 122 patients with DLBCL were analyzed to assess the correlation of CCR7 and p-ERK1/2 expression with the prognosis of DLBCL.Furthermore,in vitro and in vivo experiments were conducted to clarify the role of CCR7 in the response of DLBCL to lenalidomide treatment.Results:Our bioinformatics analysis pinpointed CCR7 as a hub gene in the context of lenalidomide treatment in DLBCL.Notably,31.14%and 36.0%(44/122)of DLBCL cases showed positive expression for CCR7 and ERK1/2 respectively,establishing them as independent prognostic factors for adverse outcomes in DLBCL via multivariate Cox regression analysis.Additionally,our studies demonstrated that the external application of the protein CCL21 promoted proliferation,migration,invasion,and activation of the ERK1/2 pathway in SU-DHL-2 and OCI-LY3 cell lines with high levels of CCR7 expression.This effect was mitigated by CCR7 silencing through siRNA,application of ERK inhibitors,or lenalidomide treatment.In vivo experiments reinforced the efficacy of lenalidomide,significantly reducing tumor growth rate,tumor mass,serum total LDH levels,and expression of CCR7 and p-ERK1/2 in a SUDHL-2 xenograft model in nude mice(p<0.05).Conclusion:Our study clarifies the potential role of the CCL21/CCR7/ERK1/2 axis in the therapeutic effects of lenalidomide in DLBCL treatment.展开更多
目的:探讨趋化因子CCL21、E选择素(E-selectins)、热休克蛋白90(heat shock protein 90,Hsp90)在实验性牙周炎大鼠牙周组织中的表达及意义。方法:选取40只10周龄雄性Wistar大鼠,随机分为4组,每组10只。A、B、C组均建立牙周炎模型,其余1...目的:探讨趋化因子CCL21、E选择素(E-selectins)、热休克蛋白90(heat shock protein 90,Hsp90)在实验性牙周炎大鼠牙周组织中的表达及意义。方法:选取40只10周龄雄性Wistar大鼠,随机分为4组,每组10只。A、B、C组均建立牙周炎模型,其余10只为空白对照组。A、B、C组分别于牙周基础治疗后4、8、12周处死并取第一、二磨牙间牙周组织进行CCL21、E-selectins、Hsp90 mRNA和蛋白表达检测。采用SPSS 25.0软件包对数据进行统计学分析。结果:A、B、C组牙周附着水平显著大于对照组(P<0.05);牙周基础治疗后,牙周附着水平呈先升高后降低趋势,牙周组织中CCL21、E-selectins、Hsp90 mRNA以及蛋白相对表达量呈降低趋势(P<0.05)。结论:CCL21、E-selectins、Hsp90mRNA在牙周炎组织中表达上调,随着牙周局部治疗,其表达水平逐渐降低。展开更多
基金Supported by Grants NSC 98-2314-B-238-001 from the National Science CouncilVIT-98-CM-01 from Vanung University,Taiwan
文摘AIM： To investigate how a complex network of CC chemokine ligands （eeLs） and their receptors influence the progression of tumor and metastasis.METHODS： In the present study, we used immunohistochemistry to examine the expression of CCL7, CCL8 and CCL21 in 194 gastric cancer samples and adjacent normal tissues. We analyzed their correlation with tumor metastasis, clinicopathologic parameters and clinical outcome.RESULTS： We found that the higher expression of CCL7 and CCL21 in cancer tissues than in normal tissues was significantly correlated with advanced depth of wall invasion, lymph node metastasis and higher tumornode metastasis stage. Moreover, Kaplan-Meier survival analysis revealed that CCL7 and CCL21 overexpression in cancer tissues was correlated with poor prognosis.CONCLUSION： These results suggest that overexpression of these two CC chemokine ligands is associ- ated with tumor metastasis and serves as a prognostic factor in patients with gastric cancer.
基金This work was supported by the National Natural Science Foundation of China (No. 3037304).
文摘Objective： To obtain recombinant human CCL21 with biological activity from eukary0tic expression system for further use in cancer gene therapy. Methods： A fragment of human CCL21 gene was obtained from pSK-hCCL21 plasmid digested by Xho I and BamH I, inserted into the responding sites of eukaryotic expression vector pVAX1, and then transfected into COS-7 cells by electroporation method. The expression of hCCL21 protein was detected by western blotting analysis. The in vitro chemotaxis assay was used to test the chemotactic function of the expression product to lymphocytes. Results： Human CCL21 protein was expressed by transfected COS-7 cells with recombinant plasmid containing hCCL21 gene, and was verified by western blotting. The in vitro chemotaxis assay demonstrated that human CCL21 protein had a potent chemotactic function to lymphocytes. Conclusion： Human CCL21 was successfully and transiently expressed in eukaryotic cells, which lays some foundation for the study of CCL21 gene therapy in murine tumor models.
基金supported by the Key Research and Development Program of Science and Technology Department of Guizhou Province(No.20204Y147).
文摘Background:The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma(DLBCL)has been reported previously.However,the detailed mechanisms of CCR7 in DLBCL,particularly regarding its interaction with lenalidomide treatment,are not fully understood.Methods:Our study utilized bioinformatics approaches to identify hub genes in SU-DHL-2 cell lines treated with lenalidomide compared to control groups.Immunohistochemical data and clinical information from 122 patients with DLBCL were analyzed to assess the correlation of CCR7 and p-ERK1/2 expression with the prognosis of DLBCL.Furthermore,in vitro and in vivo experiments were conducted to clarify the role of CCR7 in the response of DLBCL to lenalidomide treatment.Results:Our bioinformatics analysis pinpointed CCR7 as a hub gene in the context of lenalidomide treatment in DLBCL.Notably,31.14%and 36.0%(44/122)of DLBCL cases showed positive expression for CCR7 and ERK1/2 respectively,establishing them as independent prognostic factors for adverse outcomes in DLBCL via multivariate Cox regression analysis.Additionally,our studies demonstrated that the external application of the protein CCL21 promoted proliferation,migration,invasion,and activation of the ERK1/2 pathway in SU-DHL-2 and OCI-LY3 cell lines with high levels of CCR7 expression.This effect was mitigated by CCR7 silencing through siRNA,application of ERK inhibitors,or lenalidomide treatment.In vivo experiments reinforced the efficacy of lenalidomide,significantly reducing tumor growth rate,tumor mass,serum total LDH levels,and expression of CCR7 and p-ERK1/2 in a SUDHL-2 xenograft model in nude mice(p<0.05).Conclusion:Our study clarifies the potential role of the CCL21/CCR7/ERK1/2 axis in the therapeutic effects of lenalidomide in DLBCL treatment.
