Objective:To investigate the correlation and overlaps between PD-L1 expression and classical genomic aberrations in Chinese lung adenocarcinoma(LADC)patients.Methods:We reviewed 428 consecutive,surgically resected cas...Objective:To investigate the correlation and overlaps between PD-L1 expression and classical genomic aberrations in Chinese lung adenocarcinoma(LADC)patients.Methods:We reviewed 428 consecutive,surgically resected cases of LADC from October 2015 to December 2016 from our center.PD-L1 expression was evaluated based on tumor proportion score(TPS).Correlation and co-occurrence of PD-L1 expression level with those of classical driver genes,such as EGFR,ALK,ROS-1,and KRAS and with clinical variables and disease-free survival(DFS)were analyzed.Results:Seventy of the 428 cases(16.4%)showed TPS≥1%,and 21 cases(4.9%)showed TPS≥50%.PD-L1 positive expression was significantly associated with male gender,smoking,advanced TNM stage,and solid histologic subtype.Both TPS≥1% and ≥50%were correlated with the absence of an EGFR mutation(P<0.001)and the presence of ALK rearrangement(P=0.024).KRAS mutation was associated with TPS≥50%(P=0.035).PD-L1 positivity commonly overlapped with the alterations of classical driver oncogenes(58.5%with TPS≥1% and 42.9% with TPS≥50%).Approximately three-quarters of PD-L1 positive cases co-occurred with classical therapeutic-gene aberrations in cases with stage III/IV cancer or cancer progression.LADC could be divided into four subgroups based on the expression profile of current routine biomarkers for potential therapeutic strategies.Conclusions:PD-L1 expression is not only closely correlated with classic gene alterations but also commonly overlaps with the aberrations of classical driver oncogenes in Chinese LADC patients.These findings provide a useful overview of clinical strategies that rely on the profile of routinely used molecular biomarkers.展开更多
AIM: To investigate the effects of sleeve gastrectomy on adipose tissue infiltration and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression in rat aortas. METHODS: Twenty-four rats were randomi...AIM: To investigate the effects of sleeve gastrectomy on adipose tissue infiltration and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression in rat aortas. METHODS: Twenty-four rats were randomized into three groups: normal chow (control), high fat diet (HD) and high fat diet with sleeve gastrectomy (SG). After surgery, the HD and SG groups were fed a high fat diet. Animals were sacrificed and plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) levels were determined. LOX-1 protein and LOX-1 mRNA expression was also measured. Aortas were stained with Nile red to visualize adipose tissue. RESULT: Body weights were higher in the HD group compared to the other groups. HDL levels in control,HD, and SG groups were 32.9 ± 6.2 mg/dL, 43.4 ± 4.0 mg/dL and 37.5 ± 4.3 mg/dL, respectively. LDL levels in control, HD, and SG groups were 31.8 ± 4.5 mg/dL, 53.3 ± 5.1 mg/dL and 40.5 ± 3.7 mg/dL, respectively. LOX-1 protein and LOX-1 mRNA expression was greater in the HD group versus the other groups. Staining for adipose tissue in aortas was greater in the HD group in comparison to the other groups. Thus, a high fat diet elevates LOX-1 protein and mRNA expression in aorta. CONCLUSION: Sleeve gastrectomy decreases plasma LDL levels, and downregulates LOX-1 protein and mRNA expression.展开更多
Programmed cell death protein 1(PD-1)/programmed cell death ligand 1(PD-L1)blockade is an important therapeutic strategy for melanoma,despite its low clinical response.It is important to identify genes and pathways th...Programmed cell death protein 1(PD-1)/programmed cell death ligand 1(PD-L1)blockade is an important therapeutic strategy for melanoma,despite its low clinical response.It is important to identify genes and pathways that may reflect the clinical outcomes of this therapy in patients.We analyzed clinical dataset GSE96619,which contains clinical information from five melanoma patients before and after anti-PD-1 therapy(five pairs of data).We identified 704 DEGs using these five pairs of data,and then the number of DEGs was narrowed down to 286 in patients who responded to treatment.Next,we performed KEGG pathway enrichment and constructed a DEG-associated protein-protein interaction network.Smooth muscle actin 2(ACTA2)and tyrosine kinase growth factor receptor(KDR)were identified as the hub genes,which were significantly downregulated in the tumor tissue of the two patients who re-sponded to treatment.To confirm our analysis,we demonstrated similar expression tendency to the clinical data for the two hub genes in a B16F10 subcutaneous xeno-graft model.This study demonstrates that ACTA2 and KDR are valuable responsive markers for PD-1/PD-L1 blockade therapy.展开更多
Immune checkpoint inhibitors(ICIs)therapy targeting programmed cell death ligand 1(PD-L1)and programmed death protein 1(PD-1)had exhibited significant clinical benefits for cancer treatment such as triple negative bre...Immune checkpoint inhibitors(ICIs)therapy targeting programmed cell death ligand 1(PD-L1)and programmed death protein 1(PD-1)had exhibited significant clinical benefits for cancer treatment such as triple negative breast cancer(TNBC).However,the relatively low anti-tumor immune response rate and ICIs drug resistance highlight the necessity of developing ICIs combination therapy strategies to improve the anti-tumor effect of immunotherapy.Herein,the immunomodulator epigallocatechin gallate palmitate(PEGCG)and the immunoadjuvant metformin(MET)self-assembled into tumor-targeted micelles via hydrogen bond and electrostatic interaction,which encapsulated the therapeutic agents doxorubicin(DOX)-loaded PEGCG-MET micelles(PMD)and combined with ICIs(anti-PD-1 antibody)as therapeutic strategy to reduce the endogenous expression of PD-L1 and improve the tumor immunosuppressive microenvironment.The results presented that PMD integrated chemotherapy and immunotherapy to enhance antitumor efficacy in vitro and in vivo,compared with DOX or anti-PD-1 antibody for the therapy of TNBC.PMD micelles might be a potential candidate,which could remedy the shortcomings of antibody-based ICIs and provide synergistic effect to enhance the antitumor effects of ICIs in tumor therapy.展开更多
目的:探讨HMGB1基因过表达和沉默对子宫内膜癌增殖与侵袭能力的影响及其机制。方法:构建含有HMGB1重组质粒和HMGB1 sh RNA的慢病毒载体并转染人子宫内膜癌HEC-1A,建立过表达和沉默HMGB1基因的HEC-1A细胞株。采用细胞增殖/毒性活性检测...目的:探讨HMGB1基因过表达和沉默对子宫内膜癌增殖与侵袭能力的影响及其机制。方法:构建含有HMGB1重组质粒和HMGB1 sh RNA的慢病毒载体并转染人子宫内膜癌HEC-1A,建立过表达和沉默HMGB1基因的HEC-1A细胞株。采用细胞增殖/毒性活性检测试剂盒(cell counting kit-8)、Transwell小室、细胞划痕实验分析HMGB1过表达和沉默对子宫内膜癌HEC-1A细胞生长、增殖、侵袭及转移的影响。采用Western印迹和反转录PCR(reverse transcriptionPCR,RT-PCR)检测过表达和沉默HMGB1后HEC-1A细胞中NF-κB,VEGF及基质金属蛋白酶2(matrix metalloproteinase2,MMP2)的表达情况。结果:过表达HMGB1能够促进子宫内膜癌HEC-1A细胞增殖、侵袭与转移,且HEC-1A细胞中NF-κB,VEGF及MMP2表达上调;干扰HMGB1表达抑制HEC-1A细胞增殖、侵袭与转移,HEC-1A细胞中NF-κB,VEGF及MMP2表达下调。结论:HMGB1与子宫内膜癌增殖、侵袭与转移密切相关,且可能通过NF-κB,VEGF及MMP2影响子宫内膜癌的侵袭与转移;HMGB1可能成为治疗子宫内膜癌的一个重要靶点。展开更多
目的:研究大肠癌组织中高迁移率族蛋白1(high mobility group box 1,HMGB1)的表达,并探讨其与癌分化程度、肿瘤大小以及转移的关系。加入不同浓度丁酸钠后,观察SW620细胞中HMGB1的表达情况,以及不同药物浓度对癌细胞增殖活性的影响,从...目的:研究大肠癌组织中高迁移率族蛋白1(high mobility group box 1,HMGB1)的表达,并探讨其与癌分化程度、肿瘤大小以及转移的关系。加入不同浓度丁酸钠后,观察SW620细胞中HMGB1的表达情况,以及不同药物浓度对癌细胞增殖活性的影响,从而探讨HMGB1与大肠癌细胞增殖活性的关系。方法:免疫组织化学法检测70例大肠癌组织、70例癌旁组织、70例正常大肠组织HMGB1蛋白表达;培养SW620细胞,MTT法检测SW620细胞增殖情况,计算抑制率,绘制抑制率曲线;免疫细胞化学法检测HMGB1蛋白表达情况。结果:HMGB1在大肠癌中呈强阳性表达(80.0%),在癌旁组织中仅有微弱表达,正常大肠组织无表达;HMGB1的阳性率与癌分化程度无关(P>0.05);与肿瘤的大小、浸润、淋巴及血道转移呈正相关(P<0.01);加入不同浓度丁酸钠后,对SW620细胞生长均有抑制作用,且丁酸钠的抑制作用与药物浓度和作用时间呈现一定的正相关;同时,随着药物浓度的增加,HMGB1的表达也有所下降。结论:HMGB1在大肠癌中呈强阳性表达,HMGB1与大肠癌的转移与增殖有着密切的联系,可作为大肠癌生长、转移及预后的重要判定指标。展开更多
基金supported by the National Natural Science Foundation of China (Grant No. 81871860)
文摘Objective:To investigate the correlation and overlaps between PD-L1 expression and classical genomic aberrations in Chinese lung adenocarcinoma(LADC)patients.Methods:We reviewed 428 consecutive,surgically resected cases of LADC from October 2015 to December 2016 from our center.PD-L1 expression was evaluated based on tumor proportion score(TPS).Correlation and co-occurrence of PD-L1 expression level with those of classical driver genes,such as EGFR,ALK,ROS-1,and KRAS and with clinical variables and disease-free survival(DFS)were analyzed.Results:Seventy of the 428 cases(16.4%)showed TPS≥1%,and 21 cases(4.9%)showed TPS≥50%.PD-L1 positive expression was significantly associated with male gender,smoking,advanced TNM stage,and solid histologic subtype.Both TPS≥1% and ≥50%were correlated with the absence of an EGFR mutation(P<0.001)and the presence of ALK rearrangement(P=0.024).KRAS mutation was associated with TPS≥50%(P=0.035).PD-L1 positivity commonly overlapped with the alterations of classical driver oncogenes(58.5%with TPS≥1% and 42.9% with TPS≥50%).Approximately three-quarters of PD-L1 positive cases co-occurred with classical therapeutic-gene aberrations in cases with stage III/IV cancer or cancer progression.LADC could be divided into four subgroups based on the expression profile of current routine biomarkers for potential therapeutic strategies.Conclusions:PD-L1 expression is not only closely correlated with classic gene alterations but also commonly overlaps with the aberrations of classical driver oncogenes in Chinese LADC patients.These findings provide a useful overview of clinical strategies that rely on the profile of routinely used molecular biomarkers.
基金Supported by A Grant from the National Natural Science Foundation of China, No. 81000158the Special Fund for Technology of Liaoning Province, No. L2010591
文摘AIM: To investigate the effects of sleeve gastrectomy on adipose tissue infiltration and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) expression in rat aortas. METHODS: Twenty-four rats were randomized into three groups: normal chow (control), high fat diet (HD) and high fat diet with sleeve gastrectomy (SG). After surgery, the HD and SG groups were fed a high fat diet. Animals were sacrificed and plasma high density lipoprotein (HDL) and low density lipoprotein (LDL) levels were determined. LOX-1 protein and LOX-1 mRNA expression was also measured. Aortas were stained with Nile red to visualize adipose tissue. RESULT: Body weights were higher in the HD group compared to the other groups. HDL levels in control,HD, and SG groups were 32.9 ± 6.2 mg/dL, 43.4 ± 4.0 mg/dL and 37.5 ± 4.3 mg/dL, respectively. LDL levels in control, HD, and SG groups were 31.8 ± 4.5 mg/dL, 53.3 ± 5.1 mg/dL and 40.5 ± 3.7 mg/dL, respectively. LOX-1 protein and LOX-1 mRNA expression was greater in the HD group versus the other groups. Staining for adipose tissue in aortas was greater in the HD group in comparison to the other groups. Thus, a high fat diet elevates LOX-1 protein and mRNA expression in aorta. CONCLUSION: Sleeve gastrectomy decreases plasma LDL levels, and downregulates LOX-1 protein and mRNA expression.
基金This work was supported by the CAMS Innovation Fund for Medical Sciences[2017-I2M-1-010].
文摘Programmed cell death protein 1(PD-1)/programmed cell death ligand 1(PD-L1)blockade is an important therapeutic strategy for melanoma,despite its low clinical response.It is important to identify genes and pathways that may reflect the clinical outcomes of this therapy in patients.We analyzed clinical dataset GSE96619,which contains clinical information from five melanoma patients before and after anti-PD-1 therapy(five pairs of data).We identified 704 DEGs using these five pairs of data,and then the number of DEGs was narrowed down to 286 in patients who responded to treatment.Next,we performed KEGG pathway enrichment and constructed a DEG-associated protein-protein interaction network.Smooth muscle actin 2(ACTA2)and tyrosine kinase growth factor receptor(KDR)were identified as the hub genes,which were significantly downregulated in the tumor tissue of the two patients who re-sponded to treatment.To confirm our analysis,we demonstrated similar expression tendency to the clinical data for the two hub genes in a B16F10 subcutaneous xeno-graft model.This study demonstrates that ACTA2 and KDR are valuable responsive markers for PD-1/PD-L1 blockade therapy.
基金the projects of the National Key Research and Development Program(No.2021YFA0716702)the National Natural Science Foundation of China(Nos.61805122,22022404 and 22074050)+5 种基金Green Industry Science and Technology Leading Project of Hubei University of Technology(No.XJ2021003301)the National Natural Science Foundation of Hubei Province(No.2022CFA033)supported by Chinese Society of Clinical Oncology(CSCO)supported by Jiangsu Hengrui Cancer Research Foundation(No.YHR2019–0325)supported by the Fundamental Research Funds for the Central Universities(No.CCNU22QN007)supported by the Opening Fund from the Jiangsu Key Laboratory of Medical Optics,Suzhou Institute of Biomedical Engineering and Technology(No.JKLMO202203)supported by the Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science,MO(No.M2022–5).
文摘Immune checkpoint inhibitors(ICIs)therapy targeting programmed cell death ligand 1(PD-L1)and programmed death protein 1(PD-1)had exhibited significant clinical benefits for cancer treatment such as triple negative breast cancer(TNBC).However,the relatively low anti-tumor immune response rate and ICIs drug resistance highlight the necessity of developing ICIs combination therapy strategies to improve the anti-tumor effect of immunotherapy.Herein,the immunomodulator epigallocatechin gallate palmitate(PEGCG)and the immunoadjuvant metformin(MET)self-assembled into tumor-targeted micelles via hydrogen bond and electrostatic interaction,which encapsulated the therapeutic agents doxorubicin(DOX)-loaded PEGCG-MET micelles(PMD)and combined with ICIs(anti-PD-1 antibody)as therapeutic strategy to reduce the endogenous expression of PD-L1 and improve the tumor immunosuppressive microenvironment.The results presented that PMD integrated chemotherapy and immunotherapy to enhance antitumor efficacy in vitro and in vivo,compared with DOX or anti-PD-1 antibody for the therapy of TNBC.PMD micelles might be a potential candidate,which could remedy the shortcomings of antibody-based ICIs and provide synergistic effect to enhance the antitumor effects of ICIs in tumor therapy.
文摘目的:研究大肠癌组织中高迁移率族蛋白1(high mobility group box 1,HMGB1)的表达,并探讨其与癌分化程度、肿瘤大小以及转移的关系。加入不同浓度丁酸钠后,观察SW620细胞中HMGB1的表达情况,以及不同药物浓度对癌细胞增殖活性的影响,从而探讨HMGB1与大肠癌细胞增殖活性的关系。方法:免疫组织化学法检测70例大肠癌组织、70例癌旁组织、70例正常大肠组织HMGB1蛋白表达;培养SW620细胞,MTT法检测SW620细胞增殖情况,计算抑制率,绘制抑制率曲线;免疫细胞化学法检测HMGB1蛋白表达情况。结果:HMGB1在大肠癌中呈强阳性表达(80.0%),在癌旁组织中仅有微弱表达,正常大肠组织无表达;HMGB1的阳性率与癌分化程度无关(P>0.05);与肿瘤的大小、浸润、淋巴及血道转移呈正相关(P<0.01);加入不同浓度丁酸钠后,对SW620细胞生长均有抑制作用,且丁酸钠的抑制作用与药物浓度和作用时间呈现一定的正相关;同时,随着药物浓度的增加,HMGB1的表达也有所下降。结论:HMGB1在大肠癌中呈强阳性表达,HMGB1与大肠癌的转移与增殖有着密切的联系,可作为大肠癌生长、转移及预后的重要判定指标。
