BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and...BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and chemotherapy;but recently,more and more studies have shown that the stress trauma caused by surgery and the side effects of radiotherapy and chemotherapy seriously affect the prognosis of patients.AIM To determine the significance of 125I radioactive seed implantation on growth differentiation factor 11(GDF11)and programmed death receptor-1(PD-1)during treatment of OC.METHODS A total of 184 OC patients admitted to The Second Affiliated Hospital of Jiamusi University from May 2015 to May 2017 were selected as the research subjects for prospective analysis.Of these patients,89 who received 125I radioactive seed implantation therapy were regarded as the research group(RG)and 95 patients who received surgical treatment were regarded as the control group(CG).The clinical efficacy,incidence of adverse reactions and changes in GDF11 and PD-1 before treatment(T0),2 wk after treatment(T1),4 wk after treatment(T2)and 6 wk after treatment(T3)were compared between the two groups.RESULTS The efficacy and recurrence rate in the RG were better than those in the CG(P<0.05),while the incidence of adverse reactions and survival rate were not different.There was no difference in GDF11 and PD-1 between the two groups at T0 and T1,but these factors were lower in the RG than in the CG at T2 and T3(P<0.05).Using receiver operating characteristic(ROC)curve analysis,GDF11 and PD-1 had good predictive value for efficacy and recurrence(P<0.001).CONCLUSION 125I radioactive seed implantation has clinical efficacy and can reduce the recurrence rate in patients with OC.This therapy has marked potential in clinical application.The detection of GDF11 and PD-1 in patients during treatment showed good predictive value for treatment efficacy and recurrence in OC patients,and may be potential targets for future OC treatment.展开更多
OBJECTIVE To evaluate whether the IDO1 inhibitor 1-methyl-L-tryptophan(1-MT)combine calcium influx inhibitor carboxyamidotriazole(CAI)could further enhance the suppression of programmed death 1(PD-1)in CD8^+T cells an...OBJECTIVE To evaluate whether the IDO1 inhibitor 1-methyl-L-tryptophan(1-MT)combine calcium influx inhibitor carboxyamidotriazole(CAI)could further enhance the suppression of programmed death 1(PD-1)in CD8^+T cells and investigate the curative effect of the combined use.METHODS CD8^+T cells were isolated from normal mice spleen by negative selection using magnetic cell separation.The isolated CD8^+T cells were cultured in RPMI 1640 medium containing 10%FBS and 100 U·mL^(-1)IL-2 and activated by the addition of anti-CD3 and anti-CD28(1 g·L^(-1) each mabs).CD8^+T cells were pretreated for 48 h with drug and the fluo-3 as a marker of intracellular calcium concentration was detected by flow cytometry.The calcineurin(Ca N)levels were assayed with ELISA in CD8^+T cells after 48 h incubation with 10μm CAI.The nuclear translocations of NFAT and AHR were detected by immunofluorescent staining after 48 h of drug treatment.The expression of PD-1 in CD8^+T cells was analyzed by flow cytometry.RESULTS Intracellular fluorescent intensity was markedly debase due to CAI treatment(P<0.01).Meanwhile,the changes of CaN content had a resembled correlation(P<0.01).Immunofluorescence experiment showed that after combination therapy the transfer of NFAT and AHR in nuclear substantially reduced.Flow cytometry revealed that after the combination caused a significant decrease in PD-1 expression in CD8^+T cells.CONCLUSION CAI and 1-MT could inhibit markedly the expression of PD-1 in CD8^+T cells by inhibiting the nuclear translocation of NFAT and AHR,respectively and the combination of them has synergetic effect.展开更多
目的探讨胃癌组织中核转录因子-κB(nuclear factor kappa B,NF-κB)、程序性细胞死亡蛋白-1(programmed cell death protein-1,PD-1)、程序性细胞死亡蛋白配体-1(programmed cell death protein ligand 1,PD-L1)的表达及其临床意义。...目的探讨胃癌组织中核转录因子-κB(nuclear factor kappa B,NF-κB)、程序性细胞死亡蛋白-1(programmed cell death protein-1,PD-1)、程序性细胞死亡蛋白配体-1(programmed cell death protein ligand 1,PD-L1)的表达及其临床意义。方法选择2021年1月至2023年12月于南阳市第一人民医院治疗的62例胃癌患者手术切除后组织标本及癌旁正常组织标本分别作为胃癌组及癌旁组。62例患者中,男39例,女23例,年龄(61.86±2.31)岁,肿瘤长径(4.92±0.53)cm。采用免疫组织化学染色法检测NF-κB、PD-1、PD-L1表达情况。比较两组NF-κB、PD-1、PD-L1表达阳性率,分析其与胃癌临床病理特征的关系。采用χ^(2)检验。结果胃癌组NF-κB、PD-1、PD-L1表达阳性率高于癌旁组[83.87%(52/62)比33.87%(21/62)、75.81%(47/62)比30.65%(19/62)、80.65%(50/62)比40.32%(25/62)],差异均有统计学意义(χ^(2)=32.008、25.396、21.088,均P<0.05);肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者NF-κB表达阳性率高于黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[92.68%(38/41)比66.67%(14/21)、94.74(36/38)比66.67%(16/24)、92.31%(36/39)比69.57%(16/23)],差异均有统计学意义(χ^(2)=5.158、6.619、3.978,均P<0.05);肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者PD-1表达阳性率高于黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[85.37%(35/41)比57.14%(14/21)、89.47%(34/38)比54.17%(13/24)、89.74%(35/39)比52.17%(12/23)],差异均有统计学意义(χ^(2)=6.031、9.998、11.135,均P<0.05);低分化、肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者PD-L1表达阳性率高于高中分化、黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[96.00%(24/25)比70.27%(26/37)、90.24%(37/41)比61.90%(13/21)、92.11%(35/38)比62.50%(15/24)、94.87%(37/39)比56.52%(13/23)],差异均有统计学意义(χ^(2)=4.787、5.445、6.472、11.286,均P<0.05)。结论胃癌组织中NF-κB、PD-1、PD-L1表达阳性率升高,且NF-κB、PD-1表达与胃癌浸润深度、淋巴结转移及TNM分期有关,PD-L1表达与胃癌分化程度、浸润深度、淋巴结转移及TNM分期有关。展开更多
目的本研究拟证明卵巢癌细胞基因修复功能损伤的程度和程序性死亡配体-1(Programmed death ligand-1,PD-L1)之间的关系,为PD-L1治疗卵巢癌提供依据。方法采用卵巢癌组织芯片(tissue microarray,TMA)样本,非小细胞肺癌TMA为对照。采用辅...目的本研究拟证明卵巢癌细胞基因修复功能损伤的程度和程序性死亡配体-1(Programmed death ligand-1,PD-L1)之间的关系,为PD-L1治疗卵巢癌提供依据。方法采用卵巢癌组织芯片(tissue microarray,TMA)样本,非小细胞肺癌TMA为对照。采用辅助损伤修复检测(repair assisted damage detection,RADD)法和改良的RADD法检测DNA损伤及修复功能缺陷水平。应用免疫组化方法观察卵巢肿瘤细胞中DNA损伤和PD-L1蛋白表达,采用激光共聚焦显微镜对TMAs内的每个组织核芯进行成像并行图像采集。记录每个核芯的荧光强度,绘制图像并计算二者的相关性。结果RADD法和改良RADD法都能有效的检测出肿瘤组织中的DNA损伤水平,其中改良的RADD(mRADD)法检出水平更高。卵巢肿瘤中DNA氧化损伤的发生率很高。随着DNA氧化损伤水平增加,PD-L1在肿瘤中的表达也随之增加。与正常组织相比,高级别浆液性腺癌和子宫内膜样腺癌的DNA损伤水平差异最明显。而且PD-L1表达和DNA损伤水平有很好的相关性。相关性分析发现,采用改良RADD法检测高级别浆液性癌和子宫内膜样腺癌的DNA损伤水平与PD-L1之间都具有良好的相关性。卵巢粘液性腺癌中的DNA损伤水平与PD-L1表达的相关性最高。结论卵巢癌DNA氧化损伤或其与PD-L1协同表达关系可能是改善PD-L1阻断治疗有效性分类筛选中的一个潜在生物标志物。展开更多
基金Supported by Heilongjiang Provincial Health and Family Planning Commission Research Project,No.2017-413
文摘BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and chemotherapy;but recently,more and more studies have shown that the stress trauma caused by surgery and the side effects of radiotherapy and chemotherapy seriously affect the prognosis of patients.AIM To determine the significance of 125I radioactive seed implantation on growth differentiation factor 11(GDF11)and programmed death receptor-1(PD-1)during treatment of OC.METHODS A total of 184 OC patients admitted to The Second Affiliated Hospital of Jiamusi University from May 2015 to May 2017 were selected as the research subjects for prospective analysis.Of these patients,89 who received 125I radioactive seed implantation therapy were regarded as the research group(RG)and 95 patients who received surgical treatment were regarded as the control group(CG).The clinical efficacy,incidence of adverse reactions and changes in GDF11 and PD-1 before treatment(T0),2 wk after treatment(T1),4 wk after treatment(T2)and 6 wk after treatment(T3)were compared between the two groups.RESULTS The efficacy and recurrence rate in the RG were better than those in the CG(P<0.05),while the incidence of adverse reactions and survival rate were not different.There was no difference in GDF11 and PD-1 between the two groups at T0 and T1,but these factors were lower in the RG than in the CG at T2 and T3(P<0.05).Using receiver operating characteristic(ROC)curve analysis,GDF11 and PD-1 had good predictive value for efficacy and recurrence(P<0.001).CONCLUSION 125I radioactive seed implantation has clinical efficacy and can reduce the recurrence rate in patients with OC.This therapy has marked potential in clinical application.The detection of GDF11 and PD-1 in patients during treatment showed good predictive value for treatment efficacy and recurrence in OC patients,and may be potential targets for future OC treatment.
基金supported by National Natural Science Foundation of China(81402943)CAMS Major Collaborative Innovation Project(2016-I2M-1-011)PUMC Youth Fund(3332015168)
文摘OBJECTIVE To evaluate whether the IDO1 inhibitor 1-methyl-L-tryptophan(1-MT)combine calcium influx inhibitor carboxyamidotriazole(CAI)could further enhance the suppression of programmed death 1(PD-1)in CD8^+T cells and investigate the curative effect of the combined use.METHODS CD8^+T cells were isolated from normal mice spleen by negative selection using magnetic cell separation.The isolated CD8^+T cells were cultured in RPMI 1640 medium containing 10%FBS and 100 U·mL^(-1)IL-2 and activated by the addition of anti-CD3 and anti-CD28(1 g·L^(-1) each mabs).CD8^+T cells were pretreated for 48 h with drug and the fluo-3 as a marker of intracellular calcium concentration was detected by flow cytometry.The calcineurin(Ca N)levels were assayed with ELISA in CD8^+T cells after 48 h incubation with 10μm CAI.The nuclear translocations of NFAT and AHR were detected by immunofluorescent staining after 48 h of drug treatment.The expression of PD-1 in CD8^+T cells was analyzed by flow cytometry.RESULTS Intracellular fluorescent intensity was markedly debase due to CAI treatment(P<0.01).Meanwhile,the changes of CaN content had a resembled correlation(P<0.01).Immunofluorescence experiment showed that after combination therapy the transfer of NFAT and AHR in nuclear substantially reduced.Flow cytometry revealed that after the combination caused a significant decrease in PD-1 expression in CD8^+T cells.CONCLUSION CAI and 1-MT could inhibit markedly the expression of PD-1 in CD8^+T cells by inhibiting the nuclear translocation of NFAT and AHR,respectively and the combination of them has synergetic effect.
文摘目的探讨胃癌组织中核转录因子-κB(nuclear factor kappa B,NF-κB)、程序性细胞死亡蛋白-1(programmed cell death protein-1,PD-1)、程序性细胞死亡蛋白配体-1(programmed cell death protein ligand 1,PD-L1)的表达及其临床意义。方法选择2021年1月至2023年12月于南阳市第一人民医院治疗的62例胃癌患者手术切除后组织标本及癌旁正常组织标本分别作为胃癌组及癌旁组。62例患者中,男39例,女23例,年龄(61.86±2.31)岁,肿瘤长径(4.92±0.53)cm。采用免疫组织化学染色法检测NF-κB、PD-1、PD-L1表达情况。比较两组NF-κB、PD-1、PD-L1表达阳性率,分析其与胃癌临床病理特征的关系。采用χ^(2)检验。结果胃癌组NF-κB、PD-1、PD-L1表达阳性率高于癌旁组[83.87%(52/62)比33.87%(21/62)、75.81%(47/62)比30.65%(19/62)、80.65%(50/62)比40.32%(25/62)],差异均有统计学意义(χ^(2)=32.008、25.396、21.088,均P<0.05);肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者NF-κB表达阳性率高于黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[92.68%(38/41)比66.67%(14/21)、94.74(36/38)比66.67%(16/24)、92.31%(36/39)比69.57%(16/23)],差异均有统计学意义(χ^(2)=5.158、6.619、3.978,均P<0.05);肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者PD-1表达阳性率高于黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[85.37%(35/41)比57.14%(14/21)、89.47%(34/38)比54.17%(13/24)、89.74%(35/39)比52.17%(12/23)],差异均有统计学意义(χ^(2)=6.031、9.998、11.135,均P<0.05);低分化、肌层及浆膜层浸润、有淋巴结转移及Ⅲ+Ⅳ期患者PD-L1表达阳性率高于高中分化、黏膜及黏膜下层浸润、无淋巴结转移及Ⅰ+Ⅱ期患者[96.00%(24/25)比70.27%(26/37)、90.24%(37/41)比61.90%(13/21)、92.11%(35/38)比62.50%(15/24)、94.87%(37/39)比56.52%(13/23)],差异均有统计学意义(χ^(2)=4.787、5.445、6.472、11.286,均P<0.05)。结论胃癌组织中NF-κB、PD-1、PD-L1表达阳性率升高,且NF-κB、PD-1表达与胃癌浸润深度、淋巴结转移及TNM分期有关,PD-L1表达与胃癌分化程度、浸润深度、淋巴结转移及TNM分期有关。
