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1.
目的 研究难治/复发再生障碍性贫血(AA)患者骨髓T淋巴细胞内雷帕霉素靶蛋白(mTOR)/核糖体蛋白S6途径活化情况,以及mTOR抑制剂雷帕霉素(RAPA)和CD28抗原阻断剂CTLA-4免疫球蛋白(CTLA-41g)对此途径的影响.方法 采集13例难治/复发AA、8例初治重型AA(SAA)以及1O例缺铁性贫血(IDA)患者(对照组)的骨髓标本,加入RAPA和CTLA-41g进行孵育,用流式细胞术检测加药前后每组患者CD3+T淋巴细胞胞质内磷酸化mTOR(p-mTOR)、磷酸化S6(P-S6)和干扰素-γ(IFN-γ)的表达水平,并分析其与疾病的关系.结果 ①难治/复发AA组患者骨髓CD3+T细胞胞内p-mTOR、P-S6及IFN-γ的表达水平较对照组显著升高(P值均<0.01).②初治SAA患者p-mTOR和p-S6的表达水平低于难治/复发AA组(P值均<0.01),而与对照组比较差异无统计学意义(P值均>0.05);初治组IFN-γ的表达水平明显高于对照组(P值均<0.01).③RAPA和CTLA-41g作用后,难治/复发AA患者p-mTOR、p-S6及IFN-γ的表达水平较用药前明显下降(P值均<0.01).结论 CD3+T淋巴细胞内mTOR/S6途径在难治/复发AA患者中活化.RAPA和CTLA-41g均可抑制难洽/复发AA患者体内mTOR/S6途径,并下调IFN-γ.CD28/mTOR/S6和IFN-γ途径参与难治/复发AA的免疫发病机制,并且对RAPA和CTLA-41g敏感,以CD28、mTOR为治疗靶点,临床应用RAPA和CTLA-4Ig治疗此类AA患者值得探索.  相似文献   

2.
Objective To investigate the changes of PPARγ protein expression and activity of peripheral blood lymphocytes in patients with sepsis and its association with severity and prognosis of sepsis. Method Ac-cording to the guidelines to sepsis set by ACCP/SCCM consensus conference in 2003, 48 patients with sepsis ad-mitted in Emergency and Surgical ICU from December 2007 to March 2008 were enrolled in this perspective study. Sixteen healthy individuals were selected as controls. Patients with metastatic tumors, autoimmune disease, AIDS or under immunosuppressive therapy were excluded. This study was approved by the ethical committee of Zhong-shan Hospital, Fudan University. All patients were divided into mild and severe sepsis groups. Patients were also divided into survivor and non-survivor groups as per 28-day mortality. Peripheral blood lymphocytes were isolated by using Ficoll density gradient centrifugation. PPART protein expression was determined by using Westem Blot-ting. The activity of PPARγ was analyzed by using EMSA. Differences among groups were analyzed by using one-way ANOVA. Results The protein expression and activity of PPARγ were significantly increased in mild sepsis patients (0.56±0.12 and 4.13±0.22, respectively) compared with both healthy controls (0.39±0.07 and 2.42±0.17, respectively) and severe sepsis patients (0.30±0.07 and 1.63±0.12, respectively) (P < 0.05). However, the protein expression and activity of PPARγ were obviously decreased in severe sepsis patients compared with healthy individuals and mild spsis patients (P < 0.05). Survivors from sepsis had significantly higher protein expression and activity (0.54±0.11 and 3.59±0.34, respectively) than non-survivors (0.21±0.08 and 1.94 ±0.25, respectively) (P < 0.05). Conclusions These data suggest that the protein expression and activity of PPARγ in peripheral blood lymphocytes might be valuable biomarkers in assessing the severity and outcome of pa-tients with sepsis.  相似文献   

3.
Objective To investigate the expression and significance of β-catenin and peroxisome prolifera-tot-activated receptor-γ,(PPARγ) in bepatocellular carcinoma. Methods Tissue microarrays were established to detect β-catenin and PPARγ expression in 49 cases of hepatocellular carcinoma,49 cases of adjacent nontumoral liv-er tissue and 6 cases of normal liver tissue. The relationships between PPARγ and β-catenin as well as between PPARγ and clinicopathological parameters were observed. Results The aberrant expression rate of β-catenin was 69.39%,48.98 % and 0 respectively (P=0.001). The positive expression rate of PPARγ was 51.02%,30.61% and 0 respectively (P=0.016). Clinicopathological analysis revealed that the increase of PPARγ expression was not associated with age,tumor size,serum alpha fetoprotein (AFP) levels,tumor embolus of portal vein or inferior vena cava,and HBsAg infection(χ2=0.214,3.201,0.046,3.201,P>0.05 for each),but correlated with differentiation grades(χ2=4.693,P<0.05). Aberrant expression of β-catenin was associated with PPARγ expression(χ2= 5.130,P<0.05). Conclusion Aberrant expression of β-catenin may involve in the liver carcinogenesis. The high expression of PPARγ in hepatocellular carcinoma is significantly correlated with the clinicopathological characteris-tics. Detection of PPARγ is valuable for diagnosing hepatocellular carcinoma,and evaluating malignancy extent and prognosis.  相似文献   

4.
Objective To investigate the expression and significance of β-catenin and peroxisome prolifera-tot-activated receptor-γ,(PPARγ) in bepatocellular carcinoma. Methods Tissue microarrays were established to detect β-catenin and PPARγ expression in 49 cases of hepatocellular carcinoma,49 cases of adjacent nontumoral liv-er tissue and 6 cases of normal liver tissue. The relationships between PPARγ and β-catenin as well as between PPARγ and clinicopathological parameters were observed. Results The aberrant expression rate of β-catenin was 69.39%,48.98 % and 0 respectively (P=0.001). The positive expression rate of PPARγ was 51.02%,30.61% and 0 respectively (P=0.016). Clinicopathological analysis revealed that the increase of PPARγ expression was not associated with age,tumor size,serum alpha fetoprotein (AFP) levels,tumor embolus of portal vein or inferior vena cava,and HBsAg infection(χ2=0.214,3.201,0.046,3.201,P>0.05 for each),but correlated with differentiation grades(χ2=4.693,P<0.05). Aberrant expression of β-catenin was associated with PPARγ expression(χ2= 5.130,P<0.05). Conclusion Aberrant expression of β-catenin may involve in the liver carcinogenesis. The high expression of PPARγ in hepatocellular carcinoma is significantly correlated with the clinicopathological characteris-tics. Detection of PPARγ is valuable for diagnosing hepatocellular carcinoma,and evaluating malignancy extent and prognosis.  相似文献   

5.
Objective To investigate the expression and significance of β-catenin and peroxisome prolifera-tot-activated receptor-γ,(PPARγ) in bepatocellular carcinoma. Methods Tissue microarrays were established to detect β-catenin and PPARγ expression in 49 cases of hepatocellular carcinoma,49 cases of adjacent nontumoral liv-er tissue and 6 cases of normal liver tissue. The relationships between PPARγ and β-catenin as well as between PPARγ and clinicopathological parameters were observed. Results The aberrant expression rate of β-catenin was 69.39%,48.98 % and 0 respectively (P=0.001). The positive expression rate of PPARγ was 51.02%,30.61% and 0 respectively (P=0.016). Clinicopathological analysis revealed that the increase of PPARγ expression was not associated with age,tumor size,serum alpha fetoprotein (AFP) levels,tumor embolus of portal vein or inferior vena cava,and HBsAg infection(χ2=0.214,3.201,0.046,3.201,P>0.05 for each),but correlated with differentiation grades(χ2=4.693,P<0.05). Aberrant expression of β-catenin was associated with PPARγ expression(χ2= 5.130,P<0.05). Conclusion Aberrant expression of β-catenin may involve in the liver carcinogenesis. The high expression of PPARγ in hepatocellular carcinoma is significantly correlated with the clinicopathological characteris-tics. Detection of PPARγ is valuable for diagnosing hepatocellular carcinoma,and evaluating malignancy extent and prognosis.  相似文献   

6.
Objective To investigate the expression and significance of β-catenin and peroxisome prolifera-tot-activated receptor-γ,(PPARγ) in bepatocellular carcinoma. Methods Tissue microarrays were established to detect β-catenin and PPARγ expression in 49 cases of hepatocellular carcinoma,49 cases of adjacent nontumoral liv-er tissue and 6 cases of normal liver tissue. The relationships between PPARγ and β-catenin as well as between PPARγ and clinicopathological parameters were observed. Results The aberrant expression rate of β-catenin was 69.39%,48.98 % and 0 respectively (P=0.001). The positive expression rate of PPARγ was 51.02%,30.61% and 0 respectively (P=0.016). Clinicopathological analysis revealed that the increase of PPARγ expression was not associated with age,tumor size,serum alpha fetoprotein (AFP) levels,tumor embolus of portal vein or inferior vena cava,and HBsAg infection(χ2=0.214,3.201,0.046,3.201,P>0.05 for each),but correlated with differentiation grades(χ2=4.693,P<0.05). Aberrant expression of β-catenin was associated with PPARγ expression(χ2= 5.130,P<0.05). Conclusion Aberrant expression of β-catenin may involve in the liver carcinogenesis. The high expression of PPARγ in hepatocellular carcinoma is significantly correlated with the clinicopathological characteris-tics. Detection of PPARγ is valuable for diagnosing hepatocellular carcinoma,and evaluating malignancy extent and prognosis.  相似文献   

7.
Objective To investigate the expression and significance of β-catenin and peroxisome prolifera-tot-activated receptor-γ,(PPARγ) in bepatocellular carcinoma. Methods Tissue microarrays were established to detect β-catenin and PPARγ expression in 49 cases of hepatocellular carcinoma,49 cases of adjacent nontumoral liv-er tissue and 6 cases of normal liver tissue. The relationships between PPARγ and β-catenin as well as between PPARγ and clinicopathological parameters were observed. Results The aberrant expression rate of β-catenin was 69.39%,48.98 % and 0 respectively (P=0.001). The positive expression rate of PPARγ was 51.02%,30.61% and 0 respectively (P=0.016). Clinicopathological analysis revealed that the increase of PPARγ expression was not associated with age,tumor size,serum alpha fetoprotein (AFP) levels,tumor embolus of portal vein or inferior vena cava,and HBsAg infection(χ2=0.214,3.201,0.046,3.201,P>0.05 for each),but correlated with differentiation grades(χ2=4.693,P<0.05). Aberrant expression of β-catenin was associated with PPARγ expression(χ2= 5.130,P<0.05). Conclusion Aberrant expression of β-catenin may involve in the liver carcinogenesis. The high expression of PPARγ in hepatocellular carcinoma is significantly correlated with the clinicopathological characteris-tics. Detection of PPARγ is valuable for diagnosing hepatocellular carcinoma,and evaluating malignancy extent and prognosis.  相似文献   

8.
Objective To investigate the expression and significance of β-catenin and peroxisome prolifera-tot-activated receptor-γ,(PPARγ) in bepatocellular carcinoma. Methods Tissue microarrays were established to detect β-catenin and PPARγ expression in 49 cases of hepatocellular carcinoma,49 cases of adjacent nontumoral liv-er tissue and 6 cases of normal liver tissue. The relationships between PPARγ and β-catenin as well as between PPARγ and clinicopathological parameters were observed. Results The aberrant expression rate of β-catenin was 69.39%,48.98 % and 0 respectively (P=0.001). The positive expression rate of PPARγ was 51.02%,30.61% and 0 respectively (P=0.016). Clinicopathological analysis revealed that the increase of PPARγ expression was not associated with age,tumor size,serum alpha fetoprotein (AFP) levels,tumor embolus of portal vein or inferior vena cava,and HBsAg infection(χ2=0.214,3.201,0.046,3.201,P>0.05 for each),but correlated with differentiation grades(χ2=4.693,P<0.05). Aberrant expression of β-catenin was associated with PPARγ expression(χ2= 5.130,P<0.05). Conclusion Aberrant expression of β-catenin may involve in the liver carcinogenesis. The high expression of PPARγ in hepatocellular carcinoma is significantly correlated with the clinicopathological characteris-tics. Detection of PPARγ is valuable for diagnosing hepatocellular carcinoma,and evaluating malignancy extent and prognosis.  相似文献   

9.
Objective To investigate the expression and significance of β-catenin and peroxisome prolifera-tot-activated receptor-γ,(PPARγ) in bepatocellular carcinoma. Methods Tissue microarrays were established to detect β-catenin and PPARγ expression in 49 cases of hepatocellular carcinoma,49 cases of adjacent nontumoral liv-er tissue and 6 cases of normal liver tissue. The relationships between PPARγ and β-catenin as well as between PPARγ and clinicopathological parameters were observed. Results The aberrant expression rate of β-catenin was 69.39%,48.98 % and 0 respectively (P=0.001). The positive expression rate of PPARγ was 51.02%,30.61% and 0 respectively (P=0.016). Clinicopathological analysis revealed that the increase of PPARγ expression was not associated with age,tumor size,serum alpha fetoprotein (AFP) levels,tumor embolus of portal vein or inferior vena cava,and HBsAg infection(χ2=0.214,3.201,0.046,3.201,P>0.05 for each),but correlated with differentiation grades(χ2=4.693,P<0.05). Aberrant expression of β-catenin was associated with PPARγ expression(χ2= 5.130,P<0.05). Conclusion Aberrant expression of β-catenin may involve in the liver carcinogenesis. The high expression of PPARγ in hepatocellular carcinoma is significantly correlated with the clinicopathological characteris-tics. Detection of PPARγ is valuable for diagnosing hepatocellular carcinoma,and evaluating malignancy extent and prognosis.  相似文献   

10.
Objective To investigate the expression and significance of β-catenin and peroxisome prolifera-tot-activated receptor-γ,(PPARγ) in bepatocellular carcinoma. Methods Tissue microarrays were established to detect β-catenin and PPARγ expression in 49 cases of hepatocellular carcinoma,49 cases of adjacent nontumoral liv-er tissue and 6 cases of normal liver tissue. The relationships between PPARγ and β-catenin as well as between PPARγ and clinicopathological parameters were observed. Results The aberrant expression rate of β-catenin was 69.39%,48.98 % and 0 respectively (P=0.001). The positive expression rate of PPARγ was 51.02%,30.61% and 0 respectively (P=0.016). Clinicopathological analysis revealed that the increase of PPARγ expression was not associated with age,tumor size,serum alpha fetoprotein (AFP) levels,tumor embolus of portal vein or inferior vena cava,and HBsAg infection(χ2=0.214,3.201,0.046,3.201,P>0.05 for each),but correlated with differentiation grades(χ2=4.693,P<0.05). Aberrant expression of β-catenin was associated with PPARγ expression(χ2= 5.130,P<0.05). Conclusion Aberrant expression of β-catenin may involve in the liver carcinogenesis. The high expression of PPARγ in hepatocellular carcinoma is significantly correlated with the clinicopathological characteris-tics. Detection of PPARγ is valuable for diagnosing hepatocellular carcinoma,and evaluating malignancy extent and prognosis.  相似文献   

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12.
目的探讨共刺激分子CD28/CD152:CD80/CD86在强直性脊柱炎(AS)患者外周血淋巴细胞上的表达及与免疫功能的关系。方法流式细胞仪检测AS患者及健康体检者T细胞表面标志CD3、CD4、CD8、CD19的表达及CD28/CD152和CD80/CD86在外周血T、B淋巴细胞上的表达水平;采用速率散射比浊法、酶联免疫吸附试验(ELISA)测定血清中免疫球蛋白IgG、IgA、IgM及C-反应蛋白(CRP)和白细胞介素-6(IL-6)水平。结果CD3^+CD4^+T细胞及CD4^+/CD8^+比值明显高于健康对照组(P〈0.05),而CD3^+CD8^+T细胞则明显低于健康对照组(P〈0.05);CD4^+和CD8^_T细胞上CD28和CD19^+B细胞上CD80、CD86的表达均较健康对照组增高(P〈0.05),而CD152在CD4^+T淋巴细胞上的表达也比健康对照组显著增加,但在CD8%+T淋巴细胞上的表达却显著降低(P〈0.05);血清IgG、IgA及CRP、IL-6水平均较健康对照组显著增高(P〈0.05)。结论AS患者外周血淋巴细胞CD28/CD152:CD80/CD86分子的异常表达与其免疫功能紊乱有密切关系。  相似文献   

13.
目的研究胃癌患者外周血共刺激分子CD28和细胞毒性T淋巴细胞相关抗原-4(CTLA-4,CD152)及B7分子的表达水平,以探讨胃癌患者共刺激通路是否异常以及在胃癌发病机制中的作用。方法用流式细胞仪检测56例胃癌患者外周血淋巴细胞表面的CD28、CD152、CD3、CD4、CD8及B7分子的表达,并与健康对照组及胃良性肿瘤组作比较。结果胃癌患者外周血中CD3^+、CD4^+、CD3^+CD28^+、B7-1(CD80)、B7~2(CD86)的表达水平及CD4^+/CD8^+低于健康对照组及良性肿瘤组,CD3^+、CD152^+和CD8^+水平显著增高。结论胃癌患者外周血淋巴细胞低表达CD28和B7分子,高表达CTLA-4分子,导致了胃癌患者B7:CD28/CTLA-4共刺激通路异常,影响了T细胞彻底清除肿瘤细胞,从而使肿瘤逃避机体的免疫监视、免疫抑制,发生转移。  相似文献   

14.
目的 通过对慢性乙型肝炎患者外周血中CD4+/CD25+和CD8+/CD28-调节性淋巴细胞的分析,探讨其与慢性乙型肝炎患者临床状态的关系.方法 采用流式细胞技术多色荧光分析法,对280例慢性乙型肝炎患者、28例慢性病毒携带者以及22例健康体检者外周血中CD4+/CD25+和CD8+/CD28-淋巴细胞测定.结果 慢性病毒携带者外周血中CD4+/CD25+调节性淋巴细胞为(3.23±1.37)%,明显高于慢性乙型肝炎患者(1.85±1.38)%和正常健康对照(1.59±0.54)%(P<0.05),但慢性乙型肝炎患者与正常健康对照差别无统计学意义(P>0.05);而且HBeAg阴性慢性乙型肝炎(1.66±1.09)%与HBeAg阳性慢性乙型肝炎(1.96±1.43)%比较,差别无统计学意义(P>0.05).慢性乙型肝炎患者和慢性病毒携带者外周血中CD8+CD28-调节性淋巴细胞分别为(79.53±16.07)和89.30±5.12)%,均明显高于正常健康对照(63.93±7.85)%(P<0.05);另外,HBeAg阳性慢性乙型肝炎组(87.47±17.82)%,也明显高于HBeAg阴性慢性乙型肝炎组(64.90±15.26)%(P<0.05).结论 慢性病毒携带者处于病毒携带状态可能与体内调节性淋巴胞CD4+/CD25+和CD8+/CD28-的升高有关.  相似文献   

15.
B7/CD28分子激发T细胞抗多发性骨髓瘤细胞的作用   总被引:6,自引:0,他引:6  
目的探讨B7/CD28分子激发T淋巴细胞抗多发性骨髓瘤(MM)作用和提高MM细胞抗原性的机制。方法采用人B71基因对人MM细胞的转导、CD28激发型单克隆抗体(单抗)的激发、同种异体混合淋巴细胞反应(MLR)、免疫表型分析和白细胞介素2(IL2)ELISA法定量检测。结果XG细胞转染B71cDNA后,能稳定高表达B71,转染B71cDNA前后细胞表达CD11a/CD18、CD40、CD54、CD56、CD58、B72(CD86)、CD40L、HLAⅠ和HLAⅡ抗原均无明显变化,转染B7基因后可使肿瘤细胞的抗原性明显增加,在MLR中,XG71转基因细胞较XG细胞更能显著介导CD8+T细胞的活化、增殖和IL2的分泌。CD28激发型单抗与B71分子相似,能显著介导同种异体T细胞的混合淋巴细胞反应。结论人MM细胞不能有效地激发T细胞抗肿瘤的主要原因之一为其不表达B71分子,转染B71分子或者加入CD28激发型单抗均能有效地提高肿瘤细胞的抗原性和对T细胞的激发作用,CD28激发型单抗临床治疗MM更具有可行性。  相似文献   

16.
目的:探讨CD8^+CD28^+T细胞钙离子浓度的变化与心脏移植急性排斥反应(AR)的相关关系。方法:用流式细胞仪检测正常SD大鼠组(T0组)、同种心脏移植组(T1)(Wistar→SD大鼠)术后第1、3、5、7天CD8^+CD28^+T细胞内钙离子浓度的变化,分析CD8^+CD28^+T细胞内钙离子浓度的变化与心脏移植AR程度的相关关系。结果:CD8^+CD28^+T细胞内钙离子浓度升高与AR严重程度成正相关,相关系数为0.469,相关具有显著性(P〈0.05)。结论:心脏移植后CD8^+CD28^+T细胞内钙离子浓度显著升高,其升高程度与AR严重程度成正相关。  相似文献   

17.
背景:大量研究显示,肿瘤患者外周血T细胞表面共刺激分子CD28蛋白表达存在差异,提示共刺激通路异常可能与恶性肿瘤的发生进展有关.目的:观察急性髓细胞性白血病外周血单个核细胞共刺激信号分子CD28 mRNA在中的表达.方法:急性髓细胞性白血病患者80例,其中M0型7例,M1型6例,M2型18例,M3型15例,M4型17例,M5型9例,M6型8例.并根据急性白血病疗效标准将80例患者分为完全治愈组、缓解组、未缓解组.采用Taqman探针实时荧光定量PCR检测80例患者及76名健康人群外周血单个核细胞CD28 mRNA的表达.结果与结论:急性髓细胞性白血病外周血单个核细胞M1,M3和M4亚型中的CD28 mRNA表达量低于健康人群 (P < 0.05);急性髓细胞性白血病未缓解组中CD28 mRNA低于健康人群 (P < 0.05),完全治愈组和缓解组中CD28 mRNA表达与健康人群差异无显著性意义.说明急性髓细胞白血病患者外周血单个核细胞存在CD28 mRNA表达缺陷,并与临床分期、病情进展及预后有关.  相似文献   

18.
目的研究胃癌患者肿瘤浸润淋巴细胞CD8^+CD28^+细胞及CD8^+CD28^-细胞数量与外周血CD8^+CD28^+细胞及CD8^+CD28^-细胞数量的相关性。方法采用流式细胞术对60例胃癌患者的肿瘤浸润淋巴细胞及外周血淋巴细胞的CD8^+CD28^+细胞及CD8^+CD28^-细胞进行检测,采用直线相关分析两者的相关性。结果胃癌患者外周血淋巴细胞CD8^+CD28^-、CD8^+CD28^+细胞分别为(26.13±8.17)%和(8.15±4.00)%;肿瘤组织中肿瘤浸润淋巴细胞CD8^+CD28^-、CD8^+CD28^+细胞分别为(36.98±15.30)%、(6.02±4.37)%。两者之间具有正相关性(r分别为0.602、0.387,P〈0.01)。结论胃癌患者外周血CD8^+CD28^-、CD8^+CD28^+细胞的检测对了解患者的免疫状况具有一定的价值。  相似文献   

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