H3K27me3和EZH2在弥漫大B细胞淋巴瘤疗效预测中的意义

目的:探讨H3K27me3及其甲基转移酶EZH2在对弥漫大B细胞淋巴瘤(DLBCL)近期疗效和远期预后的预测意义。方法:收集福建省肿瘤医院102例初治DLBCL石蜡标本,利用TMA技术已制成的组织芯片,应用免疫组织化学方法检测H3K27me3、EZH2、BCL-2等蛋白表达,收集临床治疗后评价情况和随访信息,并结合组织芯片检测H3K27me3、EZH2、BCL-2表达情况,生存分析应用Kaplan-Meier法,Pearson相关性分析EZH2与H3K27me3表达及BCL-2的相关性,spearman相关分析上述指标与不同疗效间的相关性,比较EZH2、H3K27me3表达及两者共表达与患者疗效及预后关系。结果:EZH2高表达者占61.8%,与H3K27me3及BCL-2蛋白高表达均正相关。H3K27me3高表达及H3K27me3/EZH2共表达组完全缓解(CR)和总有效(OR)率均低于低表达组(P0.001),OS、PFS均差于低表达组(P0.001);在RCHOP组中,EZH2低表达者CR和OR率均高于高表达者(P=0.003,P=0.019),OS和PFS均优于高表达者。结论:在部分DLBCL存在EZH2高表达及H3K27me3/EZH2共表达,该类型治疗反应差,生存期短。EZH2低表达患者群体使用RCHOP方案的近期疗效及远期生存率较高表达者有改善。     

树突状细胞与肿瘤的免疫治疗

尽管化学治疗和放射治疗的进步明显提高了肿瘤治疗的缓解率 ,延长了患者的生存期 ,但许多肿瘤尚无法治愈 ,因此有必要发展其它治疗方法 ,尤其是抗肿瘤的免疫疗法。树突状细胞 (DCs)在激发 T细胞免疫方面起重要作用 ,可能成为抗肿瘤免疫疗法理想的佐剂 ,值得研究和开发。1　肿瘤抗原和抗肿瘤免疫肿瘤细胞表面存在可被 T细胞识别的抗原 ,这是抗肿瘤细胞免疫的基础 ,也是开展抗肿瘤特异性免疫治疗的前提。这些被认为具肿瘤特异性的抗原 (TSA)包括 [1 ] :(1)变异的蛋白 ,如 K- ras,p5 3,erb B2 等 ;(2 )染色体易位产生的融合基因产物 ,如在…     

强直性脊柱炎外周血破骨细胞前体细胞活性的研究

Objective To investigate the number of osteoclast (OC) precursor in the peripheral blood of patients with ankylosing spondylitis (AS) and its relationship with serum receptor activator of nuclear factor KB-ligand (RANKL) and Osteoprotegerin (OPG) concentration as well as the disease activity. Methods The peripheral blood mononuclear cells from 8 cases of AS patients and 5 healthy controls were cultured in the medium containing macrophage colony-stimulating factor (M-CSF) (25 ng/ml) and RANKL (40 ng/ml). After being cultured for 14 days, cytochemistry was applied to detect tartrate-resistant acid phosphatase (TRAP) expression and the cells with TRAP expression and ≥3 nuclei were counted and defined as OC. Bone resorption assay was used to demonstrate OC function. ELISA was used to measure serum RANKL and OPG concentration in 23 cases of AS and 17 healthy controls. The relationship was analyzed in AS patients between the number of OC precursors and serum RANKL and OPG concentration as well as the disease activity. The indicators of disease activity were Bath ankylosing spondylitis disease activity index (BASDAI), Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). T test, t' test and Spearman correlation were selec-ted. Results ① Significantly higher OC production was observed in the peripheral blood of AS patients than that of healthy control group. The OC number per ten fields was 10.9±3.4 and 6.2±1.3 respectively (P<0.05); ② There was significant difference between AS patients and healthy controls in serum concentration of OPG and RANKL and the ratio of RANKL/OPG. OPG was significantly higher in AS patients [(157±49) pg/ml] than in healthy controls [(105±20) pg/ml] (P<0.05). RANKL was significantly higher in AS patients [(5.4± 3.8) pg/ml] than in healthy controls [(1.6±0.8) pg/ml] (P<0.05). The ratio of RANKL/OPG was significantly higher in AS patients (0.037±0.026) than in healthy controls (0.016±0.008) (P<0.01 );③Significantly positive correlation was observed between the OC number and the serum concentration of RANKL (r=0.692, P=0.009), the ratio of RANKL/OPG (r=0.813, P=0.001);④ In AS patients, serum concentration of OPG was found to have significantly negative correlation with BASDAI (r=-0.444, P=0.044). Serum RANKL concentration was found to have significantly positive correlation with BASDAI (r=0.543, P=0.011). The ratio of RANKL/OPG was found to have significantly positive correlation with BASDAI (r=0.672, P=0.001). Conclusion ① More OC precursors exist in the peripheral blood of AS patients. These cells may differentiate into osteoclasts, which might play a role in joints destructions in AS;② The mechanism of high OC production is likely to be due to high RANKL concentration which is caused by inflammatory reaction.     

蛋白酶体抑制剂在治疗骨髓瘤骨病中的作用

进行性骨质破坏和新骨形成障碍是骨髓瘤骨病(MBD)的病理基础.MBD的发生与多发性骨髓瘤(MM)细胞的增殖密切相关,从而形成广泛性骨质破坏和MM进展的恶性循环.蛋白酶体抑制剂在MM中发挥抗肿瘤的作用已经得到了肯定.近年来临床前期研究和临床试验研究均证实,该类药物还可抑制破骨细胞分化与骨吸收,促进成骨细胞的骨形成,因此能调节患者的骨重建过程.由于蛋白酶体抑制剂不仅治疗MM本身,其对MBD潜在的治疗作用也备受关注,本文就此作一综述.     

热休克蛋白70-hom基因多态性与强直性脊柱炎的相关性

目的　探讨热休克蛋白 70 - hom(heat shock protein70 - hom,HSP70 - hom)基因多态性与强直性脊柱炎的关系。方法　应用聚合酶链反应 -限制性片段长度多态性方法检测了 98例强直性脊柱炎(ankylosing spondylitis,AS)患者和 70名正常人的 HSP70 - hom基因第 2 4 37核苷酸的 Nco 限制酶位点的多态性。结果　 HSP70 - hom各基因型频率在 AS组中分别为 6 0 .2 % (AA)、35 .7% (AB)和 4 .1% (BB) ,在对照者中分别为 5 8.6 % (AA)、38.6 % (AB)和 2 .9% (BB) ,两组之间的基因型频率分布的比较 ,差异无显著性(χ2 =0 .2 80 ,P>0 .0 5 ) ;AA和 BB的等位基因频率在 AS组中分别为 77.9%和 2 2 .1% ,在对照者中分别为78.1%和 2 1.9% ,两者比较 ,差异无显著性 (χ2 =0 .0 0 2 ,P>0 .0 5 )。结论　 HSP70 - hom基因多态性不是影响中国人 AS患者致病的主要因素。     

系统性红斑狼疮患者早发动脉粥样硬化的临床研究

目的 评估系统性红斑狼疮(SLE)早发动脉粥样硬化的情况.方法 选取SLE患者中未绝经女性44例,并以健康青中年女性31例作为对照,检测2组患者的颈动脉内膜中层厚度(CIMT)及臂踝脉搏波速度(baPWV),并进行统计学比较.结果 CIMT检查,SLE组中有2例存在颈动脉斑块(CAP),年龄分别为45、49岁,且病程均...     

甲氨喋呤治疗强直性脊柱炎的系统评价

目的评价甲氨喋呤(MTX)治疗强直性脊柱炎(AS)的疗效和副作用。方法计算机检索CENTRAL(Cochrane图书馆2005年第4期)、MEDLINE (1966～2005．11)、EMbase(1980～2005．11)和CINAHL(1982～2005．11)中的相关文献,语种不限。纳入所有MTX治疗AS的随机对照试验和半随机对照试验,由两名评价员独立纳入试验和提取资料,并对其方法学质量进行评价。对符合纳入标准的研究采用RevMan 4．2软件进行Meta分析。结果共纳入3个随机对照试验(n=116例)。Meta分析结果显示,在改善身体功能、疼痛、脊柱活动度、外周关节/附着点疼痛、肿胀和压痛、脊柱放射学变化、以及患者和医生总体评价等主要结局指标方面,用与不用MTX比较,其差异无统计学意义。唯一的阳性结果是,有1个试验显示MTX组与安慰剂组相比,缓解率提高36%[RR 3．18,95%CI(1．03,9．79)]。该试验中判定缓解的根据是综合晨僵、身体健康状况、Bath强直性脊柱炎活动指数(BASDAI)、Bath强直性脊柱炎功能指数(BASFI)、健康评定问卷(HAQ-S)、患者和医生总体评价等7项指标的变化值,而对所有这些指标的终点值进行分析发现。没有一项显示MTX组与安慰剂组之间有统计学差异。因此,MTX治疗强直性脊柱炎是否有益,值得怀疑。纳入的试验没有报告MTX有严重的副作用。结论目前尚没有足够的证据显示MTX对AS患者有益。还需要开展更多高质量、大样本和更长疗程的随机对照试验,验证MTX治疗强直性脊柱炎的疗效和安全性。中国循证医学杂志,2007,7(4):260～266．     

自身免疫性溶血性贫血患者输血的临床问题

输血是治疗自身免疫性溶血性贫血（ＡＩＨＡ），特别是严重ＡＩＨＡ的手段之一，然而由于患者血液中自身抗体的存在使ＡＩＨＡ的输血问题变得复杂，一般教科书上在叙述ＡＩＨＡ的治疗时，对输血问题均强调“谨慎”或“尽量避免”，不少临床医生对ＡＩＨＡ的输血望而却步，...     

骨髓间充质干细胞抑制淋巴瘤细胞增殖的实验研究

间充质干细胞（MSC）具有向肿瘤细胞定向迁移并且抑制肿瘤细胞的特性,然而其分子机理目前尚不清楚。本研究主要探讨B7-H4在骨髓MSC细胞株C3H10 T1/2（C3H10）体外对淋巴瘤细胞株EL-4增殖的影响。应用细胞免疫荧光法检测C3H10细胞中B7-H4的表达情况;利用脂质体转染法将绿色荧光素标记的FAM-siRNA转染C3H10细胞,通过荧光显微镜及流式细胞仪检测并评估siRNA的转染效率;利用RT-PCR方法测定不同浓度的siRNA-B7-H4干预C3H10细胞后B7-H4的mRNA表达水平;将单独培养的EL-4细胞作为对照组,B7-H4不同程度沉默后的C3H10细胞与EL-4细胞共培养作为实验组,48 h后通过倒置显微镜观察及CCK-8检测法比较EL-4细胞的增殖情况。结果表明：利用INTERFERinTM转染试剂转染C3H10的效率可达到72.43%,C3H10细胞中高表达B7-H4,利用siRNA技术使B7-H4表达下调可逆转C3H10对淋巴瘤细胞株EL-4增殖的抑制作用。结论：骨髓MSC细胞株C3H10可能通过表达B7-H4发挥对淋巴瘤细胞株EL-4增殖的抑制作用,这将为临床治疗淋巴瘤提供新靶点、新方向。