多发性骨髓瘤患者骨髓白细胞介素-6及其受体表达的改变及意义

目的为进一步探讨白细胞介素-6(interleukin-6,IL-6)及其受体(interleukin-6receptor,IL-6R,包括细胞膜受体IL-6R,可溶性受体sIL-6R,信号传导链GP130)与人多发性骨髓瘤发病的关系.方法本研究用MTT法、双抗体夹心ELISA法、原位杂交及RT-PCR方法检测了8例多发性骨髓瘤患者骨髓上清及其骨髓单个核细胞IL-6和IL-6R的表达情况.结果与正常人比较,患者骨髓上清中有较高水平的IL-6及sIL-6R,并且患者骨髓单个核细胞有IL-6、IL-6R、GP130mRNA的异常表达.结论IL-6及其受体的异常可能参与多发性骨髓瘤的发病.     

多发性骨髓瘤患者白细胞介素-6及其受体变化研究

多发性骨髓瘤(MM)是B淋巴细胞克隆性增生疾病。目前病因与发病机制不清，但已肯定多种细胞因子参与其调节，尤以白细胞介素-6(IL-6)的作用最为重要和关键。研究表明，在MM患者的血清中，IL-6及白细胞介素-6可溶性受体(sIL-6R)均存在较高水平，但各家报道结果有-定差异。本文检测了11例MM患者血清中IL-6、sIL-6R水平，并探讨其临床意义，现报告如下。     

白细胞介素2和6对肝癌细胞表达血管内皮生长因子D的调节

目的探讨白细胞介素(IL)-2和IL-6对肝癌细胞表达血管内皮生长因子(VEGF)-D的调节。方法采用由IL-2或IL-6分别对肝癌细胞株SMMC-7721和BEL-7402进行刺激,采取逆转录-聚合酶链式反应技术(RT-PCR)观察其VEGF-D基因表达。结果 IL-2使细胞株SMMC-7721和BEL-7402产生VEGF-D mRNA减少;IL-6对肝癌细胞株BEL-7402 VEGF-D mRNA表达存在促进效果,但是无法从作用时间上来显著判断。IL-6对肝癌细胞株SMML-7721 VEGF-D mRNA表达存在促进效果,当浓度条件满足情况下,促进作用和作用时间存在正相关。结论抑制肝癌细胞VEGF-D mRNA的表达方面,IL-2作用比较明显,对肝癌淋巴转移能够形成一定作用;肝癌细胞BEL-7402和SMML-7721 VEGF-D mRNA的表达方面,IL-6带来的促进效果明显,但是对肝癌作用需更多研究。     

多发性骨髓瘤患者血清白细胞介素-6含量与临床骨病关系的研究

目的:探讨血清白细胞介素(IL)-6水平与多发性骨髓瘤(MM)及其MM骨病的关系。方法:MM组37例,其中0分组10例,1分组6例,2分组8例,3分组11例,用ELISA方法检测血清IL-6的水平。结果:①MM组和实体瘤骨转移组血清IL-6水平明显高于正常对照组(P<0.05);②各骨损评分组间IL-6水平差异有统计学意义(P<0.05);③血钙正常组和异常组间的IL-6水平存在显著不同(P<0.05)。结论:MM患者血清IL-6水平升高,且IL-6的水平与MM骨损程度密切相关。     

三氧化二砷治疗多发性骨髓瘤的疗效及其作用机制

用三氧化二砷（AS2O3）治疗难治复发性多发性骨髓瘤（MM）患者（治疗组）13例,采用ELISA法及ABC-HRP法检测正常者（对照组）和治疗组的血清血管内皮生长因子（VEGF）、IL-6水平。结果治疗组治疗前VEGF和IL-6均明显高于对照组（P〈0．01）,治疗后两者均明显下降（P〈0．05）,但仍高于对照组（P〈0．05）。提示AS2O3治疗难治复发性MM疗效肯定,可能通过下调VEGF表达而发挥抗肿瘤作用,与IL-6的关系不明显。     

多发性骨髓瘤白细胞介素-6测定及其意义

研究表明白细胞介素 (ＩＬ) 6在多发性骨髓瘤 (ＭＭ)发生发展中起重要作用。本研究测定了 2 2例ＭＭ及 2 0例健康对照血清ＩＬ 6水平 ,并同时测定血Ｃ 反应蛋白 (ＣＲＰ)、血β2 微球蛋白 (β2 ＭＧ)及血沉作对比观察 ,探讨其临床意义。一、资料和方法1 对象 :ＭＭ患者 2 2例 ,男 12例 ,女 10例 ,年龄 46～ 6 9岁 ,中位年龄 5 4 1岁 ,均为ＩＩＩ期。根据病情分为初治组 8例 ,复发与无效组 5例和缓解组 9例。对照组 2 0例 ,为本院体检的正常老年人 ,男 12例 ,女 8例 ,年龄 48～ 6 8岁 ,中位年龄 5 1 2岁。2 测定方法 :ＩＬ 6检测用Ｂｉｏ…     

IL-2、IL-6及其受体与多发性骨髓瘤的研究

采用固相放射免疫分析法（ＲＩＡ）和双抗体夹心酶联免疫法（ＥＬＩＳＡ）,对多发性骨髓瘤（ＭＭ）患者进行血清白细胞介素２（ＩＬ－２）（ｓＩＬ－２Ｒ）,白细胞介素６（ＩＬ－６）,白细胞介素８受体（ｓＩＬ－６Ｒ）检测,并进行长期随访。结果ＭＭ患者血清ＩＬ０２、ｓＩＬ－２Ｒ和ＩＬ－６、ｓＨ－６Ｒ水平明显升高,ＩＬ－２与２微球蛋白＊β２－ＭＧ）呈负相关,ＩＬ－６,ｗＩＬ－８Ｒ与β－ＭＧ呈正相关,初诊时血清ｓＩ     

小白菊内酯对多发性骨髓瘤细胞蛋白酶体活性及白细胞介素-6表达的影响

目的探讨小白菊内酯(parthenolide,PTL)对多发性骨髓瘤(multiple myeloma,MM)细胞蛋白酶体活性及白细胞介素-6(interleukin-6,IL-6)表达的影响,以期了解PTL抗MM的分子机制。方法2006年5月至2007年3月华中科技大学同济医学院附属协和医院血液病研究所,体外培养人MM细胞系PRMI8266,与不同浓度的PTL作用不同时间。以荧光底物法检测细胞蛋白酶体活性,逆转录聚合酶链反应(RT-PCR)检测IL-6基因表达,酶联免疫吸附试验(ELISA)法检测MM细胞培养上清中IL-6的质量浓度。结果2~10μmol/L的PTL作用16h对PRMI8266细胞蛋白酶体的糜蛋白酶活性具有明显抑制作用,其效应呈现浓度依赖性;10μmol/L可达到接近50%的活性抑制。RT-PCR检测结果表明,2,5,10μmol/L的PTL作用24h,MM细胞的IL-6基因 mRNA表达强度与对照相比均明显降低;2,5,10μmol/L的PTL作用MM细胞48h后,培养上清中IL-6质量浓度分别为(92.6±4.3)ng/L、(67.1±5.7)ng/L、(43.5±4.9)ng/L,与对照组(148.7±8.2)ng/L相比,差异有显著性意义(P<0.01)。结论PTL能明显抑制PRMI8266细胞的蛋白酶体活性,降低IL-6基因表达,减少MM细胞IL-6的自分泌。提示PTL抑制蛋白酶体活性及IL-6表达可能是其抗MM的机制之一。     

老年2型糖尿病白细胞介素-6、C反应蛋白、血管内皮生长因子与大血管病变的相关性

目的探讨老年2型糖尿病(T2DM)患者血清白细胞介素(IL)-6、C反应蛋白(CRP)、血管内皮生长因子(VEGF)的变化与大血管病变的相关性。方法 53例T2DM合并大血管病变的患者纳入观察组,45例T2DM未合并大血管病变患者纳入对照组,同期同龄正常体检者30例纳入正常组,比较三组血清IL-6、CRP、VEGF水平。结果与正常组相比,观察组和对照组的甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、空腹血糖(FPG)、餐后2 h血糖(2 h PBG)、CRP、IL-6及VEGF水平具有显著性差异(P<0.05);而与对照组比较,观察组仅FPG、2 h PBG、CRP、IL-6及VEGF水平显著升高(P<0.05)。CRP及IL-6水平与TC、LDL、FPG、2 h PBG呈正相关,与HDL、TG无相关性;VEGF水平与TC、LDL、FPG、2 h PBG呈正相关,与HDL呈负相关,与TG无相关性;CRP、IL-6及VEGF间相互呈正相关。结论 T2DM合并大血管病变患者血中CRP、IL-6及VEGF水平明显升高,CRP、IL-6及VEGF可能参与T2DM大血管病变的发生和发展,对大血管病变的预测具有一定的临床意义。     

IL-6和DKK1在多发性骨髓瘤中表达的意义

目的：研究多发性骨髓瘤（MM）患者中IL-6、DKK1的表达水平,阐明其在MM发病中的临床意义。方法：采用酶链免疫和化学发光法对60例MM患者和50例对照者血清中IL-6、DKK1的表达量检测并进行比较。结果：IL-6、DKK1在对照者中表达低于MM患者,两者比较差异有统计学意义（P〈0.01）;MM患者中IL-6、DKK1的表达水平与临床分期高低有关（P〈0.01）;IL-6和DKK1表达有正相关关系（rs=0.7381,P〈0.01）。结论：IL-6和DKK1的联合检测可作为MM患者病变严重程度的早期诊断指标,为临床治疗提供帮助。     

Clinical significance of vascular endothelial growth factor and hepatocyte growth factor in multiple myeloma

Angiogenesis is a crucial process in the progression of multiple myeloma (MM). Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are multifunctional cytokines that potently stimulate angiogenesis including tumour neovascularization. Serum levels of VEGF and HGF were measured in 52 patients with MM by enzyme-linked immunosorbent assay (ELISA). Serum levels of VEGF and HGF were elevated in MM patients compared with healthy controls (VEGF: mean 0.31 ng/ml and 0.08 ng/ml respectively, P < 0.01; HGF: mean 2.17 ng/ml and 0.45 ng/ml, respectively, P < 0.001). In serial samples taken after chemotherapy, serum VEGF and HGF levels were correlated with M-protein levels. Serum levels of VEGF were higher in patients with extramedullary plasmacytomas than in patients without them (P < 0.05). They were also significantly higher in a group of patients who showed poor response to chemotherapy (P < 0.01). Serum levels of HGF were higher in patients with complications such as anaemia, hypercalcaemia and amyloidosis than in patients without these complications (P < 0.01, P < 0.05, P < 0.05 respectively). Both serum VEGF and HGF levels were significant predictors of mortality (P = 0.01, P = 0.02, respectively, log-rank test). The present study demonstrated that serum levels of VEGF and HGF are significantly elevated and dependent on the severity of MM, suggesting that measurement of VEGF and HGF may be useful for assessing disease progression and for predicting the response to chemotherapy in MM patients.     

脑源性神经营养因子在多发性骨髓瘤患者血浆中的表达

目的 :研究多发性骨髓瘤 (MM )患者血浆中脑源性神经营养因子 (BDNF)、血管内皮细胞生长因子(VEGF)的表达情况及与相应临床检测指标的关系 ,初步探讨BDNF在多发性骨髓瘤的发生与发展中的潜在作用。方法 :用酶联免疫吸附试验 (ELISA)测定MM患者与健康体检者血浆BDNF、VEGF的浓度 ,同时观察MM患者血常规、肾功能、电解质、影像学等指标。结果 :患者血浆BDNF浓度为 (4 .2 2± 0 .6 4 ) μg/L ,与健康体检者(2 .0 3± 0 .38) μg/L比较 ,差异有统计学意义 (P <0 .0 5 ) ;患者血浆VEGF浓度为 (79.35± 13.2 5 )ng/L ,与健康体检者 (34.4 1± 1.78)ng/L比较 ,差异有统计学意义 (P <0 .0 1)。BDNF与VEGF水平间存在着相关性 (r =0 .4 30 ,P =0 .0 2 5 )。结论 :MM患者血浆BDNF和VEGF显著增高 ,BDNF可能是继VEGF后又一促进血管增殖活性的细胞因子     

血管内皮细胞生长因子对小鼠CFU-GM、CFU-E、CFU-S生成的影响

目的 :研究血管内皮细胞生长因子 (VEGF)对小鼠骨髓单个核细胞 (MNC)粒 巨噬细胞系集落形成单位 (CFU GM)、红系集落形成单位 (CFU E)、脾集落形成单位 (CFU S)生成数量的影响。方法 :一部分小鼠骨髓MNC样本在加入或不加入外源性hVEGF的体系中预先培养 2 4h ,分别进行体外造血细胞集落培养和小鼠体内CFU S试验 ,计数CFU GM、CFU E、CFU S集落生成数目 ;另外对剩余骨髓样本不经处理直接在含rhVEGF的体系中进行体外CFU GM、CFU E集落培养 ,观察集落培养体系中添加VEGF对集落生成的影响。结果 :CFU GM、CFU E、CFU S数目分别为 33.2 1± 2 .84、72 .0 0± 4 .5 5和 12 .2 0± 1.32 ,显著高于未处理组 (分别为19.6 0± 2 .10、38.86± 2 .77和 6 .10± 1.5 2 ) (P <0 .0 5 ) ,但均低于正常对照组 (分别为 5 1.97± 2 .4 5、16 4 .2 0± 5 .70和 19.5 0± 2 .4 6 )。外源性hVEGF的存在使VEGF组CFU GM、CFU E产率较正常对照组显著提高 (73.12±3.80∶5 1.39± 2 .6 0 ,198.98± 4 .92∶16 4 .4 0± 5 .32 ) (P <0 .0 5 )。结论 :VEGF不仅对造血细胞集落生成能力具有保护作用 ,还具有促进造血细胞集落生成的作用。     

Correlation between serum levels of interleukin-6 and vascular endothelial growth factor in gastric carcinoma

BACKGROUND AND AIM: Vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) are associated with the disease status of gastric carcinoma. However, their relationship remains unclear. This study aims to determine and correlate serum levels of VEGF and IL-6 in gastric carcinoma. METHODS: A total of 107 patients receiving gastrectomy entered this study. Serum levels of VEGF and IL-6 were measured by using ELISA, and were analyzed by using the Student's t-test to compare means and by Pearson correlation analysis to calculate correlation coefficients with respect to pathological characteristics including depth of tumor invasion, Laurén's classification, tumor location, Borrmann classification, and the status of lymph node metastasis. RESULTS: Serum VEGF levels were significantly higher in patients with mixed type carcinoma (387.5 +/- 176.9 vs 255.3 +/- 154.1 pg/mL, P = 0.047) or lymph node metastasis (339.1 +/- 205.1 vs 223.2 +/- 197.4 pg/mL, P = 0.007). Serum IL-6 levels were significantly higher in patients with Borrmann type IV carcinoma, compared with Borrmann type II and III carcinoma. In general, no correlation was noted between serum VEGF levels and IL-6 levels (r = 0.142, P = 0.145), but significant correlation was found in patients with early gastric carcinoma (r = 0.627, P = 0.004) or mixed type carcinoma (r = 0.804, P = 0.016). CONCLUSIONS: This study supports the correlation between serum VEGF and IL-6 levels in distinct subsets of gastric carcinoma patients, and indicates that IL-6 may play a role for the angiogenesis of gastric carcinoma via modulation of VEGF.     

人脑胶质瘤中血管内皮细胞生长因子表达及其与细胞增殖的关系

为探讨人脑胶质瘤组织中血管内皮细胞生长因子 (VEGF)表达及其与细胞增殖的关系 ,应用链霉菌抗生物素蛋白 -过氧化物酶连接法 (SABC)免疫组织化学技术检测了 6 7例人脑胶质瘤、8例正常脑组织中 VEGF表达及增殖细胞核抗原 (PCNA)标记指数 (PCNA L I)。结果 VEGF在人脑胶质瘤组织中的阳性表达率为 83.6 %,正常脑组织中无表达 (P<0 .0 0 5 ) ;肿瘤组织中 VEGF表达与 PCNA L I呈显著正相关 (P<0 .0 0 5 )。认为胶质瘤细胞能分泌 VEGF,VEGF表达在肿瘤细胞增殖中起重要作用。     

血管内皮生长因子及血管内皮生长因子受体在急性肺损伤中作用的研究

血管内皮生长因子是作用于血管内皮细胞的重要血管调节因子,它通过与内皮上的特异受体结合,可发挥促进内皮细胞增殖、分化、诱导血管生成、增加微血管通透性等多种功能.近年研究显示血管内皮生长因子在不同原因、不同阶段急性肺损伤中所起的作用不同.     

Serum levels of the angiogenic cytokines basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in multiple myeloma

Angiogenesis is a crucial process in growth and progression of cancer and there is growing evidence that neovascularisation is important in hematological malignancies. Since an increased angiogenic potential has been identified in multiple myeloma, we simultaneously measured circulating serum levels of the cytokines bFGF, VEGF, HGF and IL-6 by ELISA in 67 patients with multiple myeloma or monoclonal gammopathies of undetermined significance (MGUS) and in 20 controls. Median values of bFGF were 4.7 pg/ml in healthy volunteers, 6.2 in MGUS, 6.3 in myeloma stage I, 13.4 in stage II and 21.7 in stage III. Myeloma patients had significantly higher bFGF serum levels than controls (p<0.001). Pretreatment bFGF levels differed significantly in the Salmon and Durie stages I-III (p=0.02) and were significantly elevated in stage II-III compared to stage I myeloma (p=0.02). In patients responding to chemotherapy according to the CLMTF criteria, a significant decrease in serum bFGF, VEGF and HGF levels occurred (median pretreatment values for bFGF 23.9 pg/ml, post-treatment 6.5 pg/ml; p<0.001, for VEGF 223 pg/ml versus 105 pg/ml; p=0.02 and for HGF 1429 pg/ml versus 1077 pg/ml; p=0.02, respectively). In 11 patients who did not achieve a remission, there was no significant decrease in bFGF, VEGF and HGF levels. These data show that myeloma in stages II and III is associated with an increase in serum bFGF concentrations and give the first report that effective chemo-therapy is accompanied by a significant decrease in the angiogenic factors bFGF, VEGF and HGF, while no decrease of these factors could be found in nonresponders.     

骨髓活检在多发性骨髓瘤诊断中的价值

目的：探讨骨髓活检与骨髓涂片在多发性骨髓瘤(MM)诊断中的价值。方法：对29例MM患者骨髓活检采用石蜡薄切片苏木素伊红染色，骨髓涂片采用瑞特染色。结果：骨髓活检与骨髓涂片的增生程度相符者13例(44．8％)，骨髓活检增生程度高于骨髓涂片者12例(41．4％)，骨髓涂片高于骨髓活检者4例(13．8％)。骨髓涂片和切片相结合有助于MM的诊断和分型。结论：骨髓活检可作为MM的常规检查手段。     

Expression of vascular endothelial growth factor and its receptors VEGFR-1 and 2 in gastrointestinal stromal tumors, leiomyomas and schwannomas

INTRODUCTION Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal (GI) tract that may occur from the oesophagus to the anus, including the omentum[1,2]. Despite their rarity, GISTs are the most common primary mesench…     

Interleukin-1 induces the expression of vascular endothelial growth factor in human pericardial mesothelial cells

Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells. We have studied the production of VEGF by human pericardial mesothelial cells. Mesothelial cells were separated by scraping the pericardial surface during cardiac surgery and cultured. When stimulated with interleukin (IL)-1α, pericardial mesothelial cells expressed VEGF mRNA and protein in concentration- and time-dependent manners. Hypoxia was also found to enhance mesothelial VEGF mRNA expression. The cells expressed mRNA for Flt-1 (VEGF receptor 1) and Flk-1 (VEGF receptor 2), and exogenous VEGF was found to have migration-promoting activity on cultured cells. We conclude that pericardial mesothelial cells express VEGF, which may serve as an autocrine growth-regulatory mechanism.