急性白血病患者血浆VEGF测定及其临床意义

目的 :探讨急性白血病 (AL)患者血浆血管内皮细胞生长因子 (VEGF)含量变化与临床病情的关系。方法 :用双抗体夹心酶联免疫吸附法 (ELISA)检测 5 4例AL患者血浆VEGF含量 ,同时检测骨髓涂片有核细胞中原始及幼稚白细胞数。结果 :①AL患者血浆VEGF含量 [(6 4 .76± 34.86 )ng/L]明显高于对照组 [(33.13± 11.97)ng/L](P <0 .0 1) ,且AL患者血浆VEGF升高与骨髓中原始及幼稚白细胞百分数增加呈正相关 (r =0 .4 37,P <0 .0 1) ;②初治组AL患者血浆VEGF含量 [(76 .0 1± 4 0 .18)ng/L]明显高于缓解组 [(42 .0 7± 17.75 )ng/L](P <0 .0 1) ,难治 /复发组患者血浆VEGF含量 [(78.2 1± 31.77)ng/L]又明显上升 ,与缓解组比较差异有显著性意义 (P<0 .0 1) ,而与初治组比较差异无显著性意义 (P >0 .0 5 )。结论 :①AL患者血浆VEGF含量升高与白血病细胞生长、增殖有关 ;②AL患者血浆VEGF含量与临床病情变化密切相关 ,可作为了解病情、观察疗效、判断预后的指标之一。     

急性白血病患者血清血管内皮细胞生长因子测定及临床意义

目的探讨血管内皮细胞生长因子(VEGF)在急性白血病(AL)患者中的表达和临床意义.方法采用双抗体夹心ELISA法检测了41例AL初发患者(ANLL32例,其中是M14例、M24例、M38例、M44例、M512例和ALL9例)血清VEGF含量,并且检测了其中10例获得完全缓解后的AL患者血清VEGF水平;同时留取41例AL初发患者和10例获得完全缓解后AL患者骨髓涂片,进行瑞特染色后检测骨髓原始和幼稚细胞百分率.结果血清VEGF在ANLL和ALL中分别是(807.76±347.04)ng/L、(998.18±387.80)ng/L,均高于正常对照组(461.43±127.05)ng/L,均P＜0.01;ANLL和ALL之间血清VEGF水平差异无统计学意义(P＞0.05);10例完全缓解的AL患者,其血清VEGF含量为(495.28±102.79)ng/L明显低于初发时(1263.44±490.39)ng/L,P＜0.01;AL缓解组血清VEGF含量与其骨髓中原始幼稚白细胞百分率具有一定相关性,r=0.57,P＜0.01.结论血清VEGF在AL患者中明显升高,且血清VEGF水平与病情和预后密切相关.     

沙利度胺联合三氧化二砷对急性非淋巴细胞白血病VEGF表达的影响

目的观察沙利度胺和三氧化二砷(As2O3)对急性非淋巴细胞白血病(ANLL)细胞分泌血管内皮生长因子(VEGF)的影响,并观察二者是否有协同性。方法对2001-10~2003-02中国医科大学第二临床学院的23例ANLL病人的骨髓,用Ficoll淋巴细胞分离液分离单个核细胞(MNC),培养于RPMI1640培养液中,于37℃、5%CO2饱和湿度条件下传代培养。以2×109/L的细胞加入24孔培养板。分为空白对照组、沙利度胺组(300μg·mL-1)、As2O3组(25μmol/L)和联合用药组,连续培养72h。用ELISA法检测上清液VEGF质量浓度。结果4组VEGF质量浓度分别为(1582·67±281·51)ng/L、(1206·29±264·87)ng/L、(941·72±236·34)ng/L和(639·12±211·98)ng/L。用药组与空白对照组及联合用药组与单一用药组之间差异均有显著性(P<0·05)。结论(1)白血病细胞能自分泌VEGF。(2)沙利度胺和As2O3均能抑制ANLL细胞分泌VEGF。(3)两者联合应用起协同作用。     

冠心病患者血清血管内皮生长因子水平与冠状动脉病变程度的关系

目的 :探讨冠心病 (CHD)患者血清血管内皮生长因子 (VEGF)水平与冠状动脉病变的关系。方法 :采用酶联免疫吸附法 (ELISA)检测了 12 4例经冠状动脉造影证实有一支以上主要冠状动脉狭窄≥ 5 0 %的CHD患者血清VEGF水平 ,并作相关分析。结果 :CHD组血清VEGF水平明显高于正常对照组〔(2 93.2± 12 6 .3)ng/L∶(12 0 .1± 31.5 )ng/L ,P <0 .0 1〕 ,双支和三支血管病变患者血清VEGF水平高于单支组〔(2 83.4± 85 .0 )ng/L ,(398.1± 10 5 .5 )ng/L∶ (191.7± 2 7.3)ng/L ,P <0 .0 1〕 ,随着血管狭窄程度的加重 ,血清VEGF水平升高越明显 ,两者呈显著正相关 (r =0 .78,P <0 .0 0 1) ,CHD并发高血压和 (或 )糖尿病对血清VEGF水平无显著影响 (P >0 .0 5 )。结论 :CHD患者血清VEGF水平升高 ,其升高程度与冠状动脉病变程度有良好的相关性     

急性白血病患者Survivin基因表达与耐药的关系

目的　探讨急性白血病 (AL)患者Survivin基因表达及其与临床耐药的关系。方法　应用半定量RT PCR方法检测 71例急性白血病患者 ,10例健康人的Survivin、mdr1基因mRNA表达水平 ,并分析其临床意义。结果　AL患者Survivin、mdr1mRNA表达阳性率分别为 67.61%和 49.3 0 %。急性淋巴细胞白血病 (ALL)和急性非淋巴细胞白血病 (ANLL)患者SurvivinmRNA表达阳性率均高于对照组 (分别为P <0 .0 1,P <0 .0 5 )。半定量后进行方差分析 ,ANLL和ALL患者SurvivinmRNA表达水平 (分别为 0 .64± 0 .2 1,0 .63± 0 .15 )均高于对照组 ( 0 .3 3± 0 .0 1,P <0 .0 5 )。耐药组患者SurvivinmRNA表达阳性率高于敏感组 (P <0 .0 5 )。Survivin阳性mdr1阳性患者耐药比例 ( 73 .0 8% )明显高于Survivin阴性mdr1阴性患者 ( 3 1.2 5 % ,P <0 .0 1)。在 61例初治和复发AL患者Sur vivinmRNA表达水平和mdr1mRNA表达水平呈高度正相关 (r =0 .75 4,P <0 .0 0 1)与骨髓白血病细胞百分比呈正相关 (r =0 .3 89,P =0 .0 0 5 )。结论　Survivin基因在AL患者呈高表达 ,与临床耐药密切相关 ,有望成为AL靶向治疗的一个潜在靶点     

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     

系统性硬化病肺间质病变与血管内皮细胞生长因子的关系

目的　探讨血清血管内皮细胞生长因子 (VEGF)与系统性硬化病 (SSc)肺间质病变的关系。方法　采用免疫学酶联免疫吸附测定 (ELISA)方法检测了病例组 (SSc 2 0例 )及正常对照组( 3 0名 )的血清VEGF ,并分析血清VEGF与肺功能的关系。结果　病例组血清VEGF ( 3 63± 178)ng/L较正常对照组 ( 183± 5 9)ng/L明显升高 (P <0 0 0 1) ,VEGF升高的SSc患者肺间质病变的发生率 ( 87 5 % )显著高于VEGF正常的SSc病患者肺间质病的发生率 ( 3 3 3 % ) (P <0 0 5 ) ,SSc患者血清VEGF浓度与肺活量占预计值百分比 (VC % )及肺一氧化碳弥散量占预计值百分比 (DLCO % )呈负相关 (r =- 0 86,P <0 0 0 1;r =- 0 87,P <0 0 0 1)。结论　血清VEGF水平的测定 ,对评估SSc肺间质病变的病情活动性有意义     

"血宝"对化学药物性骨髓损伤保护作用的体内实验研究

目的 :探讨“血宝”对化学药物性骨髓损伤的保护作用。方法 :昆明小鼠经大剂量环磷酰胺腹腔注射 ,约 5d后出现显著的骨髓损伤 ,外周血三系减少 ,骨髓造血功能低下。对骨髓损伤小鼠胃饲“血宝”10d后观察外周血三系细胞计数及骨髓有核细胞总数 ,并体外培养小鼠骨髓细胞 ,计数BFU E和CFU GM的集落产率。结果 :实验组外周血三系细胞数最低为WBC (3.5± 0 .9)× 10 9/L、RBC (4.7± 0 .4 )× 10 12 /L、PLT (46 7.9±4 3.3)× 10 9/L、HGB 92 .8± 4 .4 g/L ,骨髓有核细胞总数最低为 (5 .5± 0 .2 )× 10 6/股骨 ,其中RBC、PLT、HGB、骨髓有核细胞总数显著高于阴性对照组 [RBC (3.3± 0 .8)× 10 12 /L、PLT (2 39.8± 79.0 )× 10 9/L、HGB (49.2±10 .6 ) g/L、骨髓有核细胞总数 (1.3± 0 .3)× 10 6/股骨 ],P <0 .0 1;实验组BFU E和CFU GM的集落产率最低为 (11.9± 4 .6 4 ) / 3.5× 10 5BMC和 (7.9± 1.73) / 3.5× 10 5BMC ,显著高于阴性对照组 [(1.6± 1.2 ) / 3.5× 10 5BMC和 (0 .6 3± 0 .4 5 ) / 3.5× 10 5BMC],P <0 .0 0 1。结论 :“血宝”对化学药物性骨髓损伤具有保护作用 ,可明显促进骨髓损伤后造血功能的恢复     

骨髓中表达白细胞介素5受体 mRNA的CD+34 细胞与支气管哮喘气道炎症的关系

目的　探讨支气管哮喘 (简称哮喘 )小鼠骨髓 (BM)中表达CD+ 34 与白细胞介素 5受体(IL 5RmRNA+ )的造血细胞 (CD+ 34 IL 5RmRNA+ 细胞 )在气道炎症中的作用。方法　以卵白蛋白(OVA)及生理盐水致敏并激发Balb/c小鼠 ,建立各哮喘及对照组 (A组 )模型。分别于OVA及生理盐水首次激发后 1、6、12、2 4、48h处死小鼠 ,取支气管肺泡灌洗液 (BALF)、外周血 (PB)及BM标本备用。测定BALF中嗜酸性粒细胞 (EOS)、PB中有核细胞及EOS计数及BM中有核细胞数 ;用流式细胞仪分别测定PB及BM中CD+ 34 细胞占相应有核细胞的比例并推算其相对计数 ;用免疫组化结合原位杂交法分别标记骨髓细胞CD+ 34 抗原及IL 5RmRNA ,定位BM中CD+ 34 IL 5RmRNA+ 细胞并计数其占CD+ 34 细胞的比例。结果　 (1)OVA激发后 6h组 ,BALF中EOS计数为 (2 67± 1 0 0 )× 10 5/L ,与A组 [(0 46±0 0 6)× 10 5/L]比较差异有显著性 (P <0 0 1) ;OVA激发后 12h组 ,BALF中EOS、PB中EOS计数分别为 (7 74± 1 98)× 10 5/L、(2 91± 0 64 )× 10 8/L ,与A组 [(0 46± 0 0 6)× 10 5/L、(1 43± 0 3 7)× 10 8/L]比较 ,差异有显著性 (P均 <0 0 1) ;OVA激发后 2 4h组 ,BALF中EOS、PB中EOS计数分别为 (19 43±3 69)× 10 5/L、(3 93± 0 5 1)× 10     

血管内皮细胞生长因子对移植后骨髓造血微环境的影响及意义

目的　观察血管内皮细胞生长因子基因治疗对骨髓移植后造血微环境的调节作用。方法　重组腺病毒注射给小鼠 ,随后进行同基因骨髓移植 ;在不同时期检测骨髓微血管灌注面积和造血细胞容量以及外周血WBC、PLT计数。结果　移植后 2 0天时 ,VEGF组骨髓微血管灌注面积已恢复正常 (P >0 .0 5 ) ;移植后 3 0天时VEGF组骨髓细胞容积明显大于EGFP组和常规组 (P <0 .0 5 )。各时间点VEGF处理组外周血WBC、PLT计数均显著高于常规BMT组和EGFP组 (P <0 .0 5 )。结论　血管内皮细胞生长因子基因治疗促进了骨髓移植后造血微环境的恢复 ,并提高外周血WBC、PLT计数水平。     

急性白血病患者血管内皮生长因子及其受体表达的动态观察

目的探讨急性白血病(AL)患者治疗前后骨髓中血管内皮生长因子(VEGF)及其受体的表达差异以及这种表达与血管生成的相关性.方法应用EnVision免疫组织化学二步法,检测122例次成人AL患者骨髓中造血细胞VEGF及其两种特异性受体fms-样酪氨酸激酶受体(Flt-1)、激酶插入嵌合受体(KDR)蛋白的表达情况.结果化疗后获得完全缓解(CR)的患者,其VEGF、KDR蛋白的表达在治疗前为6.0(3.3～12.0)和5.3(3.3～8.0),获CR后为5.3(3.3～9.0)和2.0(1.0～4.0)差异有显著性(P<0.05;P<0.01),而在化疗后未获得CR患者中的表达差异无显著性.在缓解后复发患者中的表达又升高到初发时的水平.各组初发患者Flt-1的表达水平与对照组之间差异无显著性,但CR期Flt-1的表达水平在CR组为3.3(1.7～5.3),复发组为3.3(2.0～5.3)与初发及对照组差异有显著性(P<0.01).微血管数处于高水平组的VEGF及KDR表达显著高于微血管处于低水平组者(P<0.01).骨髓原始细胞与急性髓系白血病(AML)初发患者VEGF和KDR的表达之间成正相关(r=0.429,0.359;P=0.005,0.02);与急性淋巴细胞白血病(ALL)初发患者VEGF的表达之间成正相关(r=0.522,P=0.03).结论 VEGF及其两种特异性细胞受体Flt-1, KDR在造血细胞及血管内皮细胞中表达.提示VEGF可能是白血病细胞的一种自分泌因子,同时作为一种旁分泌因子调控患者骨髓中的血管新生反应.VEGF及其细胞受体KDR可能构成抗血管新生和抗白血病治疗的新靶点.     

Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia

The importance of angiogenesis for the progressive growth and viability of solid tumors is well established. In contrast, only few data are available for hematologic neoplasms. To investigate the role of angiogenesis in acute myeloid leukemia (AML), bone marrow biopsies from 62 adults with newly diagnosed, untreated AML (day 0) were evaluated. Further studies were done after the completion of remission induction chemotherapy (day 16 of induction chemotherapy, n = 21; complete remission, n = 20). Microvessels were scored in at least 3 areas (x500 field, 0.126 mm(2)) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for von Willebrand factor and thrombomodulin. Microvessel counts were significantly higher in patients with AML (n = 62) compared with control patients (n = 22): median (interquartile range) 24.0 (21.0-27.8)/x500 field vs 11.2 (10. 0-12.0)/x500 field, respectively (P <.001). On day 16 of induction chemotherapy, microvessel density was reduced by 60% (44-66) (P <. 001) in hypoplastic marrows without residual blasts, in contrast to only 17% (0-37) reduction in hypoplastic marrows with >/= 5% residual blasts (P <.001 for the difference between both groups). Bone marrow biopsies taken at the time of complete remission displayed a microvessel density in the same range as the controls. In conclusion, there is evidence of increased microvessel density in the bone marrow of patients with AML, which supports the hypothesis of an important role of angiogenesis in AML. Furthermore, these findings suggest that antiangiogenic therapy might constitute a novel strategy for the treatment of AML. (Blood. 2000;95:2637-2644)     

急性髓系白血病及骨髓增生异常综合征患者血管内皮生长因子表达的研究

目的了解血管内皮生长因子(VEGF)在急性髓系白血病(AML)和骨髓增生异常综合征(MDS)中血管新生的作用。方法用ELISA法检测20例AML及24例MDS患者骨髓单个核细胞培养上清VEGF的表达。结果AML患者骨髓细胞VEGF的水平(267.35～412.30ng/L)高于对照组(128.17ng/L),化疗后完全缓解组的VEGF水平明显下降(P<0.05)化疗后未缓解组的VEGF水平与治疗前比较无显著下降(P>0.05)。MDS高危型(RAEB或RAEBt)中VEGF水平与低危型(RA或RAS)及对照组相比均明显升高(P<0.05),其中RAEBt与AML患者相比差异无显著性(P>0.05)。结论AML及高危型MDS患者骨髓中存在血管新生,VEGF在AML及MDS发病中起着重要作用,VEGF的表达与MDS病程进展有关。     

Prognostic value of enhanced bone marrow angiogenesis in early B-cell chronic lymphocytic leukemia

Because tumor progression is angiogenesis-dependent, angiogenesis density was investigated by immunohistochemistry and computed image analysis in bone marrow (BM) biopsies of 45 newly diagnosed patients with Binet stage A B-cell chronic lymphocytic leukemia (BCLL) and correlated to upstaging and progression-free survival during a 40-month follow-up period. Their microvessel areas and counts were significantly higher than those of patients with anemia due to iron or vitamin B(12) deficiencies. A cutoff value of 0.90 mm(2) x 10(-2) or greater of the microvessel area identified patients with earlier upstaging and shorter progression-free survival. When the cutoff was applied to the Rai subclassification, both Rai 0 and Rai I-II patients who upstaged and shortened the progression-free survival were classified correctly. Information of this type was not given by the microvessel counts. The cutoff did not correlate with other predictors representative of tumor mass or disease progression. The microvessel area correlated with the expression of angiogenic vascular endothelial growth factor (VEGF) by tumor tissue, and serum levels of VEGF were found to be of prognostic value. A causal relationship between risk of progression and BM angiogenesis in BCLL is suggested. A risk stratification inside Rai is proposed. The prognostic usefulness of BM angiogenesis in patients with BCLL is envisaged.     

急性白血病与可溶性肿瘤坏死因子受体的相关性研究

应用ELISA法检测了60例急性白血病（AL）患者及36例正常对照者的血清可溶性肿瘤坏死因子受体（sTNFR-Ⅰ和sTNFR-Ⅱ）及血清肿瘤坏死因子α（TNFα）。结果显示,①初发未治组及复发难治组血清sTNFR-Ⅰ和sTNFR-Ⅱ浓度均明显高于正常对照组（P＜0.01）;骨髓缓解组血清sTNFR浓度与正常对照组无明显差异。AL患者与对照组比较血清TNF-α水平明显增高（P＜0.001）;②血清TNF-α水平与sTNFR-Ⅰ呈显著性正相关（r＝0.684,P＜0.01）,与sTNFR-Ⅱ无相关性（r＝0.310,P＞0.05）;血清sTNFR-Ⅰ、sTNFR-Ⅱ水平与外周血幼稚细胞数呈显著正相关（r＝0.748,P＜0.001;r＝0.384,P＜0.05）;③30例初发未治者治疗前血清sTNFR-Ⅰ＜0.89μg／L、sTNFR-Ⅱ＜1.43μg／L者的BMR率（70.0％、61.5％）明显高于sTNFR-Ⅰ≥0.89μg／L、sTNFR-Ⅱ≥1.43μg／L者的BMR率（χ     

Decrease of bone marrow angiogenesis in myeloma patients achieving a remission after chemotherapy

The impact of angiogenesis is well known for the growth and viability of solid tumors. Fewer studies have been published relating angiogenesis to clinical or pathological parameters in hematological malignancies. In this report, we have estimated the bone marrow microvessel density (MVD) before and after conventional-dose or high-dose chemotherapy with autologous stem cell transplantation. Immunohistochemical CD34-stained paraffin-embedded bone marrow biopsies of 21 patients with stage III multiple myeloma were studied. Microvessels were counted at 400x magnification, and the mean number of vessels per area in each sample was noted as the MVD. The median MVD of all patients was 53.1 vessels/mm2 (range 15.5-174.7 vessels/mm2) before treatment and 29.3 vessels/mm2 (range 0-221.1 vessels/mm2) after chemotherapy. The post-treatment MVD in the two groups of patients with and without remission was significantly different (p=0.001), whereas the pretreatment MVD was not. Responders but not nonresponders showed a significant decrease of MVD after therapy in comparison to their pretreatment levels. The progression-free survival in patients who achieved a reduction in MVD after chemotherapy was significantly longer than in patients without a decrease in MVD (P=0.006). Furthermore, we compared the MVD of patients after achievement of a remission to MVD of 15 untreated stage I myeloma patients. The MVD of patients in remission was not statistically different from the MVD in stage I myeloma. These results underscore the impact of angiogenesis in myeloma and give the first report that effective chemotherapy is accompanied by a significant decrease in bone marrow angiogenesis in this disease.     

急性白血病骨髓中的血管生成的研究

目的 研究血管生成在急性白血病发病，预后中的作用。方法 应用免疫组化法检测30例初治急性白血病患者的骨髓活检组织治疗前后微血管密度（MVD）及血管内皮生长因子（VEGF）的变化。结果 初治急性白血病患者骨髓病理组织中的MVD和VEGF阳性率明显高于正常对照组；骨髓完全缓解后其MVD及VEGF阳性率明显下降，与正常对照组无显著性差异；治疗后未完全缓解组的MVD及VEGF阳性率较治疗前无显著性下降。结论 急性白血病骨髓中存在血管生成，可能与急性白血病的预后有关。     

Relationship between bone marrow angiogenesis and plasma cell infiltration and serum β2-microglobulin levels in patients with multiple myeloma

There is growing evidence that angiogenesis is important not only in solid tumors but also in hematological malignancies. Recently, we found that bone marrow angiogenesis is a prognostic factor for disease-related survival in patients with multiple myeloma. In this report, we addressed the question of whether the microvessel density in bone marrow biopsies is correlated to other myeloma parameters, e.g., serum beta2-microglobulin (beta2-MG) and plasma cell infiltration in the bone marrow. In 22 multiple myeloma patients, immunohistochemical, CD34-stained, paraffin-embedded bone marrow biopsies before and after chemotherapy were studied. Microvessels were counted in 400x magnification, and the mean number of vessels per area in each sample was noted as the microvessel density (MVD). Pretreatment bone marrow MVD (median: 44, range: 11-175 vessels/mm2) correlated significantly with the bone marrow plasma cell infiltration (median: 30%, range: 5-90%, r = 0.642, P=0.001) and beta2-MG (median: 2.74, range: 1.4-26.1 mg/l, r = 0.749, P < 0.0005). In contrast, there was no correlation between posttreatment MVD and plasma cell infiltration or beta2-MG (median: MVD 31, range: 0-221 vessels/mm2, median plasma cell infiltration: 15%, range: 5-80%, r = 0.229, P = 0.306 and median beta2-MG: 2.65, range: 1-27.6 mg/l, r = -0.042, P = 0.853). These findings show that the strong correlations between bone marrow MVD and plasma cell infiltration as well as serum beta2-MG levels disappear after chemotherapy. The underlying mechanisms need further investigations.     

Absence of Clinical Prognostic Value of Vascular Endothelial Growth Factor and Microvessel Density in Multiple Myeloma

Vascular endothelial growth factor (VEGF) is considered a potent stimulator of angiogenesis. In multiple myeloma (MM), it has been reported that bone marrow angiogenesis parallels tumor progression and correlates with a poor prognosis. To investigate the role of angiogenesis in MM, we investigated VEGF expression and microvessel density (MVD) in the bone marrow of 75 MM patients by immunohistochemical methods. VEGF expression was observed in 87.3% (62 of 71) of patients. MVD was 69.42 +/- 9.67 (mean +/- SE) compared with the normal control values of 26.81 +/- 2.85. MVD values were 73.98 +/- 11.27 and 36.04 +/- 6.99 in the VEGF-positive and VEGF-negative groups, respectively. The MVD of patients in the VEGF-positive group was significantly higher than in the VEGF-negative group (P = .045). However, there were no significant differences in various clinical parameters, such as age, sex, hemoglobin, platelet count, serum levels of albumin, calcium, creatinine, and beta2-microglobulin, and bone marrow plasma cell percentage, between the VEGF-positive and VEGF-negative groups. Multivariate analysis revealed that age, hemoglobin, platelet count, serum levels of albumin and creatinine, and bone marrow plasma cell percentage were correlated with overall survival, whereas VEGF expression or MVD was not. In conclusion, our results suggest that VEGF is highly expressed and that MVD is increased in MM, indicating that angiogenesis may play a role in MM. Although MVD in the bone marrow of the VEGF-positive group is significantly higher compared with the VEGF-negative group (P = .045), VEGF is not correlated with overall survival. Further studies that include other angiogenic factors are needed to determine the functional role of angiogenesis in MM.     

Effects of TNF-alpha on angiogenesis in CT-26 mouse colon carcinoma homograft model]

BACKGROUND/AIMS: Tumor necrosis factor-alpha (TNF-alpha) exerts its anti-tumor effect through direct cytotoxicity on tumor cells and damage to the tumor vasculature. However, its role in tumor angiogenesis is controversial. We evaluated the angiogenic effect of TNF-alpha on BALB/c mouse colon carcinoma homograft model. METHODS: Ten BALB/c mice were inoculated intraperitoneally with CT-26 mouse colon carcinoma cells. After a week, recombinant mouse TNF-alpha (2 microg/mL) were given four times on every other day to five animals and the same volume of phosphate buffered saline was given at the same interval to five animals as control. Harvested tumor tissues were stained by immunohistochemistry with CD31 and VEGF antibodies. Number of microvessels and VEGF expression were counted by light microscope. Results: The mean microvessel counts per 200x field of TNF-alpha treated animals were 70.2+/-7.8 and those of nontreated animals were 83.8+/-8.3 (p<0.05). The VEGF score of both groups were 3. Conclusions: TNF-alpha treated animals showed decreased microvessel counts in tumor tissue but VEGF expression in both groups showed no difference. Therefore, TNF-alpha showed antiangiogenic effects on colon carcinoma homograft model.