乙酰肝素酶、碱性成纤维细胞生长因子在胃癌中表达及对血管新生和肿瘤进展的影响

目的：探讨乙酰肝素酶(Hpa)、碱性成纤维细胞生长因子(bFGF)在胃癌组织中表达及其对血管新生和肿瘤生物学行为的影响。方法：应用免疫组化SABC法检测60例胃癌组织中Hpa、bFGF表达及计数肿瘤微血管密度(MVD)。结果：Hpa、bFGF表达和MVD、浸润深度、TNM分期和淋巴结转移有关，且Hpa、bFGF共表达病例有更高MVD与单独一种阳性表达相比。Hpa表达和bFGF表达呈正相关。结论：Hpa、bFGF可加速肿瘤浸润和转移，促进肿瘤间质微血管生成。且Hpa、bFGF在促进肿瘤间质微血管生成方面有协同作用。     

右旋柠烯乳剂对人胃癌移植瘤生长和转移的抑制作用

目的　研究并探讨右旋柠烯乳剂 (D limonene)对人胃癌生长和转移的抑制作用及其机制。　方法　采用人胃癌BGC 82 3细胞株经反复传代成实体瘤的完整组织块 ,建立人胃癌裸小鼠原位移植瘤模型。将 4 0只荷瘤裸小鼠随机分成 4组 ,移植后第 5d开始分别用生理盐水灌胃、5 氟尿嘧啶 (5 FU)腹腔注射、D limonene灌胃、D limonene灌胃 +5 FU腹腔注射共 7周。第 8周处死动物 ,测量原位肿瘤瘤重并计算抑瘤率 ,检测肿瘤细胞凋亡指数 (AI)、肿瘤微血管密度 (MVD)及免疫组织化学测定肿瘤组织血管内皮生长因子 (VEGF)的表达变化 ,光镜与电镜观察组织细胞超微结构变化 ;观察荷瘤鼠腹膜、肝、其他脏器肿瘤转移及腹水情况。　结果　D limonene组、联用组分别与对照组相比 ,胃癌的原位肿瘤瘤重与抑瘤率、AI、MVD、VEGF下调 ,差异有显著性 (P <0 0 5 )。腹膜、肝转移受到明显抑制 (P <0 0 5 )。　结论　D limonene通过抑制肿瘤微血管形成 ,诱导胃癌细胞凋亡 ,抑制了体内胃癌的生长和转移。     

整合素β3 mRNA表达与胃癌微血管密度、进展及预后的关系

目的　探讨整合素 β3mRNA在胃癌中的表达及其与肿瘤微血管密度 (MVD)、生长方式、浸润转移和预后的关系。方法　应用原位杂交和免疫组织化学技术 ,检测 10 5例胃癌组织中整合素 β3mRNA和CD3 4的表达。结果　整合素 β3mRNA在非肿瘤胃黏膜中的阳性表达率为 3 0 % (6/ 2 0 ) ,显著低于胃癌组 (61 0 % ,64/ 10 5,χ2 =8 85,P =0 0 3 7) ;在浸润性生长、T3 ～T4 期、有淋巴结转移和远处转移的病例中 ,阳性率分别为 70 2 % (40 / 57)、72 1% (44/ 61)、68 6% (48/ 70 )和 85 7% (3 6/ 42 ) ,均显著高于膨胀性生长 (χ2 =14 97,P =0 0 0 2 )、T1～T2 期 (χ2 =15 2 1,P =0 0 15)、无淋巴结转移 (χ2 =17 89,P =0 0 2 5)及无远处转移的病例 (χ2 =2 0 2 2 ,P =0 0 0 5;χ2 =2 1 3 5,P =0 0 3 5) ;同样 ,它们的平均MVD均显著高于膨胀性生长 (t =10 10 5,P =0 0 0 1)、T1～T2 期 (t=5 961,P =0 0 0 1)、无淋巴结转移 (t= 3 819,P =0 0 1)和无远处转移的病例 (t =10 578,P =0 0 0 1;t =7 882 ,P =0 0 0 1) ;阳性表达组的平均血管数 (41 0 2± 8 55)个 / 0 72mm2 明显高于阴性表达组的平均微血管数 (2 5 2 6± 11 2 5)个 / 0 72mm2 (t =11 2 5,P =0 0 2 5) ,两者之间呈显著正相关 (rs=0 3     

Hypercholesterolemia impairs angiogenesis in patients with breast carcinoma and, therefore, lowers the risk of metastases

Our aim was to study the effect of hypercholesterolemia on angiogenesis induced by breast carcinoma. Of 51 patients with invasive ductal carcinoma, 28 had hypercholesterolemia and 23 had normocholesterolemia. The intratumoral microvessel density (MVD) was evaluated by using anti-CD31 antibody. The expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) on endothelial and tumor cells was examined and graded semiquantitatively. Patients with normocholesterolemia had a higher MVD (76.4 +/- 8.2) than those with hypercholesterolemia (54.6 +/- 5.1) (P < .01). The risks of recurrence and distant metastasis were higher in patients with normocholesterolemia than in patients with hypercholesterolemia (P < .01). Patients with hypercholesterolemia showed lower expression of endothelial VEGF and bFGF than patients with normocholesterolemia (P < .05 and P < .01, respectively). In addition, tumoral bFGF and VEGF expression showed negative correlation with the presence of hypercholesterolemia (P < .01). We suggest that hypercholesterolemia impairs angiogenesis by suppressing endothelial and tumoral bFGF and VEGF expression and, therefore, lowers the risk of metastases in cases of invasive breast carcinoma.     

碱性成纤维细胞生长因子与卵巢癌的关系

目的　探讨碱性成纤维细胞生长因子 (basic fibroblast growth factor,b FGF)对卵巢癌细胞增殖、浸润和肿瘤血管生成的影响 ,及 b FGF单克隆抗体 (b FGF monoclonal antibody,b FGF- MAb)的治疗作用。　方法　将人卵巢癌细胞株 SKOV3接种于 2 4孔板 ,加入不同浓度的 b FGF,每日行结晶紫染色后测定光密度 (D4 90 )值 ,绘制细胞生长曲线 ;将 SKOV3细胞团接种于铺设有细胞外基质凝胶的 4孔板 ,每日测定癌细胞在凝胶中的浸润距离 ;建立 SKOV3细胞裸鼠皮下移植瘤模型 ,每周两次分别将 b FGF、b FGF-MAb和生理盐水注射于移植瘤周围 ,8周后测量肿瘤体积 ;对移植瘤组织切片行 因子的免疫组化染色、测定肿瘤内微血管密度 (microvessel density,MVD)。　结果　 b FGF能促进 SKOV3细胞增殖并呈浓度依赖 ,实验第 5天 ,5 ng/ml、10 ng/ml组细胞 D4 90 值是对照组的 1.0 9倍和 1.2 1倍 ;b FGF能促进 SKOV3细胞浸润并呈浓度依赖 (P<0 .0 5 ) ,第 7天 ,5 ng/ml、10 ng/ml组细胞浸润距离分别是对照组的 1.5 3倍和2 .4 5倍 ;b FGF组移植瘤体积和 MVD分别是对照组的 1.80倍和 1.4 6倍 (P<0 .0 5 ) ,b FGF- MAb组移植瘤体积和 MVD分别是对照组的 6 3.7%和 6 2 .8% (P<0 .0 5 )。　结论　b FGF能明显促进卵巢癌细胞的增殖、     

FAP在胃癌间质中的表达及其与微血管密度的关系

目的 探讨FAP在胃癌间质中的表达及其与微血管密度(microvessel density,MVD)的关系.方法 收集162例胃癌组织,同时建立人胃癌细胞系SGC-7901裸鼠皮下移植瘤模型,采用免疫组织化学染色法检测FAP和CD34的表达.结果 在人胃癌组织中,FAP表达于问质成纤维细胞,表达阳性率为90.74%(147例),而胃癌细胞和正常胃组织中无表达,且FAP表达和MVD分别与胃癌的分化程度(χ2=51.882,P<0.01;χ2=46.383,P<0.01)、侵袭深度(χ2=40.193,P<0.01;χ2=21.617,P<0.01)及淋巴结转移(χ2=24.232,P<0.01;χ2=13.393,P<0.01)有关.在15例裸鼠皮下移植瘤中,所有肿瘤中FAP均不同程度在间质成纤维细胞呈阳性表达.在人胃癌组织(χ2=97.710,P<0.01)和裸鼠皮下移植瘤组织(χ2=11.100,P<0.01)中,不同强度的FAP表达组间肿瘤间质MVD的差异具有统计学意义,且随着FAP表达水平的增高,MVD也随之增加.结论 FAP的表达与胃癌的分化程度、侵袭深度及淋巴结转移有关.FAP可能通过促进肿瘤的微血管生成,加快肿瘤的生长、侵袭和转移.     

胆囊癌组织P62蛋白的表达及其与血管生成关系

目的 :检测胆囊癌组织中P6 2蛋白、碱性成纤维细胞生长因子(bFGF)的表达和微血管密度 (MVD) ,探讨它们的相互关系 ,以及与胆囊癌临床病理特征的关系。方法 :4 1例胆囊癌和 2 2例慢性胆囊炎组织中 ,P6 2蛋白和bFGF的表达用SP免疫组化染色法进行检测。胆囊癌组织中MVD用抗CD34单抗 (mAb)做SP免疫组化染色进行检测。结果 :4 1例胆囊癌组织中 ,P6 2和bFGF表达阳性率分别为 6 3.4 %和 75 .6 % ,均高于 2 2例慢性胆囊炎组织 (P <0 .0 1)。P6 2的表达与胆囊癌淋巴结转移有关 (P <0 .0 5 ) ,与癌组织的分级、临床分期无显著关系。bFGF的表达与胆囊癌临床病理分期及组织学分级有关 (P <0 .0 5 ) ,而与淋巴结转移无显著关系。P6 2表达率与bFGF表达率呈正相关关系 (r=0 .5 2 1;P <0 .0 1)。两者的表达均与患者的年龄、性别、肿瘤的种类、是否伴有胆囊结石无关。胆囊癌组织中MVD明显高于慢性胆囊炎组织 (P <0 .0 1)。P6 2及bFGF表达阳性组织MVD高于表达阴性组织 (分别P <0 .0 5和P <0 .0 1)。MVD与胆囊癌的Nevin分期及淋巴结转移有关 (P<0 .0 1) ,与患者的年龄、性别、肿瘤种类、分化程度以及是否伴有胆囊结石无关。结论 :P6 2蛋白及bFGF的表达与胆囊癌组织中血管的生成相关 ,在胆囊癌的发生和发展过程中可能具有重     

肝素酶和碱性成纤维细胞生长因子与非小细胞肺癌转移和预后的关系

目的 探讨肝素酶(heparanase)和碱性成纤维细胞生长因子(bFGF)在人非小细胞肺癌(NSCLC)组织中表达的临床意义及其与肺癌转移和预后的关系。方法 采用免疫组织化学、原位杂交和Western blot方法,检测115例人NSCLC石蜡切片和45例新鲜肺癌及对应癌旁正常组织中肝素酶和bFGF的表达情况。采用χ^2检验、t检验、生存曲线和Cox比例风险回归等方法分析肝素酶和bFGF分别表达及共表达的意义。结果 免疫组织化学染色证实肝素酶(91／115)和bFGF(89／115)主要表达在癌细胞质和(或)细胞膜中,在正常肺泡上皮和支气管上皮中则呈阴性表达。Western blot也证实肝素酶在肺癌中的表达明显增高(P=0．041)。统计分析结果显示：肝素酶和bFGF的表达具有明显的一致性(P：0．0001),二者单独表达和共表达均与肺癌的分期、血管侵袭、淋巴结转移、微血管密度和预后有关,其中,二者共表达时与分期和微血管密度的相关性更显著;另外,bFGF还与肺癌的分化程度有关。多因素分析结果显示,肺癌的分化程度、血管浸润、淋巴结转移和bFGF的表达可以作为判断肺癌预后的危险因素,但肝素酶不是影响预后的独立因素。结论 肝素酶和bFGF均与肺癌的转移、血管生成和预后密切相关。     

17-二甲基胺乙基-17-去甲氧基格尔德霉素对人胃癌裸鼠移植瘤血管内皮生长因子表达的抑制作用

目的:观察热休克蛋白90(HSP90)抑制剂17-二甲基胺乙基-17-去甲氧基格尔德霉素(17-DMAG)对人胃癌裸鼠移植瘤生长的影响,探讨17-DMAG对胃癌生长和血管生成的抑制作用。方法:用人胃癌细胞HGC-27接种于裸鼠皮下,建立裸鼠胃癌移植瘤模型;将荷瘤裸鼠随机分为3组,每组8只:17-DMAG组(腹腔注射17-DMAG 25 mg/kg)、5-氟尿嘧啶(5-FU)组(腹腔注射5-FU20 mg/kg)及对照组(腹腔注射生理盐水10mL/kg),4周后测量裸鼠移植瘤的体积及重量,HE染色观察形态学变化,同时采用免疫组化方法检测肿瘤组织中CD31(以阳性细胞数计算肿瘤微血管密度)及血管内皮生长因子(VEGF)的表达,采用Western blotting法检测VEGF的表达。结果:17-DMAG组移植瘤体积为(288.10±23.32)mm3,5-FU组移植瘤体积为(366.37±26.42)mm3,对照组移植瘤体积为(957.66±117.51)mm3,前二者与对照组比较,均差异显著(P0.05)。移植瘤重量与对照组比较,17-DMAG组(0.41±0.02)g明显低于对照组(1.12±0.08)g,P0.05;5-FU组(0.48±0.05)g也明显低于对照组(1.12±0.08)g,P0.05;17-DMAG组和5-FU组抑瘤率分别63%和57%,2组抑瘤率无明显差异。17-DMAG组微血管密度(21.72±1.24)比对照组(37.78±1.68)明显减少,P0.05;5-FU组(36.70±1.51)和对照组(37.78±1.68)之间没有显著差异;17-DMAG组肿瘤组织中VEGF的表达(15.39±4.37)明显低于对照组(36.45±7.45)和5-FU组(26.11±6.26)。结论:热休克蛋白90抑制剂17-DMAG可通过降低胃癌组织中血管内皮细胞生长因子的表达抑制肿瘤新生血管的生成,进而抑制裸鼠移植瘤的生长。     

乳腺癌组织Livin和PTEN表达与肿瘤血管生成的相关性

目的:研究乳腺癌组织中凋亡抑制蛋白Livin和抑癌基因PTEN的表达与微血管密度(MVD)的关系,探讨乳腺癌血管生成的影响机制。方法:应用免疫组化Elivision法检测90例乳腺癌和30例乳腺纤维腺瘤组织中Livin、PTEN、VEGF的表达和CD34标记的MVD值,分析Livin和PTEN表达与乳腺癌血管生成及侵袭转移的关系。结果:在90例乳腺癌中Livin、PTEN和VEGF表达阳性率分别为54.4%、48.9%和61.1%,MVD为(30.81±11.29)个/HPF,与良性对照组比较均有显著差异(P<0.01);Livin阳性表达与乳腺癌肿瘤大小、临床分期、MVD值及VEGF表达呈正相关(P<0.05),与年龄、病理分级、淋巴结转移未见显著相关(P>0.05);PTEN表达与乳腺癌淋巴结转移、临床分期和MVD呈负相关(P<0.05),与VEGF表达、年龄、肿瘤大小、病理分级未见显著相关(P>0.05)。结论:Livin和PTEN在乳腺癌的血管生成及发生发展过程中分别起促进和抑制作用,Livin的促血管生成作用可能与其上调VEGF的表达有关。     

胃癌中uPA、PAI-1表达及其与血管生成的关系

目的 观察胃癌组织中uPA、PAI-1mRNA及蛋白的表达，并探讨它们与肿瘤分化、血管生成及临床病理因素之间的关系。方法 用原位杂交及免疫组化S-P法检测110例胃癌组织中uPA、PAI-1的表达，根据CD34阳性的血管内皮细胞计数肿瘤组织微血管密度（MVD）。结果 （1）胃癌组织中uPA mRNA和蛋白、PAI-1 mRNA和蛋白阳性表达定位于胞质；uPA的表达随分化程度的降低有逐渐升高的趋势，PAI-1的表达随分化程度的降低有逐渐降低的趋势。（2）110例uPA mRNA及蛋白表达阳性组MVD值显著高于阴性组，差异均具有显著性（P值均＜0．05）。（3）uPA mRNA及蛋白的表达与临床分期呈正相关（P＜0．05），PAI-1的表达与临床分期和淋巴结转移无相关性。（4）uPA mRNA／蛋白与PAI-1 mRNA／蛋白的表达无相关性。结论uPA与促进胃癌的血管生成密切相关，阻断uPA的分泌和作用途径有望对胃癌浸润转移起抑制作用；胃癌组织中PAI-1可能担当重要的调节剂或者是肿瘤细胞防止自身降解的保护剂而不是这个系统的单纯抑制剂。     

裸鼠胃癌模型的相位衬度微血管成像

目的肿瘤血管生成与肿瘤的发生、发展等各个环节密切相关,并显著影响肿瘤的生物学行为和预后。本研究的目的在于使用相位衬度成像技术三维地、全面地观察肿瘤微血管形态。方法使用原位接种肿瘤组织块方法,建立裸鼠胃癌原位模型。实验样本分为正常组和肿瘤组。对得到的相位衬度图像进行增强、血管分割、三维重建,并且计算三维微血管密度参数。结果相位衬度成像可显示胃癌组织的微血管形态。对照组微血管密度低于胃癌组的肿瘤表面区域(P0.001),证明肿瘤微血管更加丰富。结论相位衬度成像可以更全面地显示肿瘤微血管的生成情况,有助于对胃癌的恶性程度、转移潜力等进行评估,并对治疗方案的选择、判断预后和评估抗肿瘤血管药物疗效具有重要意义。     

Hepatic arterial administration of sorafenib and iodized oil effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX2 hepatocellular carcinoma model

Aim: To investigate the therapeutic effect of the hepatic arterial administration of sorafenib in rabbit VX-2 hepatocellular carcinoma (HCC) model. Methods: Rabbit VX-2 HCC models were established via implanting VX-2 tumors into the livers, and randomly divided into four groups, respectively treated with (1) The hepatic arterial administration of iodized oil alone (TACE-i), (2) The hepatic arterial administration of iodized oil and pharmorubicin (TACE-ip), (3) The hepatic arterial administration of iodized and cis-DDP (TACE-ic), (4) The hepatic arterial administration of iodized and sorafenib (TACE-is). The growth rate and intrahepatic metastasis of implanted VX-2 tumor in each rabbit were measured. Microvessel density (MVD) in the adjacent tissues of implanted VX-2 tumor were estimated by detecting the expression of CD34 and VEGF level in tumor adjacent tissues were also examined by Immunohistochemistry. Results: Compared with other groups, TACE-is treatment group presented a better effect on inhibiting tumor growth rate and intrahepatic metastasis in rabbit VX-2 HCC model. The angiogenesis (assessed by MVD) in the adjacent tissues were suppressed more dramatically in TACE-is treated group. Moreover, TACE-is treatment did not significantly increase the levels of alanine transaminase and creatinine compared to the group with TACE-i treatment. Conclusion: The hepatic arterial administration of sorafenib and iodized oil (TACE-is) effectively attenuates tumor growth and intrahepatic metastasis in rabbit VX-2 HCC model without obvious hepatic and renal toxicity. One of the related mechanisms may be due to the inhibition of angiogenesis in the adjacent tissues. Our data indicated that TACE-is may be a secure and effective treatment for HCC.     

Photo-crosslinkable and biodegradable Pluronic/heparin hydrogels for local and sustained delivery of angiogenic growth factor

Photo-crosslinkable and biodegradable Pluronic/heparin composite hydrogels were fabricated for local and sustained delivery of basic fibroblast growth factor (bFGF) to induce angiogenesis. Terminally di-acrylated Pluronic F127 and vinyl group conjugated heparin were used as a mixed macromer precursor solution to prepare a photo-crosslinkable hydrogel. An aqueous solution containing the two macromers with different weight ratios was photo-crosslinked in the presence of bFGF to produce in situ formed bFGF loaded Pluronic/heparin hydrogels. Swelling, mass erosion, bFGF release characteristics of Pluronic/heparin hydrogels were thoroughly examined by varying the weight ratio of the two macromers. The incorporation of heparin in the composite hydrogel enabled the controlled release of bFGF over a one month period in a near zero order manner. The prolonged release of bFGF could be attributed to the specific interaction between bFGF and heparin in the hydrogel matrices. The released bFGF fraction from the degradable hydrogels also showed sufficient proliferation activity of human umbilical vein endothelial cell (HUVEC). When the Pluronic/heparin hydrogels were implanted in vivo, a significant extent of neo-vascularization was observed.     

The correlation of angiogenesis with metastasis in primary cutaneous melanoma: a comparative analysis of microvessel density, expression of vascular endothelial growth factor and basic fibroblastic growth factor

AIM: To establish whether there is a correlation between angiogenesis and metastasis in primary cutaneous melanoma (PCMM). METHODS: We studied the microvessel density and the expression of vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) in 22 cases of PCMM with metastasis at presentation (metastatic group) and 28 cases of PCMM without metastasis for 24 months or more (non-metastatic group). Microvessels were stained with CD31/PECAM-1 antibody and counted. We assessed the proportion of VEGF expression in tumour cells, lymphocytes infiltrating the tumour (TIL) and lymphocytes at the periphery of the tumour, as well as the proportion of bFGF expression in tumour cell cytoplasms, nuclei and intra- and peritumoral vessels. RESULTS: An increased microvessel density was detected in the metastatic group (15-33 [24.09 +/- 5.55] versus 2-24 [12.96 +/- 6.02]). Moreover, enhanced expression of VEGF in tumour cells and peritumoral lymphocytes (Chi-square p = 0.038 and p = 0.018) and bFGF in peritumoral vessels (chi(2) p = 0.013) correlated with the simultaneous presence of melanoma metastasis in PCMM. Furthermore, microvessel density was correlated with the expression of bFGF in peritumoral vessels (rs = 0.53, p = 0.049) and VEGF in tumour cells (rs = 0.37, p = 0.019). CONCLUSION: Microvessel density as well as the expression of both VEGF and bFGF might be informative concerning the progression of melanoma.     

结直肠癌螺旋CT征象与肿瘤血管生成的关系

目的 探讨结直肠癌螺旋CT征象与肿瘤血管生成的关系.方法40例结直肠癌患者术前均行螺旋CT多期动态扫描,术后肿瘤标本采用免疫组化SP法染色,检测血管内皮生长因子(VEGF)、基质金属蛋白酶(MMP)2和nm23的表达并计数微血管密度(MVD).结果 螺旋CT判断结直肠癌肠外、肠壁浸润的准确率为92.5%.肠外、肠壁浸润组的转移率分别为67.9%和33.3%,差异有统计学意义(P<0.05).螺旋CT结直肠癌肠壁、肠外浸润组间的CT强化程度、MVD、VEGF和MMP-2的表达差异具有统计学意义(t值分别为7.73、2.85、2.44、2.05,P均<0.05).结直肠癌腹腔内转移与无转移组间的CT强化程度、MVD和nm23表达的差异亦有统计学意义(P均<0.05).结直肠癌肠壁浸润组及腹腔内转移组癌组织CT强化程度与MVD之间呈正相关(r=0.878,P<0.05).结论 螺旋CT扫描可准确反映结直肠癌肠外浸润、腹腔内转移情况.MVD和VEGF、MMP-2表达与结直肠癌浸润密切相关.nm23的失活可能是结直肠癌转移的因素.CT强化程度可反映肿瘤血管生成,有助对结直肠癌的浸润、转移进行估计.     

Coexpression of heparanase, basic fibroblast growth factor and vascular endothelial growth factor in human esophageal carcinomas

Heparan sulfate (HS), which is degraded by heparanase, plays an important role in cell adhesion, insolubility of the extracellular matrix (ECM) and as a reservoir for various growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). In the present study, we examined the immunohistochemical expression of heparanase, bFGF and VEGF, and evaluated the correlation between their expression and microvessel density (MVD) in human esophageal carcinomas. Heparanase, bFGF and VEGF were immunolocalized predominantly to the carcinoma cells, but they were also localized to the endothelial cells of microvessels near the carcinoma cell nests. In carcinomas with invasion of the muscular layer or adventitia, heparanase staining was stronger at the invasive areas of carcinomas than the intraepithelial spread. Expression of heparanase and bFGF and the degree of MVD were associated with tumor invasion, lymph node metastasis and pathological stages. Cases with positive staining for heparanase, bFGF or VEGF tended to have a higher MVD than those without staining, and carcinomas with concomitant expression of heparanase, bFGF and VEGF showed the highest MVD. The level of heparanase mRNA expression was directly correlated with the MVD. In addition, heparanase-positive cases had a higher positive ratio of bFGF and VEGF compared with the heparanase-negative cases. These data suggest the possibility that heparanase may contribute to not only cancer cell invasion but also angiogenesis probably through degradation of HS in the ECM and release of bFGF and VEGF from the HS-containing ECM.     

细胞周期蛋白G1在喉鳞状细胞癌中的表达及其临床病理学意义

目的 探讨喉鳞状细胞癌组织中细胞周期蛋白(cyclin)G1表达与临床病理参数及p53、癌组织微血管密度(MVD)的关系,并分析其作为预测喉鳞状细胞癌预后指标的可能性.方法 采用免疫组织化学(EnVision法)检测81例喉鳞状细胞癌组织中cyclin G1、p53的表达情况,用CD34标记新生血管内皮细胞,在显微镜下观察MVD.同时测它们在20例癌旁正常喉黏膜中的表达.结果 与正常喉黏膜组织相比,肿瘤组织中cyclin G1、p53表达及MVD均明显增加.喉鳞状细胞癌组织中cyclin G1、p53的阳性表达率分别为61.7%(50/81)和65.4%(53/81),在p53蛋白表达阳性和阴性的喉鳞状细胞癌组织标本中,cyclin G1蛋白阳性率分别为71.7%(38/53)和42.9%(12/28),cyclin G1表达与p53有相关性(Kappa值为0.281,P=0.011).cyclin G1蛋白阳性组平均MVD为(51.23±16.46),阴性者(30.74±12.29),其差异有统计学意义(P=0.005).cyclin G1高表达与肿瘤组织分化程度、颈淋巴结转移以及5年生存率均有统计学意义(P值分别为0.002、0.013和0.032).结论 cyclin G1蛋白在喉鳞状细胞癌中存在高表达,并与p53、MVD关系密切,cyclin G1异常表达可能在喉鳞状细胞癌发生、发展及转移过程中发挥重要作用,并可能作为判断患者预后的指标之一.     

Prognostic significance of angiogenesis in gastrointestinal stromal tumor.

Angiogenesis is important in the growth and metastasis of various kinds of solid tumors. To investigate the potential role of angiogenesis in gastrointestinal stromal tumor (GIST), an immunohistochemical analysis was performed in 95 cases of GISTs for microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression. MVD was evaluated with immunohistochemical staining for CD31. A high level of MVD was significantly correlated with overexpression of VEGF, tumor location (intestine>stomach), tumor size (> or =5 cm), tumor grade (high>intermediate>low grade) (P=<0.0001, 0.0422, 0.0006, 0.0359, respectively). Of the 70 GISTs analyzed, KIT exon 11 mutations were detected in 45 cases (64.3%) and KIT exon 9 mutations in two cases (2.9%). No mutations were found in KIT exons 13 and 17, and platelet-derived growth factor receptor-alpha exons 12 and 18. Interestingly, VEGF expression level was significantly higher in the non-KIT exon 11 mutant group than in the KIT exon 11 mutant group (P=0.0266). In univariate analysis, tumor grade (high grade), tumor size (> or =5 cm), mitotic count (> or =5/50 high-power fields), Ki-67 labeling index (> or =4.6%), MVD (> or =7.0/0.95 mm(2)) and VEGF expression (high) were significantly associated with a shorter period of disease-free survival (P=<0.0001, 0.0199, 0.0055 0.0027, 0.0028 and 0.0302, respectively). In multivariate analysis, tumor grade and MVD were identified as independent worse prognostic factors (P=0.0007, 0.0152, respectively). In conclusion, our results suggest that the evaluation of MVD and VEGF expression is useful for predicting the aggressive biologic behavior of GIST, and that angiogenesis associated with VEGF may play an important role, at least in part, in the progression of GIST.     

VEGF、ANG-1、ANG-2、TSP-1的表达与胆管细胞性肝癌血管生成和侵润转移的关系

目的：研究血管内皮生长因子（VEGF）、血管生成素-1（ANG-1）、血管生成素-2（ANG-2）、血小板反应蛋白-1（TSP-1）的表达与胆管细胞性肝癌(CCC)血管生成和侵润转移的关系。方法： 对33例手术切除的CCC标本进行CD34、VEGF、 ANG-1、 ANG-2 和TSP-1的免疫组化染色，研究VEGF、ANG-1、ANG-2、TSP-1的表达与胆管细胞性肝癌血管生成和肿瘤门静脉侵犯、肝内转移、淋巴结转移以及肿瘤分化水平之间的关系。 结果： 本组CCC的微血管密度（MVD）为(87.2±52.6)/mm2，VEGF、ANG-1、ANG-2 和TSP-1的阳性率分别为75.6%、36.0%、57.6%和45.5%。VEGF和ANG-2的阳性表达与高MVD相关，TSP-1则与MVD负相关（P<0.01,P<0.05,P<0.01）。阳性TSP-1与肝内转移正相关（46.7% vs 5.6%，P<0.05）。结论： CCC瘤内的血管新生活跃，VEGF和ANG-2的阳性表达与CCC血管生成正相关，TSP-1则与其负相关，TSP-1的阳性表达还与肝内转移相关，VEGF、ANG-1、ANG-2的表达与肿瘤的侵润转移未见显著相关。