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1.
In this study, we examined the expression of inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) by immunohistochemical staining in 76 tissue sections collected from hepatocellular carcinoma (HCC) patients undergoing hepatectomy. Microvascular density (MVD) was determined by counting endothelial cells immunostained using anti-CD34 antibody. We performed DNA-flow cytometric analyses to elucidate the impact of iNOS and VEGF expression on the cell cycle of HCC. Most of the HCC cells that invaded stroma were markedly immunostained by iNOS antibody. The iNOS stain intensity of the liver tissue close to the tumor edge was stronger than that of HCC tissue, and the strongest was the hepatocytes closer to the tumor tissue. However, iNOS expression in 10 normal hepatic samples was undetectable. VEGF positive expression ratio was 84.8% in iNOS positive expression cases, and the ratio was 35.3% in negative cases. There was significant correlation (P=0.000) between iNOS and VEGF expression. Moreover, iNOS expression was significantly associated with bcl-2 and MVD, but without p53 expression. DNA-flow cytometric analyses showed that combined expression of iNOS and VEGF had significant impact on the cell cycle in HCC. PI (Proliferating Index) and SPF (S-phase fraction) in the combined positive expression of iNOS and VEGF group was significantly higher than that in the combined negative group. The present findings suggested that iNOS expression was significantly associated with angiogenesis, bcl-2 and cell proliferation of HCC. Project supported in part by the National Ninth-Five-Years Project Fund (No. 96909121), China  相似文献   

2.
Objective: To investigate the relationship between the expression of endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and angiogenesis in primary astrocytoma. Methods: Thirty-seven primary astrocytomas and 4 astrocytic hyperplasia samples were collected and divided into three groups according to histological grade. The expression of eNOS, VEGF and factorⅧrelated antigen (FⅧRAg) were assayed by immunohistochemistry. Microvascular density was assessed by FⅧRAg immunoreactivity. The intensity of immunoreactivity was graded according to the percentage of positive tumor cells. Results: No eNOS and VEGF were expressed in the astrocytes and vascular endothelium in astrocytic hyperplasia. The expression of eNOS or VEGF was light in low-grade astrocytoma and strong in glioblastoma. eNOS expression in astrocytoma was very positively correlated with VEGF. eNOS and VEGF expression in anaplastic astrocytoma was median in contrast to the low grade astrocytoma and glioblastoma. Lower microvascular density was found in low grade astrocytoma than that in higher grade malignant ones. The expressions of eNOS and VEGF were correlated with microvascular density and tumor malignancy. Conclusion: This finding suggests that eNOS and VEGF may have cooperative effect in tumor angiogenesis and play an important role in the pathogenesis of primary astrocytoma.  相似文献   

3.
Prognostic significance of bcl-2 and p53 expression in colorectal carcinoma   总被引:4,自引:0,他引:4  
INTRODUCTION Colorectal cancer is the most common cancer ofthe Western world and accounts for approx.Elevenpercent of all cancer deaths in the United States.Aswith other malignancies,colorectal adenocarcinomais thought to develop through the accumulation ofgenetic alterations that inhibit cell growth.Two of theoncogenes that have been implicated in this processare bcl-2and p53,the products of which are involvedin apoptosis,cell proliferation and tumor develop-ment(Garewal et al.,1996).S…  相似文献   

4.
Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evidence suggests that angiogenesis may play an important role in hematological malignancies, such as leukemia. How ever, whether HHT can relieve leukemia by anti-angiogenesis is still unknown. We investigated the anti-angiogenesis potential of HHT with the human umbilical vein endothelial cell line (ECV304) and leukemic cell line (K562) in vitro. Cellular proliferation was determined by MTT assay and apoptosis was analyzed by flow cytometry. The mRNA expression of vascular endothelial growth factor (VEGF) was assessed by RT-PCR and VEGF protein production was detected by Western blot. Inhibition of cell proliferation and induction of apoptosis by HHT were discovered in ECV304 cells, and appeared in a dose- and time-dependent manner. Also, treatment with HHT caused down-regulation of VEGF mRNA expression in K562 cells in similar dose- and time-dependent manner and inhibition of VEGF protein production in K562 cells in response to the enhancing concentration of HHT. The results demonstrated that HHT could also induce apoptosis in endothelium and down-regulate VEGF expression in K562 cells. In conclusion, we believe HHT has anti-angiogenesis potential and speculate that HHT might exert its anti-leukemia effects via reduction of angiogenesis.  相似文献   

5.
INTRODUCTION Homoharringtonine (HHT) is a cephalotoxin alkaloid with anti-leukemic activity and had been used successfully in the treatment of acute and chronic myeloid leukemias (O払rien et al., 1995; 1999; Feldman et al., 1992). The principal mecha-nism of action by HHT is the inhibition of protein synthesis in a dose- and time-dependent manner by binding to ribosome and inhibiting polypeptide chain elongation (Tujebajeva et al., 1989; Zhou et al., 1995). HHT had been shown to indu…  相似文献   

6.
为探讨凋亡相关基因bcl-2、bax、c-myc在胃癌发生发展中的作用,我们采用SP免疫组织化学方法对125例胃粘膜良恶性病变标本进行bcl 2、bax、c-myc基因蛋白的检测。结果表明,bcl-2和bax在胃癌、胃炎伴肠化生和异型增生组的阳性表达率显著高于单纯胃炎组,且bcl-2的表达与胃癌分化程度有关。此实验提示bcl-2、bax和c-myc基因可能参与胃癌的发生和发展。  相似文献   

7.
目的:探讨血管内皮生长因子(VEGF)在膀胱移行细胞癌中的表达及临床意义。方法:采用免疫组化、ELISA方法对45例膀胱移行细胞癌组织、血浆和10例正常膀胱黏膜组织、30例正常成人血浆中VEGF进行检测分析。结果:VEGF在膀胱移行细胞癌患者中呈高表达,且随分期、分级的增高而增高;膀胱癌手术前患者血浆中VEGF的浓度高于手术后。结论:1.VEGF的表达与膀胱移行细胞癌的病理分级、临床分期及生物学行为有密切关系;2.血浆中VEGF水平可有助于预测膀胱癌患者手术疗效。  相似文献   

8.
目的:研究抗凋亡基因bcl-2和促凋亡基因bax在胃癌发生、发展过程中的变化.方法:应用SP免疫组织化学方法,对80例胃癌及癌旁粘膜组织进行bcl-2、bax基因蛋白的检测.结果:胃癌组织中bcl-2阳性表达率为46.3%,癌旁组织为40.0%.光镜下对癌旁粘膜组织依有无癌前病变进行分组,其中56例伴癌前病变者bcl-2阳性表达率为57.1%,24例不伴癌前病变者无阳性表达.对53例带有癌的癌旁组织根据癌旁粘膜和癌的关系,分为移行粘膜25例,受侵粘膜28例,其中移行粘膜均伴癌前病变.bcl-2阳性表达率在移行粘膜(68.0%)和胃癌组织均明显高于受侵粘膜(3.57%).bax阳性表达率在胃癌为41.3%,癌旁组织为32.5%.伴癌前病变癌旁粘膜(14.2%)和胃癌组织及不伴癌前病变癌旁粘膜(75.0%)均有明显差异.本组实验中,bcl-2与bax共同阳性表达率在伴癌前病变癌旁粘膜(12.5%)和胃癌(13.8%)明显高于不伴癌前病变癌旁粘膜(0);移行粘膜(28.0%)明显高于受侵粘膜(3.57%).且胃癌、伴癌前病变癌旁粘膜、不伴癌前病变癌旁粘膜;胃癌、移行粘膜、受侵粘膜组间均有明显差异.结论:bcl-2、bax基因蛋白的异常表达与胃癌发生有关;在伴癌前病变癌旁粘膜组织中bcl-2表达明显高于bax.  相似文献   

9.
Objective: To investigate whether vascular endothelial growth factor (VEGF) gene plasmid carried by polytetrafluoroethylene (PTFE) vascular graft materials could transfect endothelial cells (ECs) and promote their growth. Methods: PTFE vascular graft materials carried with pCDI-hVEGF121, pCDI or pEGFP were incubated in Tris-buffer solution and the values of optical density of 260 nm at different time were plotted, then the DNA controlled release curve was made. ECs derived from human umbilical vein were seeded on the pCDI-hVEGF121/pCDI/pEGFP-PTFE materials or tissue culture plates, ECs numbers were counted and VEGF protein concentrations at different time were measured by enzyme-linked immunoadsorbent assay method. Green fluorescent protein (GFP) expression in ECs on pEGFP-PTFE materials was examined with fluorescence mi- croscopy. Results: The controlled release curve showed that the gene released from PTFE materials was rapid within 8 h, then slowed down and that the gene released continuously even after 72 h. At 24, 72 and 120 h, ECs number and proliferation rate of pCDI-hVEGFI21-PTFE materials were higher than those ofpCDI or pEGFP-PTFE materials (P〈0.05). VEGF protein concentration of pCDI-hVEGF121-PTFE materials was higher than that of pC DI or pEGFP-PTFE materials at 6, 24, 72 and 120 h (P〈0.01). GFP expression in ECs on the pEGFP-PTFE materials could be detected by fluorescence microscopy. Conclusion: PTFE graft can be used as a carrier of VEGF gene plasmid, VEGF gene carried by PTFE can transfect ECs and promote ECs growth.  相似文献   

10.
Ds-echinoside A (DSEA), a non-sulfated triterpene glycoside, was isolated from the sea cucumber Pearsonothuria graeffei. In vitro and in vivo investigations were conducted on the effects of DSEA on tumor cell adhesion, migration, invasion, and angiogenesis. In this study, we found that DSEA inhibited the proliferation of human hepatocellular liver carcinoma cells Hep G2, with a half-maximal inhibitory concentration (IC50) of 2.65 μmol/L, and suppressed Hep G2 cell adhesion, migration, and invasion in a dose-dependent manner. DSEA also reduced tube formation of human endothelial cells ECV-304 on matrigel in vitro and attenuated neovascularization in the chick embryo chorioallantoic membrane (CAM) assay in vivo. Immunocytochemical analysis revealed that DSEA significantly decreased the expression of matrix metalloproteinase-9 (MMP-9), which plays an important role in the degradation of basement membrane in tumor metastasis and angiogenesis. DSEA also increased the protein expression level of tissue inhibitor of metalloproteinase-1 (TIMP-1), an important regulator of MMP-9 activation. From the results of Western blotting, the expressions of nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) were found to be remarkably reduced by DSEA. These findings suggest that DSEA exhibits a significant antimetastatic activity through the specific inhibition of NF-κB-dependent MMP-9 and VEGF expressions.  相似文献   

11.
Angiogenesis is required for solid tumor growth and facilitates tumor progression and metastasis. The inhibition effects of O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), an angiogenesis inhibitor, and gemcitabine, a chemotherapeutic agent, on expression of growth factors were investigated using human pulmonary adenocarcinoma cell line, A549. The A549 cells were divided into four groups: control group, 10^-6 mg/ml gemcitabine treated group, 10^-4 mg/ml TNP-470 treated group and gemcitabine+TNP-470 treated group. The mRNA and protein expression of vascular endothelial growth factor (VEGF) and its receptors, FMS-like tyrosine kinase-l (FLT-1) and kinase insert domain-containing receptor (KDR), in different groups were measured. The growth of A549 cell cultured with gemcitabine or TNP-470 was inhibited in an almost dose-dependent manner. Although gemcitabine (10^-6 mg/ml) alone and TNP-470 (10^-4 mg/ml) alone had no effect on the mRNA and protein expression of VEGF and its receptors (FLT-1, KDR) in A549 cells compared to the control (P〉0.05), 10^-6 mg/ml gemcitabine in combination with 10^-4 mg/ml TNP-470 had significant effect (P〈0.01). Moreover, combination of the two drugs significantly inhibited the mRNA expression of VEGF, FLT-1 and KDR compared to either drug alone (P〈0.05). This study suggests that combined treatment with TNP-470 plus gemcitabine may augment the antiangiogenic and antineoplastic effects in lung cancer cells in vitro.  相似文献   

12.
养阴清热方抑制小鼠Lewis瘤肺转移的实验研究   总被引:3,自引:0,他引:3  
[目的]观察养阴清热中药对C57BL/6小鼠移植Lewis瘤肺转移的作用,并探讨机理.[方法]干扰素和养阴清热中药分别作用于动物模型,21 d后处死动物,统计肺转移计数,免疫组化法检测瘤体血管内皮生长因子(VEGF)和微血管内皮标记物Factor-VⅢ.[结果]肺转移灶计数,中药组与模型组比较有显著差异(P<0.05),与干扰素组无显著差异(P>0.05),中药组在VEGF表达上与模型组比较有显著差异(P<0.05),与干扰素组无显著差异(P>0.05);中药组在肿瘤微血管密度(MVD)记数与模型组比较有显著差异(P<0.05),与干扰素组无显著差异(P>0.05).[结论]养阴清热法对L.L.C的转移有明显的抑制作用,其主要机理是在降低VEGF表达的基础上,抑制肿瘤血管生成.  相似文献   

13.
MMP-9和CD15s与胃癌血管生成的相关性研究及其临床意义   总被引:2,自引:0,他引:2  
目的:探讨基质金属蛋白酶9(MMP-9)和唾液酸化Lewis X(CD15s)抗原与胃癌侵袭转移的相关性。方法:采用CD105,MMP-9,CD15s进行免疫组化S-P法染色,对47例胃癌根治性切除手术标本病理组织切片进行标记,检测CD105的微血管密度(MVD),并对MVD与MMP-9、CD15s的关系进行统计分析。结果:MMP-9、CD15s表达都呈阳性的胃癌组织微血管密度高于MMP-9和CD15s单阳性及二者均阴性的胃癌组织。结论:MMP-9高表达有利于癌组织局部浸润,CD15s高表达有利于癌细胞血行转移,MMP-9及CD15s检测对临床诊治胃癌及判断预后具有一定意义。  相似文献   

14.
近年来我们对麻黄果实进行了较为全面的研究,结果表明该果实具有抗凝血、降血压等作用。为此我们采用以芦丁为标准,用分光光度法对其总黄酮类物质含量进行了测定。  相似文献   

15.
本研究应用较灵敏的SP免疫组织化学方法,对80例胃癌组织进行bcl-2、c-myc基因蛋白的检测,并对两种基因与临床病理的关系进行了研究。结果发现,bcl-2基因蛋白在胃癌的阳性率为46.3%。高、中分化腺癌阳性率为59.4%,显著高于低、未分化腺癌(37.5%);其表达与Merkel分型有关,乳头状腺癌显著高于低分化腺癌;在lauren分型中,肠型胃癌为59.4%,显著高于弥漫型(37.5%);在Ming'S分型中,膨胀型(52.3%)显著高于浸润型胃癌(23.5%)。在伴淋巴结转移的胃癌中,bcl-2的表达率(38.6%)显著低于不伴淋巴结转移者(65.2%)。c-myc基因蛋白在胃癌的阳性率为67.5%,其表达率在低、未分化腺癌中为72.5%,显著高于粘液腺癌(25.0%);而粘液结节型腺癌(25%)明显低于粘液细胞型腺癌(81.8%)和管状腺癌(71.4%)。在膨胀型胃癌的表达率(73.0%)显著高于浸润型(47.1%)。c-myc的表达率与淋巴结转移明显关系。bcl-2、c-myc基因表达与患者性别、年龄、肿瘤发生部位、浸润深度无明显相关性。  相似文献   

16.
17.
应用免疫组化方法,比较性地研究了大肠癌组织及其同一患者形态正常大肠粘膜组织中血管内皮细胞生长因子的表达,分析血管内皮细胞生长因子表达与大肠癌发生的年龄、性别、病理分期等因素的关系。结果显示,癌组织与正常大肠粘膜的血管内皮细胞生长因子表达存在明显差异,血管内皮细胞生长因子的表达与大肠癌患者年龄、性别、分化程度等因素不存在相关性,而与Ducks分期存在明显相关性。表明肿瘤血管的生成在大肠癌的生长发展方面起着至关重要的作用,血管内皮细胞生长因子的检测可以作为大肠癌诊断的重要参考指标。  相似文献   

18.
Objective:To explore the feasibility of using regenerated silk fibroin membrane to construct artificial skin substitutes for wound healing, it is necessary to evaluate its cytocompatibility. Methods:The effects of regenerated silk fibroin film on cytotoxicity, adhesion, cell cycle, and apoptosis of L929 cells, growth and vascular endothelial growth factor (VEGF) expression of ECV304 cells, and VEGF, angiopoietin-1 (Ang-1), platelet-derived growth factor (PDGF) and fibroblast growth factor 2 (FGF2) expressio...  相似文献   

19.
目的:探讨血管内皮生长因子(VEGF)在乳癌中过表达的临床意义。方法:取乳腺腺瘤47例,乳腺癌95例,利用SABC法检测VEGF阳性率。结果:VEGF在腺瘤中阳性率为25.53%(12/47),在乳癌中阳性率为54.75%(52/95);在浸润性癌和有淋巴结转移组阳性率明显高于非浸润性组和无淋巴结转移组(P〈0.05)。结论:VEGF过表达提示患者预后不良,检测VEGF对化疗方案选择有指导意义。  相似文献   

20.
目的:通过康脑液干预观察其对脑缺血再灌注损伤大鼠血管内皮生长因子(vascular endothelial growth factor,VEGF)、脑源性神经生长因子(brain derived neurotrophic factor,BDNF)、基质金属蛋白酶(matrix metalloproteinase-9,MMP-9)表达的影响,探讨康脑液对脑缺血再灌注损伤的保护机制.方法:将雄性SD大鼠随机分为假手术组、脑缺血再灌注模型组及康脑液28.6、14.3、7.15 g·kg-1·d-1剂量组(灌胃给药7 d),改进Longa等线栓法制备大鼠右侧大脑中动脉阻塞(middle cerebral artery occlusion,MCAO)再灌注模型.于缺血2h后再灌注(分别于再灌注后6h、12h、24 h、72 h、7d处死大鼠);采用TTC染色法观察大鼠的脑梗死面积;免疫组织化学法观察大鼠脑组织VEGF、BDNF、MMP-9的表达.结果:比较各组缺血再灌注24 h大鼠脑梗死灶面积,发现28.6、14.3 g·kg--1·d-1剂量组较脑缺血再灌注模型组明显减小(P<0.05);与脑缺血再灌注模型组相比,28.6、14.3 g·kg--1·d-1剂量组各时间点的VEGF、BDNF表达量明显上调(P<0.01),MMP-9表达的阳性细胞明显减少(P<0.01),差异有统计学意义.结论:康脑液可促进大鼠局灶性脑缺血后脑组织中VEGF,BDNF的表达,同时抑制脑内MMP-9的表达,缩小脑梗死面积,发挥对神经血管单元(neurovascular unit,NVU)的保护作用,减轻脑缺血再灌注损伤.  相似文献   

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