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1.
Angiogenesis is essential for tumour growth and invasion. Vascular endothelial growth factor (VEGF) is a prime mediator of tumour angiogenesis. VEGF-C is a closely related protein that effects lymphatic endothelial cells and may be important in the process of lymphatic metastasis. The purpose of this study was to evaluate the expression of these cytokines in patients with T1 and T2a glottic, squamous cell carcinoma, in comparison with normal epithelial control tissue, to ascertain any association with radioresistance. Twenty-two tumours treated by radiotherapy (13 radiosensitive, nine radioresistant) and seven normal control tissues were studied. The minimum follow-up was 2 years after radiotherapy. Expression of VEGF and VEGF-C was evaluated by immunohistochemistry of formalin-fixed, paraffin-embedded biopsy specimens. Analysis was carried out using a quantitative computer image analyser. Both VEGF and VEGF-C were detectable in tumour and normal control specimens. There was increased expression in tumour specimens of both VEGF (P = 0.03) and VEGF-C (P < 0.001). In addition, the expression of VEGF-C was associated with tumours of higher histological grade (P = 0.021). There was, however, no difference in VEGF and VEGF-C expression between radioresistant and radiosensitive tumours. The expression of VEGF and VEGF-C is increased in early laryngeal squamous cell carcinoma (SCC). However, measuring the expression of these proteins cannot predict radioresistance in this tumour group.  相似文献   

2.
OBJECTIVE: The present study was aimed at clarifying whether the microvessel density (MVD) and the expression of vascular endothelial growth factor (VEGF) were related to the degree of local invasion and metastasis in nasopharyngeal carcinoma (NPC). STUDY DESIGN: We measured the MVD and examined whether VEGF was expressed in NPC tissue using histological study combined with immunohistochemistry. METHODS: MVD and VEGF expression was measured in 73 specimens of NPC, 15 benign tumors of nasopharyngeal region, and 20 nasopharyngeal tissue without tumor. MVD and VEGF expression in NPC was compared between a metastasis group (49 specimens) and a non-metastasis group (24 specimens). RESULTS: Both MVD and VEGF expression were markedly increased in NPC tissue as compared with those in benign tumors of nasopharyngeal region. Both MVD and VEGF expression in NPC tissue with metastasis were statistically significantly increased as compared with those in NPC without metastasis. Therefore, the invasion and metastasis of NPC cells were closely related to MVD and the expression of VEGF in NPC tissue. CONCLUSION: The metastatic potency of NPC tissue and the prognosis of the patients with NPC can be estimated by measuring MVD and the expression of VEGF in NPC tissue. Drugs that have inhibitory actions on angiogenesis could be useful to prevent metastasis of NPC cells in the patients.  相似文献   

3.
HIF-1a和VEGF在喉癌中的表达及其与血管生成的关系   总被引:1,自引:0,他引:1  
目的:研究缺氧诱导因子-1a(HIF-1a)及血管内皮生长因子(VEGF)在喉癌组织中的表达程度及其与喉癌临床病理学特征之间的关系,并探讨HIF-1a及VEGF在肿瘤血管生成中的作用。为喉癌的发生机制提供理论基础,并为喉癌的早期诊断提供新思路。方法:试验分组:60例喉癌标本及20例癌旁正常组织。采用免疫组织化学方法检测HIF-1a及VEGF表达情况,并用CD105标记血管内皮细胞,计算微血管密度(MVD)。结果:60例喉癌组织中,HIF-1a、VEGF阳性表达率分别为71.67%(43/60)、65.00%(39/60),MVD平均值为33.82±10.15;20例癌旁正常组织中,HIF-1a、VEGF阳性表达率分别为10%(2/20)、20%(4/20),MVD平均值为21.48±6.84。喉癌组织中HIF-1a、VEGF阳性表达率显著高于正常喉组织。HIF-1a在喉癌组织中的阳性表达率与癌组织的临床分期、分化程度和淋巴结转移密切相关。VEGF阳性表达率与临床分期及有无淋巴结转移相关,而与组织分化程度无关。HIF-1a与VEGF表达一致符合率为56.67%(34/60),两者表达呈明显正相关。HIF-1a、VEGF均阳性的喉癌组织MVD高于两者均为阴性者,差异有统计学意义(P〈0.01)。结论:喉癌组织中存在HIF-1a蛋白及VEGF的过表达,HIF-1a、VEGF与MVD在喉癌中的表达呈正相关,协同促进肿瘤新血管形成。  相似文献   

4.
目的:探讨喉鳞状细胞癌组织中Galectin-3和血管内皮生长因子(VEGF)蛋白表达及其在肿瘤分化,生长及转移中的相关意义.方法:应用免疫组织化学SP法和免疫印记法分别对29例喉鳞状细胞癌、18例喉良性病变组织中Galectin-3和VEGF蛋白表达水平进行了检测.结果:Galectin-3(89.7%)和VEGF(86.2%)在喉鳞状细胞癌组的阳性表达率与正常对照组比较均差异有统计学意义(均P<0.05).喉高分化鳞状细胞癌组织中Galectin-3的表达与低分化鳞状细胞癌相比差异有统计学意义(P<0.05);并凡,Galectin-3与VEGF在喉鳞状细胞癌组织中的表达呈正相关关系(r=0.423,P<0.05).结论:喉鳞状细胞癌组织中Galectin-3和VEGF的高表达可能对肿瘤的组织分化和转移起重要作用.  相似文献   

5.
OBJECTIVE: Vascular endothelial growth factor (VEGF) is one of the most potent mediators of angiogenesis, which is a mandatory process during tumor growth. The present objectives were to determine expression of VEGF in vestibular schwannomas by immunohistochemistry and to examine a possible correlation with symptom duration, tumor size, or growth rate. STUDY DESIGN: Retrospective patient file review; immunohistochemistry and light microscopy of vestibular schwannomas removed by surgery. METHODS: Vestibular schwannomas from 18 patients were immunolabelled using a polyclonal antibody against VEGF, followed by light microscopy and blinded semiquantitation of VEGF expression. Fifteen patients had a well-defined tumor growth rate defined by repeated preoperative magnetic resonance imaging scans. RESULTS: All tumors showed expression of VEGF in the Schwann cell cytoplasm, with a more intense staining of the perinuclear region of some cells. The staining intensity varied from tumor to tumor, and semiquantitation revealed a significant correlation between VEGF expression and tumor growth rate, but not symptom duration or tumor size. CONCLUSION: VEGF is expressed in vestibular schwannomas and the level of expression correlates positively with tumor growth rate, but not with tumor size and symptom duration. We conclude that VEGF seems to be a factor involved in the growth of vestibular schwannomas.  相似文献   

6.
OBJECTIVE: Recent experimental evidence indicates that angiogenesis affects tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is considered to be an important regulator of tumor angiogenesis. The present study was designed to examine the role of VEGF on angiogenesis and lymph node metastasis in primary nasopharyngeal carcinomas (NPCs). STUDY DESIGN: Formalin-fixed paraffin-embedded biopsy specimens were obtained from 29 primary NPCs that consisted of 22 differentiated nonkeratinizing carcinomas and seven undifferentiated carcinomas. METHODS: Microvessels were highlighted by staining endothelial cells with von Willebrand factor (VWF) using immunohistochemical techniques, and were counted (per x 400 field) in the most active area of angiogenesis on light microscopy. The expression of VEGF was also studied with immunohistochemistry. Positive ratio for VEGF was graded on a scale of 1 and 2. Scale 1 represents patients with less than the mean value of the positive ratio, and scale 2 represents patients with more than the corresponding value. RESULTS: There was a significant correlation between increased microvessel count and the progression of regional lymph node involvement. The microvessel counts and the progression of N factor were significantly higher in scale 2 patients than in scale 1 patients. CONCLUSION: These results suggest that VEGF plays an important role in lymph node metastasis through induction of angiogenesis in NPCs.  相似文献   

7.
Vascular endothelial growth factor (VEGF) is a key pro-angiogenic cytokine expressed by most human tumours. Two isoforms, VEGF121 and VEGF165, are soluble and can be assayed in serum. Serum VEGF has been shown to be significantly raised in patients with solid tumours and shows some promise as a potentially useful tumour marker. Serum levels of VEGF were assayed in 52 patients with untreated head and neck squamous cell carcinoma (HNSCC) and 104 healthy controls. Serum VEGF is significantly raised in patients with HNSCC (P < 0.001), but there was no association with either tumour stage or specifically the presence of nodal metastases. Sixteen patients (31%) had a higher serum VEGF than 95th centile of controls, suggesting that serum VEGF measurement is of little practical use as an initial diagnostic tool. The finding that patients with HNSCC have significantly raised serum VEGF probably relates to enhanced platelet aggregation in these patients.  相似文献   

8.
目的:研究γ-干扰素(IFN-γ)对人喉癌细胞株Hep-2细胞血管内皮生长因子-C(VEGF-C)基因及蛋白表达的影响.方法:将IFN-γ以不同浓度(103、104、105、106、107U/L)、不同作用时间(0、12、24、36、48、60、72 h)作用于Hep-2细胞,用四甲基偶氮唑蓝(MTT)比色法测定细胞增殖;用实时荧光定量PCR(Realtime-PCR)法测定IFN-γ(105U/L)不同作用时间(0、2、6、12、24、36、48、60、72 h)细胞VEGF mRNA含量;用双抗体夹心酶联免疫吸附试验、Western blot法和免疫细胞化学方法测定与Realtime-PCR相同药物浓度和作用时间细胞培养上清液和细胞质中VEGF-C蛋白含量.结果:①细胞生长受到抑制,以高浓度组表现最为明显;②不同浓度(103、104、105、106、107U/L)IFN-γ作用不同时间(0、12、24、36、48、60、72 h)后,从48 h开始,105、106、107U/L的IFN-γ对Hep-2细胞有明显的抑制作用,差异有统计学意义(P<0.05),但不随着浓度的增加而成正比;③106U/L IFN-γ作用后,在36 h后与对照组比,VEGF-C mRNA表达下调,差异有统计学意义(P<0.05),特别是48 h(P<0.01);④104U/L IFN-γ作用36 h后,Western blot显示细胞中VEGF-C蛋白含量显著下降;⑤106U/L IFN-γ作用48 h后,与对照组相比,Hep-2细胞质中的棕色颗粒明显减少.结论:IFN-γ可以在核酸和蛋白质水平下调Hep-2细胞分泌VEGF-C.  相似文献   

9.
目的探讨表皮生长因子受体(EGFR)和血管内皮生长因子(VEGF)在喉乳头状瘤(IJP)中的表达及意义。方法采用免疫组化二步法检测10例成人型喉乳头状瘤(ALP)、19例幼年型喉乳头状瘤(JLP)石蜡标本中EGFR、VEGF的表达与分布;并以10例声带息肉作为对照组。结果EGFR和VEGF在ALP、JLP组上皮层的表达水平明显高于对照组(P〈0.05)。EGFR在ALP、JLP表皮组织全层均有强阳性表达,VEGF呈现以基底层、棘层细胞显著表达,到颗粒层表达逐渐减弱的模式。VEGF在ALP、JLP和对照组间质的血管内皮细胞、炎症细胞、成纤维细胞中也有表达,但3组问VEGF的表达元显著统计学差异(P〉0.05)。JLP组上皮中VEGF的表达评分结果(7.133±0.061)比ALP组(6.934±0.041)高,两组比较有统计学意义(P〈0.05)。结论VEGF、EGFR在LP组织中的过度表达可能在LP的上皮细胞过度增生和血管大量形成中发挥重要作用,JLP比ALP具有更强的增殖活性。  相似文献   

10.
血管内皮生长因子及其受体对喉癌细胞生长的影响   总被引:4,自引:1,他引:4  
为探讨血管内皮生长因子(VEGF)在喉癌中的作用及可能的作用方式,用抗VEGF抗体及其受体flt抗体通过微波处理暴露抗原后,进行标准化的EliteABC染色;将不同浓度的抗VEGF及抗flt抗体分别加入HEP-2细胞的培养液中,培养5d后测HEP-2细胞的活性(MTT法)。结果:免疫组化染色显示VEGF及其受体flt主要在喉癌细胞和血管内皮细胞表达;不同浓度的VEGF抗体及抗flt抗体对HEP-2  相似文献   

11.
Angiogenesis is now considered to be crucial for tumor growth and metastasis. In several tumors, microvascular density has been shown to be correlated with metastasis and aggressiveness. Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific mitogen, which is induced by hypoxia and is angiogenic in vivo. VEGF has been identified in a wide variety of malignancies including head and neck squamous cell carcinomas (HNSCC). We investigated the circulating level of VEGF in sera from patients with various head and neck squamous cell carcinomas (n = 71) as well as from healthy normal controls (n = 47). Serum VEGF concentrations were determined as serum immunoreactivity by using a quantitative sandwich enzyme immunoassay technique. For statistical analysis, the Wilcoxon 2-sample test and Kruskal-Wallis test were performed. The majority of the patients with HNSCC were found to have high concentrations of serum VEGF. The levels of VEGF in the sera of patients with cancer ranged from below the detection limit to 937.1 pg/ml (mean, 144.5 pg/ml). In contrast, the VEGF serum levels in 47 healthy individuals ranged from below the detection limit to 168.1 pg/ml (mean, 32.7 pg/ml), VEGF serum concentration being significantly higher in HNSCC patients (P = < 0.001). These findings indicate that a positive angiogenesis regulator such as VEGF might function as an endocrine growth factor, particularly for solid HNSCC tumors and may be a useful marker for clinical monitoring. Received: 12 April 1999 / Accepted: 30 September 1999  相似文献   

12.
13.
14.
目的 检测鼻咽癌中血管内皮生成因子C(VEGF-C)的表达及微淋巴管密度(microlymphatic vessel density,MLVD),探讨鼻咽癌淋巴管生成及淋巴转移之间的关系.方法 采用免疫组化SP法检测58例鼻咽癌和20例鼻咽部炎性反应组织中VEGF-C的表达情况,并用淋巴管内皮细胞特异性抗体LYVE-1行免疫组化染色,计数肿瘤内MLVD,并结合临床病理特征进行分析.结果 鼻咽癌组和炎性反应对照组VEGF-C的阳性表达率分别为84.5%(49/58)和15.0%(3/20),差异有统计学意义(X2=32.309,P<0.01).鼻咽癌组织MLVD为(28.6±6.2)个/视野,鼻咽炎性反应组为(10.5 4±3.0)个/视野,两组差异有统计学意义(t=12.491,P<0.01).鼻咽癌组织中,有淋巴转移组VEGF-C阳性表达率(87.8%)明显高于无淋巴转移组(76.5%);有淋巴转移组MLVD(30.2 4±6.4)个/视野高于无淋巴转移组(24.8±3.6)个/视野,经统计学分析,差异均有统计学意义(t=3.259,P<0.01).VEGF-C的表达与MLVD(t=3.512,P<0.01)、淋巴转移(X2=7.715,P<0.01)、临床分期(X2=4.250,P<0.05),与病理分化程度无关(X2=0.000,P>0.05).VEGF-C的表达与MLVD(t=3.512,P<0.01)、淋巴转移(X2=7.715,P<0.01,r=0.712)、临床分期(X2=4.250,P<0.05,r=0.481)相关,与病理分化程度无关(X2=0.000,P>0.05).结论 在鼻咽癌组织中VEGF-C呈高表达,VEGF-C表达与鼻咽癌组织MLVD、淋巴转移、临床分期密切相关.VEGF-C可能参与了鼻咽癌发生、浸润和转移的过程.VEGF-C与肿瘤组织微淋巴管密切相关,在鼻咽癌发展过程中起重要作用,可能成为抗肿瘤治疗的潜在靶点.  相似文献   

15.
喉癌组织血管内皮生长因子的表达与喉癌临床病理关系   总被引:4,自引:0,他引:4  
目的 :探讨血管内皮生长因子 (VEGF)的表达与喉鳞状细胞癌的临床病理关系。方法 :采用SP免疫组织化学染色技术 ,评价 87例喉鳞癌患者的肿瘤组织中VEGF的表达和微血管计数 (MVC)。资料分析采用SAS软件。结果 :在喉鳞状细胞癌中 ,VEGF的免疫反应主要发生于肿瘤细胞的胞浆内 ,其阳性率为 77.0 %。肿瘤侵犯范围越广 ,VEGF的表达越强 ,肿瘤侵犯范围越小 ,VEGF的表达越弱 (P <0 .0 5 ) ;肿瘤分化越差 ,VEGF的表达越强 ,肿瘤分化越好 ,VEGF的表达越弱 (P <0 .0 5 ) ;VEGF的表达越强 ,MVC越多 ,二者呈明显的正相关(P <0 .0 1) ,且肿瘤组织中的平均MVC明显高于切缘组织中的平均MVC(P <0 .0 1)。结论 :在喉鳞状细胞癌中 ,VEGF的表达与肿瘤的临床分期和分化明显相关 ,与MVC存在着明显的正相关 ,提示VEGF在喉鳞状细胞癌的进展中具有重要的作用  相似文献   

16.
OBJECTIVES: Vascular endothelial growth factor receptor 2 (VEGFR2; Flk-1 [fetal liver kinase]/KDR [kinase insert domain containing receptor]) has been identified as a high affinity receptor for vascular endothelial growth factor (VEGF) on vascular endothelium. Head and neck squamous cell carcinomas (HNSCC) have already been shown to produce substantial amounts of VEGF. VEGFR2 is supposed to play a major role in tumor-neoangiogenesis. METHODS: We investigated 24 tumor specimens and 4 HNSCC cultured tumor cell lines for the incidence and distribution of VEGFR2 by immunohistochemistry using monoclonal antibodies (mAbs) and RT-PCR. RESULTS: Analysis of frozen sections by immunohistochemistry showed that in 90% of tumor specimens VEGFR2-positive cells were found which were associated with vascular endothelium. VEGFR2 was also expressed on tumor cells and vessels, which was confirmed by double immunolabeling of tumor cells with an a-cytokeratin mAb. Furthermore, 2 (JPPA, SCC9) of 4 HNSCC cultured tumor cell lines revealed positive VEGFR2 immunoreactivity. Synthesis of VEGFR2 mRNA on all 4 HNSCC cultured tumor cell lines (JPPA, SCC9, SCC25, and LFFR) and in 6 tumor specimens was confirmed by RT-PCR. In conclusion, our results showed that VEGFR2 is expressed in HNSCCs on tumor cells. VEGFR2 expression is associated with the beginning of vasculogenesis represented by accumulation of VEGFR2-positive cells budding into new vessels ("hot spots"). The focal expression pattern of VEGFR2 on tumor cells suggests an autocrine loop for VEGF in tumor cell growth.  相似文献   

17.
目的:探讨环氧化酶-2(COX-2)、血管内皮生长因子(VEGF)在鼻咽癌组织中的表达及其相关性。方法:用免疫组织化学SP法检测58例鼻咽癌患者(鼻咽癌组)和38例鼻咽炎症患者(对照组)黏膜组织中COX-2、VEGF的表达。结果:COX-2、VEGF在鼻咽癌组中的表达均明显高于对照组(均P<0.05)。COX-2、VEGF的表达与鼻咽癌TNM分期有关,Ⅲ~Ⅳ期明显高于Ⅰ~Ⅱ期(P<0.05);与鼻咽癌的浸润和转移有关,有颈淋巴结转移者的表达率明显高于无颈淋巴结转移者(P<0.05)。鼻咽癌组织中COX-2、VEGF的表达呈正相关(r=0.302,P<0.05)。结论:COX-2、VEGF在鼻咽癌发生、发展中起重要作用,在鼻咽癌淋巴结转移中可能有协同效应。  相似文献   

18.
Pan J  Kong L  Lin S  Chen G  Chen Q  Lu JJ 《The Laryngoscope》2008,118(11):1970-1975
Objectives/Hypothesis: To investigate the inter‐relationship of the expressions of cyclooxygenases‐2 (COX‐2), vascular endothelial growth factors (VEGF), and epidermal growth factor receptor (EGFR) in nasopharyngeal cancer (NPC) cells, and their clinical significance in association with the extent of disease at diagnosis. Study Design: Prospective. Methods: Expressions of COX‐2, VEGF, and EGFR protein were detected using immunohistochemistry in 111 patients with pathologically confirmed stage II to IV nasopharyngeal carcinoma. The correlation between the expressions of the three tumor markers and the stages of disease at diagnosis were investigated. Results: COX‐2, VEGF, and EGFR were over‐expressed in 76.6, 66.7, and 73.9% of NPC cells, respectively. The staining patterns was cytoplasmic for VEGF, membranous for EGFR, and both cytoplasmic and membranous for COX‐2 in tumor cells. Linear associations were observed between the intensity of the expressions of COX‐2 vs. VEGF, COX‐2 vs. EGFR, or VEGF vs. EGFR. Furthermore, the intensity of the expressions of all three markers was significantly associated with the extent of the tumor measured by the Tumor, Node, Metastasis classification and staging grouping of the American Joint Committee on Cancer/International Union Against Cancer staging system. Conclusion: COX‐2, VEGF, and EGFR expressions in NPC cells were interrelated, and the intensity of the expressions of all three markers were significantly associated with the stage of the disease at diagnosis. Further investigation is needed to determine the clinical applications of COX‐2, VEGF, and EGFR in predicting the long‐term outcome of NPC after definitive therapy.  相似文献   

19.
OBJECTIVE/HYPOTHESIS: Angiogenesis has been used as a prognostic indicator in a variety of cancers and is believed to be controlled by angiogenic factors, including the cytokines interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). We hypothesized that the in vivo coexpression of both IL-8 and VEGF in head and neck tumors contributes to perpetuating tumor growth and metastasis by enhancing angiogenesis. METHODS: Immunohistochemical analysis for IL-8 and VEGF was performed using specimens from 33 cancer patients and 6 control patients. We quantitatively evaluated levels of IL-8 and VEGF in tumor tissue homogenates from those same patients using enzyme-linked immunosorbent assay and radioimmunoassay. Comprehensive histories of each patient were taken and later analyzed for clinical correlations with IL-8 or VEGF levels. RESULTS: IL-8 and VEGF were found to be colocalized within the head and neck squamous cell carcinoma (HNSCCA) tumor cells. In the head and neck tumor specimens, IL-8 levels ([38,152+/-1.8]x10(5) pg/mg total protein [TP]) were 22-fold greater than controls (1,721+/-2,122 pg/mg TP). The tumor levels of VEGF (1,304+/-6,037 pg/mg TP) were nearly fourfold higher than the controls (317+/-400 pg/mg TP. Interleukin-8 and VEGF levels were found to have a positive correlation (P< or = .0001). Patients exhibiting high levels in picograms per milligram of TP and/or number of moles of IL-8 and VEGF were found to clinically have more aggressive disease manifested by higher TNM stage, more recurrences, and shorter disease-free intervals (P< or =.03) CONCLUSIONS: Marked increase in HNSCCA of IL-8 and VEGF underscores the importance of these angiogenic factors in this disease. Understanding the roles and interplay of angiogenic factors such as IL-8 and VEGF may have value in the treatment of HNSCCA.  相似文献   

20.
The cause of nasal polyps remains unknown, although there is a well‐recognized clinical association between nasal polyposis and asthma. The characteristic histological features of nasal polyps include large quantities of extracellular fluid. Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis and vascular permeability. This study aimed to compare expression of VEGF in nasal polyps from patients with asthma and those with no apparent respiratory disease. Twenty‐four asthmatic and 35 non‐asthmatic patients were studied using immunohistochemistry for VEGF. VEGF expression was identified in endothelial, inflammatory and epithelial cells. There was significantly greater endothelial expression of VEGF in asthmatic patients (P < 0.05). Greater epithelial expression was observed in asthmatic patients but this did not reach statistical significance (P = 0.07). There was no difference in the density of inflammatory cells expressing VEGF. Differences between the two groups may reflect differences in disease severity or in the nature of the inflammatory process.  相似文献   

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