Polymorphisms of fibroblast growth factor receptor 4 have association with the development of prostate cancer and benign prostatic hyperplasia and the progression of prostate cancer in a Japanese population

Fibroblast growth factor receptor 4 (FGFR4) is a member of a family of transmembrane receptors with ligand-induced tyrosine kinase activity. The Glycine (Gly) to Arginine (Arg) polymorphism at codon 388 (Gly388Arg), which encodes an amino acid in the transmembrane part of the FGFR4 gene, was reported to be associated with an increased risk in some carcinomas. We investigated the association between the Gly388Arg polymorphism or the G or A polymorphism at intron 11 (rs2011077) of FGFR4, which was located 1,213 base pairs apart from the Gly388Arg polymorphism, and the risk of prostate cancer or benign prostate hyperplasia (BPH), and the prostate cancer disease status in Japanese men. Genotypes of Gly388Arg and rs2011077 polymorphisms of FGFR4 were determined in 492 patients with prostate cancer, 165 patients with BPH and 179 male controls. Regarding the Gly388Arg polymorphism, individuals with the ArgArg genotype had a 2.207- and 1.958-fold increased risk of prostate cancer and BPH, and a 1.804-fold increased risk of metastatic prostate cancer compared with those with the GlyGly genotype. Regarding the rs2011077 polymorphism, individuals with the GG genotype had a 6.260- and 3.033-fold increased risk of prostate cancer and BPH, and a 5.550-fold increased risk of metastatic prostate cancer compared with those with the AA genotype. Our results indicate that the FGFR4 Arg allele of the Gly388Arg polymorphism and the G allele of the rs2011077 polymorphism have a significant impact on the development of prostate cancer and BPH, and the progression of prostate cancer in a Japanese population.     

EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND BASIC FIBROBLAST GROWTH FACTOR IN HUMAN NON-SMALL CELL LUNG CANCER AND THEIR CLINICAL SIGNIFICANCE

Solid tumors contain tumor cells and vascular systems[1]. The growth and metastasis of solid tumors beyond 1-2mm in diameter depends on neovascularization. So the study of neovascularization helps to explain the biologic behavior of tumor. Angiogenesis is a complicated process mediated by a variety of angiogenic factors, which include vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF). VEGF is an endothelial cell-specific mitogen with a pivotal role and may a…     

前列腺癌细胞株VEGF及其受体KDR,bFGF及其受体FGFR2的表达及意义

目的:探讨人前列腺癌细胞株血管内皮细胞生长因子(VEGF)及其受体(KDR),碱性成纤维细胞生长因子(bFGF)及其受体(FGFR2)的表达,进一步阐明前列腺癌细胞中VEGF和bFGF的自分泌机制。方法:以小鼠成纤维细胞系L929作为对照,选取三种前列腺癌细胞株(PC3、LNcap和DU145),采用免疫组化染色、RT-PCR及Westernblot,检测VEGF及其受体KDR,bFGF及其受体FGFR2的表达。结果:三种前列腺癌细胞株(PC3、LNcap和DU145)中均有VEGF、KDR及bFGF、FGFR2的表达,但表达水平略有差别。结论:在前列腺癌的血管形成中可能存在VEGF和bFGF的自分泌机制。     

良恶性前列腺疾病肿瘤血管形成的MR灌注加权成像评价

Objective: To explore the application of MR perfusion-weighted imaging (PWI) in the benign and malignant prostate diseases, and evaluate the correlations of PWI features with vascular endothelial growth factor (VEGF) and microvessel density (MVD). Methods: Seventy-four consecutive patients who were diagnosed clinically for the prostate diseases, including forty-four cases with benign prostate hyperplasia and thirty cases with prostatic cancer proved pathologically, were examined by PWI. MVD and VEGF were stained with immunohistochemical methods. Some parameters of PWI, including the steepest slope of signal intensity-time curve (SSmax) and the change in relaxation rate (△R2* peak) at lesions, were analyzed.Correlation analysis was used to determine the relationship between the results of PWI and immunohistochemistry. Results:(1) In the benign prostate hyperplasia (BPH), SSmax and △R2* peak of perfusion curve were 34.2 2.9 and 1.49±0.11,respectively; however, in the prostatic cancer (Pca), they were 58.6±4.8 and 3.18 0.49 respectively; there were statistical differences (t = 2.16 and 2.31, P ＜ 0.05). (2) The VEGF and MVD expressions of thirty Pca patients were significantly higher than those of forty-four BPH patients (X2 = 28.64, P＜0.01; t = 21.2, P＜0.01). MVD expressions of Pca and BPH groups showed positive associations with VEGF expressions (P＜0.01). On MR perfusion-weighted imaging, SSmax and △R2* peak showed associations with MVD and VEGF expressions (P＜0.01). Conclusion: On MR perfusion-weighted imaging, SSmax and △R2* peak can reflect MVD and VEGF expression levels in the benign and malignant prostate diseases and might be implied the tumor angiogenesis so as to distinguish benign from malignant and provide the important information for the surgeon to diagnose and treat the prostatic diseases.     

Prognostic significance of osteopontin expression in human prostate cancer

To test the hypothesis that expression of osteopontin (OPN), an integrin-binding glycoprotein, can independently predict the potential aggressiveness of prostate cancer, the status of OPN expression in benign and malignant prostate cancer cell lines and tissues was analysed by Western blot and immunohistochemistry. Amongst the four prostate cell lines analysed, the level of OPN expressed in the benign PNT-2 cells was set at 1, the relative level of OPN expressed in the weakly malignant cell line LNCaP was increased to 1.5. In the highly malignant cell lines Du-145 and PC-3, the level of OPN expression was further increased to 2.9 and 4.4, respectively. An increased expression of OPN was also observed in the prostate tissue samples. When the level of OPN in normal tissue was set at 1, its level in benign prostate hyperplasia (BPH) was similar at 0.99 +/- 0.2, whereas the OPN level in the highly malignant carcinoma tissue was greatly increased by nearly 6-fold to 5.9 +/- 0.3. Amongst the 116 cases examined immunocytochemically, of the 10 normal cases, 3 (30%) were unstained and 7 (70%) stained weakly positive (+). Amongst the 36 BPH samples, 32 (89%) stained weakly positive (+) and 4 (11%) were unstained (-). For the 70 carcinomas analysed, 31 (44%) stained strongly positive (+++), 20 (29%) stained moderately positive (++) and 19 (27%) stained weakly positive (+). These results showed that the level of OPN expressed between the normal and the BPH samples was not significantly different (Fisher's exact test, p = 0.16). However, in comparison to that in the BPH samples, the expression of OPN in the carcinoma tissues was significantly increased (Chi-square test, p < 0.0001). Kaplan-Meier survival analysis showed that the increased level of OPN expression was significantly (n = 70, p = 0.03) associated with reduced survival time of the patients. The OPN expression was increased with the increasing Gleason scores of the carcinomas (Chi-square test, p < 0.001). The results in our study support our hypothesis and suggest that the increased OPN level may be involved in the malignant transformation of prostate epithelial cells and OPN expression level is an important determinant for patient survival.     

VEGF和 bFGF在浅表膀胱移行细胞癌中的表达及意义

背景与目的：血管内皮生长因子（vascular endothelial growth factor,VEGF)和碱性成纤维细胞生长因子（basic fibroblast growth factior,bFGF)都能促进血管内皮细胞分裂和诱导血管形成,是肿瘤的生长,浸润,和转移过程中非常重要的物质,但它们在单发性和多发性浅表膀胱移行细胞癌中表达的差异则未见报道,本研究主要是探讨VEGF和bFGF在浅表膀胱移行细胞癌中的表达及意义。方法：采用免疫组化法对60例浅表膀胱移行细胞癌组织及10例正常膀胱组织进行VEGF和bFGF的检测,观察单发性和多发性浅表膀胱移行细胞癌组织中VEGF和bFGF表达的关系。结果：多发性浅表膀胱移行细胞癌的VEGF阳性率为55.6%,bFGF阳性率为50.0%,以及VEGF和bFGF共同表达阳性率为50.0%。均明显高于单发者的水平,而高水平表达的多发性肿瘤患者的术后复发率61.1%也明显高于单发组的复发率（单发组的复发率16.7%)。结论：VEGF和bFGF表达水平的高低与浅表膀胱移行细胞癌的生物学行为有关。     

调控VEGF的转录因子及其与肿瘤的关系

肿瘤血管生成在肿瘤发生发展中起重要作用。肿瘤血管生成是一个多因素调控的复杂过程,血管内皮生长因子（vascular endothelial growth factor,VEGF）在肿瘤血管生成中起核心作用。VEGF的表达受细胞遗传特性和肿瘤微环境中众多因素的影响,涉及转录、翻译和翻译后等多个环节,但通过转录因子对VEGF的转录进行调控是其最主要途径。本文阐述了与VEGF转录关系最密切的5个转录因子（Sp1、HIF-1、AP-1、Stat3和NF-κB）,并对其与肿瘤的关系进行了分析。实际上这些转录因子的下游靶标除了VEGF外,还包括其他的血管生成促进因子（如PDGF、FGF）。因此,以这些转录因子为靶标的生物治疗可能是有效的肿瘤抗血管治疗策略。     

宫颈癌组织血管内皮生长因子测定的临床意义

目的 :探讨血管内皮生长因子 (vascularen dothelialgrowthfactor ,VEGF)在宫颈癌诊断、治疗以及转移中的临床意义。方法 :酶联免疫吸附分析法(enzyme linkedimmunosorbentassay ,ELISA)测定 2 0例宫颈上皮内瘤样变患者和 60例宫颈癌患者组织中的VEGF含量。结果 :VEGF含量在宫颈上皮内瘤样变、宫颈癌组织中分别为 5 5 6pg/mg、410 2pg/mg ,差异有统计学意义 ,P <0 0 1。肿 瘤≥ 4cm者为 960 0 pg/mg ,淋巴结转移者为 780 5 pg/mg ,而肿瘤 <4cm者 ,淋巴结未转移者分别为 180 5 pg/mg、2 3 0 0pg/mg。差异有统计学意义 ,P <0 0 5。而在临床分期、病理分型、病理分级间差异无统计学意义。结论 :组织VEGF含量检测对宫颈癌的诊断有一定的临床价值 ,其含量变化可监测宫颈癌的转移。     

KLK10和VEGF在卵巢癌组织中的表达及其临床意义

目的：分析激肽释放酶10（kallikrein 10,KLK10）和血管内皮生长因子（vascular endothelial growth factor,VEGF）在卵巢癌组织中的表达,探讨两者在卵巢癌临床诊断、治疗及预后中的意义。方法：收集2004年1月至2009年1月在南通大学附属医院妇科收治的45例卵巢癌、10例良性和12例交界性卵巢肿瘤组织石蜡切片标本,应用免疫组化法检测标本中KLK10蛋白和VEGF的表达,并分析两者表达的相关性及与卵巢癌各临床病理指标和预后的关系。结果：KLK10 \[86.7%(39/45) vs 10.0%(1/10)、58.3%(7/12), P <0.05\]和VEGF\[（82.2%(37/45) vs 20.0%(2/10)、41.4%(5/12), P <0.05\]在卵巢癌组织中的阳性表达率均明显高于卵巢良性、交界性肿瘤组织。KLK10和VEGF表达阳性率分别与分期、肿瘤分化、淋巴结转移、5年生存率有关（ P <0.05）,与患者年龄、病理分型、血清CA125水平、腹水及残余肿瘤直径无关（ P >0.05）;KLK10和VEGF蛋白在卵巢癌中的表达呈正相关性（ r =0.5279, P =0.043）。结论：KLK10和VEGF蛋白在卵巢癌中均为高表达,两者表达呈正相关,两者均似可作为卵巢癌诊断、治疗及预后的标志物。     

成纤维细胞生长因子受体1和血管内皮生长因子在肺鳞癌中的表达及与预后的关系

目的 观察成纤维细胞生长因子受体1(FGFR1)和血管内皮生长因子(VEGF)在肺鳞癌中的表达,并分析其与预后的相关性.方法 收集肺鳞癌组织标本135例和癌旁组织标本125例.采用免疫组织化学染色法检测不同肺组织中FGFR1和VEGF的表达水平,分析两者表达与临床病理参数的关系.肺鳞癌患者预后的影响因素采用Cox多因素分析.结果 肺鳞癌组织标本中FGFR1和VEGF的阳性表达率和表达水平均高于癌旁组织(P﹤0.05);在肺鳞癌组织中,FGFR1阳性表达与肿瘤分化程度、淋巴结转移、远处器官转移及TNM分期有关(P﹤0.05),VEGF阳性表达与肿瘤分化程度、淋巴结转移及TNM分期有关(P﹤0.05);Cox多因素分析结果显示,肿瘤分化程度、淋巴结转移、TNM分期、FGFR1及VEGF均为肺鳞癌预后的独立因素(P﹤0.05).结论 肺鳞癌患者的FGFR1和VEGF表达水平升高,并在肿瘤分化、淋巴结转移、TNM分期及预后中发挥重要作用.     

Vascular endothelial growth factor (VEGF) expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix

The aim of the study was to evaluate VEGF expression in tumour biopsies as a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. A retrospective study was carried out on 100 patients. Pre-treatment tumour VEGF expression was examined immunohistochemically in formalin-fixed, paraffin-embedded biopsies using a widely available commercial antibody. A semi-quantitative analysis was made using a scoring system of 0, 1, 2, and 3, for increasing intensity of staining. High VEGF expression was associated with a poor prognosis. A univariate log rank analysis found a significant relationship with overall survival (P = 0.0008) and metastasis-free survival (P = 0.0062), but not local control (P = 0.23). There was no correlation between VEGF expression and disease stage, tumour differentiation, patient age, or tumour radiosensitivity (SF2). In a Cox multivariate analysis of survival VEGF expression was the most significant independent prognostic factor (P = 0.001). After allowing for VEGF only SF2 was a significant prognostic factor (P = 0.003). In conclusion, immunohistochemical analysis of VEGF expression is a highly significant and independent prognostic indicator of overall and metastasis-free survival for patients treated with radiotherapy for advanced carcinoma of the cervix. It is also a rapid and easy method that could be used in the clinical setting, to identify patients at high risk of failure with conventional radiotherapy who may benefit from novel approaches or chemoradiotherapy.     

晚期恶性肿瘤血清VEGF含量测定的临床意义

Objective: To elucidate the clinical significance of serum vascular endothelial growth factor (VEGF) level in patients with advanced cancer. Methods: Enzyme linked immunosorbent assay (ELISA) was used to determine the serum VEGF concentration in 40 patients with advanced cancer [non-small cell lung cancer (NSCLC), esophageal cancer (EC) and nasopharyngeal carcinoma (NPC)] before and after chemotherapy and 10 healthy volunteers as control group. Results: The serum VEGF concentrations in 40 cases of advanced cancer patients were significantly higher than those of 10 healthy control cases [(477.07 ± 374.10 ) pg/mL vs (139.09 ± 133.41 ) pg/mL; P = 0.016]. The serum VEGF concentrations in patients with NSCLC, EC and NPC were (518.53 ± 378.99) pg/mL, (399.21 ± 393.69) pg/mL and (500.68 ± 348.48) pg/mL, respectively. The differences were all statistically significant as compared with healthy control group (P values were 0.011,0.044 and 0.019, respectively). The serum VEGF concentrations of the patients in response to chemotherapy was significantly lower than those of the same patients before they undergoing chemotherapy [(400.41 332.84) pg/mL vs (777.10 ± 666.01) pg/mL; P = 0.034]. Conclusion: The serum VEGF level might be a novel and promising tumor marker of advanced malignancies and a predictor of disease progression, prognosis and therapeutic efficacy.     

血管内皮生长因子在非小细胞肺癌中的表达及意义

目的研究血清血管内皮生长因子(serumvascularendothelialgrowthfactor,sVEGF)与非小细胞肺癌(NSCLC)临床病理特征的关系,探讨其对NSCLC早期诊断及预后评价的意义。方法用酶联免疫法检测70例初治NSCLC患者和20例健康献血者sVEGF的含量。结果NSCLC患者sVEGF平均含量为888.4±131.8pg/ml,明显高于正常对照组的251.3±48.6pg/ml(P<0.01)。不同临床分期间sVEGF含量有显著性差异(P<0.01)。随着临床分期的进展,sVEGF含量呈上升趋势。结论sVEGF与NSCLC的发生、发展密切相关,可作为肺癌早期诊断和预后评价的一个可靠参考指标。     

血管内皮生长因子与肿瘤

血管形成是肿瘤生长和转移的重要条件 ,而血管内皮生长因子 (VEGF)对肿瘤的血管形成具有很突出的作用 ,就VEGF与肿瘤予以综述     

血管内皮生长因子在人脑胶质瘤中的表达及意义

目的研究人脑胶质瘤中血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)的表达及临床病理意义.方法应用SABC免疫组化技术检测67例人脑胶质瘤、8例正常脑组织中VEGF表达.结果VEGF仅在肿瘤组织中表达,阳性表达率为83.6%,而在正常脑组织中无表达.VEGF与胶质瘤恶性程度(P<0.01)及肿瘤复发(P<0.01)相关.结论胶质瘤细胞能分泌VEGF,VEGF表达与肿瘤复发及预后有关.