Effect of insulin on the secretion of VEGF and its receptor in serum-free cultured bovine thoracic aortic endothelial cells

AIM: This study was designed to investigate the secretion of VEGF and its receptor (flt-1 or flk-1/KDR) protein by cultured bovine thoracic aortic endothelial cells treated with various insulin concentrations. METHODS: Endothelial cells was isolated from bovine thoracic aorta, and cultured in serum-free medium, then incubated with different insulin concentrations (30 mU/L, 300 mU/L, 3 000 mU/L). The level of VEGF and its receptor (flt-1 or flk-1/KDR) protein were detected by immunohistochemical staining. RESULTS: As compared with no insulin group, the expression of VEGF protein in low insulin concentration (30 mU/L and 300 mU/L) groups were significantly increased (P＜0.01). The expression of VEGF protein in high insulin concentration (3 000 mU/L) group was significantly decreased (P＜0.05). Howerer, no difference of the expression of VEGF receptor (flt-1 or flk-1/KDR) protein among all groups (P＞0.05) was observed. CONCLUSION: Low concentration insulin up-regulates the VEGF protein expression while high concentration insulin down-regulates the VEGF protein expression in bovine thoracic aortic endothelial cells, but insulin had no directly effect on the VEGF receptor (flt-1 or flk-1/KDR) protein expression in bovine thoracic aortic endothelial cells.     

pAdKDR-tk自杀基因系统靶向杀伤鼻咽癌肿瘤血管的体内研究

目的探讨pAdKDR-tk自杀基因系统靶向杀伤肿瘤血管对鼻咽癌的治疗作用。方法将24只鼻咽癌荷瘤裸鼠随机分成3组,分别于0、1、7d向瘤体内注入重组腺病毒液0.1mL。第2次注射病毒液时,组Ⅰ、组Ⅱ、组Ⅲ分别腹腔注射pAdKDR-tk/PBS、pAdKDR-tk/GCV和pAdCMV-tk/GCV100mg/kg,每天1次,连续10d。观察治疗前后肿瘤体积、病理及微血管密度变化。结果组Ⅲ裸鼠移植肿瘤缩小速度最快,组Ⅱ次之,而组Ⅰ增大。病理检查显示组Ⅱ、Ⅲ肿瘤出现不同程度坏死,坏死灶中心位于病毒液注射部位。Ⅷ因子相关抗原免疫组化检查发现肿瘤血管密度组Ⅱ最低,组Ⅰ最高,两组之间差异具有统计学意义(P<0.01)。结论 pAdKDR-tk自杀基因系统对鼻咽癌肿瘤血管有良好的靶向杀伤效应,从而达到破坏肿瘤细胞的作用。     

The role of vascular endothelial growth factor and its receptor Flk-1/KDR in promoting tumour angiogenesis in feline and canine mammary carcinomas: a preliminary study of autocrine and paracrine loops

Vascular Endothelial Growth Factor (VEGF) and its receptor KDR are involved in the regulation of angiogenesis and are up-regulated in a number of tumours in humans and in particular, breast cancer. We therefore evaluated the prognostic potential of the angiogenetic process in feline and canine mammary carcinomas by the immunohistochemical assessment of VEGF expression and micro vessel density (MVD) quantification and examined the interplay between VEGF and KDR. These variables were related to some relevant clinicopathological parameters and to overall survival (OS). VEGF and KDR expression were evaluated in epithelial, stromal and endothelial compartments in order to identify autocrine and/or paracrine loops. In dogs an increased VEGF expression did not show any statistical correlation with the clinicopathological parameters examined and was not correlated to a poorer prognosis. MVD was found to be significantly correlated to the histologic type (P=0.04), tumour grading (P=0.02), and to the OS (P=0.01). In cats VEGF expression was significantly correlated to tumor grading (P=0.01) and OS (P=0.03), while no significant associations were found between MVD and the other parameters. VEGF and KDR were found to be detected on the epithelial, and/or endothelial and/or stromal cells of the carcinomas in both species, suggesting indications for some possible autocrine and paracrine loops. Our results encourage further studies on the possible prognostic role of VEGF and MVD in canine and feline mammary tumours and on the role of growth factors and their receptors in promoting tumour proliferation and an "angiogenetic shift". The VEGF/KDR system may play a role in malignant transformation and tumor progression.     

KDR等6个基因多态性与鸡生长和体组成性状的相关研究

以东北农业大学高、低脂肉鸡双向选择品系第14世代群体(NEAUHLFG14)和AA肉鸡商业随机群体(AA群体)为试验材料,利用PCR-RFLP对鸡腹脂性状的全基因组关联分析(GWAS)鉴定出6个多态位点进行单核苷酸多态性(SNPs)检测,分析这些位点的多态性与鸡生长和体组成性状的关系。结果表明,在NEAUHLFG14中KDR基因的rs14483313位点多态性对腹脂重(AFW)和腹脂率(AFP)有显著影响(P<0.05),TUSC3基因的rs13548811位点对鸡后期体重有影响,EXOC1基因的GGaluGA263078位点在两个群体中都对7周龄体重(BW7)有显著影响(P<0.05)。TUSC3、PPAT、EXOC1和KIAA1211基因的突变位点对NEAUHLFG14极低密度脂蛋白(VLDL)浓度有显著影响(P<0.05),结果显示,6个基因可能是影响鸡腹脂性状的重要基因,但多态位点是否为功能性位点仍需进一步验证。