Li V W, Folkerth R D, Watanabe H, Yu C, Rupnick M, Barnes P, Scott R M, Black P M, Sallan S E, Folkman J
Department of Surgery, Children's Hospital, Boston, MA 02115.
Lancet. 1994 Jul 9;344(8915):82-6. doi: 10.1016/s0140-6736(94)91280-7.
Tumour growth is angiogenesis-dependent; brain tumours have more intense neovascularisation than other tumours and produce basic fibroblast growth factor, a potent angiogenic mediator. Because little is known about the release of basic fibroblast growth factor from brain tumours into extracellular fluids, we tested cerebrospinal fluid (CSF) from 26 children and young adults with brain tumours and 18 controls for basic fibroblast growth factor and for proliferative activity on cultured capillary endothelial cells. We also measured the density of microvessels in tumours by immunohistochemical staining. Basic fibroblast growth factor was detected in the CSF of 62% (16 of 26) patients with brain tumours but in none of the controls. Specimens with basic fibroblast growth factor stimulated DNA synthesis of capillary endothelial cells in vitro. Endothelial proliferative activity was blocked by neutralising antibodies to basic fibroblast growth factor. Basic fibroblast growth factor correlated with mitogenic activity in CSF in vitro (p < or = 0.0001), and with density of microvessels in histological sections (p < or = 0.005). A microvessel count of > or = 68 per 200 x field was associated with tumour recurrence (p = 0.005) and with mortality (p = 0.02). Basic fibroblast growth factor in brain tumours may mediate angiogenesis as measured by microvessel density in histological sections, so has potential as both a marker for neoplasia and a target for tumour treatments. Furthermore, evaluation of cerebrospinal fluid basic fibroblast growth factor, along with microvessel quantitation in biopsied tumours, may provide improved prognostic information for the management of patients with brain tumours.
肿瘤生长依赖于血管生成；脑肿瘤的新生血管形成比其他肿瘤更为强烈，并产生碱性成纤维细胞生长因子，这是一种强大的血管生成介质。由于对脑肿瘤中碱性成纤维细胞生长因子释放到细胞外液中的情况了解甚少，我们检测了26例患有脑肿瘤的儿童和青年以及18名对照者的脑脊液（CSF）中的碱性成纤维细胞生长因子，以及其对培养的毛细血管内皮细胞的增殖活性。我们还通过免疫组织化学染色测量了肿瘤中微血管的密度。在62%（26例中的16例）患有脑肿瘤的患者的脑脊液中检测到了碱性成纤维细胞生长因子，而在对照者中均未检测到。含有碱性成纤维细胞生长因子的标本在体外刺激了毛细血管内皮细胞的DNA合成。内皮细胞增殖活性被针对碱性成纤维细胞生长因子的中和抗体所阻断。碱性成纤维细胞生长因子在体外与脑脊液中的促有丝分裂活性相关（p≤0.0001），并与组织学切片中的微血管密度相关（p≤0.005）。每200倍视野中微血管计数≥68与肿瘤复发（p = 0.005）和死亡率（p = 0.02）相关。脑肿瘤中的碱性成纤维细胞生长因子可能通过组织学切片中的微血管密度所测量的那样介导血管生成，因此具有作为肿瘤形成标志物和肿瘤治疗靶点的潜力。此外，评估脑脊液碱性成纤维细胞生长因子以及活检肿瘤中的微血管定量，可能为脑肿瘤患者的管理提供更好的预后信息。
