Kaplan F, Sawyer J, Connors S, Keough K, Shore E, Gannon F, Glaser D, Rocke D, Zasloff M, Folkman J
Division of Metabolic Bone Diseases and Molecular Orthopaedics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Clin Orthop Relat Res. 1998 Jan(346):59-65.
Angiogenesis is a prominent histopathologic feature of preosseous fibroproliferative lesions in patients who have fibrodysplasia ossificans progressiva. Basic fibroblast growth factor is an extremely potent in vivo stimulator of angiogenesis, and has been implicated in the growth of solid tumors. An enzyme linked immunosorbent assay for basic fibroblast growth factor was performed on urine samples from patients who had active (n = 28) and inactive (n = 39) fibrodysplasia ossificans progressiva, and compared with urine samples from normal age and gender matched control subjects (n = 54). Median basic fibroblast growth factor levels were 2705 pg/g of creatinine in the normal control group, 5058 pg/g of creatinine in patients with inactive fibrodysplasia ossificans progressiva (no significant difference), and 8793 pg/g of creatinine in patients with active fibrodysplasia ossificans progressiva. Female subjects, both normal and with fibrodysplasia ossificans progressiva, had higher levels of urinary basic fibroblast growth factor than did male subjects. There was no correlation of urinary basic fibroblast growth factor levels with age or severity of preexisting disability. These data document an elevation of urinary basic fibroblast growth factor during acute flareups of fibrodysplasia ossificans progressiva and provide a biochemical basis for considering antiangiogenic therapy for inhibiting endochondral osteogenesis in this disorder.
血管生成是进行性骨化性纤维发育不良患者骨前纤维增生性病变的一个显著组织病理学特征。碱性成纤维细胞生长因子是一种在体内极具效力的血管生成刺激剂,并与实体瘤的生长有关。对患有活动性(n = 28)和非活动性(n = 39)进行性骨化性纤维发育不良的患者的尿液样本进行了碱性成纤维细胞生长因子的酶联免疫吸附测定,并与年龄和性别匹配的正常对照受试者(n = 54)的尿液样本进行了比较。正常对照组中碱性成纤维细胞生长因子的中位数水平为2705 pg/g肌酐,非活动性进行性骨化性纤维发育不良患者为5058 pg/g肌酐(无显著差异),活动性进行性骨化性纤维发育不良患者为8793 pg/g肌酐。正常和患有进行性骨化性纤维发育不良的女性受试者尿碱性成纤维细胞生长因子水平均高于男性受试者。尿碱性成纤维细胞生长因子水平与年龄或既往残疾严重程度无关。这些数据证明了进行性骨化性纤维发育不良急性发作期间尿碱性成纤维细胞生长因子升高,并为考虑抗血管生成疗法抑制该疾病的软骨内成骨提供了生化依据。