Nemati M N, Stan A C, Pütz K M, Pietsch T, Walter G F, Dietz H
Neurochirurgische Klinik, Medizinische Hochschule Hannover.
Zentralbl Neurochir. 1996;57(1):12-9.
An important feature of malignant progression in human gliomas is increased polymorphism of tumor cells associated with karyotypic heterogenity and a variety of secondary changes, one of which is increased angiogenesis. The capability of brain tumors for angiogenesis most probably is the earliest sign for malignancy in 95% of cases and occurs before typical changes of histology appear. Malignant brain tumors are known to produce several angiogenic growth factors. One of the most potent of these factors is the basic fibroblast growth factor (bFGF). In an experimental study human U87 MG glioma cells (2.10(5) cells/50 microliters) were implanted through a burrhole into the cerebral cortex in a group of 25 nude rats. After 3 weeks we found a reproducible extensive tumor growth with extensive neovascularization. Immunohistochemical evaluations proved a high expression of bFGF in the tumor. A parallel group of xenotransplanted rats were treated with 33 micrograms of rabbit anti-bFGF antibodies during tumor cell implantation. Thereafter, the same dosages of antibodies were administrated intracranially twice a week for 3 weeks. We found a significant inhibition of tumor vascularization and growth compared to other groups who had no treatment or who received irrelevant immunoglobulins or saline as a control. Our results indicate that inhibition of tumor angiogenesis might contribute to inhibition of tumor growth in malignant gliomas.
人类胶质瘤恶性进展的一个重要特征是肿瘤细胞多态性增加，这与核型异质性及多种继发性改变相关，其中之一是血管生成增加。脑肿瘤的血管生成能力很可能是95%病例中恶性肿瘤的最早迹象，且发生在典型的组织学改变出现之前。已知恶性脑肿瘤会产生多种血管生成生长因子。其中最有效的因子之一是碱性成纤维细胞生长因子（bFGF）。在一项实验研究中，将人U87 MG胶质瘤细胞（2.10(5)个细胞/50微升）通过钻孔植入25只裸鼠的大脑皮质。3周后，我们发现肿瘤出现可重复的广泛生长及广泛的新生血管形成。免疫组织化学评估证实肿瘤中bFGF高表达。另一组异种移植大鼠在肿瘤细胞植入时用33微克兔抗bFGF抗体进行治疗。此后，每周两次向颅内给予相同剂量的抗体，持续3周。与未治疗或接受无关免疫球蛋白或生理盐水作为对照的其他组相比，我们发现肿瘤血管生成和生长受到显著抑制。我们的结果表明，抑制肿瘤血管生成可能有助于抑制恶性胶质瘤的肿瘤生长。
