The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model

Malignant glioma is characterised by extensive neovascularisation, principally influenced by vascular endothelial growth factor (VEGF). ZD6474 is a potent inhibitor of VEGF-R2 tyrosine kinase activity, but with additional inhibitory effects on other growth factors. In this study, we have investigated the effects of ZD6474 with regard to tumour growth, neovascularisation, proliferation and apoptosis in the intracerebral rat glioma model, BT4C. ZD6474 (50 and 100 mg kg−1) was given as a daily oral gavage. Animals were killed on day 19 and tumour volume was measured. Sections were stained for factor VIII, Ki-67 and for apoptosis. The ability of ZD6474 to inhibit cell growth directly was examined in vitro, using the glioma cell line BT4C and the transformed rat brain endothelial cell line RBE4. Cell growth was analysed with fluorometric microculture cytotoxicity assay to quantify the cytotoxic effects. ZD6474 significantly decreased tumour volume compared to controls. Microvascular density increased after treatment with ZD6474, and tumour cell proliferation index was reduced. There was also an increase in tumour cell apoptosis. In vitro, the growth of both cell lines was significantly reduced. The results reported justify further experimental investigations concerning the effects of ZD6474 in malignant glioma alone or in combination with other modalities

Tumour vascularity is of prognostic significance in adult, but not paediatric astrocytomas

Astrocytomas are the commonest type of brain tumours in adults and children. Although the most reliable prognostic indicators have been shown consistently to be patient age and tumour histological grade, biological progression in these tumours is inevitable and the overall prognosis has remained poor. Due to the evidence that vascular changes are important histological features of astrocytomas, the aim of this study was to investigate prognostic significance of tumour vascularity in paediatric and adult astrocytomas. Study population consisted of 70 patients (45 adult and 25 children) with histologically proven diagnosis of astrocytoma with no history of previous therapy. Histological quantification of tumour vascularity was performed using three different methods: microvessel density, vascular grading and Chalkley counting. Histological classification and grading were also assessed using the World Health Organization system. In contrast to the results in paediatric astrocytomas, tumour vascularity in adult tumours correlated significantly with postoperative survival by univariate analysis (P < 0.05). Microvessel density appeared to be an independent indicator of prognosis by multivariate analysis (P = 0.001). Likewise, patients with microvessel density of 70 or greater had significantly shorter survival than the remaining group (P < 0.001). Patient age and tumour histological grade were also correlated with survival. We conclude that histological quantification of tumour vascularity is a significant prognosticator in adult astrocytomas, but not in children. Our data do not support the validity of applications of antiangiogenic agents in paediatric astrocytic tumours, particularly pilocytic astrocytomas

Oclusión espontánea de malformación arteriovenosa cerebral parcialmente embolizada: reporte de dos casos Spontaneous occlusion of previously cerebral embolized residual arteriovenous malformation: report of two cases

OBJETIVO: Mostrar dos casos de oclusión espontánea de remanente malformativo previamente embolizado y analizar sus probables causas. MÉTODO: Revisión retrospectiva de pacientes con malformaciones arteriovenosas cerebrales (MAV) embolizadas entre Enero de 1999 y Agosto de 2005 en nuestra institución y análisis de dos casos de oclusión de MAV remanentes. RESULTADOS: Se presentan dos casos de MAV tratadas por vía endovascular, con remanentes del nido malformativo post-embolización, que posteriormente en controles angiográficos presentan desaparición completa de las lesiones sin mediar otro tratamiento. CONCLUSIÓN: La oclusión espontánea de un remanente arteriovenoso es un hecho infrecuente. Se discuten diversos mecanismos relacionados.<br>OBJECTIVE: To report two cases of spontaneous occlusion of residual malformations that had previously been embolized and to analyze their probable causes. METHOD: Retrospective review of patients with embolized arteriovenous malformations (AVMs) between January 1999 and August 2005 in our institution and analysis of two cases of occlusion in residual AVMs. RESULTS: Two cases of AVMs that received endovascular treatment and had post-embolization residual nidus malformation, which in later angiographic controls showed a complete disappearance of the lesions without other treatment. CONCLUSION: The spontaneous occlusion of residual arteriovenous malformations is an infrequent occurrence. Several related mechanisms are discussed