[Meningeal gliomatosis model in nude mice]

The nude mouse has been proposed as a model animal for testing the chemosensitivity of human cancer cells, and encouraging results have been obtained. Murine brain tumor models were successfully prepared by direct inoculation of glioma cells into the cerebral hemisphere, an immunologically privileged area. However, the blood-brain barrier was destroyed mechanically by this manipulation. Accordingly, experimental models of MG were established by intracisternal inoculation of human glioma cells (ONS-6, -12, and -16). These cell lines were established by primary explant technique from our biopsy specimens. The outgrown cells were trypsinized and cultured in monolayers. Tumor cells (10(7) in 0.1 ml) were inoculated transcutaneously into the cisterna magna of BALB/c nu/nu mice using a 27-gauge needle. Tumor growth generally occur in no more than 10-20% of nude mice transplanted subcutaneously. Also, nude mice which were transplanted with these 10(7) glioma cells rejected the tumor. MG models which were inoculated with the same tumors intrathecally, however, all died within a month after inoculation. In in vitro studies, the doubling time (DT) of ONS-6, -12, and -16 were 30.5 h, 41.5 h and 60.9 h, respectively. Median survival time (MST) of MG models inoculated with ONS-6, -12, and -16 glioma cells were 8.5 days, 15.5 days and 18.5 days, respectively. These DTs were well correlated with the MST. Clinicopathological features observed in MG models were similar to those seen in diffuse leptomeningeal involvement of glioma in human beings. Tumor cells were disseminated in the diffuse arachnoid space, involving the cerebral hemisphere, spinal cord and throughout the cauda equina. Some tumor cells infiltrated the cerebral parenchyma and Virchow-Robin space. The models will be useful for investigating the pathophysiology of MG and the efficacy of chemotherapeutic agents.