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Abstract:The clinical manifestations of human glioma are known to be diverse, ranging from aggressive growth and invasion to apparent dormancy; however, the molecular mechanism underlying this diversity has been largely unexplored. In the present study, we characterized four human glioma cell lines, T98G, A172, U251, and NAC6, each of which has distinct growth properties. A172 and U251 cells continue to grow after confluency, whereas the growth of T98G and NAC6 cells is contact inhibited. Northern and western blot analyses revealed that at high cell density, the expression of p27 Kip1 cyclin-dependent kinase inhibitor was dramatically enhanced at both the RNA and the protein levels in T98G and NAC6 cells but not in A172 or U251. These facts together with the finding that overexpression of p27 Kip1 caused G1 arrest in A172 and T98G cells suggest that the induction of p27 Kip1 represents an important determinant of growth at high cell density. Immunohistochemical analyses of 42 primary gliomas revealed an inverse correlation between the level of p27 protein and the Ki-67 proliferative index. Kaplan-Meier plots demonstrated that a low level of p27 in tumors is associated with decreased overall survival. Thus, disrupted regulation of p27 expression at high cell density may play an important role in determining the clinical behavior of human gliomas as well as the prognosis for glioma patients. Key Words: p27 Kip1 -Glioma-Contact inhibition-Prognostic index-Cell cycle. J. Neurochem. 74, 1393Neurochem. 74, -1399Neurochem. 74, (2000.Human gliomas are known for their unique clinical features. Some gliomas grow very rapidly and invade surrounding tissue, whereas others do not grow and remain in a dormant state. Although some biological characteristics of glioma cells, such as anchorage dependency and growth factor dependency, have been studied in vitro (De Ridder et al., 1987), the molecular mechanisms underlying their clinical features remain to be elucidated.It is well known that contact between cells at a high cell density causes normal cells to enter the quiescent stage of the cell cycle (Polyak et al., 1994a). Recently, it has been reported that several signal transduction pathways are activated in contact-inhibited cells, such as those associated with changes in protein kinase C and phosphatidylinositol 3-kinase expression (Moreton et al., 1995;Daduang et al., 1998). These observations suggest that a signal(s) from a cell-cell contact may lead to changes in the expression of genes involved in the regulation of the cell cycle. The p27 Kip1 cyclin-dependent kinase (Cdk) inhibitor has been implicated in the negative regulation of G1 progression in response to a number of antiproliferative signals (Wang et al., 1996). Polyak et al. (1994a) reported that the expression of p27 in Mv1Lu mink epithelial cells is associated with some aspect of the contact inhibition mechanism. However, little is known about the signaling pathway involved in the contact inhibition of glial cell growth. Low levels of p27 protein in cance...

A 39-year-old male presented with an exceedingly rare primary intracranial epithelioid angiosarcoma in the right parietal lobe manifesting as weakness of the left hand. Neuroimaging revealed a well-defined intensely enhanced lesion in the right parietal lobe with peripheral cerebral edema. The tumor was grossly totally removed. Light microscopy of the surgical specimens revealed features typical of an epithelioid vascular tumor. The tumor cells showed intense positive immunohistochemical staining for cytokeratin and vimentin and focally positive staining for both Ulex europaeus agglutinin and anti-human endothelial cells, CD31. Tumor regrowth required two further operations. This progressive growth was consistent with an angiosarcoma. The tumor was diagnosed as an epithelioid angiosarcoma based on the histological and clinical characteristics. He became progressively obtunded and finally died. This is the first intracranial epithelioid angiosarcoma which expressed epithelial markers detectable by immunohistochemical methods.