Culture of human normal brain and malignant brain tumors for cellular, molecular, and pharmacological studies.

Human brain neoplasms comprise a highly heterogeneous and biologically diverse group of tumors, the most common and most malignant of which are those of neuroepithelial origin (1) Despite intensive research, little is still understood about the cellular and molecular processes involved in the genesis, progression, and response to therapy of these tumors. Much of the progress made to date, however, has resulted, in part from advances in the ability to culture and propagate cells of both normal and neoplastic brain tissue in vitro (2, 3) For example, in vitro cultures have contributed significantly to the development of techniques, such as bromodeoxyuridine labeling, that are used to estimate the cell-growth kinetics of gliomas in patients (4) Normal brain and brain tumor cultures have also played a central role in research directed at a better understanding of the complex interplay between the cellular components of the brain, such as that between various glial cells, neurons, and endothelial cells (5, 6) In studies of the molecular and cellular mechanisms involved in brain tumor resistance to therapy, in vitro cultures of human glioma cells have played a significant role in the identification of O(6)-alkylguanine DNA alkyltransferase (7), glutathione, and glutathione S-transferases (8), as critical factors in human brain tumor alkylator resistance, findings that are providing the basis for novel therapies for human gliomas. Neurobiology and neurooncology research will therefore continue to be critically dependent on appropriate in vitro models of normal and neoplastic brain cells.