Chemotherapeutic trials on human malignant astrocytomas in organ culture

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Abstract
A technique of organ culture based on a 3-dimensional porous matrix was employed for chemotherapeutic trials in human malignant astrocytomas. This method allows neoplasms to retain the morphological identity and the histological characteristics they possess in vivo. Success in culture was greatest with high grade astrocytomas, the majority of which showed definite infiltration of the matrix. Low grade tumors, if viable, did not display active penetration. Drug trials in 8 malignant astrocytomas included BCNU [1,3-bis-(2-chloroethyl)-1-nitrosourea], methyl CCNU [1-(2-chloroethyl)-3,4-methylcyclohexyl-1-nitrosourea], VP 16-213 [4''-demethylepipodophyllotoxin-.beta.-D-ethylidene], and Solu-Medrol. Cyanide and luciferase were used as experimental metabolic toxins. Evidence of cytotoxicity was assessed qualitatively by histological changes in microscopic preparations of treated and control cultures. Microfluorometric determinations of NADH were applied to these trials in an effort to detect a quantitative biochemical index of drug effects. A variable rise in mean NADH levels above controls was recorded from the majority of treated cultures although correlation with microscopic changes was inconsistent. Because of its potential merits, organ culture may be a valuable tool for further work on pharmacological management of malignant gliomas.