悪性脳腫瘍に対するmumps virusによる抗腫瘍療法の基礎的研究

Abstract

Viral oncolysis has been clinically observed for a long time without practical application, because it has lacked basic study of its mechanism and needed special conditions between tumor and virus. Since Asada reported improvements of 79 patients from 90 terminal cancer cases with administration of mumps virus (MV) (1974), many good results of following trials have appeared in the literature, which have never included papers on the tumors of the central nervous system. The author planned to apply this attractive therapy by the administration of MV vaccine in the malignant brain tumors. So this paper reported the author's experimental results about whether MV had the affinity with tumors in the central nervous system and what was the mechanism of oncolytic effects of MV if it existed.Materials and methods: MV was used as the purified M V solution for vaccinal injection and target cells were cultured human glioma cells of an established cell line (MG-178) and cultured brain tumor cells taken from operative specimens of 49 tumors of 12 kinds. The trypsinized cells were cultured in monolayer sheet and challenged to MV. Thereafter, intracellular MV antigen by the direct fluorescein antibody methods was checked and followed by the measurements of virus titer, which were indicated as MV proliferation curve. MV-infected cultured brain tumor cells were chronologically sampled for cell growth curve by trypan blue exclusion method, viability tests using the fluorescein diacetate, cell kinetic studies with the propidium iodide through a flow cytometry, and morphological studies. Human brain tumor cells were cultivated on the chorioallantoic membrane (CAM) of fertile chicken eggs and challenged to MV in the same manner. After nodule formation of cultured cells, MV antigens and proliferation of MV were studied with morphological observation.Results and summary:1) M V antigens were demonstrated in 19 cases of 20 sampled tumors. Three days after the inoculation of MV, morphologically cytolytic changes began to appear in the infected tumor cells in parallel with proliferation of MV. This phenomenon resulted in the growth inhibition of cultured brain tumor cells in MG-178 cells and 39 cases of 49 sampled tumors (79.6%).2 ) In this experimental model, MV showed a good affinity with brain tumor cells and monophasically excellent proliferation. It is thought to be more sensitive to the cells with more cellular activities. Brain tumor cells showed cytolytic changes in parallel with the decrease of viability of cultured tumor cells. These biomorphological changes of brain tumor cells might come from the disappearance of the cells in S and G2 M phase followed by no progression to S phase, showing a quite different pattern from that of known anticancer agents.3) This phenomenon might be considered as the mechanism of destruction of cultured brain tumor cells by MV inoculation, i. e., oncolysis by MV'. MV in tumor nodules on CAM did not cause morphological changes in cultivated brain tumors, so this experiment gave us the knowledge of antitumor effects (oncolytic) of MV, and, moreover, suggested that we have to develop the method for administration of more dosis of MV for nodule-type brain tumors.