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The kinetics of human glioblastomas maintained in an organ culture system

An in vitro autoradiographic study

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Summary

Five human glioblastomas maintained in an organ culture system were studied by autoradiography to determine, after 8 days in vitro, the growth fraction (GF) of the explants, their total cell cycle time (T C) and cell cycle phase durations (T S,T G1,T G2 andT M), and their potential doubling time (T pot) after pulse-labeling with [3H] TdR for 1 h. These parameters were derived from computer analysis of fraction of labeled mitoses (FLM) curves. The results fell into two groups.

In two tumors, the cultures had a GF of 0.25 and 0.23. From the FLM curves were derived aT C of 89 and 83 h, aT S of 16.5 and 9.5 h, and aT G1 of 60 and 61 h.T M was estimated at 0.9 and 0.6 h, andT G2 12h. TheT pot was 12 days. These values approximate those reported for glioblastomas and other human malignancies in vivo.

The explants of three other glioblastomas gave different FLM curves: the derivedT S were increased to 36 and 55 h, estimatedT M ranged from 2.4 to 4.5 h, andT G2 ranged from 11 to 20 h.T C andT G1 could not be estimated. In two tumors the GF was reduced to 0.12 and 0.11, with aT pot of respectively 52 and 39 days. These values are comparable to those reported for astrocytomas of intermediate malignancy. In the third tumor, the GF was only 0.014. The reduction in GF and the lengthening of cell cycle components in this group of explants are similar to the kinetic changes reported in some in vivo tumors and three-dimensional in vitro systems that have reached a plateau stage of growth. They are probably related to the greater opportunities for cell-to-cell contacts and the resulting increased differentiation favored by the organ culture technique.

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Supported by Research Grant CA-31271 (LJR) from the National Cancer Institute, by Graduate Neuropathology Research Training Grant 5T32 NS 7111 (LJR) from the National Institute of Neurological and Communicative Diseases and Stroke, USPHS, and by an R. S. McLaughlin Foundation Fellowship Award (JM)

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Hess, J.R., Michaud, J., Sobel, R.A. et al. The kinetics of human glioblastomas maintained in an organ culture system. Acta Neuropathol 61, 1–9 (1983). https://doi.org/10.1007/BF00688379

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