Cell kinetics of glial tumors

Abstract

The development of monoclonal antibodies against bromodeoxyuridine (BUdR) has made it possible to study the cell kinetics of individual brain tumors more extensively and more rapidly than previously possible. Over the past several years, we have performed in situ labeling studies of 502 neuroectodermal tumors with BUdR. The results have shown that the BUdR labeling index (LI), or percentage of cells in DNA synthesis, is generally higher in malignant gliomas; that histologically similar tumors may have different proliferative potentials, demonstrated by differences in the BUdR LIs; and that a higher LI indicates a higher proliferative potential as well as a shorter time to recurrence and duration of survival. Double-labeling studies with BUdR and iododeoxyuridine, performed to analyze the cell cycle progression in 29 gliomas, revealed that S-phase duration (Ts) was fairly uniform (mean +/- SD: 8.9 +/- 2.0 hours) regardless of the differences in the LIs. Nevertheless, the potential doubling time (the time for a tumor cell population to double in the absence of cell loss) varied from 2 days to over a month, being very short for tumors with a high LI, and correlated with the BUdR LIs (Tp = 17.8/LI0.77; r = 0.95). The cell cycle time calculated for gliomas with LIs of 1-20% was 1-2 days. These parameters are useful in determining the dose, duration, and interval of chemotherapy and in evaluating the effectiveness of treatment. Thus, cell kinetics studies not only elucidate the growth characteristics of individual gliomas but may also benefit to patients by providing a more precise prognosis and may be considered in the selection of treatment modalities.