Estimation of growth fraction with bromodeoxyuridine in human central nervous system tumors

Abstract

Twenty-five patients with tumors of the central nervous system received bromodeoxyuridine (BUdR), 200 mg/sq m, by intravenous infusion every 8 hours for 3 days before surgery. Excised tumor specimens were fixed in chilled 70% ethanol, embedded in paraffin, and cut into 6-micron sections. Each section was reacted with monoclonal antibodies against BUdR and stained with immunoperoxidase to identify nuclei that had incorporated BUdR. The growth fraction of each tumor was estimated by calculating the ratio of BUdR-positive nuclei to the total number of tumor cells in three to six microscopic fields in viable areas of the tumor. In seven cases, the tumor doubling time was measured from the serial computerized tomography scans and an attempt was made to estimate the cell cycle time. The growth fractions ranged from 9.1% to 46.5% in malignant gliomas, 2.0% to 6.7% in low-grade gliomas, 11.2% to 43.2% in metastatic brain tumors, 0.8% to 1.9% in pituitary adenomas, 3.9% to 4.6% in acoustic neurinomas, and 6.2% to 8.2% in meningiomas and cerebellar hemangioblastomas. The estimated cell cycle time was 5 to 12 days in most malignant gliomas and brain metastases; however, the actual cell cycle time should be substantially shorter because cell loss was not considered in the calculation. Although the growth fraction appeared to correlate with the biological malignancy of each tumor, the tumor doubling time did not reflect growth potential. It is possible that unpredictable cell loss plays an important role in tumor growth at certain sizes. Therefore, the cell cycle times calculated in this study are considerably overestimated and should be interpreted with caution.

Flow cytometric measurement of cell cycle kinetics in rat Walker‐256 carcinoma following in vivo and in vitro pulse labelling with bromodeoxyuridine

“…More recently, lower doses of BrdUrd have been reported in studies of cell cycle kinetics in human central nervous tumors without evidence of toxic side effect (20). Moreover, the current study suggests that it is possible to derive relevant estimates of cell cycle kinetics from biopsy specimens immediately after tumor excision.…”

Simulated Brain Tumor Growth Dynamics Using a Three-Dimensional Cellular Automaton

“…For macroscopic glial tumors (the latter three time points) cell numbers, tumor volumes, and volumetric doubling time measurements, including growth and necrotic fractions and survival times, were taken from Hoshino & Wilson (1975); Hoshino & Wilson (1979), Yamashita & Kuwabara (1983), Yoshii et al (1986), Alvord (1995), Blankenberg et al (1995), Pierallini et al (1996) and Burgess et al (1997). For the microscopic spheroid level, doubling times as well as viable rim diameter, rim cell fractions, necrotic fractions and cell shedding data were taken from Haji- Karim & Carlsson (1978), Carlsson et al (1983), Carlsson & Acker (1988), Freyer & Schor (1989) and Landry et al (1981).…”

Gene therapy of maliganant brain tumors: A rat glioma line bearing the herpes simplex virus type 1‐thymidine kinase gene and wild type retrovirus kills other tumor cells

“…A related parameter is the growth fraction, or the relative proportion of cells proliferating in the tumor at any one time. The growth fraction in this tumor type is about 30%, with the remaining 70% of cells being in Go, a resting phase (cells in Go may die or may reenter the active cell cycle; Yoshii et al, 1986). While the 30% of glioblastoma cells that are actively dividing contribute to the lethal progression of this tumor, the 70% that are quiescent are responsible for the resistance of the tumor cells to a number of chemotherapeutic agents that target proliferating cells.…”