Analysis of the cycling and noncycling cell population of human solid tumors

Abstract

The size and kinetics of the cell population of six advanced human solid tumors were analyzed following the continuous infusion of H3-TDR for a period of 6 to 21 days. By using the labelling indices of the cells in interphase and mitosis, and the rate of label incorporation, it was found the only 10 to 40% of the tumor cell population was replicating at any given time. Fifty-five percent to 85% of the remaining cell mass eventually entered into cycle at least once. Anywhere from 5% to 40% of the cell population remained arrested in G2 or G0 in individual cases during the period of observation. The significant size of the "resting" cell compartment is undoubtedly one explanation for the relative insensitivity of advanced adult solid tumors to current cell cycle-oriented therapeutic regimens.

Long-duration intracavitary infusion of methotrexate with systemic leucovorin protection in patients with malignant effusions.

“…This principle is firmly established for cytosine arabinoside, whose therapeutic ratio against acute leukemia increases with duration of infusion (7). The general application of this principle is limited by the fact that most human tumors proliferate much more slowly than normal marrow and gut cells (8)(9)(10), and in the case of MTX, bone marrow exposure must be limited to 36-40 h to avoid serious myelosuppression (11,12).…”

The cell cycle kinetics of human breast cancer

“…In one patient infused for 19 days with [3H]thymidine, the breast cancer LI increased to 65%. 24 In another study, two patients' LI (initial < 1%) increased to 2-6% after 72-hour exposure. 12 Previously, we demonstrated that percentage labelled mitosis (PLM) curves from two separate lesions of a patient were similar (20).…”

1. Introduction

“…A S . In clinical materials cells of different sensitivities are often present (92,298), the tumor size could vary considerably and so could the absorbed dose distribution delivered to different parts of the tumor volume. All these factors lead to a decreased slope of the clinically observed dose response relation relative to a uniform cell line of given size.…”