For many years oncologists have been frustrated by the apparent lack of progress in obtaining clinically useful cell kinetic measurements of human solid tumors. The technique of in vivo administration of tritiated thymidine (3H-TdR) followed by multiple biopsies, to determine the fraction of labeled mitoses, has largely remained unchanged during the past 15 years, and the limitations of this procedure are well known and do not need re-emphasis. Although in vitro measurement of 3H-TdR-labeling indices (LI) and in vitro estimation of DNA synthesis time (Ts) have been practiced for many years, there have been few controlled studies to determine whether the in vitro results are really comparable to those found in vivo. In addition, only indirect measurements of growth fraction (GF) have been possible. It was with these problems in mind that our laboratory began investigations into rapid techniques with clinical applicability for measuring cytokinetic parameters. From the start it was understood that our results probably would not detect the nuances and would be a pragmatic approach to the problem. The mode chosen for the development of techniques was the spontaneous mammary tumor of the C3H/He mouse. The spontaneous tumor model was chosen because of its relatively well differentiated histology, low GF, and potential variation in growth rates, and because the vascular patterns are far different from transplantable tumors. The limitation of this model is primarily that of relatively few tumor animals. This report will describe the comparison between in vitro and in vivo studies of the measured cytokinetic parameters which include: number of cells in DNA synthesis, Ts, estimate of GF, and the derived parameters of cell-cycle time (Tc) and potential doubling time (Tpot). Since these in vitro studies are applicable at the point-in-time of the biopsy, the perturbations of the tumor cytokinetics by drug or radiation therapy can be experimentally determined. A recent study in our laboratory showed that a time-sequenced course of vincristine (VCR) and cyclophosphamide (CYT) would cure an otherwise lethal transplantable T1699 tumor guided by the methods described in this paper; this study will be described in detail later. This report will include initial studies of the effects of VCR on the C3H/He spontaneous mammary tumor and a comment about some of the potential uses to which these techniques may be put.
|Original language||English (US)|
|Number of pages||12|
|Journal||Cancer treatment reports|
|State||Published - Dec 1 1976|
ASJC Scopus subject areas
- Cancer Research