No abstract

Current methods for measuring the cell kinetics of human tumours are made and interpreted within the context of a simplistic two compartment model for cell proliferation, consisting of cells that are cycling and those that are not. It is now recognized that the non-cycling compartment of many tumours is heterogeneous, composed of non-reproductive end-stage cells and reproductive cells that are dormant/quiescent. We have developed an in vitro analysis that distinguishes for the first time quiescent reproductive cells from non-reproductive end-stage cells and have integrated this analysis with monolayer clonogenic and suicide assays to simultaneously quantitate the duration of the cell cycle and reproductive cells that are: cycling, quiescent, clonogenic, and non-reproductive end-stage cells. We have defined a new parameter, the Cycling Reproductive Fraction (CRF), which is the cycling cell population referenced specifically to the reproductive cell population. Measurements of CRF from 72 tumour biopsies and from 5 normal foreskins showed that CRF approached 100% in some tumours; however, CRF showed near normal values (< 1%) in others suggesting that cell cycle control may be maintained in some tumours. Because of CRF's improved specificity, we believe that CRF may enhance classification, prognostication, and the optimization and prediction of response to chemotherapy.

No abstract

The newly described adhesive tumor cell culture system (ATCCS) offers a distinct advantage over other assays in that it has a high plating efficiency requiring low cell inoculum, it affords workable assays in approximately 70% of specimens from the heterogenous tumor types, and it has the ability to assay up to nine drugs at four different concentrations. Clinical correlations based on the ATCCS were obtained in 65 patients undergoing 71 clinical trials. Patients with melanoma, lung cancer, and sarcoma dominated the group. The most active in vitro drug was correlated per clinical trial. Thirteen of 17 (76%) sensitive in vitro predictions and 51 of 54 (94%) resistant in vitro predictions were accurate. The assay in this study had a sensitivity of 81% and specificity of 93%. These preliminary results are encouraging and warrant prospective trials to establish the true value of this assay to patients.

The intrinsic radiosensitivity of human tumor cell cultures correlates with the clinical radiosensitivity of several different tumor histologies, as evidenced by analyses of low dose parameters of radiation survival curves generated from a large number of cell lines. Such radiosensitivity has therefore served as a basis of attempts to develop predictive assays of tumor radiocurability. In this study, the tumors from 72 patients with head and neck squamous carcinoma have been grown in an adhesive tumor-cell assay system and radiosensitivity (S2: survival at 2.0 Gy) values have been measured. The characteristics of these cultures, such as growth rate, clonogenicity and growth enhancement by epidermal growth factor, do not correlate with S2. The average S2 value of the 72 cultures is 0.33, which is lower than for cultures derived from melanomas and lung adenocarcinomas. Twenty-six patients followed up for at least 15 months have been evaluated for local tumor control. The average S2 value of the seven patients with recurrences in this group is slightly higher (0.43) than that from the other patients (0.30). There is considerable overlap of S2 values in the two groups, and more patients must be evaluated before the groups can be compared statistically.