Paul G. Braunschweiger

The cell kinetics of human mammary cancers

The cellular kinetics of human mammary tumors were studied by in vitro methods. These techniques include single 3HTdR labeling to measure the 3HTdR LI, double labeling with 3HTdR and 14CTdR to measure DNA synthesis time, and an estimation of the growth fraction by the PDP index. Calculations of the potential doubling time and cell cycle time were made from these measurements. The 3HTdR LI of primary malignant tumors was greater than that of benign tumors, but only half that of metastatic lesions. There was considerable heterogeneity in the 3HTdI LI of primary tumors, but the DNA synthesis times were relatively invariant. Estimation of the growth fraction by the PDP index also revealed extensive heterogeneity, but the primary tumors were not different from metastases. There appear to be subsets of tumors with high and low proliferative values that correlate with some clinical parameters, such as age and nodal positivity. This material provides a data base for stratification of patients for future protocols and the use of cell kinetics in treatment programs.

Preliminary observations on the correlation of proliferative phenomena with in vivo 31P NMR spectroscopy after tumor chemotherapy.

The pioneering studies of Gene Cronkite, and his associates, on the methodology, theory, and reality of mammalian cell kinetics are well known. During the initial years of study of animal and human hematopoiesis, there was a tacit assumption that, in addition to dissecting the physiology of proliferating systems, we would eventually use cell kinetic techniques for the management of various hematologic and malignant conditions. This has been very slow in coming to fruition which has been disappointing to many scientists and clinicians. The reasons for it are quite clear, however, and

Tumor cell proliferation and sequential chemotherapy after partial tumor resection in C3H/HeJ mammary tumors

SummaryChanges in tumor cell proliferation and chemosensitivity after partial (up to 3/4) surgical resection were studied in C3H/HeJ mammary tumors, In all studies surgical cytoreduction stimulated tumor cell proliferation in the residual tumor, as evidenced by increases in the3H-TdR labelling index between 24 and 72 hrs after surgery. The time of maximal proliferative activity was directly related to the amount of tumor removed. In spontaneous mammary tumors, proliferative recovery after 1/2 resection could be delayed by giving dexamethasone 24 hrs after resection. The regrowth delay after surgery and various combinations of dexamethasone, vincristine, 5-FU, and cyclophosphamide, was used to assess the significance of the kinetic changes in the residual tumor for the design of adjuvant therapeutic strategies.The results indicated that the chemosensitivity of C3H/HeJ mammary tumors was substantially increased after surgical cytoreduction, and that these post-surgical changes were directly correlated with changes in tumor cell proliferative activity.

The cytokinetic basis for the design of efficacious radiotherapy protocols

Abstract Studies were performed to investigate the perturbing effects of ionizing radiations on the cell kinetics of T1699 transplantable mouse mammary tumors (MMT). Cell kinetic parameters included the 3H-TdR labeling index (LI), the DNA synthesis time (TS) and the primer dependent DNA polymerase labeling index (PDPI), an estimate of tumor growth fraction; they were determined by in vitro methods at various times after acute (400–1200 R) and fractionated (1000 R) X-irradiation. The cell kinetic response after both acute and fractionated treatment was generally similar and could be divided into four phases. (1) The initial phase of the response, occurring within the first 24 hr, was characterized by a decrease in 3H-TdR LI, an increase in PDPI and a concomitant lengthening of the TS. (2) The second phase was characterized by a variable, dose dependent interval of decreased cellular proliferation, as evidenced by a lengthening of TS and decreases in both PDPI and 3H-TdR LI. (3) The third phase of the response, the recovery phase, was characterized by increased cellular proliferation as evidenced by the recovery of TS to normal and increases in both PDPI and 3 H-TdR LI to above control levels, in most cases. (4) The fourth phase of the response was characterized by a reestablishment of normal proliferative patterns. Studies with continuing radiotherapy schedules showed that the most effective schedules for local control and ILS were those in which radiation fractions were given just prior to initiation of observed proliferative recovery. The least effective schedules were those in which radiation fractions coincided with the time of maximal proliferative activity.