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Biomedical subjects

G G Steel

Publications and source records attributed to G G Steel.

At least 145 records · Page 8Linked to original sources
PubMed1977

Cell survival in B16 melanoma after treatment with combinations of cytotoxic agents: lack of potentiation.

The extent of tumour, cell kill, produced by treating B16 melanomas with vincristine, cyclophosphamide, 5-fluorouracil and gamma-rays, alone and in combination, was determined using an in vitro colony assay. Cell kill by vincristine was revealed as a reduction in the yield of cells obtained by trypsinization, and as a decrease in the colony-forming ability of the extracted cells. The reduction in cell yield was interpreted as evidence of rapid cell lysis. Cyclophosphamide and gamma-rays also reduced both cell yield and surviving fraction, but in this case the small decrease in cell yield was due to an increase in cell volume. FU had no effect on cell yield, but surviving fraction was reduced. Tumour weight was also measured, and used in conjunction with cell yield and surviving fraction data to calculate the fraction of surviving cells per tumour following treatment with the agents. In combination studies, single doses of two different cytotoxic agents were given either simultaneously, or up to 24 h apart in either sequence, and assays were performed 24 h after the second drug was given. Combinations of vincristine + cyclophosphamide and 5-fluorouracil + gamma-rays were chosen because they had been shown by other workers to exhibit marked schedule dependency, including considerabl potentiation, against leukaemic cell lines. However, in the B16 melanoma there was no evidence of schedule-dependent cell killing with either of these combinations. For all sequences studied, the fraction of surviving cells per tumour was slightly greater than the predicted additive response calculated from single-drug controls.

Animals↗
PubMed1977

Influence of tumour size on hypoxic fraction and therapeutic sensitivity of Lewis lung tumour.

Radiation survival curves for Lewis lung tumours in the lungs ranging in size from 0-5 to 20 mm3 have been obtained, and a size-dependent variation in hypoxic fraction was found. Cell-survival studies following treatment of various sizes of s.c. tumours indicated that the effects of 60Co gamma-rays and the chemotherapeutic agents 1,3-bas(2-chloroethyl)-1-nitrosourea (BCNU) and cyclophosphamide are all size-dependent. Large pulmonary nodules which had regressed but had not been cured by cyclophosphamide regrew with a radiosensitivity that was characteristic of previously untreated tumours. The results give additional experimental support to the clinical interest in early adjuvant therapy of micrometastases, and sequential combined modality therapy for larger tumours.

Animals↗
PubMed1977

Clonogenic assays in the B16 melanoma: response to cyclophosphamide.

The survival of clonogenic cells in the B16 melanoma has been studied simultaneously by 3 methods: an in vitro assay in soft agar, a lung-colony assay, and the end-point dilution technique. Details of the first 2 methods have previously been reported, but those of the third are described here. The 3 methods have agreed well in investigations of the response of the B16 melanoma to cyclophosphamide.

Cell Count↗
PubMed1977

Enhancement by cytotoxic agents of artificial pulmonary metastasis.

The formation of lung colonies by i.v. injected Lewis lung-tumour cells in syngeneic recipients was greatly enhanced by prior treatment of the mice with cyclophosphamide. The lung-cloning efficiency was linearly related to cyclophosphamide dose and the optimum time of treatment was 2-4 days before the injection of tumour cells. The resulting lung colonies had a similar size distribution to colonies in untreated recipients. Bleomycin, local thoraric irradiation and whole-body irradiation were much less effective in enhancing the lung-cloning efficiency. Cyclophosphamide also enhanced the take probability of i.m. implanted tumour cells.

Animals↗
PubMed1976

Size dependence of the response of Lewis lung tumors to BCNU.

The survival of Lewis lung tumor cells has been studied after a single ip dose of BCNU. In dissectible subcutaneous and intramuscular tumors and artificial lung metastases survival was measured by colony formation in soft agar and in vivo in the lung. The long-term control of small lung nodules by single doses of BCNU was studied and cell-survival estimates were inferred. The results demonstrate that the cytotoxic action of BCNU shows a strong dependence upon tumor size.

Animals↗
PubMed1975

Growth kinetics of human large bowel cancer growing in immune-deprived mice and some chemotherapeutic observations.

Xenografts of human large bowel cancer have been grown in immune-deprived mice. Studies have been made of their intermitotic time and other proliferative characteristics, and their response to single doses of a number of chemotherapeutic agents has been measured. The indications from this study are that, although the growth rate of xenografts is much faster than that for tumors in man, this is likely to be due largely to a difference in rate of cell loss, and the intermitotic time and growth fraction may not have changed substantially. The spectrum of response to chemotherapeutic agents is in line with clinical experience and, although there are many uncertainties and problems still to be resolved, it is indicated that xenografts could provide a useful experimental system for the laboratory study of the chemotherapy of large bowel cancer.

Animals↗
PubMed1975

The growth kinetics of xenografts of human colorectal tumours in immune deprived mice.

The technique of labelled mitoses was used to examine cell proliferation within grafts of human colonic and rectal tumours in immune deprived mice. Most of the data were obtained on the first passage but in some cases up to the third passage was used. It was found to be difficult to obtain precise kinetic data on this type of tumour material, but the results did allow some estimates to be made, particularly of the duration of the G2 and S phases of the mitotic cycle. The average G2 duration was 6 h and the average S phase was 14 h. It is concluded that whilst xenografts may differ in a number of respects from the tumour in the patient, they nevertheless constitute a type of experimental tumour that is worthy of further study.

Aged↗
PubMed1975

A comparison of computer methods for the analysis of fraction labelled mitoses curves.

Computer methods developed by the authors for analysis of fraction labelled mitoses curves (FLM curves) have been compared. Four test examples were used in the study; the first example was the synthesis of a FLM curve with fixed parameters and the others involved fitting actual data. Experimental FLM curves showing various degrees of damping were used in the curve fitting tests. In each test example the comparison was based on the assumptions of exponential growth, a growth fraction of unity and no cell loss. In three of the test examples good agreement between the methods was observed but in one example some important discrepancies arose in the analysis of a heavily damped FLM curve.

Animals↗
PubMed1975

Rate and time of DNA synthesis of individual Chinese hamster cells.

The duration of DNA synthesis of a diploid cell line of Chinese hamster fibroblasts was determined in a comparative study by the FLM technique, and also by a new technique for measuring the rate of DNA synthesis of individual cells. These methods produced comparable results when applied during exponential growth of the cells. The rate of DNA synthesis was measured by means of quantitative autoradiography following a short-term incubation of the cells with 5 X 10(-6) M FUdR and 10(-5) M 14C-TdR. The choice of the medium for this purpose did not seem to be critical. The autoradiographic silver grains over cells and 14C-standard sources are counted by microphotometry using incident light bright-field. The direct measurements of DNA synthesis rate are 'compartment' statistics which have been converted into 'flux' parameters for comparison with the FLM method and applicability in cell-kinetic calculations. Frequency distributions of the rate of DNA synthesis of individual cells thus obtained may resemble normal distributions quite closely. They result from several factors: differences in the rate of synthesis in different parts of the S-phase, the density distribution of cells within the S-phase, the variation in the time of DNA synthesis among individual cells, and the experimental error. In the case of a pronounced partial synchronization as probably has been present in one experiment performed in the lag phase, an incorrect time of DNA synthesis may result from the rate values. Due to the variation in DNA synthesis rate in different parts of the S-phase it is not possible to determine the duration of DNA synthesis of an individual cell. However, the mean values of DNA synthesis time are reliable. The new method will be preferentially applied for determining the duration of DNA synthesis of human cells in as far as difficulties are encountered with the classical methods. In addition, it may be used to advantage for studying cells which make up low percentages in mixed populations. It finally permits a safer morphological classification of the cells under study than is possible with the classical methods.

Autoradiography↗
PubMed1975

Tumor size dependency in the radiation response of the Lewis lung carcinoma.

Tumor cell survival characteristics were assessed following 60Co gamma-irradiation of the Lewis lung carcinoma as 500-cu mm s.c. tumors or as 0.5-cu mm (1 mm in diameter) pulmonary metastases. Cells in the small pulmonary tumors were markedly more radiosensitive (D0 = 106 rads; hypoxic fraction less than 0.005) than were those in large s.c. tumors (final D0, 315 rads; hypoxic fraction, 0.36). When pulmonary metastases were excised and irradiated intact under well-oxygenated conditions in vitro, the hypoxic fraction rose to 0.30. This implies that, under normal in situ conditions, these nodules contain a microvascular system that achieves adequate oxygen supply to the great majority of tumor cells. Thus, the tumor cells within these small metastatic implants were more sensitive to irradiation, largely due to better oxygenation, and may be more sensitive to chemotherapy, due to better drug availability.

Animals↗
PubMed1975

The therapeutic response of three human tumor lines maintained in immune-suppressed mice.

Studies were made of the growth and therapeutic response of three lines of human tumor serially transplanted in immune-suppressed mice. They included a well-differentiated colonic carcinoma (HX 13), a poorly differentiated colonic carcinoma (HX 18), and undifferentiated small-cell carcinoma of the bronchus (HX 29). Their histological appearance and growth rates were stable, with volume-doubling times ranging from 6 to 12 days. Studies by the technique of labeled mitoses showed that the growth kinetics of the three tumor lines were very similar, with median intermitotic times in the range of 26 to 35 hr. An analysis of the incidence of single and double takes revealed evidence for variation in susceptibility among the recipient mice. One tumor (HX 18) was transplantable with single-cell suspensions but 10(5) cells were required for 50 percent takes. The response of the tumors to a range of chemotherapeutic agents was studied. There was evidence that drugs that are known to be effective in the treatment of patients did well, in particular 5-fluorouracil against the colonic tumors and cyclophosphamide against the bronchial carcinoma. Long-term regressions induced by cyclophosphamide in the bronchial carcinoma may reflect assistance from host defense mechanisms.

Animals↗
PubMed1975

Stem-cell survival and tumor control in the Lewis lung carcinoma.

The stem-cell response of the Lewis lung carcinoma to single doses of cyclophosphamide has been studied by three assay techniques: in vitro colony formation, lung colony formation, and the end-point dilution assay. These three techniques have given comparable results, and the end-point dilution results showed that 50 percent takes could be achieved with as few as 1 to 3 cells. Studies have been made of the growth of small i.m. implants and of the time following implantation at which they could be eradicated by cyclophosphamide. The results were compared with the curability that would be expected on the basis of cell survival studies. It was found that older (and therefore larger) implants were cured than might have been expected. It seems unlikely that this discrepancy was due to additional cell kill caused by an immune response. An alternative explanation, that the surviving fraction following a dose of cyclophosphamide was lower in small implants than in larger i.m. tumors, was supported by studies of cell survival in dissectable lung colonies.

Animals↗