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K T Wheeler

Publications and source records attributed to K T Wheeler.

At least 73 records · Page 4Linked to original sources
PubMed1981

Cell subpopulations dispersed from solid tumours and separated by centrifugal elutriation.

The degree of non-neoplastic host-cell infiltration was assessed in 3 in vivo-in vitro tumour models commonly used in radiobiological studies: EMT6/Ro mammary carcinoma, 9L/Ro tumour and KHT sarcoma. While the 2 former tumour models have been shown to be moderately to highly immunogenic when grown s.c., the KHT sarcoma is apparently non-immunogenic. Using differential staining on single-cell suspensions from enzymatically dissociated solid tumours, all 3 tumour types were found to contain large proportions (30-60%) of non-neoplastic host cells. The actual host-cell component found in the cell suspensions differed both in type and percentage for the 3 tumours studied. These host and neoplastic cells in the cell suspensions prepared from the solid tumours could be readily separated by centrifugal elutriation. After separation the clonogenic potential of the neoplastic cells was assessed, and was found to be higher than the clonogenic capacity of the unseparated cell suspension by a factor directly related to the host/neoplastic cell ratio. Even after the removal of the host cells, the clonogenic capacities of the neoplastic EMT6 and 9L tumour cells were lower than that of the corresponding in vitro sublines (approximately 30 vs 75%). However, in the KHT sarcoma the removal of the host cell component raised the plating efficiency to approximately 60%, which was similar to the value for the in vitro cell subline of this tumour.

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PubMed1981

Efficacy of continuous treatment with radiation in a rat brain-tumor model.

Rats bearing intracerebral 9L/Ro tumors were treated with 10 daily fractions of cesium-137 gamma-rays, BCNU, or combinations of these to agents beginning on either Day 10 or Day 12 after implantation. The treatments were administered either 5 days/week for 2 weeks, with the weekend off, or 10 consecutive days. The median day of death for untreated tumor-bearing rats was Day 15, so Day 12 tumors can be considered late tumors and Day 10 tumors can be considered moderately early. Although all single- and multiple-agent treatments significantly (p less than 0.05) increased the lifespan of tumor-bearing rats over that of the untreated controls, and all multiple-agent schedules significantly (p less than 0.05) increased the lifespan over that of the single-agent therapies, none of the 10 consecutive day schedules increased the lifespan of tumor-bearing rats significantly (p less than 0.2) over that obtained with the 5-day/week schedules. Thus, the evidence from this tumor model suggests that no significant improvement in lifespan would be expected if malignant brain tumors were treated with radiation 7 days a week, either alone or in combination with chemotherapeutic agents such as BCNU.

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PubMed1981

Review of factors influencing the response of experimental brain tumors to therapy.

This review summarizes the problems and pitfalls encountered when increased life span studies are performed with brain tumor model systems. The biological factors reviewed include tumor size and growth rate, the immune response, cell kinetics, and cell recovery processes. The analytical factors reviewed include data collection, data presentation, covariate analysis, and statistical analysis. Examples of how these factors can influence the ultimate interpretation of results from brain tumor therapy trials are presented.

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PubMed1981

Influence of location within a tumor on cell survival as measured by a clonogenic assay.

In order to elucidate the influence of the location of a cell within a tumor on cell survival, 12 to 16 samples from an individual 9L s.c. tumor were assayed for colony formation. These samples (4 to 6 mg) were taken from untreated, heated, or irradiated tumors, and the variances of the mean relative colony-forming efficiency (RCFE) for individual tumors or groups of similarly treated tumors were compared. These comparisons allowed determination of the effect of location and treatment on the intratumor variability in cell survival. Three factors can influence variability of the RCFE's across tumors: (a) inherent differences in clonogenic capacities; (b) unequal dose distribution of the treatment agent, and (c) different sensitivities of cells to the treatment. Considerable variability was found in the cell survival of control tumors, and treatment of tumors in air-breathing or nitrogen-asphyxiated rats with X-rays did not change the magnitude of this variability. However, the variance of the mean RCFE of heated tumors was an order of magnitude greater than that observed in either control or irradiated tumors. Of the three possible factors that could influence cell survival within a tumor, all were shown to contribute to the variances of the mean RCFE measured in 9L s.c. tumors. However, our study demonstrated that the relative contribution of each of these factors to the variance will probably depend on the treatment agent(s).

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PubMed1980

Synchronization of 9L rat brain tumor cells by centrifugal elutriation.

Asynchronous 9L cells were separated into relatively homogeneously-sized populations using centrifugal elutriation with both a conventional collection method and a long collection method. A substantial increase in the homogeneity of the volume distributions and in the degree of synchrony of the separated fractions was obtained using the long collection method. Autoradiographic data indicated that fractions containing greater than or equal to 97% G1 cells, greater than or equal to 80% S cells, and 70-75% G2 cells could be routinely recovered with this procedure. Recovery in these fractions varied from 5 to 8% of the total number of cells elutriated. The colony forming efficiency (CFE) of cells from fractions representing each phase of the cell cycle was a constant 60-70%, which was comparable to the 60-80% usually found for asynchronous 9L cells. The percentage of cells in the G1, S, and G2 phases in the elutriated fractions was more accurately determined from the volume distribution than from computer fits of the DNA histogram obtained from flow cytometry. In genereal, the degree of synchrony was related to the coefficient of variation (CV) of the volume distributions of the elutriated fractions. The CV was about 14% for all elutriated fractions. When the greater than or equal to 97% G1 population was allowed to progress to S and G2, the CVs were about 17 and 20.2%, respectively. Thus, the best nonperturbing method for obtaining synchronous 9L cells in the S or G2 phases was direct elutriation with the long collection method.

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PubMed1980

Is cell survival a determinant of the in situ response of 9L tumours?

The influence fo growth rate, location, size and PLD recovery on the cellular radiosensitivity, the tumour response (increase in life-span) and the relationship between these two end points was studied using two sublines of the 9L rat brain tumour, designated 9L/Ro and 9L/SF. The median day of death of rats bearing the intracerebral (i.c.) 9L/Ro tumours was 16-18 days; for i.c. 9L/SF tumours it was 23-25 days. The doubling time of 9L/Ro cells was slightly faster than that for 9L/SF cells both in culture and in the brain. The cellular radiosensitivity of both i.c. tumour cell sublines was identical when measured immediately after irradiation by an in vitro colony formation assay. However, subcutaneous (s.c.) 9L/Ro tumour cells were more resistant (D0 = 332 rad cf 180 rad). There was no evidence of a substantial hypoxic fraction in either site. When i.c. 9L/Ro and 9L/SF tumours of similar size were treated with fractionated doses of BCNU, X-rays or combinations of the two, the responses of the two tumours were essentially identical. The rate of recovery from radiation-induced potentially lethal damage (PLD) was identical in the two sublines and the two sites, although the extent of the PLD recovery was apparently greater in s.c. tumours. Increase in life-span of rats bearing i.c. 9L/Ro tumours appeared to be correlated with the tumour cell kill measured after completion of PLD recovery rather than with the tumour cell kill determined immediately after irradiation.

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PubMed1979

Cellular response of a rat brain tumor to a therapeutic carbon ion beam.

Clonogenic cell survival of in situ 9L brain tumors was measured in air-breathing rats and rats killed with nitrogen. Animals were irradiated with BEVALAC accelerated carbon ions in the plateau and spread-out Bragg peak regions of the specific ionization curve. The relative biological effectiveness (RBE) for carbon ions in the plateau was 1.2 +/- 0.1 for oxic cells and 1.3 +/- 0.1 for anoxic cells; in the Bragg peak the RBE was 1.6 +/- 0.1 for oxic cells and 2.0 +/- 0.1 for anoxic cells. The oxygen enhancement ratio (OER) in the plateau was 2.0 +/- 0.1, not significantly different from the 2.1 +/- 0.2 found for x rays. The OER in the Bragg peak was reduced to 1.7 +/- 0.1. For cells having the same radiobiological sensitivity as in situ 9L cells, the neon ion beam may be therapeutically superior; however, this does not preclude selection of the carbon ion beam in many clinical situations.

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