Growth and cell population kinetics of single and multiple KHT sarcomas.
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Animals↗
Biomedical subjects
S Rockwell
Publications and source records attributed to S Rockwell.
Effect of a perfluorochemical emulsion on the development of artificial lung metastases in mice.
Intravenous infusions of perfluorochemical emulsions, combined with administration of inspired oxygen or carbogen have been found to improve tumor oxygenation and increase the response of solid tumors in animals to radiotherapy. Fluosol-DA 20 per cent, the only perfluorochemical emulsion currently approved for testing in humans in the United States, has recently entered clinical trials as an adjunct to radiotherapy in the treatment of head and neck carcinoma. The studies reported here were undertaken as part of our laboratory evaluation of the safety and clinical potential of this oxygen-transport fluid as an adjunct to cancer therapy; they asked whether single or multiple treatments with Fluosol and an oxygen-enriched atmosphere produced immunologic perturbations, pulmonary damage, or other effects which altered the development of artificial lung metastases in experimental animals. Neither single nor multiple treatments with clinically relevant regimens of Fluosol and carbogen (95 per cent O2/5 per cent CO2) had any effect on the development of lung nodules from intravenously injected EMT6 tumor cells.
Animals↗
A new potent radiosensitizer: 1-(2',3'-dideoxy-alpha-D-erythro-hex-2'-enopyranosyl)-2-nitroimidazole (RA-263).
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Animals↗
Mitomycin-C as a prototype bioreductive alkylating agent: in vitro studies of metabolism and cytotoxicity.
The bioreductive alkylating agents are prodrugs for chemotherapy which are enzymatically reduced within cells to species capable of alkylating biological molecules and producing cytotoxic damage. Studies presented in this report show that MIT-C has the characteristics expected of a bioreductive alkylating agent: activation to alkylating species occurs more readily under hypoxic conditions and the drug is selectively cytotoxic to hypoxic cells.
Alkylating Agents↗
Porfiromycin as an adjunct to radiotherapy in young and old mice.
Radiobiological data and measurements with O2 microelectrodes show that EMT6 tumors implanted into aged mice have a higher proportion of radioresistant, hypoxic cells than do tumors implanted into young adult animals; radiation is less effective in killing cells in tumors in old mice than in tumors in young adult mice. The studies reported here examine the effects of porfiromycin (POR), a bioreductive alkylating agent shown previously to be preferentially toxic to hypoxic EMT6 cells in vitro and in solid tumors in young adult mice. POR was effective in attacking the hypoxic cells of tumors in aged mice; regimens combining POR with x-rays overcame the radioresistance of tumors in the old animals. Comparisons of the distribution of 3H-labeled POR in young and old mice showed that tumors in aged mice had a slightly larger proportion of areas with necrotic features, which bound higher levels of tritiated POR than did healthy tumor regions without necrotic features. Studies of histology, lissamine green distributions, binding of tritiated POR, and radiation and POR cytotoxicity suggested that tumors in old mice contained a larger proportion of poorly perfused tumor cells, and that cells in these regions were resistant to radiation and sensitive to POR. Studies of the distribution of POR in normal tissues and of the toxicity of POR to bone marrow progenitor cells (CFU-GM) revealed no differences between young and old animals, showing that the differences observed in tumors reflected differences in the microenvironments within the tumors, rather than differences in the processing of drug in young and old animals.
Aging↗
Modulation of the cytotoxicity of porfiromycin by dicoumarol in vitro and in vivo.
The effects of dicoumarol (DIC) on the cytotoxicity of porfiromycin (POR) were studied in vitro using EMT6 mammary tumor cells in monolayer cultures and in vivo using solid EMT6 tumors and bone marrow stem cells. In vitro, POR was more toxic to hypoxic EMT6 cells than to aerobic cells. Exposure of aerobic cultures to DIC protected against POR; in contrast, DIC sensitized hypoxic cells to POR. Treatment of mice with DIC produced a slight increase in the toxicity of POR to cells in solid tumors. The toxicity of POR to marrow stem cells (CFU-GM and CFU-MK) was not altered by DIC. Pretreatment of mice with DIC therefore produced a small improvement in the therapeutic ratio.
Animals↗
Physical examination as a screening test for pelvic fractures in blunt trauma patients.
This article describes our study of 82 awake, alert blunt trauma victims over the age of 18 with Glasgow Coma Scores of 14 or 15. The purpose was to assess whether the examining physicians were able to determine without benefit of X-ray whether the patients had pelvic fractures. Physicians were asked to complete a questionnaire regarding pain on examination of the pelvis, and were then asked if they believed a fracture was clinically present. Seventy-one patients were tested for alcohol; 15 were positive, and 11 had levels greater than 100 mg%. Fifty-five were tested for mind-altering drugs; 20 were positive. Nine had pelvic fractures; seven required no treatment. Eighteen had pain on examination in at least one plane. Seven of these had fractures; six were suspected clinically. Sixty-four patients had no pain; two had fractures that were not suspected clinically and required no specific treatment. We conclude that selective use of pelvic x-rays in awake, alert blunt trauma patients does not result in any clinically significant missed fractures.
Adult↗