Results of conservative treatment of breast cancer at ten and 15 years.
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The ten-year survival of patients at the Cleveland Clinic treated by operations less than radical mastectomy was 45% compared with 43% in identically staged patients of the "National Cancer Registry" treated predominantly by radical mastectomy. The five and ten-year survival rates of patients treated by simple operations was higher than that of a similar group of patients treated by radical operations, but at 15 years there was no difference. The late deaths from cancer in the patients treated conservatively occurred in patients with favorably staged cancers who never had local recurrences and most of whom had no involvement of nodes. The incidence of local recurrence was no higher after simple operations than after the radical procedure. The ten-year incidences of local recurrence and of death from cancer were the same after partial mastectomy as after total mastectomy. It is pointed out that differences in staging the cancers and in reporting the survival rates invalidate comparisons of results from different institutions. The figures presented suggest that conservative operations and radical operations give the same survival rates at ten and at 15 years. (+info)
Measurement of vitamin B12-binding proteins of plasma. I. Technique.
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The unsaturated binding capacities (UBBC) of individual vitamin B12-binding proteins in plasma were measured by a two-step procedure. Transcobalamin II (TC II) was separated by precipitation with ammonium sulfate; the "R"-type binders remaining soluble were then divided into two components by bath separation with anion exchange on DEAE-cellulose. The two R components were designated alpha1-R (TC 1) and alpha2-R (third binder, fetal binder, PV binder, TC III). Ten normal sera were studied by this technique giving a separation into TC III and total plasma R identical to that obtained simultaneously by gel filtration. The mean UBBC of TC II was 969 plus or minus 204 pg of 57 Co B12 per ml of serum. The mean contamination of the precipitated TC III with plasma R was 3%. The UBBCs of alpha 2-R and alpha 1-R were 127 plus or minus 42 and 40 plus or minus 12 pg/ml, respectively. The mean contamination of the R fraction by TC II was 14% as evaluated by gel filtration. By isoelectric focusing it was found that the alpha1-R contained principally those components isoelectric at pH isoelectric at pH of 2.9-3.2, while alpha2-R was made up of those components isoelectric at pH of 3.6 or greater. (+info)
Repair of radiation damage in Lewis lung carcinoma cells following in situ treatment with fast neutrons and gamma-rays.
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Lewis lung tumor cells were irradiated with 60Co gamma-rays or cyclotron-produced neutrons in situ as solid s.c. tumors or in vitro as single cell suspensions. Cell survival was assayed by colony formation both in vitro in soft agar and in the lungs of isogeneic recipient mice. Survival curve characteristics measured in vitro were: Do = 111 rads, Dq = 342 rads, n = 22 for gamma-rays, and Do = 61 rads, Dq = 46 rads, n = 2 for neutrons. In situ, the hypoxic fraction was 0.36. Irradiation in situ gave, for the hypoxic subpopulation, Do = 315 rads for gamma-rays and Do = 91 rads for neutrons. The oxygen-enhancement ratio for gamma-rays was 2.8 and for neutrons was 1.5. Using the split-dose technique, in which two equal doses were administered, separated by 4 hr chronically hypoxic tumor cells repaired sublethal damage, assayed by leaving tumor cells in situ up to 24 hr posttreatment, could not be detected after neutrons, but after gamma-rays it was observed as a 3- to 6-fold increase in survival. The repair of potentially lethal damage increased the relative biological effectiveness of neutrons from 3.7 at a survival level of 5% when assayed immediately after treatment to 4.7 when assayed 6 to 24 hr after treatment. These observations, primarily limited to the chronically hypoxic subpopulation of tumor cells, suggest that decreased repair of potentially lethal damage as well as sublethal damage may be an important radiobiological difference between the effects of high and low linear energy transfer radiation. (+info)
The role of apoptosis in 2',2'-difluoro-2'-deoxycytidine (gemcitabine)-mediated radiosensitization.
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The nucleoside analogue Gemcitabine [2',2'-difluoro-2'-deoxycytidine (dFdCyd)] is active against a wide variety of solid tumors and is a potent radiation sensitizer. Because apoptosis has been shown to be an important mechanism of cell death for many cancers, we wished to investigate the role of apoptosis in dFdCyd-mediated radiosensitization. We evaluated HT29 colon cancer cells, UMSCC-6 head and neck cancer cells, and A549 lung cancer cells, which differ substantially in the ability to undergo radiation-induced apoptosis. We hypothesized that if dFdCyd produced radiosensitization by potentiating preexisting death pathways, then only the apoptotic-prone HT29 cells would show a substantial increase in apoptosis when treated with the combination of dFdCyd and radiation and that UMSCC-6 cells and A549 cells would be radiosensitized through nonapoptotic mechanisms. We found that the radiosensitization of HT29 cells (enhancement ratio, 1.81 +/- 0.16) was accompanied by an increase in apoptosis and by caspase activation and that inhibition of this activation by the caspase inhibitor Z-Asp-Glu-Val-Asp-fluoromethylketone (DEVD) significantly decreased radiosensitization (to 1.36 +/- 0.24; P < 0.05). In contrast, UMSCC-6 cells and A549 cells were modestly radiosensitized (enhancement ratio, 1.47 +/- 0.24 and 1.31 +/- 0.04, respectively) via a nonapoptotic mechanism. These findings suggest that although apoptosis can contribute significantly to dFdCyd-mediated radiosensitization, the role of apoptosis in dFdCyd-mediated radiosensitization depends on the cell line rather than representing a general property of the drug. (+info)
Effects of combined radiation and thermal burn injury on the survival of skin allograft and immune function in rats.
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OBJECTIVES: To investigate the effects of combined radiation and thermal burn injury on the survival of skin allografts and to analyze the relationship between the prolongation of allograft survival and the changes of immune functions of the thymocytes and splenocytes in rats. METHODS: Wistar rats were irradiated with 3, 4, 5, 6 and 8 Gy of gamma rays. Thirty minutes after radiation, 15% TBSA III-degree burn was inflicted to the rats. Twenty-four hours after the burn injury, allografts were used to cover the burn wounds. In the 8 Gy group, 1 hour before skin grafting, the bone marrow cells (4 x 10(8)) from the same donor were also transplanted. All rats were carefully observed after injury. The rats with single radiation injury of 5 Gy gamma rays, with single burn injury and with combined radiation-burn injury were killed 3, 7, 10, 15 and 30 days after skin grafting for immunological assay and pathological study. RESULTS: All the allografts in the single burn group were rejected in 10 days. In the combined injury groups, the survival rates of the allografts in rats undergoing 3 and 4 Gy radiation were 20% and 30%, respectively. In the combined injury groups undergoing 5, 6 and 8 Gy radiation, the 10-day survival rates of the allografts were 69%, 88% and 100% respectively, and the 30-day survival rates in the three groups were 36%, 42% and 100% separately. The grafted allogenic skin, with normal epithelial cells and good vascularity, healed well with the recipient's skin. Hairs grew well from the allografts 30 days after grafting. Three, 7 and 15 days after allografting, in the single burn group, the proliferative activities of the thymocytes were 90%, 185% and 130% of the preinjury level, and the antibody forming capacities of the splenocytes were 200%, 171% and 300% of the preinjury level, respectively; in the combined injury groups, the proliferative activities were 6%, 99% and 91% of the preinjury level, and the forming capacities were 2%, 36% and 90% of the preinjury level. CONCLUSIONS: The survival rate of allograft in rats undergoing combined radiation and thermal burn injury rises with the increase in radiation dosage. The allograft covering single bun injury is severely rejected by immune reaction. The prolongation of the survival of allograft in combined injury group mainly results from radiation that suppresses immune functions. (+info)
The factors controlling stem cell recirculation. i. Migration of hemopoietic stem cells in adrenalectomized mice.
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The influence of bilateral adrenalectomy on hemopoietic stem cell (CFU) migration in mice has been studied. Formation of endogenous spleen colonies in lethally irradiated, leg-shielded mice was sharply increased by prior adrenalectomy, and this increase was not dependent on the volume of shielded bone marrow. Adrenalectomy was shown to increase endogenous spleen colony formation in sublethally irradiated mice as well. However, it had no affect on formation of spleen colonies in lethally irradiated mice injected with syngeneic bone marrow. The CFU content of murine bone marrow decreased acutely after removal of the adrenals, and this decrease was accompanied by a concomitant increase in the peripheral blood and splenic CFU. Thus, adrenalectomy appeared to have no affect on the splenic plating efficiency or proliferative rate of hemopoietic stem cells, but it did result in increased migration of stem cells from the bone marrow to the blood, and thence to the spleen. It is concluded that the adrenal steroids may be of physiologic importance in the regulation of ehmopoietic stem cell migration. (+info)
Practical applications of radioimmunoassay theory. A simple procedure yielding linear calibration curves.
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The fundamental equation describing radioimmunoassays under equilibrium conditions has been recast into a "working equation" in a form more directly applicable to the requirements of the analytical laboratory. Plotting total counts over counts bound vs. ligand concentration, which is conveniently linear over most of its course, is shown readily to yield quantitative data relative to binding site concentration and the equilibrium constant and to provide a means for deriving apparent labeled ligand concentration. Such data are helpful in establishing optimum assay conditions and can serve a continuing quality-control function. The working equation also characterizes the binder and tracer reagents used in the assay. The determination of working-equation parameters has been illustrated for the vitamin B-12 assay. Data are presented for seven different assay procedures, involving more than 600 calibration curves and 100 different lots of binding agent and tracer reagent, showing a consistently high correlation coefficient (r greater than 0.990), between ligand concentration and the response variable. (+info)
Detection of biological weapons is a primary concern in force protection, treaty verification, and safeguarding civilian populations against domestic terrorism. One great concern is the detection of Bacillus anthracis, the causative agent of anthrax. Assays for detection in the laboratory often employ inactivated preparations of spores or nonpathogenic simulants. This study uses several common biodetection platforms to detect B. anthracis spores that have been inactivated by two methods and compares those data to detection of spores that have not been inactivated. The data demonstrate that inactivation methods can affect the sensitivity of nucleic acid- and antibody-based assays for the detection of B. anthracis spores. These effects should be taken into consideration when comparing laboratory results to data collected and assayed during field deployment. (+info)