UMLS:C0011849 - FACTA Search

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Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor growth and the incorporation of [3H]thymidine into tumor DNA in vivo are increased about 3 times in adult rats (greater than 250 g) after 1 to 2 days of starvation or the induction of diabetes with streptozotocin. These tumor growth responses require hyperlipemia and are reversed by refeeding or insulin treatment, respectively. They do not occur in young tumor-bearing rats (less than about 150 g) that lack appreciable fat stores. A direct relationship between the increased rates of both [3H]thymidine incorporation and tumor growth and host hyperlipemia suggests that tumor cell renewal in vivo in fed rats is limited by substances that are present in hyperlipemic blood. In this study we used a procedure for perfusion of solid tumors in situ to measure the sensitivity of tumor [3H]thymidine incorporation to hyperlipemic blood and to identify the rate-limiting substances. Tissue-isolated Morris hepatomas (7288CTC) growing in young or adult Buffalo rats were perfused with blood from donor rats. Hyperlipemic blood for perfusion was obtained from 2-day starved tumor-bearing (Buffalo) or non-tumor-bearing (Buffalo or Lewis) rats. At the end of the perfusions the tumors were labeled with a pulse of [3H]thymidine (2 microCi/g estimated tumor wet weight). [3H]Thymidine incorporation in tumors growing in fed adult rats was increased from 80 +/- 5 (SD) dpm/micrograms DNA at zero time (before perfusion) to 209 +/- 9 dpm/micrograms DNA (n = 3) after perfusion for 3 h. Tumors growing in fed or starved young rats showed similar responses, and hyperlipemic blood from non-tumor-bearing rats was as effective as hyperlipemic blood from tumor-bearing rats. Perfusion of tumors growing in starved rats with normolipemic blood from fed adult rats decreased [3H]thymidine incorporation from 211 +/- 13 dpm/micrograms DNA before perfusion to 68 +/- 9 dpm/micrograms DNA (n = 3) after perfusion for 3 h. Cells, plasma, and plasma subfractions from hyperlipemic blood were reconstituted to whole blood using plasma, cells, and whole blood, respectively, from fed rats and the mixtures were perfused into tumors growing in fed adult rats. Mixtures containing hyperlipemic plasma, lipid extracts (ethanol:acetone, 1:1) of hyperlipemic plasma, or albumin from hyperlipemic plasma increased tumor [3H]thymidine incorporation. Free fatty acid concentrations were increased about five times in hyperlipemic plasma and perfusion of tumors with normolipemic blood containing added linoleic and arachidonic acids increased [3H]thymidine incorporation. Blood mixtures containing palmitic, stearic, and oleic acids were inactive.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Identification of linoleic and arachidonic acids as the factors in hyperlipemic blood that increase [3H]thymidine incorporation in hepatoma 7288CTC perfused in situ. 313 Jan 86

A case report of a 37-year-old previously healthy man who contracted hypertension and insulin-dependent diabetes mellitus. Urinary catecholamine excretion was elevated. A total of nine benign pheochromocytomas with characteristic histological appearance were successfully removed. Most of the tumors were located extra-adrenally in the upper abdomen and in the pelvis. Two of the tumors were found in organ plexuses in the mesocolon sigmoideum and in the anterior wall of prostata. Because of asynchronous tumor growth a life-long follow-up is recommended.
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PMID:A case of multiple extra-adrenal pheochromocytomas. 335 55

The effects of acute diabetes mellitus on the growth of Morris hepatoma 7288CTC and Jensen sarcoma were studied in fed, young (less than 200 g), and adult (greater than 250 g) rats. Animals were matched for tumor size and growth; the rates of tumor growth were the same in fed, young and adult nondiabetic rats. Diabetes was induced by the i.v. injection of streptozotocin (65 mg/kg total body weight) into tumor-bearing rats and changes in arterial blood nutrient concentrations were compared to changes in the rates of tumor growth and DNA synthesis. In young rats acute diabetes did not increase the blood concentrations of the fat store-derived nutrients and did not increase the rate of tumor growth. In adult rats, however, acute diabetes raised the arterial blood free fatty acid, glycerol, triglyceride, and ketone body concentrations to high levels and increased the rate of tumor growth about three times over that observed in untreated rats. Progress curves for the mobilization of host fat stores and for incorporation of [methyl-3H]thymidine into tumor DNA during the onset of diabetes showed that these activities were closely correlated in adult rats. Both processes began to increase 2 to 4 h after streptozotocin treatment, reached an initial peak at 12 to 16 h, decreased to a low point at 18 to 20 h, and then increased again to the new steady state after 23 to 24 h. The results indicate that the rate of tumor growth in rats in vivo is limited by the availability of a substance(s) present in the hyperlipemic blood of adult diabetic rats. The tight relationship between host lipolysis and tumor growth suggests that the substance(s) is derived from host fat stores.
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PMID:Stimulation of tumor growth in adult rats in vivo during acute streptozotocin-induced diabetes. 381 72

Starvation-induced hypoglycaemia and streptozotocin-induced diabetes suppressed the growth of Ehrlich ascites tumor in mice. The suppression of tumor growth by diabetes was alleviated by administration of insulin. The number of glucose carriers on tumour cells was found to be reduced in diabetes and partial resumption of glucose carriers was observed in tumour cells of diabetes after insulin administration. Insulin had no direct effect on tumour growth in vivo and did not affect the number of glucose carriers on tumour cells in vitro. The physiological significance of these observations is discussed.
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PMID:Suppression of Ehrlich ascites tumor growth in mice by starvation and streptozotocin-induced diabetes. 390 10

The effect of oral administration of diazoxide on rats bearing mammary carcinomas induced by dimethylbenzanthracene (7,12-DMBA) or methylnitrosourea (MNU) was investigated. Administration of 300 mg/kg diazoxide caused mild reversible diabetes with maximum glucose levels of 305 +/- 74 (control: 119 +/- 12) mg/dl and related insulin levels of 15 +/- 5 (control: 24 +/- 11) microU/ml after 4 hr in tumor-bearing animals. Following the same dose of diazoxide a more than 90% inhibition of tumor growth was observed in 7,12-DMBA- and MNU-induced autochthonous rat mammary carcinomas as well as remission of the median total tumor volume per group in 7,12-DMBA-induced lesions. Frequently, onset of remissions and median remission duration proved to be dose-dependent in 7,12-DMBA-induced mammary carcinoma and, with the exception of the median remission duration, in MNU-induced tumors too. After cessation of diazoxide application, 30% rebound responses were observed in 7,12-DMBA-induced tumors of animals that had had a first remission due to diazoxide. Application of insulin (2 IU per rat) together with diazoxide (300 mg/kg) reversed the tumor-inhibiting effect of diazoxide in MNU-induced tumors. The diazoxide effect might in part be due to a decrease in the percentage of proliferating cells caused by insulin depletion as indicated by a lower amount of cells in S-phase, as measured by DNA-flow cytometry. Marked toxicity was observed after effective doses of diazoxide; the experiments indicate that induction of reversible diabetes might be a useful tool in the treatment of hormone-dependent mammary carcinoma.
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PMID:Effects of diazoxide-induced reversible diabetes on chemically induced autochthonous mammary carcinomas in Sprague-Dawley rats. 391 48

Diabetic mouse serum was found to be toxic to F-10 melanoma cells in vitro. However, when F-10 cells were injected intravenously into streptozotocin-induced diabetic mice there was a significant increase in the number of lung tumors. Contrarily, when streptozotocin was injected after F-10 cells there was a 5-fold decrease in lung metastases. Reversal of the diabetes in these mice by nicotinamide or insulin injection did not increase the lung metastases. Solid tumors (resulting from the subcutaneous injection of F-10 cells) grew at similar rates in both control and diabetic mice. Streptozotocin injected after F-10 cells resulted in a 6 day delay in the appearance of solid tumors. Triglycerides, the toxic factors in vitro, were elevated to similar extents in both tumor-bearing control and diabetic mice. Most of the differences in tumor growth between control and streptozotocin injected mice were attributable to the antitumor activity of streptozotocin, rather than the diabetic state.
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PMID:Differential effects of streptozotocin and streptozotocin-induced diabetes mellitus on tumor metastases and growth in mice. 623 Sep 83

The hormonal environments require by human breast cancer cells MCF-7 to produce solid tumors in nude mice are described. A 100% take was obtained within 7 days following inoculation of 2X10(6) actively growing (log phase) MCF-7 cells into the mammary fat pads of intact, athymic BALB/c nude mice. Tumors failed to develop, even with an inoculum of 20X10(6) cells/mouse, in ovariectomized mice or in mice made diabetic with streptozotocin and observed for 90 days after cell inoculation. A 100% incidence of tumors was obtained in mice that were either hypophysectomized or made diabetic but received injections of 0.2 IU insulin/day/mouse. A 100% incidence of tumors was also obtained in ovariectomized mice that received 17 beta-estradiol in the form of a pellet placed subcutaneously in the interscapular region at the time of cell inoculation. Palpable tumors also developed in ovariectomized mice treated with prolactin, perphenazine, estrone, or estriol, but no takes were observed in ovariectomized mice treated with progesterone, 5 alpha-dihydrotestosterone, or hydrocortisone. Growth of the MCF-7 tumor was stimulated five- to sixfold in both intact and hypophysectomized mice that each received a 17 beta-estradiol pellet. Removal of the 17 beta-estradiol pellets form tumor-bearing ovariectomized mice failed to induce tumor regression. Tumors that continued to grow in ovariectomized mice deprived of 17 beta-estradiol regressed by 50% or more of their initial volume when tamoxifen was injected for 7 days at 5 micrograms/mouse/day) +/- theophyline (1 mg/mouse/day), tumor growth arrest was observed during the 2-to 3-week treatment period. Streptozotocin-induced diabetes in tumor-bearing mice always resulted in complete tumor regression following a 3-week treatment period.
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PMID:Role of hormones in the growth and regression of human breast cancer cells (MCF-7) transplanted into athymic nude mice. 626 82

Sixty-one 150- to 180-g Fischer rats were assigned to one of four experimental groups: nondiabetic, tumor bearer (ND-TB, n = 15); diabetic, non-tumor bearer (D-NTB, n = 19); diabetic, tumor bearer (D-TB, n = 16); or nondiabetic, weight-matched control, tumor bearer (WM-TB, n = 11). The WM group was housed in metabolic cages and fed H2O ad libitum and rat chow to achieve appropriate carcass weight (comparable to D-NTB). Diabetes was induced with a single dose of streptozocin (STZ) 40 mg/kg body wt iv, 10 days prior to tumor inoculation. Viable methylcholanthrene-induced sarcoma cells (1 X 10(6) ) were injected into the right flank on Day O. Body weight and tumor volume were assessed every 3 days. On the day of death, the animal and excised tumor were weighed. Dividing the growth curves versus time into two phases based on tumor volumes 0-20 and 20-60 cm3 defined a significant early growth (0-20 cm3) delay of 5 days in the D-TB and WM groups vs the ND-TB group. The growth rate from 20-60 was not different in any group. Tumor growth retardation seen in STZ-induced diabetic animals can be mimicked and exceeded in a pair-fed, weight-matched control group. Diabetic and starved animals have smaller tumors and live longer than ad lib fed, nondiabetic animals. The delay in tumor growth is a reflection of the retardation in the early (0-20 cm3) growth rate.
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PMID:The effects of streptozocin-induced diabetes and weight-matched pair feeding on tumor growth and survival in Fischer rats. 670 99

An aplastic mammary carcinoma (AMC) grew slower in hypoglycemic mice (caused by fasting or by daily insulin injections) and in hyperglycemic mice (caused by alloxan or streptozotocin, or by daily injections of glucose) than in normoglycemic mice. The tumor was able to adapt to the unfavourable conditions of the diabetes; cells, when transplanted from diabetic donors into diabetic recipients, secreted immunoreactive insulin (IRI) and immunoreactive glucagon (IRG), which are deficient in the diabetic hosts. In the terminal (hypoglycemic) phase of tumor growth, the concentrations of glucose, IRI and IRG decreased. The immunological reactivity of the host animals was reduced in the hypoglycemic terminal phase. The tumor cells taken from hosts in this phase behaved differently from the cells taken in the normoglycemic phase. The "hypoglycemic" cells grew more slowly in healthy mice; the intensity of their DNA synthesis was diminished, their response to antitumor therapy was weaker. Furthermore, it was necessary to transplant more of these cells to obtain tumors in all recipients, and they lost their ability to adapt to diabetic conditions (i.e. secreted neither IRI nor IRG). Hypoglycemia was apparently the immediate cause of death in mice with AMC. Injections of glucose or glucagon into mice with AMC eliminated the hypoglycemia temporarily and postponed the death by 4 days. Mice treated with glucagon and with chemotherapy or immunotherapy survived 6-9 days longer than mice treated with chemo- or immunotherapy alone. Some of these differences between the end-stage and the progressively growing tumors could be explained in terms of tumor cell kinetics but some could be attributed to metabolic conditions of the host caused in part by the tumor.
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PMID:Different endocrinological properties, growth rate and sensitivity to chemotherapy of aplastic mammary carcinoma in normo- and hypoglycemic phase of tumor growth. 675 72

The role of insulin as a regulator of estrogen receptors (ER's) was investigated in 7,12-dimethylbenz(a)anthracene-induced mammary tumors in diabetic and insulin-treated rats. Induction of diabetes with streptozotocin produced regression of lesions classified as insulin dependent; lesions that continued to grow in diabetic rats were classified as insulin independent. Compared to tumors in intact hosts [ER, 39 +/- 4 (S.E.) fmol/mg cytosol protein], regressing insulin-dependent lesions had ER levels of 8.5 +/- 0.7 fmol, and insulin-independent tumors had ER levels of 24 +/- 3 fmol. Treatment of diabetic rats with insulin 8 IU/day, caused insulin-dependent regressing tumors to resume growth; these lesions had ER levels of 53 +/- 10 fmol. Insulin-independent lesions in diabetic rats demonstrated two patterns after treatment with insulin; continued growth resulted in tumors having ER levels of 28 +/- 11 fmol, whereas insulin-induced tumor regression resulted in tumors that demonstrated ER levels of 40 +/- 6 fmol/mg cytosol protein, a value equal to the level of ER in tumors growing in intact rats. Scatchard analysis of the saturation-binding data gave linear representations, and the estimated Kd for the ER was comparable for all groups, ranging from 0.44 to 1.90 x 10(-9) M. Several additional tumors were classified as demonstrating static growth. When this behavior represented a response due to insulin treatment, ER levels were elevated. Static tumors remaining static after insulin treatment demonstrated low ER levels. We conclude that (a) cessation of tumor growth after induction of diabetes resulted in reduction of ER levels, (b) treatment with insulin that resulted in an altered tumor growth was accompanied by elevated ER levels, and (c) insulin may play a role in regulation of ER independent of tumor growth.
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PMID:Regulation of estrogen-binding capacity by insulin in 7,12-dimethylbenz(a)anthracene-induced mammary tumors in rats. 677 Sep 98

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