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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between tumor and host tissue proliferation as a function of protein calorie deficiency followed by balanced nutritional repletion was examined in a series of C3H female mice with MA16/C tumors. Tumor and host tissue DNA synthesis was determined in animals with subcutaneously implanted tumors who were randomized to either regular diet (RD) or a totally protein-free diet (PFD) for 5 days followed by refeeding for 4, 8, 12, 24, 36, 48, or 72 hr. Animals maintained on a protein-free diet demonstrated a decrease in DNA synthetic activity in both tumor and host tissues. Following refeeding of a regular diet to animals fed the protein-free diet, resumption of DNA synthesis in tumor preceded that of liver and was greatest by four hours of refeeding. In the liver, return of DNA synthetic activity was delayed but exceeded control levels by 36 hr. Compared to our previous studies examining the effects of starvation, we found that an isocaloric protein-free diet caused a smaller decrease in tumor DNA synthetic activity and an earlier resumption in tumor proliferation with the reinstitution of a normal protein diet. These studies suggest a nutrient-specific response for tumor and host tissues with nutritional deprivation and refeeding.
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PMID:Nutritional modulation of tumor growth. 339 85

Histones isolated from Reuber H35 rat hepatoma cells treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) were examined for possible alterations in phosphorylation. Incorporation of 32P orthophosphate into individual acid-extracted histones was monitored by autoradiography and scintillation counting of polyacrylamide gels or by reverse-phase high performance liquid chromatography. Treatment of quiescent H35 cells (arrested by serum starvation) with submicromolar doses of TPA resulted in a rapid and specific increase in phosphorylation of histones H2B and H1(0). Smaller increases in phosphorylation were observed for H4. No significant change in phosphorylation of the major H1 histones or H2A were observed after 1 h of treatment. The phosphorylation was TPA dose-dependent, with a maximum increase of approximately 14-fold for H2B, 11-fold for H1(0), and 2-fold for H4 achieved at 0.8 M TPA. The nonpromoting parent compound phorbol did not induce any of these changes. Furthermore, the mitogenic hormone insulin did not cause a similar pattern of histone phosphorylation, suggesting that the effect observed was not due to a general mitogenic response in the H35 hepatoma cells. Addition of 8-Br-cAMP also failed to reproduce the effect of TPA on histone phosphorylation, suggesting that cAMP-dependent protein kinases are not likely to be involved in mediating this response to TPA.
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PMID:Phosphorylation of histones is stimulated by phorbol esters in quiescent Reuber H35 hepatoma cells. 352 91

Progressive weight loss and anorexia are frequent phenomena in cancer patients. Although cachexia is an expected occurrence in the terminal stages of nearly all malignancies, it may be a presenting sign when the tumor burden is quite small. Lipid depletion occurs out of proportion to the protein loss and accounts for most of the weight loss in cancer. Lipids, more specifically fatty acids, are the major source of fuel in mammals and may also be used in the synthesis of new cell products. Lipolysis and lipogenesis are under the influence of several important enzymes and peptide hormones that may be modulated by a variety of exogenous factors. There is evidence that cancer patients have lost the normal homeostatic responses to decreased energy intake or starvation that allow a decrease in oxygen consumption and protein sparing. An increase in Cori cycle activity or futile recycling of metabolic products occurs with a net energy expenditure rather than energy production. Clinical studies have shown that the body lipid depletion accompanying tumor progression is not solely secondary to decreased food intake and may be reproduced by the transplantation of certain noninvasive tumors to normal hosts. Elevated basal lipolysis has occasionally been seen early in tumor growth. Such findings suggest the presence of a tumor-associated factor responsible for this increase in lipid mobilization. Some of the potential mechanisms for the altered lipid metabolism seen in cancer have been discussed. Metabolic substrates may be remodeled and directed away from fuel-efficient into energy-requiring pathways. An increased energy expenditure may occur as a result of the energy costs of tumor synthesis, an uncoupling of oxidative phosphorylation, or energy-requiring futile cycling. An overall depletion of lipid may be the final outcome of the inhibition of lipid deposition. TNF/cachectin has recently been found to suppress the activity and synthesis of several key lipogenic enzymes, including lipoprotein lipase. Abnormalities in insulin secretion or sensitivity may be involved in the decrease of fat storage in malignancy. Insulin also exerts a significant antilipolytic effect by its antagonism of hormone-sensitive lipase. Mediators of lipolysis and abnormal lipid metabolism may occur in a number of clinical conditions and include ectopic hormone production, growth factors, and tumor-associated lipolytic factors (lipid mobilizing factor, toxohormone).
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PMID:Fat metabolism and cancer. 353 75

The purpose of this study was to identify the effects of tumor burden and benign inflammatory disease on peripheral tissue metabolism independent of antecedent weight loss. This was accomplished by comparing forearm substrate flux profiles in cachectic cancer and benign disease patients to those of normal subjects before and after 10 days of total protein calorie depletion. Tumor-bearing patients (CA), benign disease patients (BD), and starved (ST) normal volunteers had similar weight loss. Resting energy expenditure was not significantly different between the study populations. Efflux of total amino acids (TAA [nmole/100 ml tissue-min]) decreased significantly (P less than 0.05) in the normals after 10 days of starvation (-886 +/- 185 postabsorptive (PA) vs -278 +/- 60 (ST]. CA patients had TAA efflux of -428 +/- 52 which was significantly (P less than 0.05) less than PA normals. In contrast, BD patients had a significantly (P less than 0.05) elevated TAA efflux of -895 +/- 165 compared to ST normals. CA patients had a significantly (P less than 0.05) elevated glucose uptake and lactate efflux compared to ST normals (glucose: +1.12 +/- 0.21 (CA) vs +0.11 +/- 0.09 (ST), lactate: -0.84 +/- 0.13 (CA) vs -0.38 +/- 0.13 (ST) [mumole/100 ml tissue-min]). The data suggest that tumor-bearing patients are able to maintain their peripheral tissue protein sparing adaptation to nutritional depletion in the presence of accelerated glucose utilization. However, clinically stable patients with benign disease do not demonstrate this adaptation and may be at greater risk for lean tissue dissolution than previously appreciated.
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PMID:Peripheral tissue metabolism in man with varied disease states and similar weight loss. 370 91

The sandwich system was recently developed as a tumor analog; like spheroids, sandwiches are diffusion-limited multicellular systems which exhibit a necrotic center and a viable cell border. Using sandwiches of the 9L cell line, we compared the X-ray sensitivity of cells in the inner half of the viable border, adjacent to the necrotic center, with that of cells in the outer half of the viable border, adjacent ot the medium. No cells were hypoxic at the time of irradiation. The cells in the inner half of the viable border exhibited an increased radioresistance over cells in the outer half. The effect was dose multiplying with a multiplying factor of 1.5. Besides the sandwich studies, the X-ray sensitivity of 9L plateau monolayer cultures (induced by starvation) was compared to exponentially growing monolayer cultures. The plateau cultures exhibited an increased radioresistance over the exponentially growing cultures. The effect was also dose multiplying with a multiplying factor of 1.5.
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PMID:Differences in the X-ray sensitivity of cells in different regions of the sandwich, a diffusion-limited system for cell growth. 377 67

The metabolic responses associated with the tumor-bearing state, as compared to states of sepsis and prolonged starvation, were examined. Tumor-bearing rats manifested significant elevation of triglycerides, significant reduction of glucose and insulin levels, significantly increased plasma skeletal muscle proteolysis-inducing activity, and an unchanged hepatic protein synthetic activity compared to control rats. Prolonged starvation produced an adaptation characterized by significant hypoglycemia and hypoinsulinemia, reduced hepatic protein synthesis, and increased peripheral protolysis compared to controls. Septic animals had glucose, insulin, and lipid levels similar to control animals but had increased hepatic protein synthesis. Each state manifested its own unique metabolic response compared to controls. It appears that the metabolic consequences of cancer in this sarcoma rat model is different than septic and prolonged starvation states.
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PMID:Tumor-associated metabolism in the rat is a unique physiologic entity. 388 27

We have attempted to determine the appropriate parameter of energy status associated with the survival of CHO fibroblasts under starvation conditions. Survival correlated well with adenylate energy charge (EC) but not so well with the phosphorylation potential or ATP concentration. Starved cells exhibited the capacity to resist (transiently) decreases in both EC and survival. A fall in EC was associated with decreased survival. Using this correlation, we subsequently investigated whether killing after thermal stress occurred by a mechanism analogous to starvation, perhaps due to inhibition of energy yielding pathways. This hypothesis proved to be false; over 99% of cells were killed before a decrease was observed in any of the parameters of energy status. Cells were, however, sensitized to heat under nutritionally deprived conditions, a finding which may be significant for tumor treatment by heat in vivo.
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PMID:Investigation of adenylate energy charge, phosphorylation potential, and ATP concentration in cells stressed with starvation and heat. 390 97

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

There are many tumors that have paraneoplastic syndromes. Furthermore, location of certain tumors can result in very specific effects on the host, especially tumors in the hypothalamus, the intestinal tract, or the liver. Finally, tumors of the immune system can have significant distant consequences. However, from direct experimental evidence, from model systems, and from the utilization of nutritional manipulation in the treatment of cancer, the data suggest very strongly that there is no unique cancer malnutrition. Early diagnosed cancer does not show malnutrition as a presenting symptom. Furthermore, all metabolic disturbances can be explained on the basis of the metabolic differences of tumor cells and normal cells and are very frequently proportional to the bulk of the tumor. The cachexia that is associated with malignancies is more likely cachexia in cancer patients than it is a specific cancer cachexia, unless the tumor burden is very large. This point was clearly made in a short review of the causes of cachexia in nearly 1500 cancer patients in Russia (145). Brennan also feels that most cases of malnutrition are uncomplicated starvation, and cancer cachexia has many features seen in major injury or sepsis (16). This distinction has great implications in the management of cancer patients.
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PMID:Nutrition and cancer: physiological interrelationships. 392 50

Tumor-bearing animals provided with intravenous glucose and amino acids (TPN) exhibit enhanced response to S-phase-specific chemotherapeutic agents (H. M. Reynolds, J. M. Daly, B. Rowlands, S. J. Dudrick, and E. M. Copeland. Cancer 45: 3069, 1980; M. H. Torosian, J. L. Mullen, E. E. Miller, et al. J. Parenter. Enteral Nutr. 7: 337, 1983). To determine the mechanism of this response, DNA synthesis rate during starvation or a 48-hr infusion of glucose/amino acids (Glu/AA) was evaluated in tumor, liver, and terminal ileal cells of 68 rats. Tumor cells exhibited a rapid increase in DNA synthesis following the initiation of an infusion of Glu/AA. This increase was most marked after 2 hr of infusion and returned to control levels within 24 hr. Liver DNA synthesis rate increased in both starved and Glu/AA animals over 48 hr with a larger increase in animals receiving Glu/AA. Ileal DNA synthesis decreased equally in both groups. Short pulse Glu/AA produced transient increases in tumor DNA synthesis. Changes in host tissues occurred but followed a different temporal sequence. This may indicate the existence of a period of time following initiation of metabolic manipulation when tumor susceptibility to phase-specific chemotherapeutic agents will be enhanced while host tissues will be spared from increased toxicity.
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PMID:The effects of glucose and amino acids on tumor and host DNA synthesis. 393 82


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