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Biomedical subjects

S A Beck

Publications and source records attributed to S A Beck.

At least 19 recordsLinked to original sources
PubMed1992

Lipid metabolism in cancer cachexia.

The effect of cancer cachexia on the oxidative metabolism of lipids has been studied in mice transplanted either with the MAC16 adenocarcinoma, which induces profound loss of body weight and depletion of lipid stores, or the MAC13 adenocarcinoma, which is the same histological type, but which grows without an effect on host body weight or lipid stores. While oxidation of D-[U-14C]glucose did not differ between animals bearing tumours of either type and non-tumour bearing controls, oxidation of [1-14C]triolein administered by intragastric intubation was significantly (P less than 0.05) higher in animals bearing the MAC16 tumour than in either non tumour-bearing controls or in animals bearing the MAC13 tumour. Intestinal absorption of [14C]lipid was significantly (P less than 0.05) reduced in animals bearing the MAC13 tumour when compared with either non tumour-bearing animals or MAC16 tumour-bearing animals, but was not significantly different in the latter two groups. The level of labelled lipids in heart and adipose tissue after an oral [14C]lipid load was significantly lower in animals bearing the MAC16 tumour compared with the other two groups. The level of tumour lipids was also higher in the MAC16 than in the MAC13 tumour after both an oral [14C]lipid load or by direct injection of [U-14C]palmitate complexed to albumin into epididymal fat pads. Oxidation of [U-14C]palmitate was also significantly enhanced in liver and heart homogenates from animals bearing the MAC16 tumour. These results suggest that in cachectic tumour-bearing animals mobilisation of body lipids is accompanied by an increased utilisation.

Adenocarcinoma↗
PubMed1991

Anticachectic and antitumor effect of eicosapentaenoic acid and its effect on protein turnover.

The effect of the polyunsaturated fatty acids eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) on host body weight loss and tumor growth has been investigated in mice bearing a cachexia-inducing colon adenocarcinoma, the MAC16. EPA effectively inhibited both host weight loss and tumor growth rate in a dose-related manner with optimal effects being observed at a dose level of 1.25 to 2.5 g/kg. At these concentrations host body weight was effectively maintained, and there was a delay in the progression of growth of the tumor, such that overall survival was approximately doubled in EPA-treated animals, using the criteria dictated by the United Kingdom Coordinating Committee for the welfare of animals with neoplasms. Even when tumor growth resumed, weight loss did not occur. Animals bearing the MAC16 tumor showed a decreased protein synthesis and an increased degradation in skeletal muscle. Treatment with EPA significantly reduced protein degradation without an effect on protein synthesis. The effect of GLA on both host body weight loss and tumor growth was much less pronounced than that of EPA, with an effect only being seen at a dose of 5 g/kg, at which some toxicity was observed. In vitro studies showed that while EPA was effective in inhibiting tumor-induced lipolysis, GLA was ineffective in this respect. However, prostaglandin E1, which is formed from GLA in vivo, showed partial reversal of tumor-induced lipolysis and probably accounted for the anticachectic effect of GLA. These results suggest that EPA as the pure fatty acid should be considered for clinical investigation as both an anticachectic and antitumor agent, since prior work has shown that the other major component of fish oil docosahexaenoic acid is without pharmacological activity in this system.

Animals↗
PubMed1991

Inhibition of tumour-induced lipolysis in vitro and cachexia and tumour growth in vivo by eicosapentaenoic acid.

Stimulation of lipolysis in murine adipocytes in response to a lipid-mobilizing factor produced by a cachexia-inducing murine adenocarcinoma was inhibited by eicosapentaenoic acid (EPA) with a Ki value of 104 microM. The inhibitory effect was strictly structurally specific, since other related fatty acids of both the (n-3) and (n-6) series were ineffective as inhibitors of the lipolytic process. Induction of lipolysis by both salbutamol and ACTH was also inhibited by EPA, suggesting that the effect is exerted on a step central to the process of lipolysis. Lipolysis induced with the tumour lipid-mobilizing factor was associated with a prolonged elevation of the intracellular level of cyclic AMP in adipocytes, in contrast with ACTH and salbutamol. The elevation of adipocyte cyclic AMP in response to the tumour lipid-mobilizing factor and lipolytic hormones was inhibited by EPA. In vivo, administration of pure EPA to weight losing mice bearing the MAC16 adenocarcinoma completely prevented weight loss and tumour growth rate. In contrast both the other (n-3) fatty acid present in fish oil, docosahexaenoic acid (DHA), and linoleic acid were ineffective in inhibiting weight loss or the growth of the MAC16 tumour. This suggests that inhibition of tumour lipolytic activity accounts for the anticachectic effect of EPA, and that a correlation may exist between the inhibition of cachexia and the inhibition of tumour growth.

Adenocarcinoma↗
PubMed1991

Changes in activity of lipoprotein lipase, plasma free fatty acids and triglycerides with weight loss in a cachexia model.

The effect of weight loss during cancer cachexia on the plasma levels of free fatty acids (FFA) and triglycerides, and on the tissue levels of lipoprotein lipase (LPL), has been studied in mice bearing an experimental colon adenocarcinoma (MAC16). Despite extensive mobilisation of host body fat reserves, plasma levels of triglycerides were reduced irrespective of the extent of weight loss. The plasma levels of FFA also showed an initial decrease with weight loss, followed by a rise peaking at a weight loss of about 2 g, and thereafter the levels decreased with increasing weight loss. The level of LPL in both heart and adipose tissue showed an initial rise with increasing weight loss also peaking at a weight loss of approximately 2.5 g, followed by a decrease with further weight loss. The increased LPL would provide an increased level of fatty acids for oxidation in the cachectic state and would account for the effect on plasma FFAs and triglycerides.

Adenocarcinoma↗
PubMed1991

Lipid mobilising factors specifically associated with cancer cachexia.

Both urine and plasma from mice and humans with cancer cachexia have been shown to contain higher levels of lipid mobilising activity than normal controls, even after acute starvation. There was no significant increase in the urinary lipid mobilising activity of either mice or humans after acute starvation, suggesting that the material in the cachectic situation was probably not due to an elevation of hormones normally associated with the catabolic state in starvation. Further characterisation of the lipid mobilising activity in the urine of cachectic mice using Sephadex G50 exclusion chromatography showed four distinct peaks of activity of apparent molecular weights of greater than 20, 3, 1.5 and less than 0.7 kDa. No comparable peaks of activity were found in the urine of a non tumour-bearing mouse. The high molecular weight activity was probably formed by aggregation of low molecular weight material, since treatment with 0.5 M NaCl caused dissociation to material with a broad spectrum of molecular weights between 3 and 0.7 kDa. Lipolytic species of similar molecular weights were also found in the urine of cachectic cancer patients, but not in normal urine even after 24 h starvation. The lipid mobilising species may be responsible for catabolism of host adipose tissue in the cachectic state.

Adipose Tissue↗
PubMed1991

Egg hypersensitivity and measles-mumps-rubella vaccine administration.

Because reports have described egg-sensitive individuals in whom anaphylaxis developed after measles vaccination, current recommendations include delaying administration of egg-derived vaccines until skin testing can be performed. Specifically, the 1988 Red Book recommends skin testing via scratch, prick, or puncture with 1:10 dilution of the vaccine and, if the result is negative, intradermal testing is suggested. The purpose of this study was to evaluate the likelihood of reaction to measles-mumps-rubella (MMR) vaccine in patients with documented egg sensitivity and to delineate the efficacy of skin-prick testing (SPT) to MMR as a predictor of hypersensitivity to the vaccine. Egg sensitivity was documented by initial SPT to egg and then, if possible, double-blind placebo-controlled food challenge (DBPCFC). Patients with a positive DBPCFC to egg or a history of anaphylactic egg sensitivity had a SPT with the MMR vaccine and then were given the MMR vaccine. Additionally, children with atopic dermatitis who had been previously proven egg sensitive via DBPCFCs were evaluated retrospectively for sensitivity to the MMR vaccine. Sixteen children with a history of egg sensitivity underwent SPT to egg, with a positive result 3 mm greater than the negative control found in 12 patients. Eight of these children had a positive DBPCFC to egg. The SPT to MMR vaccine was negative in all 16 children; vaccine administration followed with no resultant systemic problems. Three children had a local reaction at the site of injection. Twelve additional children with atopic dermatitis and egg sensitivity were reviewed. Each child had a positive SPT and DBPCFC to egg.(ABSTRACT TRUNCATED AT 250 WORDS)

Child, Preschool↗
PubMed1990

Lipolytic factors associated with murine and human cancer cachexia.

We have identified a lipolytic factor in extracts of a cachexia-inducing murine carcinoma (MAC16) that shows characteristics of an acidic peptide and appears to be composed of three fractions of apparent molecular weights corresponding to 3 kd, 1.5 kd, and 0.7 kd, as determined by exclusion chromatography. Material with identical chromatographic and molecular weight characteristics was also present in the serum of patients with clinical cancer cachexia but absent from normal serum, even under conditions of starvation. The MAC16 lipid factor, when injected into animals bearing the non-cachexia-inducing tumor MAC13, was capable of inducing weight loss without a significant reduction in food intake. Similar lipolytic material, although in lower concentration, was also found in the MAC13 tumor extracts. These findings suggest that cachexia may arise from the enhanced expression of a lipolytic factor associated with tumor cells.

Adenocarcinoma↗
PubMed1990

Effect of megestrol acetate on weight loss induced by tumour necrosis factor alpha and a cachexia-inducing tumour (MAC16) in NMRI mice.

The effect of the synthetic progesterone, megestrol acetate, on weight loss induced by both tumour necrosis factor alpha (TNF) as a model for the cachexia accompanying the acquired immunodeficiency syndrome and by a cachexia-inducing tumour (MAC16) has been studied in NMRI mice. Megestrol acetate was effective in preventing weight loss in both model systems with treated animals having an increase in intake of both food and water. Megestrol acetate was unable to prevent loss of body weight in animals pair-fed with TNF treated animals, suggesting that the increase in food and water intake was responsible for the increase in body weight. Analysis of body composition showed that the major contribution to the increase in body weight in animals treated with megestrol acetate was an increase in water content, although there was also an increase in carcass fat in animals bearing the MAC16 tumour given the high dose of megestrol acetate. Animals bearing the MAC16 tumour had a significant increase in tumour weight after treatment with megestrol acetate, possibly owing to the increased plasma glucose levels. These results suggest that an increase in appetite and weight gain alone are not sufficient to justify the anticachectic effect of a particular agent and that body composition analysis and tumour growth rate are very important parameters.

Adenocarcinoma↗
PubMed1990

Alteration of serum and urinary lipolytic activity with weight loss in cachectic cancer patients.

The possibility that weight loss in cancer patients may be augmented by tumour produced catabolic factors, which stimulate lipid mobilisation, was investigated in a group of cancer patients with total body weight loss ranging from 0 to 50%. The serum and urine lipolytic activity has been determined using freshly isolated murine adipocytes in an in vitro assay. As a control group, we have used patients with Alzheimer's disease, in which some patients may lose a considerable amount of weight, without an obvious cause. The serum lipolytic activity for the Alzheimer's group with weight loss (0.11 +/- 0.02 mumols glycerol released 10(5) adipocytes-1 ml-1 serum) was not significantly different from the group without weight loss (0.11 +/- 0.02 mumols glycerol released 10(5) adipocytes-1 ml-1) or from a healthy control group (0.07 +/- 0.02 mumols glycerol released 10(5) adipocytes-1 ml-1), but all three groups were significantly (P less than 0.005) lower than the cancer patient group (0.20 +/- 0.03 mumols glycerol 10(5) adipocytes-1 ml-1), irrespective of weight loss. A similar difference between the cancer and the control group was observed for the urinary lipolytic activity (0.67 +/- 0.03 versus 0.28 +/- 0.03 mumols glycerol released 10(5) adipocytes-1 mg creatinine-1 respectively, P less than 0.01). Weight loss in animals bearing the MAC16 adenocarcinoma was paralleled by a corresponding rise in serum lipolytic activity which peaked when the loss of carcass weight was 16%. A similar decrease in serum lipolytic activity was also observed in cancer patients at high percentages loss in body weight. However, a linear relationship was observed between both the serum and urinary lipolytic activity and weight loss in cancer patients (correlation coefficients 0.79 and 0.70 respectively) when the total body weight loss did not exceed 20%. This suggests that weight loss in cancer patients may be attributed, at least in part, to an, as yet, unidentified lipolytic factor.

Adipose Tissue↗
PubMed1990

Alterations in serum lipolytic activity of cancer patients with response to therapy.

The effect of chemotherapy on the serum lipid mobilising activity of a group of cancer patients with or without weight loss has been determined. The pre-treatment level of serum lipolytic activity in all cancer patients, with or without weight loss, was higher than normal controls (0.22 +/- 0.01 versus 0.06 +/- 0.01 mumols glycerol released ml-1 serum respectively). The pre-treatment levels of lipid mobilising activity in the patients serum was proportional to the extent of weight loss (correlation coefficient 0.81), if the extent of weight loss was small (less than 14 kg). Patients who showed a positive response to chemotherapy also showed a decrease in their plasma levels of lipolytic activity, while a patient who showed no response to therapy also showed no change in the serum lipolytic activity. There was no correlation between the serum lipolytic activity and response to megestrol acetate, a synthetic orally active progestogen, which is currently under investigation as an anticachectic agent. Serum from cancer patients showed lipolytic activity which was retained on a DEAE cellulose column and eluted by a salt gradient, in contrast with normal controls. Response to chemotherapy was associated with a decrease of the retained material, although the profile did not return to the normal state. These results need confirmation in a larger group of patients using more specific methods to determine tumour lipolytic activity, but suggest that it may be possible to monitor response to therapy by measurement of the serum lipolytic activity.

Female↗
PubMed1989

Nitrogen excretion in cancer cachexia and its modification by a high fat diet in mice.

Animals transplanted with the MAC16 colon adenocarcinoma showed a loss of body weight as the tumor weight increased, without a reduction in food intake. Both adipose tissue and muscle mass decreased in tumor-bearing animals, although loss of body fat exceeded that of muscle mass for given tumor weight. Urinary nitrogen excretion was significantly elevated when the weight loss did not exceed 3 to 4 g, but above this weight loss there was a conservation of nitrogen and the excretion level fell to or below that found in non-tumor-bearing animals. The presence of a tumor alone was not sufficient to account for the elevated nitrogen excretion, since animals bearing a related colon adenocarcinoma (MAC13) that did not induce weight loss had a nitrogen excretion pattern similar to that of non-tumor-bearing controls. Feeding an isocaloric isonitrogenous diet in which 80% of the calories were supplied as medium chain triglycerides, which significantly elevated plasma levels of ketone bodies, reduced both tumor weight and host weight loss and restored both the nitrogen balance and urea excretion to that of non-tumor-bearing animals. The plasma levels of amino acids, which were reduced in the cachectic state, were also restored to control values in animals fed the medium chain triglyceride diet. These results suggest that excessive nitrogen catabolism in the cachectic state can be prevented by suitable dietary modification.

Adenocarcinoma↗
PubMed1989

Effect of insulin on weight loss and tumour growth in a cachexia model.

A comparison has been made between the effects of daily insulin injection and a ketogenic diet on weight loss and tumour weight in an experimental model of cancer cachexia (MAC16). Weight loss associated with the MAC16 tumour was significantly reduced both by a ketogenic diet (80% MCT) and by daily insulin injections without an increase in either food or water consumption. Animals fed the 80% MCT diet had a significantly reduced tumour weight compared with controls fed a normal laboratory diet, while in animals administered 20 U insulin kg-1 day-1 the tumour weight was 50% greater than in saline infused controls. The stimulation of tumour growth by insulin was counteracted by the inclusion of 3-hydroxybutyrate in the drinking water without any alteration in the extent of weight loss. Depletion of both carcass fat and muscle dry weight in animals bearing the MAC16 tumour was reversed in animals administered either insulin or an 80% MCT diet. Animals bearing the MAC16 tumour had a reduced nitrogen balance compared with non-tumour-bearing controls, mainly due to excess urea excretion, and this was reversed towards control values in animals fed an 80% MCT diet, but not in animals administered insulin. These results suggest that a ketogenic diet is more effective than insulin administration in reversing the cachectic process and has the advantage of a concomitant reduction in tumour weight.

Adenocarcinoma↗
PubMed1989

Immunotoxicology.

Explore the source record for details and available documents.

Environmental Exposure↗
PubMed1988

Comparison of weight loss induced by recombinant tumour necrosis factor with that produced by a cachexia-inducing tumour.

A comparison has been made of the cachectic effects produced by the transplantable murine adenocarcinoma of the mouse colon (MAC16) with tumour necrosis factor-alpha (cachectin). Tumour necrosis factor-alpha (TNF-alpha) produced a dose-related weight reduction that was accompanied by a decrease in both food and water intake. The degree of weight loss was directly proportional to the decreased food and water intake. In contrast weight loss produced by the MAC16 tumour occurred without a reduction in fluid or nutrient intake. Both the MAC16 tumour and TNF-alpha produced hypoglycaemia and a reduction in the circulatory level of free fatty acids (FFA), but had opposite effects on the level of plasma triglycerides with the MAC16 tumour-induced cachexia causing a decrease and TNF-alpha producing an increase. The MAC16 tumour elaborated a lipolytic factor which caused an immediate release of FFA from adipose tissue. In contrast TNF-alpha had no effect on mobilization of adipose triglycerides over a short time period. Both TNF-alpha and extracts from the MAC16 tumour caused an enhanced release of amino acids from mouse diaphragm, which was suppressible with indomethacin and heat labile. No TNF was detected in the MAC16 tumour or in the serum of tumour-bearing animals. Both tumour and non-tumour-bearing animals responded with a similar elevation of their serum TNF levels 90 min after a single injection of endotoxin. It is concluded that weight loss produced by TNF-alpha arises from an anorexic effect and that this differs from the complex metabolic changes associated with cancer cachexia.

Adenocarcinoma↗
PubMed1987

Production of lipolytic and proteolytic factors by a murine tumor-producing cachexia in the host.

Animals given transplants of the MAC16 colon adenocarcinoma show a progressive decrease in carcass weight as the tumor size increases without a reduction in either fluid or caloric intake when compared with non-tumor-bearing controls. There is a decrease in both carcass fat and muscle mass which is directly proportional to the weight of the tumor. In male animals weight loss occurs when the tumor mass comprises more than 0.3% of the body weight and reaches 30% when the tumor represents 3% of the body weight. There is evidence for the production by the tumor of both lipolytic and proteolytic factors, which may be responsible for the cachexia, since two related mouse adenocarcinomas, which do not produce weight loss, have little lipolytic or proteolytic activity. The lipolytic factor is nondialyzable and is destroyed by both heat and acid. Both insulin and 3-hydroxybutyrate suppress the lipolytic activity of the tumor extract. The MAC16 tumor also contains a serine protease, the activity of which is also completely abolished by insulin and 3-hydroxybutyrate. Animals bearing the MAC16 tumor have an elevated plasma lipolytic and proteolytic activity when compared with non-tumor-bearing controls, suggesting a peripheral effect of the tumor products. The catabolic factors elaborated by the MAC16 adenocarcinoma may be responsible for the loss of both the fat and nonfat carcass mass, but they do respond to normal metabolic controls.

Adenocarcinoma↗
PubMedDate not supplied

Cancer cachexia.

Cancer cachexia has been listed as a major cause of death in cancer patients. In order to investigate the metabolic effects of the tumor on the host, we have evaluated an experimental model of cancer cachexia in the mouse (MAC16 colon adenocarcinoma), in which weight loss can reach 30-40% of initial weight with a tumor burden of only 2.5%, without a reduction in the intake of either food or water. The weight loss appears not to arise from tumor necrosis factor production, which is associated with a marked reduction in both food and water intake, but may be a result of catabolic factors produced by the tumor and present in the circulation. Both insulin and 3-hydroxybutyrate are effective inhibitors of the tumor catabolic factors in vitro and protect, to some extent, weight loss in vivo. However, whereas 3-hydroxybutyrate was associated with a reduction in tumor weight, insulin caused an enhancement, suggesting that the former may be more appropriate than the latter in the clinical treatment of cancer cachexia.

Animals↗