KWWSVGRLRUJ316 3XEOLVKHGRQOLQHEDPEULGJH8QLYHUVLW3UHVV 1993b This suggests that depleti ID: 938659
Download Pdf The PPT/PDF document "Nutrition Society Clinical Nutrition and..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Nutrition Society Clinical Nutrition and Nutrition Society and Enteral Nutrition K W W S V G R L R U J 3 1 6 3 X E O L V K H G R Q O L Q H E \ & D P E U L G J H 8 Q L Y H U V L W \ 3 U H V V 1993b). This suggests that depletion skeletal muscle proteins during the process cachexia is not simply to undernutrition, but a much more complex metabolic problem. CANCER CACHEXIA Tumour necrosis factor-a (TNF-a) the anorexia- cachexia syndrome in trypanosome-infected rabbits was given the name cachectin indicate its role process (Beutler in particular interleukins- and -6 (IL- and IL-6 respectively), interferon-? and leukaemia- been suggested to play a role cachexia. All cytokines produce a profound anorexia and weight The effect adipose tissue was thought to mediated through an inhibition the cleaving lipoprotein lipase 3.1.1.34; LPL), which would prevent adipocytes fatty acids from plasma lipoproteins storage. However, inhibition LPL alone unlikely to induce massive depletion seen in in type 1 hyperlipidaemia there an inherited deficiency and yet cachectic. Although studies show that muscle protein degradation is significantly increased by effect must be since Goldberg (1988) were unable to a catabolic after incubation skeletal muscle with 1994) and IL-1 (Goldberg 1988) have also been shown be incapable inducing muscle protein degradation It has been difficult the extent cancer patients, although that cachexia a local a tumour. Thus, patients with solid tumours and a weight loss was detected in serum samples using pg/ml (Socher 1988). However, in another study, serum were found to pg/ml and correlated with the extent disease (Scagliotti 1995). Thompson (1993) were unable to detect elevated levels in cancer patients and, furthermore, neither total LPL activity nor for LPL were significantly different between cancer controls. Thus, while elevated TNF-a present in cancer patients, there absolute requirement this cytokine for the cancer cachexia. In contrast to been much easier elevated levels IL-6 in main cytokine involved with acute- phase protein (APP) sy
nthesis, and patients with colon cancer and an ongoing APP response had an concentration (Fearon Unfortunately, all patients this study had lost weight and further studies required to determine whether cachectic cancer suggest that some other involved in CATABOLIC FACTORS CANCER CACHEXIA order to study mechanisms responsible for the and adipose tissue during the process cachexia, we have utilized a transplantable murine adenocarcinoma (MAC1 1987). This tumour induces weight when the tumour mass comprises more than the host body weight and weight tumour represents body weight reduction in host body weight occurs without a decrease in and water intake, proportional to tumour mass and reversible when tumour is excised. Cachexia this model differs from that expected with cytokines such as K W W S V G R L R U J 3 1 6 3 X E O L V K H G R Q O L Q H E \ & D P E U L G J H 8 Q L Y H U V L W \ 3 U H V V ANOREXIA-CACHEXIA SYNDROME which produces a decrease body weight in direct proportion to a decreased food and water intake (Mahony cachexia induced was accompanied a marked cytokines) produce results, together with inability to detect production by the MAC16 tumour, suggested that some other factor(s) Since the most obvious body composition in mice bearing the MAC16 tumour were a depletion adipose tissue triacylglycerols skeletal muscle proteins, bioassays were developed to tumour products of host breakdown were non-esterified fatty from freshly-isolated epididymal adipocytes (Beck protein breakdown was detected from fresh gastrocnemius muscles under tension (Smith Tisdale, 1993). Using these bioassays, there was evidence for the both lipid- and factors, while related tumours, which not produce cachexia, showed little bioassays (Beck 1987; Smith suggests that these factors for the cachexia. In lipid-mobilizing activity was detected in the serum and cancer patients with weight loss, while it was undetectable in patients with weight loss due 1990). A linear relationship observed between both the serum and urinary lipid-mobilizing activity and weight loss in pa
tients, when total body loss did not exceed 20 Moreover, patients showing a response showed a plasma levels lipid-mobilizing activity, suggesting that this catabolic factor emanated from the Other workers have also described tumour-derived lipid-mobilizing factors. Costa show that weight in particular Krebs-2 carcinoma reproduced with a non-viable preparation of tumour. When lymphoma-bearing mice was injected into normal mice it produced an immediate fat mobilization, providing further evidence for catabolic factor extracts and culture medium lymphoma cell showing that it was a the tumour, rather being produced host tissues. Another was isolated from the ascitic fluid patients with hepatoma and sarcoma 180 (Masuno 1981, 1984). material was with an molecular mass 70-75 kDa. Trypsin the active material produce a molecular mass, which was still biologically active, suggesting that only part the molecule may be responsible biological effects. low-molecular-mass, acidic, lipid-mobilizing also isolated from the human melanoma cell line, A375 (Taylor murine adipocytes involving activation both human murine tumours to be elaborating lipid- mobilizing factors. present in serum (Beck 1990b) and Tisdale, 1991) cachetic cancer patients has been shown to display identical molecular mass and chromatographic characteristics to found in the MAC tumour, suggesting that mediated by the characteristics tumour lipid-mobilizing which distinguishes the lipolytic hormones a strong negative physiological pH, and this K W W S V G R L R U J 3 1 6 3 X E O L V K H G R Q O L Q H E \ & D P E U L G J H 8 Q L Y H U V L W \ 3 U H V V characteristic has been utilized in this factor a MAC16 tumour homogenate. Using a combination ion-exchange, exclusion and hydrophobic chromatography, a lipid-mobilizing factor been isolated, representing total protein present tumour (McDevitt 1995). It was noted that animals transplanted with the MAC16 tumour, and with a delayed weight loss, contained serum antibodies that recognized a material molecular mass Western blots and which co-purified wit
h Such antibodies were not present in the serum mice bearing a related tumour (MAC13) which not induce cachexia, suggesting that directed against the factor inducing cachexia rather the tumour itself. Splenocytes from the MAC16 tumour, and with a delayed weight loss, were fused with mouse myeloma produce hybridomas. hybridomas were cloned to produce antibody reactive to the material molecular mass 24 kDa (Todorov monoclonal antibody was then used to purify using a combination hydrophobic chromatography give a single species representing the total protein present in the tumour material was shown to a sulphated glycoprotein or proteoglycan containing a short peptide chains linked both serine and asparagine residues. Using Western blotting with the MAC16 monoclonal antibody the material was found to cancer patients, absent from the urine normal subjects, patients with weight loss due to major multiple injuries or surgery-associated and sepsis, or from the urine patients with or no weight loss. Material isolated from urine patients was found to chemically, immunologically functionally identical to that found the MAC studies showed that intravenous administration of purified material of molecular mass 24 kDa non-tumour-bearing mice produced a weight loss 2 g over a 24 h period, without a reduction in and water loss was attenuated pretreatment with the MAC16 monoclonal antibody, showing Body composition analysis showed weight was lost from the skeletal muscle mass and there was no in body water. material to be direct release tyrosine from isolated gastrocnemius muscle, and this effect could also MAC16 monoclonal antibody. These results suggest that kDa material catabolism during been carried out protein catabolic factors than lipid catabolic in cancer, Belizario found evidence circulatory skeletal-muscle proteolysis-inducing patients with weight loss greater effect appeared to IL-1, this acted in cooperation with unidentified factors. Thus, tissue breakdown during is associated with tumour-produced catabolic present in the circulation, appear to distinct from recognized cytokines. outstanding question that s
till requires tumours produce such Tumours have acids and have specific requirements others such as cysteine (Uren Lazarus, 1979), methionine (Tisdale, 1980), tyrosine and phenylalanine Brennan, 1982), serine and threonine (Pfizer Regan, 1972). Also tumours have a poor capacity to synthesize their own lipids. Nutritional conditions which to catabolism host adipose tissues in rats, such as 1987a) and acute streptozotocin-induced diabetes (Sauer Dauchy, 1987b), result K W W S V G R L R U J 3 1 6 3 X E O L V K H G R Q O L Q H E \ & D P E U L G J H 8 Q L Y H U V L W \ 3 U H V V tumour growth, suggesting that the products from host fat stores limiting for tumour growth most likely that effect results from fatty acids as linoleic arachidonic acids. Metabolites derived from cyclooxygenase pathways essential fatty acids have been shown to transduce growth-related signals regulate cell addition, products and 15-lipoxygenase pathways arachidonic acid appear to play important physiological regulating apoptosis the cytokines, elaborate catabolic factors cause direct protein stores. The importance to tumour homeostasis is indicated the conservation the mechanism the development therapeutic agents capable inhibiting the steps in the process. such agent, the polyunsaturated fatty eicosapentaenoic acid, is capable lipid (Tisdale 1991) and protein (Smith and has weight gain cancer (Wigmore Attacking the not only anti-cachectic agents, but also offers the tissues are (1988). Proliferative insulin and epidermal growth factor epithelial cells primary culture. Enhancement hydroxyeicosatetraenoic acids and synergism Biological Chemistry Barton, C. Tisdale, M. serum lipolytic activity cancer patients (1990b). Lipolytic murine and cancer cachexia. National Cancer Institute (1987). Production and proteolytic a murine tumor-producing the host. mobilising factors specifically associated cancer cachexia. Raw, C. (1991). Bioactivity skeletal muscle proteolysis-inducing proteins from cancer patients weight loss. (1985). Identity tumour necrosis macrophage-secreted factor cach
ectin. a transplantable adenocarcinoma the mouse colon producing cachexia in recipient National Cancer H., Gartenhaus, W. (1981). Compartmental cancer patients nitrogen, potassium and water. (1977). Cachexia, metabolic component neoplastic disease. Cancer Research (1966). Effects Krebs-2 carcinoma Lane, W. W., Vincint, G., Siebold, (1980). Weight (1982). Tumoricidal potential nutritional manipulation. De Wys, (1985). Management Cancer Research lung cancer. K W W S V G R L R U J 3 1 6 3 X E O L V K H G R Q O L Q H E \ & D P E U L G J H 8 Q L Y H U V L W \ 3 U H V V M. J. TISDALE Moran, E., D. (1985). Limited impact total parenteral nutrition nutritional status during treatment for small cell lung cancer. Cancer Research C. H., McMillan, C., Preston, Elevated circulating interleukin-6 an acute phase response but reduced hepatic protein J., Dinarello, C. (1989). Infusion tumor necrosis factorlcachectin promotes muscle catabolism in the Clinical Investigation Argiles, J. (1994). Interleukin-6 does not activate protein breakdown in rat skeletal muscle. Epidermal growth factor stimulates linoleic acid metabolism in BALBlc 3T3 fibroblasts. Molecular Pharmacology Fagan, J. (1988). Activation protein breakdown E2 production rat skeletal muscle fever macrophage product distinct Clinical Investigation (1989). Symptoms potentially in a cancer population. Groundwater, P., Barton, C., Adamson, C., (1990). Alteration urinary lipolytic activity weight loss in cachectic cancer patients. lipid mobilizing factor tumour-bearing mice. four doses megestrol acetate cancer anorexia Loprinzi, C. L., Schaid, J., Dose, composition changes gain weight receiving megestrol acetate. Clinical Oncology McDevitt, T. T., Beck, lipid-mobilizing factor associated with cachexia-inducing tumors mice and humans. Cancer Research Simpson, J. Preston, T., Watson, W., Fearon, H. J. Mcardle, C. (1994). Effect megestrol acetate on weight loss, body composition gastrointestinal cancer patients. Clinical Nutrition M., Beck, Tisdale, M. J. (1988). Comparison recombinant tumour necrosis factor t
hat produced cachexia-inducing tumour. lipolytic factor (toxohormone-L) from cell free ascites Sarcoma 180. Cancer Research (1984). Isolation lipolytic factor (toxohormone-L) from ascites hepatoma and its effect feeding behaviour. Clinical Oncology Mortensen, E. (1993). Effect dietary counseling food intake, weight, response rate, survival and quality cancer patients undergoing prospective, randomized study. Clinical Oncology Regan, J. D. (1972). Basis for the serine requirement leukemic and normal human the enzymes the phosphorylated pathway. National Cancer Blood nutrient concentrations and tumor growth the onset an acute fast. Cancer Research L. A. (19876). Stimulation tumor growth adult rats during acute streptozotocin-induced diabetes. Cancer Research Pozzi, E. (1995). serum and pleural patients with lung cancer. International Journal J. (1993). Mechanism muscle protein degradation in cancer cachexia. (1988). Tumour necrosis factor patients with clinical cancer cachexia. National Cancer Institute (1996). Arachidonate lipoxygenases survival and apoptosis. National Academy Jenio, L. (1992). Identification human tumor-derived lipolysis-promoting factor. Cancer Research Thompson, M. Tuckey, J. (1993). Increased expression for the hormone-sensitive lipase adipose tissue cancer patients. Biochimica et Biophysica Acta K W W S V G R L R U J 3 1 6 3 X E O L V K H G R Q O L Q H E \ & D P E U L G J H 8 Q L Y H U V L W \ 3 U H V V methionine replacement homocysteine on International Report tumour-induced lipolysis and cachexia and tumour eicosapentaenoic acid. Biochemical Pharmacology a cancer cachectic factor. M., Cariuk, P., B., Deacon, M. muscle protein degradation and weight loss by tumour product. Cancer Research L-Cyst(e)ine requirements cells and progress towards depletion Treatment Reports Tisdale, M. Carter, D. polyunsaturated fatty acids on the cachexia in patients with pancreatic K W W S V G R L R U J 3 1 6 3 X E O L V K H G R Q O L Q H E \ & D P E U L G J H 8 Q L Y H U V L W \ 3 U H V