We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine
Published Online:https://doi.org/10.2217/fon.10.20

Both cytokines and tumor factors have been implicated in tissue loss in cancercachexia. Loss of adipose tissue is most likely due to the tumor (and host) factorzinc-α2-glycoprotein because of its direct lipolytic effect, ability to sensitizeadipocytes to lipolytic stimuli and increased expression in cachexia. TNF-α andthe tumor factor proteolysis-inducing factor are the major contenders for skeletalmuscle at rophy; both increase protein degradat ion through theubiquitin–proteasome pathway and depres s protein synthesis throughphosphorylation of eukaryotic initiation factor 2α. However, while most studiesreport proteolysis-inducing factor levels to correlate with the appearance ofcachexia, there is some disagreement regarding a correlation between serumlevels of TNF-α and weight loss. Furthermore, only antagonists to proteolysisinducingfactor prevent muscle loss in cancer patients, suggesting that tumorfactors are the most important.

Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

Bibliography

  • Teunissen SC, Wesker W, Kruilwagen C et al.: Symptom prevalence in patients with incurable cancer: a systematic review. J. Pain Symptom Manage.34,94–104 (2007).
  • Tan BHL, Fearon KCH: Cachexia: prevalence and impact in medicine. Curr. Opin. Clin. Nutr. Metab. Care11,400–407 (2008).
  • DeWys WD, Begg C, Lavin PT et al.: Prognostic effect of weight loss prior to chemotherapy in cancer patients. Am. J. Med.69,491–497 (1980).
  • Marinoho LA, Rettori O, Vieira-Matos AN: Body weight loss as an indicator of breast cancer recurrence. Acta Oncologica40,832–837 (2001).
  • Cohn SA, Gartenhaus W, Sawitsky A et al.: Compartmental body composition of cancer patients with measurement of total body nitrogen, potassium and water. Metabolism30,222–229 (1981).
  • Fearon KCH: The mechanisms and treatment of weight loss in cancer. Proc. Nutr. Soc.51,251–265 (1992).
  • Heymsfield SB, McManus CB: Tissue components of weight loss in cancer patients. Cancer55,2238–2242 (1985).
  • Evans WK, Makuch R, Clamon GH et al.: Limited impact of total parenteral nutrition on nutrition status during treatment for small cell lung cancer. Cancer Res.45,3347–3352 (1985).
  • Loprinzi CL, Schaid DJ, Dose AM, Burnham NL, Jensen MD: Body composition changes in patients who gain weight while receiving megestrol acetate. J. Clin. Oncol.11,152–154 (1993).
  • 10  Simons JP, Schols AM, Hoefnagels JM, Westerterp KR, ten Velde GP, Wouters EF: Effects of medroxyprogesterone acetate on food intake, body composition and resting energy expenditure in patients with advanced, non-hormone-sensitive cancer. Cancer82,553–560 (1998).
  • 11  Bosneus I, Daneryd P, Svanberg E, Lundholm K: Dietary intake and resting energy expenditure in relation to weight loss in unselected cancer patients. Int. J. Cancer93,380–383 (2001).▪▪ Study of 297 cancer patients that demonstrated that weight loss could not be accounted for by diminished dietary intake, since energy intake in absolute amounts was not reduced.
  • 12  Bing C, Brown M, King P, Collins P, Tisdale MJ, Williams G: Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle UCP2 and UCP3 in MAC16-induced cancer cachexia. Cancer Res.60,2405–2410 (2000).▪ Comprehensive review of cancer cachexia.
  • 13  Fan W, Boston BA, Keterson RA, Hruby VJ, Cone RD: Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature365,165–168 (1997).
  • 14  Wisse BE, Frayo RS, Schwartz MW, Cumings DE: Reversal of cancer anorexia by blockage of central melanocortin receptors in rats. Endocrinology14,3292–3301 (2001).
  • 15  Marks DL, Ling N, Cone RD: Role of central melanocortin system in cachexia. Cancer Res.61,1432–1438 (2001).
  • 16  Billingsley KG, Fraker DL, Strassman G, Loeser C, Fliot HM, Alexander HR: Macrophage-derived tumor necrosis factor and tumor-derived leukaemia inhibitory factor and interleukin-6: possible cellular mechanisms of cancer cachexia. Ann. Surg. Oncol.3,29–35 (1996).
  • 17  Bing C, Bao U, Jenkins J et al.: Zinc-α2-glycoprotein, a lipid mobilising factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia. Proc. Natl Acad. Sci. USA101,2500–2505 (2004).▪▪ ZAG gene is expressed at high levels in the MAC16 tumor, liver and brown adipose tissue, and at a moderate level in heart, lung, skeletal muscle and epididymal white adipose tissue.
  • 18  Cariuk P, Lorite MJ, Todorov PT, Field WN, Wigmore SJ, Tisdale MJ: Induction of cachexia in mice by a product isolated from the urine of cachectic cancer patients. Br. J. Cancer76,606–613 (1997).
  • 19  Tisdale MJ: Mechanism of cancer cachexia. Physiol. Rev.89,381–340 (2009).
  • 20  Bing C, Russell S, Becket E et al.: Adipose atrophy in cancer cachexia morphologic and molecular analysis of adipose tissue in tumour-bearing mice. Br. J. Cancer95,1028–1037 (2006).
  • 21  Agustsson T, Ryden M, Hoffstedt J et al.: Mechanism of increased lipolysis in cancer cachexia. Cancer Res.67,5531–5537 (2007).▪▪ Lipolytic effects of catecholamines and natriuretic peptide were increased two- to three-fold in cachexia.
  • 22  Ryden M, Agustsson T, Laurencikiene J et al.: Lipolysis – not inflammation, cell death, or lipogenesis – is involved in adipose tissue loss in cancer cachexia. Cancer113,1695–1704 (2008).▪▪ Subcutaneous white adipose tissue does not contribute to the systemic inflammatory reaction.
  • 23  Drott C, Persson H, Lundholm K: Cardiovascular and metabolic response to adrenaline infusion in weight-losing patients with and without cancer. Clin. Physiol.9,427–439 (1989).
  • 24  Shaw JH, Wolfe RR: Fatty acid and glycerol kinetics in septic patients and in patients with gastrointestinal cancer. The response to glucose infusion and parenteral feeding. Ann. Surg.205,368–376 (1987).
  • 25  Islam-Ali B, Khan S, Price SA, Tisdale MJ: Modulation of adipocyte G-protein expression in cancer cachexia by a lipid-mobilising factor (LMF). Br. J. Cancer85,758–763 (2001).
  • 26  Thompson MP, Cooper ST, Parry BR, Tuckey JA: Increased expression of the mRNA for hormone-sensitive lipase in adipose tissue of cancer patients. Biochim. Biophys. Acta1180,236–242 (1993).
  • 27  Laurencikiene J, Stenson BM, Nordström EA et al.: Evidence for an important role of CIDEA in human cancer cachexia. Cancer Res.68,9247–9254 (2008).▪▪ CIDEA overexpression in vitro increased the oxidation of fatty acids and decreased the oxidation of glucose and increased the expression of PDK 1 and PDK4.
  • 28  Lundholm K, Daneryd P, Körner U, Hyltander A, Bosaeus I: Evidence that long-term COX-treatment improves energy homeostasis and body composition in cancer patients with progressive cachexia. Int. J. Oncol.24,505–512 (2004).
  • 29  Virtanen KA, Lidell ME, Orava J et al.: Functional brown adipose tissue in healthy adults. N. Eng. J. Med.360,1518–1525 (2009).▪▪ First recognition of functional brown adipose tissue in humans.
  • 30  Shellock FG, Riedinger MS, Fishbein MC: Brown adipose tissue in cancer patients: possible cause of cancer-induced cachexia. J. Cancer Res. Clin. Oncol.111,82–85 (1986).
  • 31  Collins P, Bing C, McCulloch P, Williams G: Muscle UCP-3 mRNA levels are elevated in weight loss associated with gastrointestinal adenocarcinoma in humans. Br. J. Cancer86,372–375 (2002).
  • 32  Beutler B, Cermai A: Cachectin and tumor necrosis factor as two sides of the same biological coin. Nature320,584–588 (1986).
  • 33  Hirai K, Hussey HJ, Barber MD, Price SA, Tisdale MJ: Biological evaluation of a lipid-mobilizing factor isolated from the urine of cancer patients. Cancer Res.58,2359–2365 (1998).▪▪ First evidence for identity of zinc-α2-glycoprotein and lipid-mobilizing factor and selective lipid loss in vivo.
  • 34  Zhang HH, Halbleib M, Ahmad F, Manganiello VC, Greenberg AS: Tumor necrosis factor-α stimulates lipolysis in differentiated human adipocytes through activation of extracellular signal-related kinase and elevation of intracellular cAMP. Diabetes51,2929–2935 (2002).▪▪ Provides evidence for direct lipolysis by TNF-α.
  • 35  Bing C, Russell ST, Beckett EE et al.: Expression of uncoupling proteins-1, -2 and -3 mRNA is induced by an adenocarcinoma-derived lipid-mobilising factor. Br. J. Cancer86,612–618 (2002).
  • 36  Busquets S, Sanchis D, Alvarez B, Ricquier D, Lopez-Soriano FJ, Argiles JM: In the rat, tumor necrosis factor α administration results in an increase in both UCP2 and UCP3 mRNA in skeletal muscle: a possible mechanism for cytokine-mediated thermogenesis? FEBS Lett.440,348–350 (1998).
  • 37  Sanders PM, Tisdale MJ: Effect of zinc-α2-glycoprotein (ZAG) on expression of uncoupling proteins in skeletal muscle and adipose tissue. Cancer Lett.212,71–81 (2004).
  • 38  Russell ST, Hirai K, Tisdale MJ: Role of β3-adrenergic receptors in the action of a tumor lipid mobilising factor. Br. J. Cancer86,424–428 (2002).▪▪ Lipid-mobilizing factor was found to bind to the β3-adrenergic receptor, but the binding affinity was 100-fold less than synthetic β3-agonists.
  • 39  Hyltander A, Daneryd P, Sandstrom R et al.: β-adrenoreceptor activity and resting energy metabolism in weight losing cancer patients. Eur. J. Cancer36,330–334 (2000).
  • 40  Mracek T, Ding Q, Tzanavati T et al.: The adipokine zinc-α2-glycoprotein is down reguated with fat mass expansion in obesity. Clin Endocrinol. DOI: 10.111/j.1365–2265.2009.0.3658.x (2010) (Epub ahead of print).
  • 41  Rolli V, Radosavljevic M, Astier V et al.: Lipolysis is altered in MHC class I zinc-α2-glycoprotein deficient mice. FEBS Lett.581,394–400 (2007).
  • 42  Bao Y, Bing C, Hunter L, Jenkins JR, Wabitsch M, Trayhurn P: zinc-α2-glycoprotein, a lipid mobilising factor, is expressed and secreted by human (SGBS) adipocytes. FEBS Lett.579,41–47 (2005).
  • 43  Khal J, Hine AV, Fearon KCH, Dejong CHC, Tisdale MJ: Increased expression of proteasome subunits in skeletal muscle of cancer patients with weight loss. Int. J. Biochem. Cell Biol.37,2196–2206 (2005).
  • 44  Eley HL, Skipworth RJE, Deans DAC, Fearon KCH, Tisdale MJ: Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2α may signal skeletal muscle atrophy in weight-losing cancer patients. Br. J. Cancer98,442–449 (2008).
  • 45  Emery PW, Edwards RHT, Rennie MJ, Souhami RL, Halliday D: Protein synthesis in muscle measured in vivo in cachectic patients with cancer. Br. Med. J.289,584–588 (1984).
  • 46  Eley HL, Tisdale MJ: Skeletal muscle atrophy, a link between depression of protein synthesis and increase in degradation. J. Biol. Chem.282,7087–7097 (2007).▪▪ Phosphorylation of PKR has been shown to be central to the depression of protein synthesis and increase in protein degradation in skeletal muscle.
  • 47  Llovera M, Lopez-Soriano FJ, Argiles JM: Effects of tumor necrosis factor-α on muscle protein turnover in female Wistar rats. J. Natl Cancer Inst.85,1334–1339 (1993).
  • 48  Tsujinaka T, Fujita J, Ebisui C et al.: Interleukin 6 receptor antibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice. J. Clin. Invest.97,244–249 (1996).
  • 49  Llovera M, Carbo N, Lopez-Soriano FJ et al.: Different cytokines modulate ubiquitin gene expression in rat skeletal muscle. Cancer Lett.13,83–87 (1998).▪▪ In vivo study showing that TNF-α and IFN-γ increase protein degradation in skeletal muscle through the ubiquitin–proteasome pathway, while IL-6 and leukemia-inhibitory factor do not.
  • 50  Batgalvis KA, Berger FG, Pena MMD, Davis JM, Muga SJ, Carson JA: Interleukin-6 and cachexia in ApcMin/+mice. Am. J. Physiol. Regul. Integr. Comp. Physiol.294,R393–R401 (2008).
  • 51  Garcia Martinez C, Llovera M, Agell N et al.: Ubiquitin gene expression in skeletal muscle is increased during sepsis. Involvement of TNF-α but not IL-1. Biochem. Biophys. Res. Commun.217,839–844 (1995).
  • 52  Lorite MJ, Smith HJ, Arnold JA, Morris A, Thompson MG, Tisdale MJ: Activation of ATP-ubiquitin-dependent proteolysis in skeletal muscle in vivo and murine myotubes in vitro by a proteolysis-inducing factor (PIF). Br. J. Cancer85,297–302 (2001).▪▪ Provides evidence for direct activation of the ubiquitin–proteasome pathway by proteolysis-inducing factor (PIF).
  • 53  Li Y-P, Chen Y, John J et al.: TNF-α acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin 1/MAFbx in skeletal muscle. FASEB J.19,362–370 (2005).
  • 54  Li Y-P, Schwartz RJ, Waddell ID, Holloway BR, Reid MB: Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-κB activation in response to tumor necrosis factor α. FASEB J.12,871–880 (1998).
  • 55  Russell ST, Eley H, Tisdale MJ: Role of reactive oxygen species in protein degradation in murine myotubes induced by proteolysis-inducing factor and angiotensin II. Cell. Sig.19,1797–1806 (2007).
  • 56  Eley HL, Russell ST, Tisdale MJ: Attenuation of depression of muscle protein synthesis induced by lipopolysaccharide, tumor necrosis factor, and angiotensin II by β-hydroxy-β-methylbutyrate. Am. J. Physiol. Endocrinol. Metab.295,E1409–E1416 (2008).▪▪ Provides evidence that TNF-α, lipopolysaccharide and angiotensin II depress protein synthesis in muscle by the same mechanism as PIF.
  • 57  Schwarzkopf M, Coletti D, Sassoon D, Marazzi G: Muscle cachexia is regulated by a p53-PW1/Peg3-dependent pathway. Genes Develop.20,3440–3452 (2006).
  • 58  Gutteridge DC, Mayo MW, Madrid LV, Wang CY, Baldwin AS Jr: NF-κB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science289,2363–2366 (2000).
  • 59  Ling PR, Schwartz JH, Bistrian BR: Mechanisms of host wasting induced by administration of cytokines in rats. Am. J. Physiol. Endocrinol. Metab.272,E333–E339 (1997).▪▪ Tissue wasting caused by cytokines includes a metabolic component, which is different from and additive to that caused by anorexia.
  • 60  Lorite MJ, Thompson MG, Drake JL, Carling G, Tisdale MJ: Mechanism of muscle protein degradation induced by a cancer cachectic factor. Br. J. Cancer78,850–856 (1998).
  • 61  Lorite MJ, Cariuk P, Tisdale MJ: Induction of muscle protein degradation by a tumour factor. Br. J. Cancer76,1035–1040 (1997).
  • 62  Llovera M, Lopez-Soriano FJ, Argiles JM: Effects of tumor necrosis factor-α on muscle protein-turnover in female Wistar rats. J. Natl Cancer Inst.85,1334–1339 (1993).
  • 63  Norton JA, Morley JF, Green MV et al.: Parabiotic transfer of cancer anorexia/cachexia in male rats. Cancer Res.45,5547–5552 (1985).
  • 64  Todorov P, Cariuk P, McDevitt T, Coles B, Fearon K, Tisdale M: Characterization of a cancer cachectic factor. Nature379,739–742 (1996).
  • 65  Todorov PT, Field WN, Tisdale MJ: Role of a proteolysis-inducing factor (PIF) in cachexia induced by a human melanoma (G361). Br. J. Cancer80,1734–1737 (1990).
  • 66  Monitto CL, Dong S-M, Jen J, Sidransky D: Characterization of a human homologue of proteolysis-inducing factor and its role in cancer cachexia. Clin. Cancer Res.10,5862–5869 (2004).
  • 67  Todorov PT, Deacon M, Tisdale MJ: Structural analysis of a tumor-produced sulfated glycoprotein capable of initiating muscle protein degradation. J. Biol. Chem.272,12279–12288 (1997).▪▪ Demonstrates that both the biological and immunological effects of PIF are mediated through the oligosaccharide chains, and that 85% of PIF is carbohydrate.
  • 68  Schittek B, Hipfel R, Sauer B et al.: Dermicidin: a novel human antibiotic peptide secreted by sweat glands. Immunol. Nat.2,1133–1137 (2001).
  • 69  Wang Z, Corey E, Hass GM et al.: Expression of the human cachexia-associated protein (HCAP) in prostate cancer and in a prostate cancer animal model of cachexia. Int. J. Cancer105,123–129 (2003).
  • 70  Wigmore SJ, Todorov PT, Barber MD, Ross JA, Tisdale MJ, Fearon KCH: Characteristics of patients with pancreatic cancer expressing a novel cancer cachectic factor. Br. J. Surg.87,53–58 (2000).
  • 71  Cabal-Manzano R, Bhargava P, Torres-Duarte A, Marshall J, Bhargava P, Wainer IW: Proteolysis-inducing factor is expressed in tumours of patients with gastrointestinal cancers and correlates with weight loss. Br. J. Cancer84,1599–1601 (2001).▪▪ Provides evidence that tumors are the source of PIF in humans.
  • 72  Williams ML, Torres-Duarte A, Brant LJ, Bhargava P, Marshall J, Wainer IW: The relationship between a urinary cachectic factor and weight loss in advanced cancer patients. Cancer Invest.22,866–870 (2004).
  • 73  Wieland BM, Stewart GD, Skipworth RJE et al.: Is there a human homologue to the murine proteolysis-inducing factor? Clin. Cancer Res.13,4984–4992 (2007).
  • 74  Kamoshida S, Watanabe, Suzuki M et al.: Expression of cancer cachexia-related factors in human cancer xenografts: an immunohistochemical analysis. Biomed. Res.27,275–281 (2006).
  • 75  Karayiannakis AJ, Syrigos KN, Polychronidis A et al.: Serum levels of tumor necrosis factor-α and nutritional status in pancreatic cancer patients. Anticancer Res.21,1355–1358 (2001).
  • 76  Bossola M, Muscaritoli M, Bellantone R et al.: Serum tumor necrosis factor-α levels in cancer patients correlate with weight loss. Eur. J. Clin. Invest.30,1107–1112 (2000).
  • 77  Ebrahimi B, Tuker SL, Li D et al.: Cytokines in pancreatic carcinoma. Cancer101,2727–2736 (2004).
  • 78  Socher SH, Martinez D, Craig JB, Kuhn JG, Oliff A: Tumor necrosis factor not detectable in patients with clinical cancer cachexia. J. Natl Cancer Inst.50,595–598 (1998).
  • 79  Maltoni M, Fabbri L, Nanni O et al.: Serum levels of tumour necrosis factor and other cytokines do not correlate with weight loss and anorexia in cancer patients. Support. Care Cancer5,130–135 (1997).
  • 80  Adami F, Guarini A, Pini M et al.: Serum levels of tumour necrosis factor-α in patients with B-cell chronic lymphocytic leukaemia. Eur. J. Cancer30A,1259–1263 (1994).
  • 81  McKeowa DJ, Brown DFJ, Kelly A et al.: The relationship between circulating concentrations of C-reactive protein, inflammatory cytokines and cytokine receptors in patients with nonsmall cell lung cancer. Br. J. Cancer91,1993–1995 (2004).
  • 82  Costelli P, Bossola M, Muscaritoli M et al.: Anticytokine treatment prevents the increase in the activity of the ATP-ubiquitin-and Ca2+-dependent proteolytic systems in the muscle of tumour-bearing rats. Cytokine19,1–5 (2002).
  • 83  Goldberg RM, Loprinzi CL, Malliard JA et al.: Pentoxyifylline for treatment of cancer anorexia and cachexia? A randomised, double-blind, placebo-controlled trial. J. Clin. Oncol.13,2856–2859 (1995).
  • 84  Costelli P, Carbo N, Tessitore L et al.: Tumor necrosis factor-α mediates changes in tissue protein turnover in a rat cancer cachexia model. J. Clin. Invest.92,2783–2789 (1993).
  • 85  Widenmann B, Malfertheiner P, Freiss H et al.: A multicenter Phase II study of infliximab plus gemcitabine in pancreatic cancer cachexia. J. Support. Oncol.6,18–25 (2008).▪▪ Antibody to TNF-α failed to attenuate cachexia in cancer patients.
  • 86  Wyke SM, Russell ST, Tisdale MJ: Induction of proteasome expression in skeletal muscle is attenuated by inhibitors of NF-κB activation. Br. J. Cancer91,1742–1750 (2004).
  • 87  Eley HL, Russell ST, Tisdale MJ: Attenuation of muscle atrophy in a murine model of cachexia by inhibition of the dsRNA-dependent protein kinase. Br. J. Cancer96,1216–1222 (2007).
  • 88  Eley HL, Russell ST, Tisdale MJ: Effect of branched-chain amino acids on muscle atrophy in cancer cachexia. Biochem. J.407,113–120 (2007).
  • 89  Russell ST, Siren PMA, Siren MJ, Tisdale MJ: Attenuation of skeletal muscle atrophy in cancer cachexia by D-myo-inositol 1, 2 6-triphosphate. Cancer Chemother. Pharmacol.64,517–527 (2009).▪▪ Provides evidence for a role of divalent metal ions in the cachectic process.
  • 90  Smith HJ, Mukerji P, Tisdale MJ: Attenuation of proteasome-induced proteolysis in skeletal muscle by β-hydroxy-β-methylbutyrate in cancer-induced muscle loss. Cancer Res.65,277–283 (2005).
  • 91  Beck SA, Smith KL, Tisdale MJ: Anticachectic and antitumour effect of eicosapentaenoic acid and its effect on protein turnover. Cancer Res.51,6089–6093 (1991).
  • 92  Todorov PT, Wyke SM, Tisdale MJ: Identification and characterisation of a membrance receptor for proteolysis-inducing factor in skeletal muscle. Cancer Res.67,11419–11427 (2007).
  • 93  Wigmore SJ, Barber MD, Ross JA, Tisdale MJ, Fearon KCH: Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer. Nutr. Cancer36,177–184 (2000).
  • 94  Fearon KCH, van Meyenfeldt MF, Moses AGW et al.: Effect of a protein and energy dense n-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut52,1479–1486 (2003).
  • 95  May PE, Barber A, D’Olimpio JT, Hourihane A, Abumrad NN: Reversal of cancer-related wasting using oral supplementation with a combination of β-hydroxy-β-methylbutyrate, arginine, and glutamine. Am. J. Surg.183,471–479 (2002).
  • 96  Deans DAC, Tan BHL, Ross JA et al.: Cancer cachexia is associated with the IL10-1082 gene promoter polymorphism in patients with gastroesophageal malignancy. Am. J. Clin. Nutr.89,1164–1172 (2009).▪▪ Suggests that some patients may be more susceptible to the development of cachexia due to polymorphisms of genes for some cytokines.
  • 97  Lainscak M, Podbregar M, Anker SD: How does cachexia influence survival in cancer, heart failure and other chronic diseases? Curr. Opin. Support. Pall. Care1,299–305 (2007).