Cancer cachexia: Impact, mechanisms and emerging treatments

Journal of Cachexia, Sarcopenia and Muscle

Volumn 4, Issue 2, 2013, Pages 95-109

  Vaughan, Vanessa C ^a   Martin, Peter ^a,b   Lewandowski, Paul A ^a  

^a DEAKIN UNIVERSITY   (Australia)

^b Palliative Care Services   (Australia)

Author keywords

Antioxidant; Cancer cachexia; Eicosapentaenoic acid; Oxidative stress; Oxypurinol

Indexed keywords

15 HYDROXYICOSATETRAENOIC ACID; ARACHIDONIC ACID; C REACTIVE PROTEIN; CARNITINE; CELECOXIB; GLUTATHIONE PEROXIDASE; IBUPROFEN; ICOSAPENTAENOIC ACID; INDOMETACIN; INTERLEUKIN 1; INTERLEUKIN 6; MEDROXYPROGESTERONE ACETATE; MEGESTROL ACETATE; MESSENGER RNA; OXIPURINOL; REACTIVE OXYGEN METABOLITE; SUPEROXIDE DISMUTASE; THALIDOMIDE; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; UNCOUPLING PROTEIN 2; UNCOUPLING PROTEIN 3; XANTHINE DEHYDROGENASE; XANTHINE OXIDASE;

ANOREXIA; APPETITE; AUTOPHAGY; BLOATING; CACHEXIA; CALORIC INTAKE; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER SURVIVAL; CELL METABOLISM; CONFORMATIONAL TRANSITION; CYTOKINE PRODUCTION; DECREASED APPETITE; DEPRESSION; DISEASE COURSE; DRUG MEGADOSE; EXERCISE; FOOD INTAKE; GLYCOGEN SYNTHESIS; HUMAN; INTESTINAL DYSMOTILITY; LEAN BODY WEIGHT; NONHUMAN; NUTRITIONAL STATUS; NUTRITIONAL SUPPORT; OXIDATIVE STRESS; PHYSICAL ACTIVITY; POLYPHARMACY; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN METABOLISM; PROTEIN SYNTHESIS; QUALITY OF LIFE; RESTING ENERGY EXPENDITURE; REVIEW; TASTE; TASTE DISORDER; UBIQUITINATION; VITAMIN SUPPLEMENTATION; WEIGHT REDUCTION;

EID: 84879199167     PISSN: 21905991     EISSN: 21906009     Source Type: Journal    
DOI: 10.1007/s13539-012-0087-1     Document Type: Review

References (206)

1. Fearon KCH, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12: 489-95.
2. Evans WJ, Morley JE, Argilés J, Bales C, Baracos V, Guttridge DC, et al. Cachexia: a new definition. Clin Nutr. 2008;27: 793-9.
3. Tisdale MJ. Cachexia in cancer patients. Nat Rev Cancer. 2002;2: 862-71.
4. Congleton J. The pulmonary cachexia syndrome: aspects of energy balance. Proc Nutr Soc. 1999;58: 321-8.
5. von Haehling S, Lainscak M, Springer J, Anker SD. Cardiac cachexia: a systematic overview. Pharmacol Ther. 2009;121: 227-52.
6. Springer J, von Haehling S, Anker SD. The need for a standardized definition for cachexia in chronic illness. Nat Clin Pract Endocrinol Metabol. 2006;2: 416-7.
7. Lainscak M, Filippatos GS, Gheorghiade M, Fonarow GC, Anker SD. Cachexia: common, deadly, with an urgent need for precise definition and new therapies. Am J Cardiol. 2008;101: 8E-10E.
8. Hopkinson JB, Wright DNM, McDonald JW, Corner JL. The prevalence of concern about weight loss and change in eating habits in people with advanced cancer. J Pain Symptom Manag. 2006;32: 322-31.
9. von Haehling S, Anker SD. Cachexia as a major underestimated and unmet medical need: facts and numbers. J Cachexia Sarcopenia Muscle. 2010;1: 1-5.
10. Diffee GM, Kalfas K, Al-Majid S, McCarthy DO. Altered expression of skeletal muscle myosin isoforms in cancer cachexia. Am J Physiol Cell Physiol. 2002;283: C1376-82.
11. Tijerina AJ. The biochemical basis of metabolism in cancer cachexia. Dimens Crit Care Nurs. 2004;23: 237-43.
12. Teunissen SCCM, Wesker W, Kruitwagen C, de Haes HCJM, Voest EE, de Graeff A. Symptom prevalence in patients with incurable cancer: a systematic review. J Pain Symptom Manag. 2007;34: 94-104.
13. Argilés JM. Cancer-associated malnutrition. Eur J Oncol Nurs. 2005;9 Suppl 2: S39-50.
14. Skipworth RJE, Stewart GD, Dejong CHC, Preston T, Fearon KCH. Pathophysiology of cancer cachexia: much more than host-tumour interaction? Clin Nutr. 2007;26: 667-76.
15. Giordano A, Calvani M, Petillo O, Carteni M, Melone MRAB, Peluso G. Skeletal muscle metabolism in physiology and in cancer disease. J Cell Biochem. 2003;90: 170-86.
16. Tisdale MJ. Cancer cachexia: metabolic alterations and clinical manifestations. Nutrition. 1997;13: 1-7.
17. Fouladiun M, Körner U, Bosaeus I, Daneryd P, Hyltander A, Lundholm KG. Body composition and time course changes in regional distribution of fat and lean tissue in unselected cancer patients on palliative care-correlations with food intake, metabolism, exercise capacity, and hormones. Cancer. 2005;103: 2189-98.
18. DeWys WD, Begg C, Lavin P, Band P. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Am J Med. 1980;69: 491-7.
19. Fearon KCH, Voss AC, Hustead DS. Cancer Cachexia Study Group. Definition of cancer cachexia: effect of weight loss, reduced food intake, and systemic inflammation on functional status and prognosis. Am J Clin Nutr. 2006;83: 1345-50.
20. Bachmann J, Heiligensetzer M, Krakowski-Roosen H, Büchler MW, Friess H, Martignoni ME. Cachexia worsens prognosis in patients with resectable pancreatic cancer. J Gastrointest Surg. 2008;12: 1193-201.
21. Ravasco P, Monteiro-Grillo I, Vidal PM, Camilo ME. Cancer: disease and nutrition are key determinants of patients' quality of life. Support Care Canc. 2004;12: 246-52.
22. Caissie A, Culleton S, Nguyen J, Zhang L. What QLQ-C15-PAL symptoms matter most for overall quality of life in patients with advanced cancer? World J Oncol. 2011;2: 166-74.
23. Fouladiun M, Körner U, Gunnebo L, Sixt-Ammilon P, Bosaeus I, Lundholm K. Daily physical-rest activities in relation to nutritional state, metabolism, and quality of life in cancer patients with progressive cachexia. Clin Cancer Res. 2007;13: 6379-85.
24. Muscaritoli M, Bossola M, Aversa Z, Bellantone R, Rossi Fanelli F. Prevention and treatment of cancer cachexia: new insights into an old problem. Eur J Cancer. 2006;42: 31-41.
25. Prado CMM, Baracos VE, McCargar LJ, Mourtzakis M, Mulder KE, Reiman T, et al. Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity. Clin Cancer Res. 2007;13: 3264-8.
26. Prado CMM, Baracos VE, McCargar LJ, Reiman T, Mourtzakis M, Tonkin K, et al. Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res. 2009;15: 2920-6.
27. Andreyev HJ, Norman AR, Oates J, Cunningham D. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies? Eur J Cancer. 1998;34: 503-9.
28. Fearon KCH. Cancer cachexia: developing multimodal therapy for a multidimensional problem. Eur J Cancer. 2008;44: 1124-32.
29. Lissoni P, Paolorossi F, Tancini G, Barni S, Ardizzoia A, Brivio F, et al. Is there a role for melatonin in the treatment of neoplastic cachexia? Eur J Cancer. 1996;32A: 1340-3.
30. Goldberg RM, Loprinzi CL, Mailliard JA, O'Fallon JR, Krook JE, Ghosh C, et al. Pentoxifylline for treatment of cancer anorexia and cachexia? A randomized, double-blind, placebo-controlled trial. J Clin Oncol. 1995;13: 2856-9.
31. McClement S. Cancer anorexia-cachexia syndrome: psychological effect on the patient and family. J Wound Ostomy Continence Nurs. 2005;32: 264-8.
32. Illman J, Corringham R, Robinson Jr D, Davis HM, Rossi J, Cella D, et al. Are inflammatory cytokines the common link between cancer-associated cachexia and depression? J Support Oncol. 2005;3: 37-50.
33. Chochinov HM. Depression in cancer patients. Lancet Oncol. 2001;2: 499-505.
34. Raison CL, Miller AH. Depression in cancer: new developments regarding diagnosis and treatment. Biol Psychiatry. 2003;54: 283-94.
35. Strasser F, Binswanger J, Cerny T, Kesselring A. Fighting a losing battle: eating-related distress of men with advanced cancer and their female partners. A mixed-methods study. Palliat Med. 2007;21: 129-37.
36. Reid J, McKenna H, Fitzsimons D, McCance T. Fighting over food: patient and family understanding of cancer cachexia. Oncol Nurs Forum. 2009;36: 439-45.
37. Reid J, McKenna H, Fitzsimons D, McCance T. The experience of cancer cachexia: a qualitative study of advanced cancer patients and their family members. Int J Nurs Stud. 2009;46: 606-16.
38. Hughes N, Neal RD. Adults with terminal illness: a literature review of their needs and wishes for food. J Adv Nurs. 2000;32: 1101-7.
39. Feuz A, Rapin C-H. An observational study of the role of pain control and food adaptation of elderly patients with terminal cancer. J Am Diet Assoc. 1994;94: 767-70.
40. Shragge JE, Wismer WV, Olson KL, Baracos VE. Shifting to conscious control: psychosocial and dietary management of anorexia by patients with advanced cancer. Palliat Med. 2007;21: 227-33.
41. McClement SE, Degner LF, Harlos M. Family responses to declining intake and weight loss in a terminally ill relative. Part 1: fighting back. J Palliat Care. 2004;20: 93-100.
42. Evans WK, Makuch R, Clamon GH, Feld R, Weiner RS, Moran E, et al. Limited impact of total parenteral nutrition on nutritional status during treatment for small cell lung cancer. Cancer Res. 1985;45: 3347-53.
43. 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. 1993;11: 152-4.
44. Simons JPFHA, Schols AMWJ, Hoefnagels JMJ, Westerterp KR, ten Velde GPM, Wouters EFM. Effects of medroxyprogesterone acetate on food intake, body composition, and resting energy expenditure in patients with advanced, nonhormone-sensitive cancer: a randomized, placebo-controlled trial. Cancer. 1998;82: 553-60.
45. Morley JE, Thomas DR, Wilson M-MG. Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr. 2006;83: 735-43.
46. Evans WK, Nixon DW, Daly JM, Ellenberg SS, Gardner L, Wolfe E, et al. A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer. J Clin Oncol. 1987;5: 113-24.
47. Ovesen L, Allingstrup L, Hannibal J, Mortensen EL, Hansen OP. Effect of dietary counseling on food intake, body weight, response rate, survival, and quality of life in cancer patients undergoing chemotherapy: a prospective, randomized study. J Clin Oncol. 1993;11: 2043-9.
48. Laviano A, Meguid MM, Rossi Fanelli F. Improving food intake in anorectic cancer patients. Curr Opin Clin Nutr Metab Care. 2003;6: 421-6.
49. Pascual López A, Roqué i Figuls M, Urrútia Cuchi G, Berenstein EG, Almenar Pasies B, Balcells Alegre M, et al. Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome. J Pain Symptom Manag. 2004;27: 360-9.
50. American College of Physicians, McGreer AJ, Detsky AS, O'Rourke K. Parenteral nutrition in patients receiving cancer chemotherapy. American College of Physicians. Ann Intern Med. 1989;110: 734-6.
51. Kotler DP. Nutritional alterations associated with HIV infection. J Acquir Immune Defic Syndr. 2000;25 Suppl 1: S81-7.
52. Barber MD. Cancer cachexia and its treatment with fish-oil-enriched nutritional supplementation. Nutrition. 2001;17: 751-5.
53. Bozzetti F, Gavazzi C, Mariani L, Crippa F. Artificial nutrition in cancer patients: which route, what composition? World J Surg. 1999;23: 577-83.
54. Bruera E, Sweeney C. Cachexia and asthenia in cancer patients. Lancet Oncol. 2000;1: 138-47.
55. Ravasco P, Monteiro-Grillo I, Vidal PM, Camilo ME. Dietary counseling improves patient outcomes: a prospective, randomized, controlled trial in colorectal cancer patients undergoing radiotherapy. J Clin Oncol. 2005;23: 1431-8.
56. Muscaritoli M, Molfino A, Gioia G, Laviano A, Rossi Fanelli F. The parallel pathway: a novel nutritional and metabolic approach to cancer patients. Int Emerg Med. 2011;6: 105-12.
57. DeWys WD, Walters K. Abnormalities of taste sensation in cancer patients. Cancer. 1975;36: 1888-96.
58. Nielsen SS, Theologides A, Vickers ZM. Influence of food odors on food aversions and preferences in patients with cancer. Am J Clin Nutr. 1980;33: 2253-61.
59. Ripamonti C, Zecca E, Brunelli C, Fulfaro F, Villa S, Balzarini A, et al. A randomized, controlled clinical trial to evaluate the effects of zinc sulfate on cancer patients with taste alterations caused by head and neck irradiation. Cancer. 1998;82: 1938-45.
60. Johnson FM. Alterations in taste sensation: a case presentation of a patient with end-stage pancreatic cancer. Canc Nurs. 2001;24: 149-55.
61. Ravasco P. Aspects of taste and compliance in patients with cancer. Eur J Oncol Nurs. 2005;9 Suppl 2: S84-91.
62. Wickham RS, Rehwaldt M, Kefer C, Shott S, Abbas K, Glynn-Tucker E, et al. Taste changes experienced by patients receiving chemotherapy. Oncol Nurs Forum. 1999;26: 697-706.
63. Sherry V. Taste alterations among patients with cancer. Clin J Oncol Nurs. 2002;6: 1-5.
64. Wright AL, King JC, Baer MT, Citron LJ. Experimental zinc depletion and altered taste perception for NaCl in young adult males. Am J Clin Nutr. 1981;34: 848-52.
65. Silverman JE, Weber CW, Silverman S, Coulthard SL, Manning MR. Zinc supplementation and taste in head and neck cancer patients undergoing radiation therapy. J Oral Med. 1983;38: 14-6.
66. Halyard MY, Jatoi A, Sloan JA, Bearden III JD, Vora SA, Atherton PJ, et al. Does zinc sulfate prevent therapy-induced taste alterations in head and neck cancer patients? Results of phase III double-blind, placebo-controlled trial from the North Central Cancer Treatment Group (N01C4). Int J Radiat Oncol Biol Phys. 2007;67: 1318-22.
67. Strasser F. The silent symptom early satiety: a forerunner of distinct phenotypes of anorexia/cachexia syndromes. Support Care Canc. 2006;14: 689-92.
68. Davis MP, Walsh D, Lagman R, Yavuzsen T. Early satiety in cancer patients: a common and important but underrecognized symptom. Support Care Canc. 2006;14: 693-8.
69. Dworzak F, Ferrari P, Gavazzi C, Maiorana C, Bozzetti F. Effects of cachexia due to cancer on whole body and skeletal muscle protein turnover. Cancer. 1998;82: 42-8.
70. Tisdale MJ. Loss of skeletal muscle in cancer: biochemical mechanisms. Front Biosci. 2001;6: D164-74.
71. Acharyya S, Ladner KJ, Nelsen LL, Damrauer J, Reiser PJ, Swoap S, et al. Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. J Clin Invest. 2004;114: 370-8.
72. Jeevanandam M, Horowitz GD, Lowry SF, Brennan MF. Cancer cachexia and protein metabolism. Lancet. 1984;1: 1423-6.
73. Fearon KC, Hansell DT, Preston T, Plumb JA, Davies J, Shapiro D, et al. Influence of whole body protein turnover rate on resting energy expenditure in patients with cancer. Cancer Res. 1988;48: 2590-5.
74. Rossi Fanelli F, Cangiano C, Muscaritoli M, Conversano L, Torelli GF, Cascino A. Tumor-induced changes in host metabolism: a possible marker of neoplastic disease. Nutrition. 1995;11: 595-600.
75. Holroyde CP, Gabuzda TG, Putnam RC, Paul P, Reichard GA. Altered glucose metabolism in metastatic carcinoma. Cancer Res. 1975;35: 3710-4.
76. Lieffers JR, Mourtzakis M, Hall KD, McCargar LJ, Prado CMM, Baracos VE. A viscerally driven cachexia syndrome in patients with advanced colorectal cancer: contributions of organ and tumor mass to whole-body energy demands. Am J Clin Nutr. 2009;89: 1173-9.
77. van Norren K, Kegler D, Argilés JM, Luiking Y, Gorselink M, Laviano A, et al. Dietary supplementation with a specific combination of high protein, leucine, and fish oil improves muscle function and daily activity in tumour-bearing cachectic mice. Br J Cancer. 2009;100: 713-22.
78. Knox LS, Crosby LO, Feurer ID, Buzby GP, Miller CL, Mullen JL. Energy expenditure in malnourished cancer patients. Ann Surg. 1983;197: 152-62.
79. Fredrix EW, Soeters PB, Wouters EF, Deerenberg IM, von Meyenfeldt MF, Saris WH. Effect of different tumor types on resting energy expenditure. Cancer Res. 1991;51: 6138-41.
80. Dempsey DT, Knox LS, Mullen JL, Miller C, Feurer ID, Buzby GP. Energy expenditure in malnourished patients with colorectal cancer. Arch Surg. 1986;121: 789-95.
81. Gibney E, Elia M, Jebb S, Murgatroyd P, Jennings G. Total energy expenditure in patients with small-cell lung cancer: results of a validated study using the bicarbonate-urea method. Metabolism. 1997;46: 1412-7.
82. Falconer JS, Ross JA, Fearon KCH, Hawkins RA, O'Riordain MG, Carter DC. Effect of eicosapentaenoic acid and other fatty acids on the growth in vitro of human pancreatic cancer cell lines. Br J Cancer. 1994;69: 826-32.
83. Zylicz Z, Schwantje O, Wagener DJ, Folgering HT. Metabolic response to enteral food in different phases of cancer cachexia in rats. Oncology. 1990;47: 87-91.
84. Cao D-X, Wu G-H, Zhang B, Quan Y-J, Wei J, Jin H, et al. Resting energy expenditure and body composition in patients with newly detected cancer. Clin Nutr. 2010;29: 72-7.
85. Fearon KCH, Barber MD, Falconer JS, McMillan DC, Ross JA, Preston T. Pancreatic cancer as a model: inflammatory mediators, acute-phase response, and cancer cachexia. World J Surg. 1999;23: 584-8.
86. Pepys MB, Hirschfield GM, Tennent GA, Gallimore JR, Kahan MC, Bellotti V, et al. Targeting C-reactive protein for the treatment of cardiovascular disease. Nature. 2006;440: 1217-21.
87. den Brekel AJ S-v, Dentener MA, Schols AM, Buurman WA, Wouters EF. Increased resting energy expenditure and weight loss are related to a systemic inflammatory response in lung cancer patients. J Clin Oncol. 1995;13: 2600-5.
88. Scott HR, McMillan DC, Crilly A, McArdle CS, Milroy R. The relationship between weight loss and interleukin 6 in non-small-cell lung cancer. Br J Cancer. 1996;73: 1560-2.
89. Blay JY, Negrier S, Combaret V, Attali S, Goillot E, Merrouche Y, et al. Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma. Cancer Res. 1992;52: 3317-22.
90. Falconer JS, Fearon KC, Ross JA, Elton R, Wigmore SJ, Garden OJ, et al. Acute-phase protein response and survival duration of patients with pancreatic cancer. Cancer. 1995;75: 2077-82.
91. O'Gorman P, McMillan D, McArdle C. Impact of weight loss, appetite, and the inflammatory response on quality of life in gastrointestinal cancer patients. Nutr Canc. 1998;32: 76-80.
92. Barber MD, Ross JA, Fearon KCH. Changes in nutritional, functional, and inflammatory markers in advanced pancreatic cancer. Nutr Canc. 1999;35: 106-10.
93. Reeds PJ, Fjeld CR, Jahoor F. Do the differences between the amino acid compositions of acute-phase and muscle proteins have a bearing on nitrogen loss in traumatic states? J Nutr. 1994;124: 906-10.
94. Barber MD, Fearon KC, McMillan DC, Slater C, Ross JA, Preston T. Liver export protein synthetic rates are increased by oral meal feeding in weight-losing cancer patients. Am J Physiol Endocrinol Metab. 2000;279: E707-14.
95. Argilés JM, Busquets S, Toledo M, López-Soriano FJ. The role of cytokines in cancer cachexia. Curr Opin Support Palliat Care. 2009;3: 263-8.
96. MacDonald N, Easson AM, Mazurak VC, Dunn GP, Baracos VE. Understanding and managing cancer cachexia. J Am Coll Surg. 2003;197: 143-61.
97. Ross JA, Fearon KCH. Eicosanoid-dependent cancer cachexia and wasting. Curr Opin Clin Nutr Metab Care. 2002;5: 241-8.
98. Tisdale MJ. The 'cancer cachectic factor'. Support Care Canc. 2003;11: 73-8.
99. Baracos VE, Mazurak VC, Ma DWL. n-3 Polyunsaturated fatty acids throughout the cancer trajectory: influence on disease incidence, progression, response to therapy and cancer-associated cachexia. Nutr Res Rev. 2004;17: 177-92.
100. Tisdale MJ. Biology of cachexia. J Natl Canc Inst. 1997;89: 1763-73.
101. Barber MD, Fearon KCH, Tisdale MJ, McMillan DC, Ross JA. Effect of a fish oil-enriched nutritional supplement on metabolic mediators in patients with pancreatic cancer cachexia. Nutr Canc. 2001;40: 118-24.
102. 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. 1988;80: 595-8.
103. Todorov PT, Cariuk P, McDevitt TM, Coles B, Fearon KCH, Tisdale MJ. Characterization of a cancer cachectic factor. Nature. 1996;.
104. Todorov PT, Deacon M, Tisdale MJ. Structural analysis of a tumor-produced sulfated glycoprotein capable of initiating muscle protein degradation. J Biol Chem. 1997;272: 12279-88.
105. 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. 2000;87: 53-8.
106. Tisdale MJ. Molecular pathways leading to cancer cachexia. Physiology. 2005;20: 340-8.
107. Lorite MJ. Activation of ATP-ubiquitin-dependent proteolysis in skeletal muscle in vivo and murine myoblasts in vitro by a proteolysis-inducing factor (PIF). Br J Cancer. 2001;85: 297-302.
108. 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 Cancer. 1997;76: 606-13.
109. Watchorn TM, Waddell I, Dowidar N, Ross JA. Proteolysis-inducing factor regulates hepatic gene expression via the transcription factors NF-(kappa)B and STAT3. FASEB J. 2001;15: 562-4.
110. Baracos VE. Reply to letter to the editor: a response to the letter of M. Tisdale. Clin Cancer Res. 2008;14: 2245-5.
111. Wieland BM, Stewart GD, Skipworth RJE, Sangster K, Fearon KCH, Ross JA, et al. Is there a human homologue to the murine proteolysis-inducing factor? Clin Cancer Res. 2007;13: 4984-92.
112. Monitto CL, Dong SM, Jen J, Sidransky D. Characterization of a human homologue of proteolysis-inducing factor and its role in cancer cachexia. Clin Cancer Res. 2004;10: 5862-9.
113. Tada T, Ohkubo I, Niwa M, Sasaki M, Tateyama H, Eimoto T. Immunohistochemical localization of Zn-alpha 2-glycoprotein in normal human tissues. J Histochem Cytochem. 1991;39: 1221-6.
114. Hale LP, Price DT, Sanchez LM, Demark-Wahnefried W, Madden JF. Zinc alpha-2-glycoprotein is expressed by malignant prostatic epithelium and may serve as a potential serum marker for prostate cancer. Clin Cancer Res. 2001;7: 846-53.
115. Díez-Itza I, Sánchez LM, Allende MT, Vizoso F, Ruibal A, López-Otín C. Zn-alpha 2-glycoprotein levels in breast cancer cytosols and correlation with clinical, histological and biochemical parameters. Eur J Cancer. 1993;29A: 1256-60.
116. Rydén M, Agustsson T, Andersson J, Bolinder J, Toft E, Arner P. Adipose zinc-2-glycoprotein is a catabolic marker in cancer and noncancerous states. J Intern Med. 2012;271: 414-20.
117. Islam-Ali BS, Tisdale MJ. Effect of a tumour-produced lipid-mobilizing factor on protein synthesis and degradation. Br J Cancer. 2001;84: 1648-55.
118. Tisdale MJ. Mechanisms of cancer cachexia. Physiol Rev. 2009;89:381-410.
119. Bandyopadhyay U, Das D, Banerjee RK. Reactive oxygen species: oxidative damage and pathogenesis. Curr Sci. 1999;77: 658-66.
120. Arthur PG, Grounds MD, Shavlakadze T. Oxidative stress as a therapeutic target during muscle wasting: considering the complex interactions. Curr Opin Clin Nutr Metab Care. 2008;11: 408-16.
121. Barreiro E, de la Puente B, Busquets S, López-Soriano FJ, Gea J, Argilés JM. Both oxidative and nitrosative stress are associated with muscle wasting in tumour-bearing rats. FEBS Lett. 2005;579: 1646-52.
122. 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 Signal. 2007;19: 1797-806.
123. Rubin H. Cancer cachexia: its correlations and causes. Proc Natl Acad Sci USA. 2003;100: 5384-9.
124. Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39: 44-84.
125. Sullivan-Gunn MJ, Campbell-O'Sullivan SP, Tisdale MJ, Lewandowski PA. Decreased NADPH oxidase expression and antioxidant activity in cachectic skeletal muscle. J Cachexia Sarcopenia Muscle. 2011;2: 181-8.
126. Gauss KA, Nelson-Overton LK, Siemsen DW, Gao Y, DeLeo FR, Quinn MT. Role of NF-kappaB in transcriptional regulation of the phagocyte NADPH oxidase by tumor necrosis factor-alpha. J Leukoc Biol. 2007;82: 729-41.
127. Groemping Y, Rittinger K. Activation and assembly of the NADPH oxidase: a structural perspective. Biochem J. 2005;386: 401-16.
128. Frey RS, Ushio Fukai M, Malik AB. NADPH oxidase-dependent signaling in endothelial cells: role in physiology and pathophysiology. Antioxidants & Redox Signal. 2009;11: 791-810.
129. Meneshian A, Bulkley GB. The physiology of endothelial xanthine oxidase: from urate catabolism to reperfusion injury to inflammatory signal transduction. Microcirculation. 2002;9: 161-75.
130. Kono H, Chen C-J, Ontiveros F, Rock KL. Uric acid promotes an acute inflammatory response to sterile cell death in mice. J Clin Invest. 2010;120: 1939-49.
131. Doehner W, Rauchhaus M, Florea VG, Sharma R, Bolger AP, Davos CH, et al. Uric acid in cachectic and noncachectic patients with chronic heart failure: relationship to leg vascular resistance. Am Hear J. 2001;141: 792-9.
132. Pasupathi P, Ramachandran T, Sindhu P, Saravanan G, Bakthavathsalam G. Enhanced oxidative stress markers and antioxidant imbalance in HIV infection and AIDS patients. J Sci Res. 2009;1: 370-80.
133. Smith JK, Carden DL, Korthuis RJ. Role of xanthine oxidase in postischemic microvascular injury in skeletal muscle. Am J Physiol. 1989;257: H1782-9.
134. Kaynar H, Meral M, Turhan H, Keles M, Celik G, Akcay F. Glutathione peroxidase, glutathione-S-transferase, catalase, xanthine oxidase, Cu-Zn superoxide dismutase activities, total glutathione, nitric oxide, and malondialdehyde levels in erythrocytes of patients with small cell and non-small cell lung cancer. Cancer Lett. 2005;227: 133-9.
135. Ryan MJ, Jackson JR, Hao Y, Leonard SS, Alway SE. Inhibition of xanthine oxidase reduces oxidative stress and improves skeletal muscle function in response to electrically stimulated isometric contractions in aged mice. Free Radic Biol Med. 2011;51: 38-52.
136. Hellsten Y, Frandsen U, Orthenblad N, Sjödin B, Richter EA. Xanthine oxidase in human skeletal muscle following eccentric exercise: a role in inflammation. J Physiol. 1997;498: 239-48.
137. Mantovani G, Maccio A, Madeddu C, Mura L, Gramignano G, Lusso MR, et al. Antioxidant agents are effective in inducing lymphocyte progression through cell cycle in advanced cancer patients: assessment of the most important laboratory indexes of cachexia and oxidative stress. J Mol Med. 2003;81: 664-73.
138. Williams A, Sun X, Fischer JE, Hasselgren PO. The expression of genes in the ubiquitin-proteasome proteolytic pathway is increased in skeletal muscle from patients with cancer. Surgery. 1999;126: 744-9. discussion 749-50.
139. Costelli P, Tullio RD, Baccino FM, Melloni E. Activation of Ca(2+)-dependent proteolysis in skeletal muscle and heart in cancer cachexia. Br J Cancer. 2001;84: 946-50.
140. Costelli P, Bossola M, Muscaritoli M, Grieco G. Anticytokine treatment prevents the increase in the activity of ATP-ubiquitin-and Ca2 + -dependent proteolytic systems in the muscle of tumour-bearing rats. Cytokine. 2002;19: 1-5.
141. Langhans W. Peripheral mechanisms involved with catabolism. Curr Opin Clin Nutr Metab Care. 2002;5: 419-26.
142. Costelli P, Baccino FM. Mechanisms of skeletal muscle depletion in wasting syndromes: role of ATP-ubiquitin-dependent proteolysis. Curr Opin Clin Nutr Metab Care. 2003;6: 407-12.
143. Cohen S, Brault JJ, Gygi SP, Glass DJ, Valenzuela DM, Gartner C, et al. During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation. J Cell Biol. 2009;185: 1083-95.
144. Cosper PF, Leinwand LA. Myosin heavy chain is not selectively decreased in murine cancer cachexia. Int J Cancer. 2011;130: 2722-7.
145. Rolland Y, Lauwers-Cances V, Cesari M, Vellas B, Pahor M, Grandjean H. Physical performance measures as predictors of mortality in a cohort of community-dwelling older French women. Eur J Epidemiol. 2006;21: 113-22.
146. Gale CR, Martyn CN, Cooper C, Sayer AA. Grip strength, body composition, and mortality. Int J Epidemiol. 2007;36: 228-35.
147. Evans WJ, Lambert CP. Physiological basis of fatigue. Am J Phys Med Rehabil. 2007;86: S29-46.
148. Cella D, Lai J-S, Chang C-H, Peterman A, Slavin M. Fatigue in cancer patients compared with fatigue in the general United States population. Cancer. 2002;94: 528-38.
149. Anker SD, Swan JW, Volterrani M, Chua TP, Clark AL, Poole-Wilson PA, et al. The influence of muscle mass, strength, fatigability and blood flow on exercise capacity in cachectic and non-cachectic patients with chronic heart failure. Eur Heart J. 1997;18: 259-69.
150. Tan BHL, Birdsell LA, Martin L, Baracos VE, Fearon KCH. Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res. 2009;15: 6973-9.
151. Bossola M, Muscaritoli M, Costelli P, Grieco G, Bonelli G, Pacelli F, et al. Increased muscle proteasome activity correlates with disease severity in gastric cancer patients. Ann Surg. 2003;237: 384-9.
152. Khal J, Wyke SM, Russell ST, Hine AV, Tisdale MJ. Expression of the ubiquitin-proteasome pathway and muscle loss in experimental cancer cachexia. Br J Cancer. 2005;93: 774-80.
153. 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. 2005;37: 2196-206.
154. Wyke SM, Tisdale MJ. NF-kappaB mediates proteolysis-inducing factor induced protein degradation and expression of the ubiquitin-proteasome system in skeletal muscle. Br J Cancer. 2005;92: 711-21.
155. Bossola M, Muscaritoli M, Costelli P, Bellantone R, Pacelli F, Busquets S, et al. Increased muscle ubiquitin mRNA levels in gastric cancer patients. Am J Physiol Reg I. 2001;280: R1518-23.
156. Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002;82: 373-428.
157. Solomon V, Baracos V, Sarraf P, Goldberg AL. Rates of ubiquitin conjugation increase when muscles atrophy, largely through activation of the N-end rule pathway. Proc Natl Acad Sci USA. 1998;95: 12602-7.
158. Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science. 2001;294: 1704-8.
159. Lecker SH, Jagoe RT, Gilbert A, Gomes M, Baracos V, Bailey J, et al. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J. 2004;18: 39-51.
160. Muscaritoli M, Bossola M, Doglietto GB, Fanelli FR. The ubiquitin/proteasome system in cancer cachexia. In: Mantovani G, Anker SD, et al., editors. Cachexia and wasting: a modern approach. Italy: Springer; 2006.
161. de Palma L, Marinelli M, Pavan M, Orazi A. Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy. Joint Bone Spine. 2007;75: 53-7.
162. Fischer D. The gene expression of ubiquitin ligase E3α is upregulated in skeletal muscle during sepsis in rats-potential role of glucocorticoids. Biochem Biophys Res Commun. 2000;267: 504-8.
163. Jatoi A, Alberts SR, Foster N, Morton R, Burch P, Block M, et al. Is bortezomib, a proteasome inhibitor, effective in treating cancer-associated weight loss? Preliminary results from the North Central Cancer Treatment Group. Support Care Canc. 2005;13: 381-6.
164. Wiedenmann B, Malfertheiner P, Friess H, Ritch P, Arseneau J, Mantovani G, et al. A multicenter, phase II study of infliximab plus gemcitabine in pancreatic cancer cachexia. J Support Oncol. 2008;6: 18-25.
165. Jatoi A, Ritter HL, Dueck A, Nguyen PL, Nikcevich DA, Luyun RF, et al. A placebo-controlled, double-blind trial of infliximab for cancer-associated weight loss in elderly and/or poor performance non-small cell lung cancer patients (N01C9). Lung Cancer. 2010;68: 234-9.
166. Smith IJ, Aversa Z, Hasselgren P, Pacelli F, Rosa F, Doglietto GB, et al. Calpain activity is increased in skeletal muscle from gastric cancer patients with no or minimal weight loss. Muscle Nerve. 2011;43: 410-4.
167. Jagoe RT, Redfern CP, Roberts RG, Gibson GJ, Goodship TH. Skeletal muscle mRNA levels for cathepsin B, but not components of the ubiquitin-proteasome pathway, are increased in patients with lung cancer referred for thoracotomy. Clin Sci. 2002;102: 353-61.
168. Op den Kamp CM, Langen RC, Minnaard R, Kelders MC, den CM OdK, et al. Pre-cachexia in patients with stages IIII non-small cell lung cancer: systemic inflammation and functional impairment without activation of skeletal muscle ubiquitin proteasome system. Lung Cancer. 2012;76: 112-7.
169. Paul PK, Gupta SK, Bhatnagar S, Panguluri SK, Darnay BG, Choi Y, et al. Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice. J Cell Biol. 2010;191: 1395-411.
170. Sandri SM. Autophagy in skeletal muscle. FEBS Lett. 2010;584: 1411-6.
171. Muscaritoli M, Bossola M, Bellantone R, Fanelli FR. Therapy of muscle wasting in cancer: what is the future? Curr Opin Clin Nutr Metab Care. 2004;7: 459-66.
172. Sacheck JM, Ohtsuka A, McLary SC, Goldberg AL. IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1. Am J Physiol Endocrinol Metab. 2004;287: E591-601.
173. McMillan DC, O'Gorman P, Fearon KCH, McArdle CS. A pilot study of megestrol acetate and ibuprofen in the treatment of cachexia in gastrointestinal cancer patients. Br J Cancer. 1997;76: 788-90.
174. Preston T, Fearon KC, McMillan DC, Winstanley FP, Slater C, Shenkin A, et al. Effect of ibuprofen on the acute-phase response and protein metabolism in patients with cancer and weight loss. Br J Surg. 1995;82: 229-34.
175. McMillan DC, Wigmore SJ, Fearon KCH, O'Gorman P, Wright CE, McArdle CS. A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss. Br J Cancer. 1999;79: 495-500.
176. Lundholm K, Gelin J, Hyltander A, Lönnroth C, Sandström R, Svaninger G, et al. Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors. Cancer Res. 1994;54: 5602-6.
177. Wigmore SJ, Falconer JS, Plester CE, Ross JA, Maingay JP, Carter DC, et al. Ibuprofen reduces energy expenditure and acute-phase protein production compared with placebo in pancreatic cancer patients. Br J Cancer. 1995;72: 185-8.
178. Mantovani G, Madeddu C. Cyclooxygenase-2 inhibitors and antioxidants in the treatment of cachexia. Curr Opin Support Palliat Care. 2008;2: 275-81.
179. Mantovani G, Maccio A, Madeddu C, Gramignano G, Lusso MR, Serpe R, et al. A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress. Canc Epidemiol Biomarkers Prev. 2006;15: 1030-4.
180. Mantovani G, Maccio A, Madeddu C, Serpe R, Massa E, Dessi M, et al. Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia. Oncologist. 2010;15: 200-11.
181. Maggiore RJ, Gross CP, Hurria A. Polypharmacy in older adults with cancer. Oncologist. 2010;15: 507-22.
182. Madeddu C, Dessì M, Panzone F, Serpe R, Antoni G, Cau MC, et al. Randomized phase III clinical trial of a combined treatment with carnitine + celecoxibmegestrol acetate for patients with cancer-related anorexia/cachexia syndrome. Clin Nutr. 2012;31: 176-82.
183. Burns CP, Halabi S, Clamon GH, Hars V, Wagner BA, Hohl RJ, et al. Phase I clinical study of fish oil fatty acid capsules for patients with cancer cachexia: cancer and leukemia group B study 9473. Clin Cancer Res. 1999;5: 3942-7.
184. Barber MD, Fearon KC. Tolerance and incorporation of a high-dose eicosapentaenoic acid diester emulsion by patients with pancreatic cancer cachexia. Lipids. 2001;36: 347-51.
185. Murphy RA, Mourtzakis M, Chu QSC, Baracos VE, Reiman T, Mazurak VC. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer. 2011;117: 3774-80.
186. Wigmore SJ, Ross JA, Falconer JS, Plester CE, Tisdale MJ, Carter DC, et al. The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer. Nutrition. 1996;12: S27-30.
187. Wigmore SJ, Fearon KCH, Maingay JP, Ross JA. Down-regulation of the acute-phase response in patients with pancreatic cancer cachexia receiving oral eicosapentaenoic acid is mediated via suppression of interleukin-6. Clin Sci. 1997;92: 215-21.
188. Donohoe CL, Ryan AM, Reynolds JV. Cancer cachexia: mechanisms and clinical implications. Gastroenterol Res Pract. 2011;2011: 1-13.
189. Smith HJ, Tisdale MJ. Induction of apoptosis by a cachectic-factor in murine myotubes and inhibition by eicosapentaenoic acid. Apoptosis. 2003;8: 161-9.
190. Whitehouse AS, Tisdale MJ. Increased expression of the ubiquitin-proteasome pathway in murine myotubes by proteolysis-inducing factor (PIF) is associated with activation of the transcription factor NF-kappaB. Br J Cancer. 2003;89: 1116-22.
191. Bhoj VG, Chen ZJ. Ubiquitylation in innate and adaptive immunity. Nature. 2009;458: 430-7.
192. Whitehouse AS, Smith HJ, Drake JL, Tisdale MJ. Mechanism of attenuation of skeletal muscle protein catabolism in cancer cachexia by eicosapentaenoic acid. Cancer Res. 2001;61: 3604-9.
193. Wigmore SJ, Barber MD, Ross JA, Tisdale MJ, Fearon KCH. Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer. Nutr Canc. 2000;36: 177-84.
194. Jatoi A, Rowland K, Loprinzi CL, Sloan JA, Dakhll SR, MacDonald N, et al. An eicosapentaenoic acid supplement versus megestrol acetate versus both for patients with cancer-associated wasting: a North Central Cancer Treatment Group and National Cancer Institute of Canada collaborative effort. J Clin Oncol. 2004;22: 2469-76.
195. Li M, Zhu Q, Hu C, Giesy JP, Kong Z, Cui Y. Protective effects of eicosapentaenoic acid on genotoxicity and oxidative stress of cyclophosphamide in mice. Environ Toxicol. 2011;26: 217-23.
196. Russell ST, Tisdale MJ. The role of glucocorticoids in the induction of zinc-alpha2-glycoprotein expression in adipose tissue in cancer cachexia. Br J Cancer. 2005;92: 876-81.
197. Barber MD, McMillan DC, Preston T, Ross JA, Fearon KCH. Metabolic response to feeding in weight-losing pancreatic cancer patients and its modulation by a fish-oil-enriched nutritional supplement. Clin Sci. 2000;98: 389-99.
198. Barber MD, Ross JA, Preston T, Shenkin A, Fearon KCH. Fish oil-enriched nutritional supplement attenuates progression of the acute-phase response in weight-losing patients with advanced pancreatic cancer. J Nutr. 1999;129: 1120-5.
199. Laviano A, Muscaritoli M, Rossi Fanelli F. Phase II study of high-dose fish oil capsules for patients with cancer-related cachexia: a Cancer and Leukemia Group B study. Cancer. 2005;103: 651-2.
200. Tiryaki-Sönmez G, Schoenfeld B, Vatansever-Ozen S. Omega-3 fatty acids and exercise: a review of their combined effects on body composition and physical performance. Biomed Hum Kinet. 2011;3: 23-9.
201. Penna F, Busquets S, Pin F, Toledo M, Baccino FM, López-Soriano FJ, et al. Combined approach to counteract experimental cancer cachexia: eicosapentaenoic acid and training exercise. J Cachexia Sarcopenia Muscle. 2011;2: 95-104.
202. Pacher P, Nivorozhkin A, Szabó C. Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev. 2006;58: 87-114.
203. Springer J, Hartmann A, Palus S, Adams V, von Harsdorf R, Anker SD, et al. The xanthine oxidase inhibitors oxypurinol and allopurinol reduce wasting and improve cardiac function in experimental cancer cachexia. J Card Fail. 2009;15: S22-2.
204. Day RO, Graham GG, Hicks M, McLachlan AJ, Stocker SL, Williams KM. Clinical pharmacokinetics and pharmacodynamics of allopurinol and oxypurinol. Clin Pharmacokinet. 2007;46: 623-44.
205. Deby C, Deby-Dupont G, Noël FX, Lavergne L. In vitro and in vivo arachidonic acid conversions into biologically active derivatives are enhanced by uric acid. Biochem Pharmacol. 1981;30: 2243-9.
206. von Haehling S, Morley JE, Coats AJ, Anker SD. Ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle. J Cachexia Sarcopenia Muscle. 2010;1:7-8.