Novel treatments for cancer cachexia

Expert Opinion on Investigational Drugs

Volumn 16, Issue 8, 2007, Pages 1241-1253

  Bossola, Maurizio ^a   Pacelli, Fabio ^a   Doglietto, Giovan Battista ^a  

^a CATHOLIC UNIVERSITY   (Italy)

Author keywords

Anorexia; Cancer cachexia; Existing therapies; Novel treatments

Indexed keywords

AH 130; ANABOLIC AGENT; APPETITE STIMULANT; CALPASTATIN; CANNABINOID; CYTOKINE; FISH OIL; GHRELIN; GLYCOGEN SYNTHASE KINASE 3 INHIBITOR; GLYCOGEN SYNTHASE KINASE 3BETA INHIBITOR; HORMONE RECEPTOR BLOCKING AGENT; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; I KAPPA B; ICOSAPENTAENOIC ACID; INTERLEUKIN 6; MEGESTROL ACETATE; MELANOCORTIN RECEPTOR 3 ANTAGONIST; MELANOCORTIN RECEPTOR 4 ANTAGONIST; MELATONIN; MYOSTATIN; PENTOXIFYLLINE; PLACEBO; PROTEIN KINASE INHIBITOR; PROTEIN KINASE R INHIBITOR; SODIUM CHLORIDE; SOMATOMEDIN C; SURAMIN; THALIDOMIDE; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; UBIQUITIN; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANOREXIA; ANTIINFLAMMATORY ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTIFICIAL FEEDING; CACHEXIA; CALORIC INTAKE; CANCER; CANCER MORTALITY; CLINICAL FEATURE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; COST EFFECTIVENESS ANALYSIS; CYTOKINE PRODUCTION; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG MECHANISM; ENZYME ACTIVITY; FOOD INTAKE; GENE THERAPY; GENE TRANSFER; HOSPITALIZATION; HUMAN; METASTASIS; MORBIDITY; MUSCLE ATROPHY; NITROGEN BALANCE; NONHUMAN; NUTRITIONAL STATUS; PANCREAS CANCER; PERITONEAL DIALYSIS; PHENOTYPE; PROGNOSIS; PROTEIN DEGRADATION; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; REVIEW; UNSPECIFIED SIDE EFFECT; VISUAL ANALOG SCALE; WEIGHT GAIN;

ANIMALS; ANTINEOPLASTIC AGENTS; CACHEXIA; DRUGS, INVESTIGATIONAL; HUMANS; NEOPLASMS;

EID: 34548201879     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.16.8.1241     Document Type: Review

References (125)

1. MUSCARITOLI M, BOSSOLA M, AVERSA Z et al.: Prevention and treatment of cancer cachexia: new insights into and old problem. Eur. J. Cancer (2006) 42:31-41.
2. MACDONALD N, EASSON AM, MAZURAK VC et al.: Understanding and managing cancer cachexia. J. Am. Coll. Surg. (2003) 197:143-161.
3. LAVIANO A, MEGUID MM, ROSSI FANELLI F: Cancer anorexia: clinical implications, pathogenesis, and therapeutic strategies. Lancet Oncol. (2003) 4:686-694.
4. DEMPSEY DT, KNOX LS, MULLEN JL et al.: Energy expenditure in malnourished patients with colorectal cancer. Arch. Surg. (1996) 121:789-795.
5. GIBNEY E, ELIA M, JEBB SA et al.: Total energy expenditure in patients with non small-cell lung cancer: results of a validated study using the bicarbonate-urea method. Metabolism (1997) 46:1412-1417.
6. THOMPSON MP, COOPER ST, PARRY BR et al.: Increased expression of the mRNA for hormone-sensitive lipase in adipose tissue of cancer patients. Biochem. Biophys. Acta (1993) 1180:236-242.
7. TODOROV P, CARIUK E MCDEVITT T et al.: Characterization of a cancer cachectic factor. Nature (1996) 379:739-742.
8. ACHARYYA S, GUTTRIDGE DC: Cancer cachexia signalling pathways continue to emerge yet much still points to the proteasome. Clin. Cancer Res. (2007) 13:1356-1361.
9. WILLIAMS AB, DECOURTEN-MYERS GM, FISCHER JE et al.: Sepsis stimulates release of myofilaments in skeletal muscle by a calcium-dependent mechanism. FASEB J. (1999) 13:1435-1443.
10. COSTELLI P, TULLIO RD, BACCINO FM et al.: Activation of Ca(2+)-dependent proreolysis in skeletal muscle and heart in cancer cachexia. Br. J Cancer (2001) 84:946-950.
11. COSTELLI P, BOSSOLA M, MUSCARITOLI M et al.: Anticytokine treatment prevents the increase in the activity of ATP-ubiquirin- and Ca(2+)-dependent proteolytic systems in the muscle of turnour-bearing rats. Cytokine (2002) 19:1-5.
12. 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) 6:407-412.
13. BOSSOLA M, MUSCARITOLI M, COSTELLI P et al.: Increased muscle ubiquitin mRNA levels in gastric cancer patients. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2001) 280:R1518-R1523.
14. BOSSOLA M, MUSCARITOLI M, COSTELLI P et al.: Increased muscle proteasome activity correlates whit disease severity in gastric cancer patients. Ann. Surg. (2003) 237:384-389.
15. BODINE SC, LATRES E, BAUMHUETER S et al.: Identification of ubiquitin ligases required for skeletal muscle atrophy. Science (2001) 294:1704-1708.
16. GUTTRIDGE DC, MAYO MW, MADRID LV et al.: NF-κB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science (2000) 289:2363-2366.
17. COSTELLI P, MUSCARITOLI M, BOSSOLA M et al.: Skeletal muscle wasting in turnour-bearing rats is associated with MyoD down-regulation. Int. J. Oncol. (2005) 26:1663-1668.
18. PENNA F, REFFO P, SONETTO A et al.: Myostatin expression is up-regulated in cancer cachexia. 27th ESPEN Congress, 27 - 30 August 2005 (Abstract P299).
19. KAMBADUR R, SHARMA M, SMITH TP, BASS JJ: Mutations in myostatin (GDF8) in double-muscled Belgian blue and piedmontese cattle. Genome Res. (1997) 7:910-916.
20. SZABO G, DALLMANN G, MULLER G et al.: A deletion in the myostatin gene causes the compact (Cmpt) hypermuscular mutation in mice. Mamm. Genome (1998) 9:671-672.
21. ZIMMERS TA, DAVIES MV, KONIARIS LG et al.: Induction of cachexia in mice by systemically administered myostatin. Science (2002) 296:1486-1488.
22. MCCROSKERY S, THOMAS M, MAXWELL L et al.: Myoscatin negatively regulates satellite cell activation and self-renewal. J. Cell Biol. (2003) 162:1135-1147.
23. LANGLEY B, THOMAS M, BISHOP A et al.: Myostatin inhibits myoblast differentiation by down-regulating MyoD expression. J. Biol. Chem. (2002) 277:49831-49840.
24. GONZALEZ-CADAVID NF, BHASIN S: Role of myostatin in metabolism. Curr. Opin. Clin. Nutr. Metab. Care (2004) 7:451-457.
25. LOPEZ AP, ROQUE FIGULS M, CUCHI GU et al.: Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome. J. Pain Sympt. Manag. (2004) 27:360-369.
26. FIDE E, BREGMAN T, KIRKHAM TC et al.: Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood. Exp. Biol. Med. (2005) 230:225-234.
27. JATOI A, WINDSCHILTL HE, LOPRINZI CL et al.: Dronabinol versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment study. J. Clin. Oncol. (2002) 20:567-573.
28. STRASSER F, LUFTNER D, POSSINGER K et al.: Comparison of orally administered cannabis extract and delara-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome. A multicenter, Phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J. Clin. Oncol. (2006) 24:3394-3400.
29. BALDWIN C, PARSONS T, LOGAN S: Dietary advice for illness-related malnutrition in adults. Cochrane Database Syst. Rev. (2001) 2:CD002008.
30. MILNE AC, POTTER J, AVENELL A: Protein and energy supplementation in elderly people at risk of malnutrition. Cochrane Database Syst. Rev. (2002) 3:CD003288.
31. MIRHOSSEINI N, FAINSINGER. RL, BARACOS V: Parenteral nutrition in advanced cancer: indications and clinical practice guidelines. J. Pall. Med. (2005) 8:914-918.
32. American Society for parenteral and Enteral Nutrition Board of Directors. Guidelines for the use of parenteral and enteral nutrition in adult pediatric patients. JPEN J. Farenter. Enteral, Nutr. (2002) 26:SA1-SA138.
33. ARENDS J, BODOKY G, BOZZETTI F et al.: ESPEN guidelines on enteral nutrition: non-surgical oncology. Clin. Nutr. (2006) 25:245-259.
34. WHITEHOUSE AS, SMITH HJ, DRAKE JL et al.: Mechanism of attenuation of skeletal muscle protein catabolism in cancer cachexia by eicosapentaenoic acid. Cancer Res. (2001) 61:3604-3609.
35. BARBER MD, ROSS JA, VOSS AC et al.: The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. Br. J. Cancer (1999) 81:80-86.
36. WIGMORE Sj, BARBER MD, ROSS JA: Effect of oral eicosapemaenoic acid on weight loss in patients with pancreatic cancer. Nutr. Cancer (2000) 36:177-184.
37. JATOI A, KENDRITH R, LOPRINZI CL et al.: An eicosapentaenoic acid supplement versus megestrol acetate versus both in patients with cancer-associated wasting: a North Central Cancer Treatment Group and National Cancer Institute of Canada colaborative efforts. J. Clin. Oncol. (2004) 22:2469-2476.
38. FEARON KC, BARBER MD, MOSES AG et al.: Double-blind, placebo controlled, randomised study of eicosapentaenoic acid diester in patients with cancer cachexia. J. Clin. Oncol. (2006) 24:3401-3407.
39. CONE RD: Anatomy and regulation of the central melanocortin system. Nat. Neurosci. (2005) 8:571-578.
40. MARKS DL, CONE RD: The role of the melanocortin-3 receptor in cachexia. Ann. NY Acad. Sci. (2003) 994:3401-3266.
41. MARKS DL, LING N, CONE RD: Role of the central melanocortin system in cachexia. Cancer Res. (2001) 61:1432-1438.
42. FOSTER AC, CHEN C, MARKISON S, MARKS DL: MC4 receptor antagonists: a potential treatment for cachexia. Drugs (2005) 8:314-319.
43. WISSE BE, FRAY0 RS, SCHWARTZ MW, CUMMINGS DE: Reversal of cancer anorexia by blockade of central melanocortin receptors in rats. Endocrinology (2001) 142:3292-3301.
44. MARKISON S, FOSTER AC, CHEN C et al.: The regulation of feeding and metabolic rate and the prevention of routine cancer cachexia with a small-molecule melanocortin-4 receptor antagonist. Endocrinology (2005) 146:2766-2773.
45. NICHOLSON JR, KOHLER G, SCHAERER F et al.: Peripheral administration of a melanocortin4-receptor inverse agonist prevents loss of a lean body mass in tumor-bearing mice. J. Pharmacol. Exp. Ther. (2006) 317:771-777.
46. VOS TJ, CARACOTI A, CHE JL et al.: Identification of 2-[2-[2-(5-bromo-2-methoxyphenyl)-ethyl]-3-fluorophenyl]- 4,5-dihydro-]H-imidazole (ML00253764) a small molecule melanocortin 4 receptor antagonist that effectively reduces tumor-induced weight loss in a mouse model. J. Med. Chem. (2004) 47:1602-1604.
47. GIL-CAMPOS M, AGUILERA CM, CANETE R et al.: Ghrelin: a hormone regulating food intake and energy homeostasis. Br. J. Nutr. (2006) 96:201-226.
48. NAGAYA N, UEMATSU M, KOJIMA M et al.: Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation (2001) 104:1430-1435.
49. HANADA T, TOSHINAI K, KAJIMURA N et al.: Anticachectic effect of ghrelin in nude mice bearing human melanoma cells. Biochem. Biophys. Res. Commun. (2003) 301:275-279.
50. DEBOER MD, ZHU XX, LEVASSEUR P et al.: Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia. Endocrinology (2007) 148(6):3004-3012.
51. WREN AM, SEAL LJ, COHEN MA et al.: Ghrelin enhances appetite and increases food intake in humans. J. Endocrinot. Metab. (2001) 86:5992-5995.
52. SCHMID DA, HELD K, ISING M et al.: Ghrelin stimulates appetite, imagination of food, GH, ACTH, and cortisol, but does not affect leptin in normal controls. Neuropsychopharmacology (2005) 30:1187-1192.
53. DRUCE MR, NEARY NM, SMALL CJ et al.: Subcutaneous administration of ghrelin stimulates energy intake in healthy lean human volunteers. Int. J. Obes. (2006) 30:293-296.
54. NAGAYA N, ITOH T, MURAKAMI S et al. Treatment of cachexia with ghrelin in patients with COPD. Chest (2005) 128:1187-1193.
55. WYNNE K, GIANNITSOPOULOU K, SMALL CJ et al.: Subcutaneous ghrelin enhances acute food intake in malnourished patients who receive maintenance peritonea] dialysis: a randomized, placebo-controlled trial. J. Am. Soc. Nephrol. (2005) 16:2111-2118.
56. NEARY NM, SMALL CJ, WREN AM et al.: Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J. Clin. Endocrin. Metab. (2004) 89:3401-2836.
57. COMBARET L, RALLIERE C, TAILLANDIER D et al.: Manipulation of the ubiquitin-proteasome pathway in cachexia: pentoxifylline suppresses the activation of the 20S and 26S proteasomes in muscles from turnout bearing rats. Mol. Biol. Rep. (1999) 26:95-101.
58. COSTELLI P, BOSSOLA M, MUSCARITOLI M et al.: Anticytokine treatment prevents the increase in the activity of ATP-ubiquitin- and Ca(2+)-dependent proteolytic systems in the muscle of tumour-bearing rats. Cytokine (2002) 19:1-5.
59. GOLDBERG RM, LOPRINZI CL, MAILLARD JA et al.: Pentoxifylline for treatment of cancer anorexia and cachexia? A randomised, double-bind, placebo controlled trial. J. Clin. Oncol. (1995) 13:2856-2859.
60. PEUCKMANN V, FISCH M, BRUERA E: Potential novel uses of thalidomide: focus on palliative care. Drugs (2000) 60:273-292.
61. BRUERA E, NEUMANN CM, PITUSKIN E et al.: Thalidomide in patients with cachexia due to terminal cancer: preliminary report. Ann. Oncol. (1999) 10:857-859.
62. KHAN ZH, SIMPSON EJ, COLE AT et al.: Oesophageal cancer and cachexia: the effect of short term treatment with thalidomide on weight loss and lean body mass. Aliment. Pharmacol. Ther. (2003) 17:677-683.
63. GORDON JN, TREBBLE TM, ELLIS RD et al.: Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut (2005) 54:540-545.
64. BRZEZINSKI A: Melatonin in humans. N. Engl. J. Med. (1997) 336:186-195.
65. LISSONI P, PAOLOROSSI F, TANCINI G et al.: Is there a role for melatonin in treatment of neoplastic cachexia. Eur. J. Cancer (1996) 32:340-1343.
66. PEARSON C, GLIMELIUS B, RONNELID J et al.: Impact of fish oil and melatonin on cachexia in patients with advanced gastrointestinal cancer: a randomised pilot study. Nutrition (2005) 21:170-178.
67. GHEZZI P, CERAMI A: Tumor necrosis factor as a pharmacological target. Mol. Biotechnol. (2005) 31:239-244.
68. LLOVERA M, CARBO N, GARCIA-MARTINEZ C et al.: Anti-TNF treatment reverts increased muscle ubiquitin gene expression in tumour-bearing rats. Biochem. Biaphys. Res. Commun. (1996) 221:653-635.
69. TRUYENS C, TORRICO F, ANGELO-BARRIOS A et al.: The cachexia associated with trypanosoma cruzi acute infection in mice is attenuated by anti-TNF-α, but not by anti-IL-6 or anti-IFN-γ antibodies. Parasite Immunol. (1995) 17:561-568.
70. SHEALY DJ, WOOLEY PH, EMMELL E et al.: Anti-TNF-α antibody allows healing of joint damage in polyarthritic transgenic mice. Arthritis Res. (2002) 4:R7.
71. SHARMA R, ANKER SD: Cytokines, apoptosis and cachexia: the potential for TNF antagonism. Int. J. Cardiol. (2002) 85:161-171.
72. ARGILES JM, BUSQUETS S, LOPEZ-SORIANO FJ: Cytokines as mediators and targets for cancer cachexia. Cancer Treat. Res. (2006) 130:199-217.
73. BRIOT K, GARNERO P, LE HENANFF A et al.: Body weight, body composition, and bone turnover changes in patients with spondyloarthropathy receiving anti-tumour necrosis factor {α} treatment. Ann. Rheum. Dis. (2005) 64:1137-1140.
74. MARCORA S, CHESTER KR, MITTAL G et al.: Randomized Phase II trial of anti-tumor necrosis factor therapy for cachexia in patients with early rheumatoid arthritis Am. J. Clin. Nutr. (2006) 84:1463-1472.
75. MUSCARITOLI M, COSTELLI P, BOSSOLA M et al.: Effects of simvastatin administration in an experimental model of cancer cachexia. Nutrition (2003) 19:936-939.
76. ENOMOTO A, RHO MC, FUKAMI A et al.: Suppression of cancer cachexia by 20S,21-epoxy-resibufogenin-3-acetate, a novel nonpeptide IL-6 receptor antagonist. Biochem. Biophys. Res. Comm. (2004) 323:1096-1102.
77. KURODA K, HORIGUCHI Y, NAKASHIMA J et al.: Prevention of cancer cachexia by a novel nuclear factor κB inhibitor in prostate cancer. Clin. Cancer Res. (2005) 11:5590-5594.
78. NAI YJ, JIANG ZW, WANG ZM et al.: Prevention of cancer cachexia by pyrrolidine dithiocarbamate (PDTC) in colon 26 tumor-bearing mice. JPEN J. Parenter. Enteral. Nutr. (2007) 31:18-25.
79. FUJIKI F, MUKAIDA N, HIROSE K et al.: Prevention of adenocarcinoma colon-26-induced cachexia by interleukin 10 gene transfer. Cancer Res. (1997) 57:94-99.
80. CARBO N, LOPEZ-SORIANO J, COSTELLI P et al.: Interleukin-15 antagonizes muscle protein waste in tumour-bearing rats. Br. J. Cancer (2000) 83:526-531.
81. QUINN LS, ANDERSON BG, DRIDAHL RH et al.: Overexpression of interleukin-15 induces skeleatt muscle hypertrophy in vitro: implications for treatments of muscle wasting disorders. Exp. Cell Res. (2002) 280:55-63.
82. NENCIONI A, GRUNEBACH F, PATRONE F et al.: Proteasome inhibitors: antitumor effects and beyond. Leukemia (2007) 21:30-36.
83. HOBLER SC, TIAO G, FISCHER JE et al.: Sepsis-induced increase in muscle proteolysis is blocked by specific proteasome inhibitors. Am. Physiol. (1998) 274:R30-R37.
84. BEEHLER BC, SLEPH PG, BENMASSAOUD L, GROVER GJ: Reduction of skeletal muscle atrophy by a proteasome inhibitor in a rat model of denervation. Exp. Biol. Med. (2006) 231:335-341.
85. MAY PE, BARBERA, D'OLIMPIO JT et al.: Reversal of cancer-related wasting using oral supplementation with a combination of β-hydroxy-β-methylburyrate, arginine, and glutamine. Am. J. Surg. (2002) 183:471-479.
86. 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. (2005) 65:3401-3283.
87. SMITH HJ, WYKE SM, TISDALE MJ: Mechanism of the attenuation of proteolysis-inducing factor stimulated protein degradation in muscle by β-hydroxy-β-methylbutyrate. Cancer Res. (2004) 64:3401-8735.
88. COSTELLI P, REFFO P, PENNA F et al.: Ca(2+)-dependent proteolysis in muscle wasting. Int. J. Biochem. Cell Biol. (2005) 37:2134-2146.
89. WEI W, FAREED MU, EVENSON A et al.: Sepsis stimulates calpain activity in skeletal muscle by decreasing calpastatin activity but does not activate caspase-3. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2005) 288:R580-R590.
90. FAREED MU, EVENSON AR, WEI W et al.: Treatment of rats with calpain inhibitors prevents sepsis-induced muscle proteolysis independent of atrogin-1/MAFbx and MuRFI expression. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) 290:R1589-R1597.
91. GILSON H, SCHAKMAN O, COMBARET L et al.: Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy. Endocrinolvgy (2007) 148:452-460.
92. WHITTEMORE LA, SONG K, LI X et al.: Inhibition of myostatin in adult mice increases skeletal muscle mass and strength. Biochem. Biophys. Res. Commun. (2003) 300:965-971.
93. BOGDANOVICH S, KRAG TOB, BARTON ER et al.: Functional improvement of dystrophic muscle by myostatin blockade. Nature (2002) 420:418-421.
94. BOGDANOVICH S, PERKINS KJ, KRAG TO et al.: Myostatin propeptide-mediated amelioration of dystrophic pathophysiology. FASEB J. (2005) 19:543-549.
95. AMTHOR H, MACHARIA, R, NAVARRETE R et al.: Lack of myostatin results in excessive muscle growth but impaired force generation. Proc. NatI. Acad. Sci. USA (2007) 104:1835-1840.
96. STEWART CE, ROTWEIN P: Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. Physiol. Rev. (1996) 76:1005-1026.
97. JONES JI, CLEMMONS DR: Insulin-like growth factors and their binding proteins: biological actions. Endocrinol. Rev. (1995) 16:3-34.
98. LAZARUS DD, KAMBAYASHI T, LOWRY SF et al.: The lack of an effect by insulin or insulin-like growth factor-1 in attenuating colon-26-mediated cancer cachexia. Cancer Lett. (1996) 103:71-77.
99. MAURAS N, HORBER FF, HAYMOND MW: Low-dose recombinant human IGF-1 fails to affect protein anabolism but inhibits islet cell secretion in humans. J. Clin. Enaocrinol. Metab. (1992) 75:1192-1197.
100. YARWOOD GD, ROSS RJ, MEDBAK S et al.: Administration of human recombinant IGF-1 in critically ill patients. Crit. Care Med. (1997) 25:1352-1361.
101. YOUNG SC, UNDERWOOD LE, CELNIKER A et al.: Effects of recombinant IGF-1 and growth hormone on serum IGF-binding proteins in calorically restricted adults. J. Clin. Endocrinol. Metab. (1992) 75:603-608.
102. BALLARD FJ, WALTON PE, BASTIAN S et al.: Effects of interactions between IGFBPs and IGFs on the plasma clearance and in vivo biological activities of IGFs and IGF analogs. Growth Regul. (1993) 3:40-44.
103. SVANBERG E, OHLSSON C, KIMBALL SR et al.: RbIGF-1/IGFBP-3 complex, but not free rhIGF-1, supports muscle protein biosynthesis in rats during semistarvation. Eur. J. Clin. Invest. (2000) 30:438-446.
104. WANG W, IRESJO BM, KARLSSON L et al.: Provision of rhIGF-1/IGFBP3 complex attenuated development of cancer cachexia in an experimental turnout model. Clin. Nutr. (2000) 19:127-132.
105. BAXTER RC: Signalling pathways involved in antiproliferative effects of IGFBP-3: a review. J. Clin. Pathol. Mol. Pathol. (2001) 54:145-148.
106. FURSTENBERGER G, SENN HJ: Insulin-like growth factors and cancer. Lancet Oncol. (2002) 3:298-302.
107. ALILA H, COLEMAN M, NITTA H et al.: Expression of biologically active human insulin like growth factor-I following intramuscular injection of a formulated plasmid in rats. Hum. Gen. Ther. (1997) 8:1785-1795.
108. BARTON-DAVIS ER, SHOTURMA DI, MUSARÓ A et al.: Viral mediated expression of insulin-like growth factor-1 blocks the aging-related loss of skeletal muscle function. Proc. Natl. Acad. Sci. USA (1998) 95:15603-15607.
109. JESCHKE MG, BARROW RE, HAWKINS HK et al.: IGF-I gene transfer in thermally injured rats. Gene Ther. (1999) 6:1015-1020.
110. SHIOTANI A, FUKUMARA M, MAEDA M et al.: Skeletal muscle regeneration after insulin-like growth factor-1 gene transfer by recombinant Sendai virus vector. Gene Ther. (2001) 8:1043-1050.
111. TONE CM, CARDOZA DM, CARPENTER RH et al.: Long-term effects of plasmid-mediated growth hormone releasing hormone in dogs. Cancer Gene Ther. (2004) 11:389-396.
112. WYKE SM, RUSSELL ST, TISDALE MJ: Induction of proteasome expression in skeletal muscle is attenuated by inhibitors of NF-κB activation. Br. J. Cancer (2004) 91:1742-1750.
113. BUSQUETS S, FUSTER G, AMETLLER E et al.: Resveratrol does not ameliorate muscle wasting in different types of cancer cachexia models. Clin. Nutr. (2007) 26:239-244.
114. ELEY HL, TISDALE MJ: Skeletal muscle atrophy: a link between depression of protein synthesis and increase in degradation. J. Biol. Chem. (2007) 282:7087-7097.
115. 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. Cancer (2007) 96:1216-1222.
116. GLASS DJ: Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nat. Cell Biol. (2003) 5:87-90.
117. COSTELLI P, MUSCARITOLI M, BOSSOLA M et al.: Lithium administration modulates muscle GSK3-β but does not prevent muscle loss in AH-130 bearing rats. 28th ESPEN Congress, Istanbul, Turkey, 19 - 22 October 2006 (Abstract 039).
118. EVENSON AR, FAREED MU, MENCONI MJ et al.: GSK-3β inhibitors reduce protein degradation in muscles from septic rats and in dexamethasone-treated myotubes. Int. J. Biochem. Cell Biol. (2005) 37:2226-2238.
119. LANGER CJ, HOFFMAN JP, OTTERY FD et al.: Clinical significance of weight loss in cancer patients: rationale for the use of anabolic agents in the treatment of cancer-related cachexia. Nutrition (2001) 17(Suppl.):S1-S20.
120. SHEFFIELD MOORE M: Androgens and the control of skeletal muscle protein synthesis. Ann. Med. (2000) 32:181-186.
121. DEMLING RH, DESANTI L: Oxandrolone induced lean mass gain during recovery from severe burns is maintained after discontinuation of the anabolic steroid. Burns (2003) 29:793-797.
122. EARTHMAN CP, REID PM, HARPER IT et al.: Body cell mass repletion and improved quality of life in HIV-infected individuals receiving oxandrolone. JPEN J. Paremer. Enteral. Nutr. (2002) 26:357-365.
123. CREUTZBERG EC, WOUTERS EF, MOSTERT R et al.: A role for anabolic steroids in therehabilitation of patients with COPD? A double-blind, placebo-controlled, randomized trial. Chest (2003) 104:1733-1742.
124. CHLEBOWSKI RT, HERROLD J, ALI I et al.: Influence of nandrolone decanoate on weight loss in advanced non-small cell lung cancer. Cancer (1986) 58:183-186.
125. TCHEKMEDYIAN S, FESEN M, PRICE LM et al.: Ongoing placebo-controlled study of oxandrolone in cancer-related weight loss. Int. J Radiat Oncol. Biol. Phys. (2003) 57(Suppl.): S283-S284.