Muscle Atrophy pp 329-346 | Cite as

Muscle Atrophy in Cancer

  • Jian Yang
  • Richard Y. Cao
  • Qing Li
  • Fu Zhu
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1088)


Cancer is a prevalent disease with high mortality and morbidity. Muscle atrophy is a severe and disabling clinical condition that frequently accompanies cancer development such as muscle atrophy in pancreatic cancer, lung cancer, and bladder cancer. The majority of cancer patients are accompanied with cachexia. Cancer-associated cachexia is characterized by weight loss and muscle atrophy. Muscle wasting is a pivotal feature of cancer cachexia. Muscle atrophy refers to the reduction of muscle mass caused by muscle itself or the dysfunction of nervous system. Muscle atrophy causes serious clinical consequences such as physical impairment, poor life quality, reduced tolerance to treatments, and short survival. Although many reports have studied cancer-related muscle atrophy, there is still no clear understanding of it. Here we will describe the prevalence, mechanisms, pathophysiological effects, and current clinical treatments of muscle atrophy in cancer.


Muscle atrophy Cancer Cachexia 


Competing Financial Interests

The authors declare no competing financial interests.


  1. 1.
    Kadoguchi T, Takada S, Yokota T, Furihata T, Matsumoto J, Tsuda M, Mizushima W, Fukushima A, Okita K, Kinugawa S (2018) Deletion of NAD(P)H oxidase 2 prevents angiotensin ii-induced skeletal muscle atrophy. Biomed Res Int 2018:3194917. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Pearn J (1978) Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. J Med Genet 15(6):409–413CrossRefGoogle Scholar
  3. 3.
    Sheng-Yuan Z, Xiong F, Chen YJ, Yan TZ, Zeng J, Li L, Zhang YN, Chen WQ, Bao XH, Zhang C, Xu XM (2010) Molecular characterization of SMN copy number derived from carrier screening and from core families with SMA in a Chinese population. Eur J Hum Genet 18(9):978–984. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Xie M, Chen X, Qin S, Bao Y, Bu K, Lu Y (2018) Clinical study on thalidomide combined with cinobufagin to treat lung cancer cachexia. J Cancer Res Ther 14(1):226–232. CrossRefPubMedGoogle Scholar
  5. 5.
    Wheelwright S, Darlington AS, Hopkinson JB, Fitzsimmons D, Johnson C (2016) A systematic review and thematic synthesis of quality of life in the informal carers of cancer patients with cachexia. Palliat Med 30(2):149–160. CrossRefPubMedGoogle Scholar
  6. 6.
    Donohoe CL, Ryan AM, Reynolds JV (2011) Cancer cachexia: mechanisms and clinical implications. Gastroenterol Res Pract 2011:601434. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Cohen MH, Rothmann M (2001) Gemcitabine and cisplatin for advanced, metastatic bladder cancer. J Clin Oncol 19(4):1229–1231. CrossRefPubMedGoogle Scholar
  8. 8.
    Braun TP, Szumowski M, Levasseur PR, Grossberg AJ, Zhu X, Agarwal A, Marks DL (2014) Muscle atrophy in response to cytotoxic chemotherapy is dependent on intact glucocorticoid signaling in skeletal muscle. PLoS One 9(9):e106489. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    MacDonald V (2009) Chemotherapy: managing side effects and safe handling. Can Vet J 50(6):665–668PubMedPubMedCentralGoogle Scholar
  10. 10.
    Yamamoto H, Ishihara K, Takeda Y, Koizumi W, Ichikawa T (2013) Changes in the mucus barrier during cisplatin-induced intestinal mucositis in rats. Biomed Res Int 2013:276186. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Fanzani A, Zanola A, Rovetta F, Rossi S, Aleo MF (2011) Cisplatin triggers atrophy of skeletal C2C12 myotubes via impairment of Akt signalling pathway and subsequent increment activity of proteasome and autophagy systems. Toxicol Appl Pharmacol 250(3):312–321. CrossRefPubMedGoogle Scholar
  12. 12.
    Marinho R, Alcantara PSM, Ottoch JP, Seelaender M (2017) Role of Exosomal MicroRNAs and myomiRs in the Development of Cancer Cachexia-Associated Muscle Wasting. Front Nutr 4:69. CrossRefPubMedGoogle Scholar
  13. 13.
    Argiles JM, Alvarez B, Lopez-Soriano FJ (1997) The metabolic basis of cancer cachexia. Med Res Rev 17(5):477–498CrossRefGoogle Scholar
  14. 14.
    Tisdale MJ (2010) Cancer cachexia. Curr Opin Gastroenterol 26(2):146–151. CrossRefPubMedGoogle Scholar
  15. 15.
    Solheim TS, Laird BJA, Balstad TR, Bye A, Stene G, Baracos V, Strasser F, Griffiths G, Maddocks M, Fallon M, Kaasa S, Fearon K (2018) Cancer cachexia: rationale for the MENAC (Multimodal-Exercise, Nutrition and Anti-inflammatory medication for Cachexia) trial. BMJ Support Palliat Care. CrossRefGoogle Scholar
  16. 16.
    Chen MC, Chen YL, Lee CF, Hung CH, Chou TC (2015) Supplementation of Magnolol Attenuates Skeletal Muscle Atrophy in Bladder Cancer-Bearing Mice Undergoing Chemotherapy via Suppression of FoxO3 Activation and Induction of IGF-1. PLoS One 10(11):e0143594. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Vainshtein A, Hood DA (2016) The regulation of autophagy during exercise in skeletal muscle. J Appl Physiol 120(6):664–673. CrossRefPubMedGoogle Scholar
  18. 18.
    Penna F, Busquets S, Pin F, Toledo M, Baccino FM, Lopez-Soriano FJ, Costelli P, Argiles JM (2011) Combined approach to counteract experimental cancer cachexia: eicosapentaenoic acid and training exercise. J Cachexia Sarcopenia Muscle 2(2):95–104. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Varian BJ, Goureshetti S, Poutahidis T, Lakritz JR, Levkovich T, Kwok C, Teliousis K, Ibrahim YM, Mirabal S, Erdman SE (2016) Beneficial bacteria inhibit cachexia. Oncotarget 7(11):11803–11816. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Rockey DC (2013) Current opinion in gastroenterology. Editorial Curr Opin Gastroenterol 29(3):241–242. CrossRefPubMedGoogle Scholar
  21. 21.
    Morley JE, Thomas DR, Wilson MM (2006) Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr 83(4):735–743CrossRefGoogle Scholar
  22. 22.
    Walker J, Baran R, Velez N, Jellinek N (2016) Koilonychia: an update on pathophysiology, differential diagnosis and clinical relevance. J Eur Acad Dermatol Venereol 30(11):1985–1991. CrossRefPubMedGoogle Scholar
  23. 23.
    Alway SE, Siu PM (2008) Nuclear apoptosis contributes to sarcopenia. Exerc Sport Sci Rev 36(2):51–57. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Segura A, Pardo J, Jara C, Zugazabeitia L, Carulla J, de Las PR, Garcia-Cabrera E, Luz Azuara M, Casado J, Gomez-Candela C (2005) An epidemiological evaluation of the prevalence of malnutrition in Spanish patients with locally advanced or metastatic cancer. Clin Nutr 24(5):801–814. CrossRefPubMedGoogle Scholar
  25. 25.
    Schols AM, Broekhuizen R, Weling-Scheepers CA, Wouters EF (2005) Body composition and mortality in chronic obstructive pulmonary disease. Am J Clin Nutr 82(1):53–59CrossRefGoogle Scholar
  26. 26.
    Anker SD, Negassa A, Coats AJ, Afzal R, Poole-Wilson PA, Cohn JN, Yusuf S (2003) Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitors: an observational study. Lancet 361(9363):1077–1083. CrossRefPubMedGoogle Scholar
  27. 27.
    Tisdale MJ (2009) Mechanisms of cancer cachexia. Physiol Rev 89(2):381–410. CrossRefPubMedGoogle Scholar
  28. 28.
    Iwata Y, Suzuki N, Ohtake H, Kamauchi S, Hashimoto N, Kiyono T, Wakabayashi S (2016) Cancer cachexia causes skeletal muscle damage via transient receptor potential vanilloid 2-independent mechanisms, unlike muscular dystrophy. J Cachexia Sarcopenia Muscle 7(3):366–376. CrossRefPubMedGoogle Scholar
  29. 29.
    Lucia S, Esposito M, Rossi Fanelli F, Muscaritoli M (2012) Cancer cachexia: from molecular mechanisms to patient's care. Crit Rev Oncog 17(3):315–321CrossRefGoogle Scholar
  30. 30.
    Evans WJ (2010) Skeletal muscle loss: cachexia, sarcopenia, and inactivity. Am J Clin Nutr 91(4):1123S–1127S. CrossRefPubMedGoogle Scholar
  31. 31.
    Evans WJ, Morley JE, Argiles J, Bales C, Baracos V, Guttridge D, Jatoi A, Kalantar-Zadeh K, Lochs H, Mantovani G, Marks D, Mitch WE, Muscaritoli M, Najand A, Ponikowski P, Rossi Fanelli F, Schambelan M, Schols A, Schuster M, Thomas D, Wolfe R, Anker SD (2008) Cachexia: a new definition. Clin Nutr 27(6):793–799. CrossRefPubMedGoogle Scholar
  32. 32.
    Vagnildhaug OM, Balstad TR, Almberg SS, Brunelli C, Knudsen AK, Kaasa S, Thronaes M, Laird B, Solheim TS (2017) A cross-sectional study examining the prevalence of cachexia and areas of unmet need in patients with cancer. Support Care Cancer. CrossRefGoogle Scholar
  33. 33.
    von Haehling S, Anker MS, Anker SD (2016) Prevalence and clinical impact of cachexia in chronic illness in Europe, USA, and Japan: facts and numbers update 2016. J Cachexia Sarcopenia Muscle 7(5):507–509. CrossRefGoogle Scholar
  34. 34.
    Piao XM, Byun YJ, Kim WJ, Kim J (2018) Unmasking molecular profiles of bladder cancer. Investigative and Clinical Urology 59(2):72–82. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Adikrisna R, Tanaka S, Muramatsu S, Aihara A, Ban D, Ochiai T, Irie T, Kudo A, Nakamura N, Yamaoka S, Arii S (2012) Identification of pancreatic cancer stem cells and selective toxicity of chemotherapeutic agents. Gastroenterology 143(1):234–245 e237. CrossRefPubMedGoogle Scholar
  36. 36.
    Hedayati KK, Dittmar M (2010) Prevalence of sarcopenia among older community-dwelling people with normal health and nutritional state. Ecol Food Nutr 49(2):110–128. CrossRefPubMedGoogle Scholar
  37. 37.
    Lamarca F, Carrero JJ, Rodrigues JC, Bigogno FG, Fetter RL, Avesani CM (2014) Prevalence of sarcopenia in elderly maintenance hemodialysis patients: the impact of different diagnostic criteria. J Nutr Health Aging 18(7):710–717. CrossRefPubMedGoogle Scholar
  38. 38.
    Eley HL, Tisdale MJ (2007) Skeletal muscle atrophy, a link between depression of protein synthesis and increase in degradation. J Biol Chem 282(10):7087–7097. CrossRefPubMedGoogle Scholar
  39. 39.
    Covi JA, Bader BD, Chang ES, Mykles DL (2010) Molt cycle regulation of protein synthesis in skeletal muscle of the blackback land crab, Gecarcinus lateralis, and the differential expression of a myostatin-like factor during atrophy induced by molting or unweighting. J Exp Biol 213(1):172–183. CrossRefPubMedGoogle Scholar
  40. 40.
    Petruzzelli M, Wagner EF (2016) Mechanisms of metabolic dysfunction in cancer-associated cachexia. Genes Dev 30(5):489–501. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Glass DJ (2010) Signaling pathways perturbing muscle mass. Current Opinion in Clinical Nutrition and Metabolic Care 13(3):225–229CrossRefGoogle Scholar
  42. 42.
    Glass DJ (2003) Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nat Cell Biol 5(2):87–90. CrossRefPubMedGoogle Scholar
  43. 43.
    Lee SJ, Glass DJ (2011) Treating cancer cachexia to treat cancer. Skelet Muscle 1(1):2. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulos GD, Glass DJ (2001) Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol 3(11):1009–1013. CrossRefPubMedGoogle Scholar
  45. 45.
    Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, Gonzalez M, Yancopoulos GD, Glass DJ (2004) The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol Cell 14(3):395–403CrossRefGoogle Scholar
  46. 46.
    Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, Walsh K, Schiaffino S, Lecker SH, Goldberg AL (2004) Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 117(3):399–412CrossRefGoogle Scholar
  47. 47.
    Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, Zlotchenko E, Scrimgeour A, Lawrence JC, Glass DJ, Yancopoulos GD (2001) Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol 3(11):1014–1019. CrossRefPubMedGoogle Scholar
  48. 48.
    Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, Burden SJ, Di Lisi R, Sandri C, Zhao J, Goldberg AL, Schiaffino S, Sandri M (2007) FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab 6(6):458–471. CrossRefPubMedGoogle Scholar
  49. 49.
    Blaauw B, Canato M, Agatea L, Toniolo L, Mammucari C, Masiero E, Abraham R, Sandri M, Schiaffino S, Reggiani C (2009) Inducible activation of Akt increases skeletal muscle mass and force without satellite cell activation. FASEB J 23(11):3896–3905. CrossRefPubMedGoogle Scholar
  50. 50.
    Lai KM, Gonzalez M, Poueymirou WT, Kline WO, Na E, Zlotchenko E, Stitt TN, Economides AN, Yancopoulos GD, Glass DJ (2004) Conditional activation of akt in adult skeletal muscle induces rapid hypertrophy. Mol Cell Biol 24(21):9295–9304. CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Peng XD, Xu PZ, Chen ML, Hahn-Windgassen A, Skeen J, Jacobs J, Sundararajan D, Chen WS, Crawford SE, Coleman KG, Hay N (2003) Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes Dev 17(11):1352–1365. CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Ohanna M, Sobering AK, Lapointe T, Lorenzo L, Praud C, Petroulakis E, Sonenberg N, Kelly PA, Sotiropoulos A, Pende M (2005) Atrophy of S6K1(-/-) skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control. Nat Cell Biol 7(3):286–294. CrossRefPubMedGoogle Scholar
  53. 53.
    Leger B, Vergani L, Soraru G, Hespel P, Derave W, Gobelet C, D'Ascenzio C, Angelini C, Russell AP (2006) Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a reduction in Akt and an increase in atrogin-1. FASEB J 20(3):583–585. CrossRefPubMedGoogle Scholar
  54. 54.
    Pritt ML, Hall DG, Recknor J, Credille KM, Brown DD, Yumibe NP, Schultze AE, Watson DE (2008) Fabp3 as a biomarker of skeletal muscle toxicity in the rat: comparison with conventional biomarkers. Toxicol Sci 103(2):382–396. CrossRefPubMedGoogle Scholar
  55. 55.
    Dobrowolny G, Aucello M, Musaro A (2011) Muscle atrophy induced by SOD1G93A expression does not involve the activation of caspase in the absence of denervation. Skelet Muscle 1(1):3. CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Price SR, Gooch JL, Donaldson SK, Roberts-Wilson TK (2010) Muscle atrophy in chronic kidney disease results from abnormalities in insulin signaling. J Ren Nutr 20(5 Suppl):S24–S28. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Zhang L, Wang XH, Wang H, Du J, Mitch WE (2010) Satellite cell dysfunction and impaired IGF-1 signaling cause CKD-induced muscle atrophy. J Am Soc Nephrol 21(3):419–427. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Price SR, Bailey JL, Wang X, Jurkovitz C, England BK, Ding X, Phillips LS, Mitch WE (1996) Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin-proteasome proteolytic pathway by a mechanism including gene transcription. J Clin Invest 98(8):1703–1708. CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Favier FB, Costes F, Defour A, Bonnefoy R, Lefai E, Bauge S, Peinnequin A, Benoit H, Freyssenet D (2010) Downregulation of Akt/mammalian target of rapamycin pathway in skeletal muscle is associated with increased REDD1 expression in response to chronic hypoxia. Am J Physiol Regul Integr Comp Physiol 298(6):R1659–R1666. CrossRefPubMedGoogle Scholar
  60. 60.
    Mallinson JE, Constantin-Teodosiu D, Sidaway J, Westwood FR, Greenhaff PL (2009) Blunted Akt/FOXO signalling and activation of genes controlling atrophy and fuel use in statin myopathy. J Physiol 587(1):219–230. CrossRefPubMedGoogle Scholar
  61. 61.
    Crossland H, Constantin-Teodosiu D, Gardiner SM, Constantin D, Greenhaff PL (2008) A potential role for Akt/FOXO signalling in both protein loss and the impairment of muscle carbohydrate oxidation during sepsis in rodent skeletal muscle. J Physiol 586(22):5589–5600. CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Smith IJ, Lecker SH, Hasselgren PO (2008) Calpain activity and muscle wasting in sepsis. Am J Phys Endocrinol Metab 295(4):E762–E771. CrossRefGoogle Scholar
  63. 63.
    Sugita H, Kaneki M, Sugita M, Yasukawa T, Yasuhara S, Martyn JA (2005) Burn injury impairs insulin-stimulated Akt/PKB activation in skeletal muscle. Am J Phys Endocrinol Metab 288(3):E585–E591. CrossRefGoogle Scholar
  64. 64.
    Penna F, Bonetto A, Muscaritoli M, Costamagna D, Minero VG, Bonelli G, Rossi Fanelli F, Baccino FM, Costelli P (2010) Muscle atrophy in experimental cancer cachexia: is the IGF-1 signaling pathway involved? Int J Cancer 127(7):1706–1717. CrossRefPubMedGoogle Scholar
  65. 65.
    Sishi BJ, Engelbrecht AM (2011) Tumor necrosis factor alpha (TNF-alpha) inactivates the PI3-kinase/PKB pathway and induces atrophy and apoptosis in L6 myotubes. Cytokine 54(2):173–184. CrossRefPubMedGoogle Scholar
  66. 66.
    Dogra C, Changotra H, Wedhas N, Qin X, Wergedal JE, Kumar A (2007) TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine. FASEB J 21(8):1857–1869. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Zheng B, Ohkawa S, Li H, Roberts-Wilson TK, Price SR (2010) FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy. FASEB J 24(8):2660–2669. CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Zhao W, Qin W, Pan J, Wu Y, Bauman WA, Cardozo C (2009) Dependence of dexamethasone-induced Akt/FOXO1 signaling, upregulation of MAFbx, and protein catabolism upon the glucocorticoid receptor. Biochem Biophys Res Commun 378(3):668–672. CrossRefPubMedGoogle Scholar
  69. 69.
    Zhang L, Du J, Hu Z, Han G, Delafontaine P, Garcia G, Mitch WE (2009) IL-6 and serum amyloid A synergy mediates angiotensin II-induced muscle wasting. J Am Soc Nephrol 20(3):604–612. CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Lokireddy S, McFarlane C, Ge X, Zhang H, Sze SK, Sharma M, Kambadur R (2011) Myostatin induces degradation of sarcomeric proteins through a Smad3 signaling mechanism during skeletal muscle wasting. Mol Endocrinol 25(11):1936–1949. CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Lokireddy S, Mouly V, Butler-Browne G, Gluckman PD, Sharma M, Kambadur R, McFarlane C (2011) Myostatin promotes the wasting of human myoblast cultures through promoting ubiquitin-proteasome pathway-mediated loss of sarcomeric proteins. Am J Physiol Cell Physiol 301(6):C1316–C1324. CrossRefPubMedGoogle Scholar
  72. 72.
    Peter AK, Crosbie RH (2006) Hypertrophic response of Duchenne and limb-girdle muscular dystrophies is associated with activation of Akt pathway. Exp Cell Res 312(13):2580–2591. CrossRefPubMedGoogle Scholar
  73. 73.
    Gurpur PB, Liu J, Burkin DJ, Kaufman SJ (2009) Valproic acid activates the PI3K/Akt/mTOR pathway in muscle and ameliorates pathology in a mouse model of Duchenne muscular dystrophy. Am J Pathol 174(3):999–1008. CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Peter AK, Ko CY, Kim MH, Hsu N, Ouchi N, Rhie S, Izumiya Y, Zeng L, Walsh K, Crosbie RH (2009) Myogenic Akt signaling upregulates the utrophin-glycoprotein complex and promotes sarcolemma stability in muscular dystrophy. Hum Mol Genet 18(2):318–327. CrossRefPubMedGoogle Scholar
  75. 75.
    Kim MH, Kay DI, Rudra RT, Chen BM, Hsu N, Izumiya Y, Martinez L, Spencer MJ, Walsh K, Grinnell AD, Crosbie RH (2011) Myogenic Akt signaling attenuates muscular degeneration, promotes myofiber regeneration and improves muscle function in dystrophin-deficient mdx mice. Hum Mol Genet 20(7):1324–1338. CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Proud CG (2007) Signalling to translation: how signal transduction pathways control the protein synthetic machinery. Biochem J 403(2):217–234. CrossRefPubMedGoogle Scholar
  77. 77.
    Jin LQ, Pennise CR, Rodemer W, Jahn KS, Selzer ME (2016) Protein synthetic machinery and mRNA in regenerating tips of spinal cord axons in lamprey. J Comp Neurol 524(17):3614–3640. CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Vattem KM, Staschke KA, Wek RC (2001) Mechanism of activation of the double-stranded-RNA-dependent protein kinase, PKR: role of dimerization and cellular localization in the stimulation of PKR phosphorylation of eukaryotic initiation factor-2 (eIF2). Eur J Biochem 268(13):3674–3684CrossRefGoogle Scholar
  79. 79.
    Ma D, Morris JF (2002) Protein synthetic machinery in the dendrites of the magnocellular neurosecretory neurons of wild-type Long-Evans and homozygous Brattleboro rats. J Chem Neuroanat 23(3):171–186CrossRefGoogle Scholar
  80. 80.
    Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K (2002) Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110(2):177–189CrossRefGoogle Scholar
  81. 81.
    Glickman MH, Ciechanover A (2002) The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 82(2):373–428. CrossRefPubMedGoogle Scholar
  82. 82.
    Combaret L, Bechet D, Claustre A, Taillandier D, Richard I, Attaix D (2003) Down-regulation of genes in the lysosomal and ubiquitin-proteasome proteolytic pathways in calpain-3-deficient muscle. Int J Biochem Cell Biol 35(5):676–684CrossRefGoogle Scholar
  83. 83.
    Kodadek T (2010) No Splicing, no dicing: non-proteolytic roles of the ubiquitin-proteasome system in transcription. J Biol Chem 285(4):2221–2226. CrossRefPubMedGoogle Scholar
  84. 84.
    Broekaart DWM, van Scheppingen J, Geijtenbeek KW, Zuidberg MRJ, Anink JJ, Baayen JC, Muhlebner A, Aronica E, Gorter JA, van Vliet EA (2017) Increased expression of (immuno)proteasome subunits during epileptogenesis is attenuated by inhibition of the mammalian target of rapamycin pathway. Epilepsia 58(8):1462–1472. CrossRefPubMedGoogle Scholar
  85. 85.
    Khal J, Hine AV, Fearon KC, Dejong CH, Tisdale MJ (2005) Increased expression of proteasome subunits in skeletal muscle of cancer patients with weight loss. Int J Biochem Cell Biol 37(10):2196–2206. CrossRefPubMedGoogle Scholar
  86. 86.
    Kanzaki K, Kuratani M, Mishima T, Matsunaga S, Yanaka N, Usui S, Wada M (2010) The effects of eccentric contraction on myofibrillar proteins in rat skeletal muscle. Eur J Appl Physiol 110(5):943–952. CrossRefPubMedGoogle Scholar
  87. 87.
    Svanberg E, Ennion S, Isgaard J, Goldspink G (2000) Postprandial resynthesis of myofibrillar proteins is translationally rather than transcriptionally regulated in human skeletal muscle. Nutrition 16(1):42–46CrossRefGoogle Scholar
  88. 88.
    Kadowaki M, Harada N, Takahashi S, Noguchi T, Naito H (1989) Differential regulation of the degradation of myofibrillar and total proteins in skeletal muscle of rats: effects of streptozotocin-induced diabetes, dietary protein and starvation. J Nutr 119(3):471–477CrossRefGoogle Scholar
  89. 89.
    Jagoe RT, Redfern CP, Roberts RG, Gibson GJ, Goodship TH (2002) 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 102(3):353–361PubMedGoogle Scholar
  90. 90.
    Acharyya S, Ladner KJ, Nelsen LL, Damrauer J, Reiser PJ, Swoap S, Guttridge DC (2004) Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. J Clin Invest 114(3):370–378. CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Hardee JP, Montalvo RN, Carson JA (2017) Linking Cancer Cachexia-Induced Anabolic Resistance to Skeletal Muscle Oxidative Metabolism. Oxidative Med Cell Longev 2017:8018197. CrossRefGoogle Scholar
  92. 92.
    Bossola M, Marzetti E, Rosa F, Pacelli F (2016) Skeletal muscle regeneration in cancer cachexia. Clin Exp Pharmacol Physiol 43(5):522–527. CrossRefPubMedGoogle Scholar
  93. 93.
    Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294(5547):1704–1708. CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Goodman MN (1994) Interleukin-6 induces skeletal muscle protein breakdown in rats. Proc Soc Exp Biol Med 205(2):182–185CrossRefGoogle Scholar
  95. 95.
    Hengartner MO (2000) The biochemistry of apoptosis. Nature 407(6805):770–776. CrossRefPubMedGoogle Scholar
  96. 96.
    Schwartzman RA, Cidlowski JA (1993) Apoptosis: the biochemistry and molecular biology of programmed cell death. Endocr Rev 14(2):133–151. CrossRefPubMedGoogle Scholar
  97. 97.
    Dirks A, Leeuwenburgh C (2002) Apoptosis in skeletal muscle with aging. American Journal of Physiology Regulatory, Integrative and Comparative Physiology 282(2):R519–R527. CrossRefPubMedGoogle Scholar
  98. 98.
    Dirks-Naylor AJ, Lennon-Edwards S (2011) Cellular and molecular mechanisms of apoptosis in age-related muscle atrophy. Curr Aging Sci 4(3):269–278PubMedGoogle Scholar
  99. 99.
    Fanzani A, Conraads VM, Penna F, Martinet W (2012) Molecular and cellular mechanisms of skeletal muscle atrophy: an update. J Cachexia Sarcopenia Muscle 3(3):163–179. CrossRefPubMedPubMedCentralGoogle Scholar
  100. 100.
    Argiles JM, Busquets S, Felipe A, Lopez-Soriano FJ (2005) Molecular mechanisms involved in muscle wasting in cancer and ageing: cachexia versus sarcopenia. Int J Biochem Cell Biol 37(5):1084–1104. CrossRefPubMedGoogle Scholar
  101. 101.
    Baracos VE (2001) Management of muscle wasting in cancer-associated cachexia: understanding gained from experimental studies. Cancer 92(6 Suppl):1669–1677CrossRefGoogle Scholar
  102. 102.
    Matsuyama T, Ishikawa T, Okayama T, Oka K, Adachi S, Mizushima K, Kimura R, Okajima M, Sakai H, Sakamoto N, Katada K, Kamada K, Uchiyama K, Handa O, Takagi T, Kokura S, Naito Y, Itoh Y (2015) Tumor inoculation site affects the development of cancer cachexia and muscle wasting. Int J Cancer 137(11):2558–2565. CrossRefPubMedGoogle Scholar
  103. 103.
    Gullett N, Rossi P, Kucuk O, Johnstone PA (2009) Cancer-induced cachexia: a guide for the oncologist. J Soc Integr Oncol 7(4):155–169PubMedGoogle Scholar
  104. 104.
    Baracos VE (2006) Cancer-associated cachexia and underlying biological mechanisms. Annu Rev Nutr 26:435–461. CrossRefPubMedGoogle Scholar
  105. 105.
    Mantovani G, Maccio A, Madeddu C, Serpe R, Antoni G, Massa E, Dessi M, Panzone F (2010) Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia. J Mol Med 88(1):85–92. CrossRefPubMedGoogle Scholar
  106. 106.
    Palazzolo I, Stack C, Kong L, Musaro A, Adachi H, Katsuno M, Sobue G, Taylor JP, Sumner CJ, Fischbeck KH, Pennuto M (2009) Overexpression of IGF-1 in muscle attenuates disease in a mouse model of spinal and bulbar muscular atrophy. Neuron 63(3):316–328. CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Denti MA, Rosa A, D'Antona G, Sthandier O, De Angelis FG, Nicoletti C, Allocca M, Pansarasa O, Parente V, Musaro A, Auricchio A, Bottinelli R, Bozzoni I (2006) Body-wide gene therapy of Duchenne muscular dystrophy in the mdx mouse model. Proc Natl Acad Sci U S A 103(10):3758–3763. CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Barton ER, Morris L, Musaro A, Rosenthal N, Sweeney HL (2002) Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice. J Cell Biol 157(1):137–148. CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Bruno G, Cencetti F, Bernacchioni C, Donati C, Blankenbach KV, Thomas D, Meyer Zu Heringdorf D, Bruni P (2018) Bradykinin mediates myogenic differentiation in murine myoblasts through the involvement of SK1/Spns2/S1P2 axis. Cell Signal 45:110–121. CrossRefPubMedGoogle Scholar
  110. 110.
    Bitto FF, Klumpp D, Lange C, Boos AM, Arkudas A, Bleiziffer O, Horch RE, Kneser U, Beier JP (2013) Myogenic differentiation of mesenchymal stem cells in a newly developed neurotised AV-loop model. Biomed Res Int 2013:935046. CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    Florini JR, Ewton DZ, Magri KA (1991) Hormones, growth factors, and myogenic differentiation. Annu Rev Physiol 53:201–216. CrossRefPubMedGoogle Scholar
  112. 112.
    Coleman ME, DeMayo F, Yin KC, Lee HM, Geske R, Montgomery C, Schwartz RJ (1995) Myogenic vector expression of insulin-like growth factor I stimulates muscle cell differentiation and myofiber hypertrophy in transgenic mice. J Biol Chem 270(20):12109–12116CrossRefGoogle Scholar
  113. 113.
    Musaro A, McCullagh K, Paul A, Houghton L, Dobrowolny G, Molinaro M, Barton ER, Sweeney HL, Rosenthal N (2001) Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Nat Genet 27(2):195–200. CrossRefPubMedGoogle Scholar
  114. 114.
    Stewart CE, Rotwein P (1996) Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. Physiol Rev 76(4):1005–1026. CrossRefPubMedGoogle Scholar
  115. 115.
    Sandri M (2008) Signaling in muscle atrophy and hypertrophy. Physiology 23:160–170. CrossRefGoogle Scholar
  116. 116.
    Glass DJ (2005) Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol 37(10):1974–1984. CrossRefPubMedGoogle Scholar
  117. 117.
    Fearon K, Arends J, Baracos V (2013) Understanding the mechanisms and treatment options in cancer cachexia. Nat Rev Clin Oncol 10(2):90–99. CrossRefPubMedGoogle Scholar
  118. 118.
    Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vandewoude M, Zamboni M, European Working Group on Sarcopenia in Older People (2010) Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing 39(4):412–423. CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Thomas DR (2007) Loss of skeletal muscle mass in aging: examining the relationship of starvation, sarcopenia and cachexia. Clin Nutr 26(4):389–399. CrossRefPubMedGoogle Scholar
  120. 120.
    Goodpaster BH, Park SW, Harris TB, Kritchevsky SB, Nevitt M, Schwartz AV, Simonsick EM, Tylavsky FA, Visser M, Newman AB (2006) The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. J Gerontol A Biol Sci Med Sci 61(10):1059–1064CrossRefGoogle Scholar
  121. 121.
    Kurz MJ, Stergiou N (2003) The aging human neuromuscular system expresses less certainty for selecting joint kinematics during gait. Neurosci Lett 348(3):155–158CrossRefGoogle Scholar
  122. 122.
    Vandervoort AA (2002) Aging of the human neuromuscular system. Muscle Nerve 25(1):17–25CrossRefGoogle Scholar
  123. 123.
    Dedkov EI, Borisov AB, Carlson BM (2003) Dynamics of postdenervation atrophy of young and old skeletal muscles: differential responses of fiber types and muscle types. J Gerontol A Biol Sci Med Sci 58(11):984–991CrossRefGoogle Scholar
  124. 124.
    Williams AD, Selig S, Hare DL, Hayes A, Krum H, Patterson J, Geerling RH, Toia D, Carey MF (2004) Reduced exercise tolerance in CHF may be related to factors other than impaired skeletal muscle oxidative capacity. J Card Fail 10(2):141–148CrossRefGoogle Scholar
  125. 125.
    Massie BM, Simonini A, Sahgal P, Wells L, Dudley GA (1996) Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure. J Am Coll Cardiol 27(1):140–145. CrossRefPubMedGoogle Scholar
  126. 126.
    Schaufelberger M, Eriksson BO, Lonn L, Rundqvist B, Sunnerhagen KS, Swedberg K (2001) Skeletal muscle characteristics, muscle strength and thigh muscle area in patients before and after cardiac transplantation. Eur J Heart Fail 3(1):59–67CrossRefGoogle Scholar
  127. 127.
    Gehrig SM, Lynch GS (2011) Emerging drugs for treating skeletal muscle injury and promoting muscle repair. Expert Opin Emerg Drugs 16(1):163–182. CrossRefPubMedGoogle Scholar
  128. 128.
    Speck RM, Courneya KS, Masse LC, Duval S, Schmitz KH (2010) An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. J Cancer Surviv 4(2):87–100. CrossRefPubMedGoogle Scholar
  129. 129.
    Mishra SI, Scherer RW, Geigle PM, Berlanstein DR, Topaloglu O, Gotay CC, Snyder C (2012) Exercise interventions on health-related quality of life for cancer survivors. Cochrane Database Syst Rev 8:CD007566. CrossRefGoogle Scholar
  130. 130.
    Mishra SI, Scherer RW, Snyder C, Geigle PM, Berlanstein DR, Topaloglu O (2012) Exercise interventions on health-related quality of life for people with cancer during active treatment. Cochrane Database Syst Rev 8:CD008465. CrossRefGoogle Scholar
  131. 131.
    Puetz TW, Herring MP (2012) Differential effects of exercise on cancer-related fatigue during and following treatment: a meta-analysis. Am J Prev Med 43(2):e1–e24. CrossRefPubMedGoogle Scholar
  132. 132.
    Gould DW, Lahart I, Carmichael AR, Koutedakis Y, Metsios GS (2013) Cancer cachexia prevention via physical exercise: molecular mechanisms. J Cachexia Sarcopenia Muscle 4(2):111–124. CrossRefPubMedGoogle Scholar
  133. 133.
    Camera DM, Smiles WJ, Hawley JA (2016) Exercise-induced skeletal muscle signaling pathways and human athletic performance. Free Radic Biol Med 98:131–143. CrossRefPubMedGoogle Scholar
  134. 134.
    Mann S, Beedie C, Balducci S, Zanuso S, Allgrove J, Bertiato F, Jimenez A (2014) Changes in insulin sensitivity in response to different modalities of exercise: a review of the evidence. Diabetes Metab Res Rev 30(4):257–268. CrossRefPubMedGoogle Scholar
  135. 135.
    Vainshtein A, Grumati P, Sandri M, Bonaldo P (2014) Skeletal muscle, autophagy, and physical activity: the menage a trois of metabolic regulation in health and disease. J Mol Med 92(2):127–137. CrossRefPubMedGoogle Scholar
  136. 136.
    Snijders T, Nederveen JP, McKay BR, Joanisse S, Verdijk LB, van Loon LJ, Parise G (2015) Satellite cells in human skeletal muscle plasticity. Front Physiol 6:283. CrossRefPubMedPubMedCentralGoogle Scholar
  137. 137.
    Hojman P, Fjelbye J, Zerahn B, Christensen JF, Dethlefsen C, Lonkvist CK, Brandt C, Gissel H, Pedersen BK, Gehl J (2014) Voluntary exercise prevents cisplatin-induced muscle wasting during chemotherapy in mice. PLoS One 9(9):e109030. CrossRefPubMedPubMedCentralGoogle Scholar
  138. 138.
    Donatto FF, Neves RX, Rosa FO, Camargo RG, Ribeiro H, Matos-Neto EM, Seelaender M (2013) Resistance exercise modulates lipid plasma profile and cytokine content in the adipose tissue of tumour-bearing rats. Cytokine 61(2):426–432. CrossRefPubMedGoogle Scholar
  139. 139.
    Lira FS, Antunes Bde M, Seelaender M, Rosa Neto JC (2015) The therapeutic potential of exercise to treat cachexia. Curr Opin Support Palliat Care 9(4):317–324. CrossRefPubMedGoogle Scholar
  140. 140.
    Schultz K, Jelusic D, Wittmann M, Kramer B, Huber V, Fuchs S, Lehbert N, Wingart S, Stojanovic D, Gohl O, Alma HJ, de Jong C, van der Molen T, Faller H, Schuler M (2018) Inspiratory muscle training does not improve clinical outcomes in 3-week COPD rehabilitation: results from a randomised controlled trial. Eur Respir J 51(1). CrossRefGoogle Scholar
  141. 141.
    Heydari A, Farzad M, Ahmadi hosseini SH (2015) Comparing Inspiratory Resistive Muscle Training with Incentive Spirometry on Rehabilitation of COPD Patients. Rehabil Nurs 40(4):243–248. CrossRefPubMedGoogle Scholar
  142. 142.
    Mourtzakis M, Bedbrook M (2009) Muscle atrophy in cancer: a role for nutrition and exercise. Appl Physiol Nutr Metab 34(5):950–956. CrossRefPubMedGoogle Scholar
  143. 143.
    Muscaritoli M, Molfino A, Gioia G, Laviano A, Rossi Fanelli F (2011) The "parallel pathway": a novel nutritional and metabolic approach to cancer patients. Intern Emerg Med 6(2):105–112. CrossRefPubMedGoogle Scholar
  144. 144.
    Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, Davis M, Muscaritoli M, Ottery F, Radbruch L, Ravasco P, Walsh D, Wilcock A, Kaasa S, Baracos VE (2011) Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 12(5):489–495. CrossRefPubMedGoogle Scholar
  145. 145.
    Prado CM, Sawyer MB, Ghosh S, Lieffers JR, Esfandiari N, Antoun S, Baracos VE (2013) Central tenet of cancer cachexia therapy: do patients with advanced cancer have exploitable anabolic potential? Am J Clin Nutr 98(4):1012–1019. CrossRefPubMedGoogle Scholar
  146. 146.
    Chevalier S, Winter A (2014) Do patients with advanced cancer have any potential for protein anabolism in response to amino acid therapy? Curr Opin Clin Nut Metab Care 17(3):213–218. CrossRefGoogle Scholar
  147. 147.
    Engelen MP, van der Meij BS, Deutz NE (2016) Protein anabolic resistance in cancer: does it really exist? Current Opinion in Clinical Nutrition and Metabolic Care 19(1):39–47. CrossRefPubMedPubMedCentralGoogle Scholar
  148. 148.
    Ryall JG, Schertzer JD, Lynch GS (2007) Attenuation of age-related muscle wasting and weakness in rats after formoterol treatment: therapeutic implications for sarcopenia. J Gerontol A Biol Sci Med Sci 62(8):813–823CrossRefGoogle Scholar
  149. 149.
    Degens H (2010) The role of systemic inflammation in age-related muscle weakness and wasting. Scand J Med Sci Sports 20(1):28–38. CrossRefPubMedPubMedCentralGoogle Scholar
  150. 150.
    Sanchis-Gomar F, Gomez-Cabrera MC, Vina J (2011) The loss of muscle mass and sarcopenia: non hormonal intervention. Exp Gerontol 46(12):967–969. CrossRefPubMedGoogle Scholar
  151. 151.
    Drescher C, Konishi M, Ebner N, Springer J (2016) Loss of muscle mass: Current developments in cachexia and sarcopenia focused on biomarkers and treatment. Int J Cardiol 202:766–772. CrossRefPubMedGoogle Scholar
  152. 152.
    Birnkrant DJ, Bushby K, Bann CM, Alman BA, Apkon SD, Blackwell A, Case LE, Cripe L, Hadjiyannakis S, Olson AK, Sheehan DW, Bolen J, Weber DR, Ward LM, Group DMDCCW (2018) Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. CrossRefGoogle Scholar
  153. 153.
    Thakur SS, Swiderski K, Ryall JG, Lynch GS (2018) Therapeutic potential of heat shock protein induction for muscular dystrophy and other muscle wasting conditions. Philos Trans R Soc Lond Ser B Biol Sci 373(1738). CrossRefGoogle Scholar
  154. 154.
    Winter A, MacAdams J, Chevalier S (2012) Normal protein anabolic response to hyperaminoacidemia in insulin-resistant patients with lung cancer cachexia. Clin Nutr 31(5):765–773. CrossRefPubMedGoogle Scholar
  155. 155.
    Jafri SH, Previgliano C, Khandelwal K, Shi R (2015) Cachexia Index in Advanced Non-Small-Cell Lung Cancer Patients. Clin Med Insights Oncol 9:87–93. CrossRefPubMedPubMedCentralGoogle Scholar
  156. 156.
    van Dijk DP, van de Poll MC, Moses AG, Preston T, Olde Damink SW, Rensen SS, Deutz NE, Soeters PB, Ross JA, Fearon K, Dejong CH (2015) Effects of oral meal feeding on whole body protein breakdown and protein synthesis in cachectic pancreatic cancer patients. J Cachexia Sarcopenia Muscle 6(3):212–221. CrossRefPubMedPubMedCentralGoogle Scholar
  157. 157.
    Molfino A, Formiconi A, Rossi Fanelli F, Muscaritoli M (2014) Cancer cachexia: towards integrated therapeutic interventions. Expert Opin Biol Ther 14(10):1379–1381. CrossRefPubMedGoogle Scholar
  158. 158.
    Ruiz Garcia V, Lopez-Briz E, Carbonell Sanchis R, Gonzalvez Perales JL, Bort-Marti S (2013) Megestrol acetate for treatment of anorexia-cachexia syndrome. The Cochrane Database of Systematic Reviews 3:CD004310. CrossRefGoogle Scholar
  159. 159.
    Argiles JM, Anguera A, Stemmler B (2013) A new look at an old drug for the treatment of cancer cachexia: megestrol acetate. Clin Nutr 32(3):319–324. CrossRefPubMedGoogle Scholar
  160. 160.
    Brisbois TD, de Kock IH, Watanabe SM, Mirhosseini M, Lamoureux DC, Chasen M, MacDonald N, Baracos VE, Wismer WV (2011) Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial. Ann Oncol 22(9):2086–2093. CrossRefPubMedGoogle Scholar
  161. 161.
    Chen JH, Liu TY, Wu CW, Chi CW (2001) Nonsteroidal anti-inflammatory drugs for treatment of advanced gastric cancer: cyclooxygenase-2 is involved in hepatocyte growth factor mediated tumor development and progression. Med Hypotheses 57(4):503–505. CrossRefPubMedGoogle Scholar
  162. 162.
    Reid J, Mills M, Cantwell M, Cardwell CR, Murray LJ, Donnelly M (2012) Thalidomide for managing cancer cachexia. The Cochrane Database of Systematic Reviews 4:CD008664. CrossRefGoogle Scholar
  163. 163.
    Davis M, Lasheen W, Walsh D, Mahmoud F, Bicanovsky L, Lagman R (2012) A Phase II dose titration study of thalidomide for cancer-associated anorexia. J Pain Symptom Manag 43(1):78–86. CrossRefGoogle Scholar
  164. 164.
    Yennurajalingam S, Willey JS, Palmer JL, Allo J, Del Fabbro E, Cohen EN, Tin S, Reuben JM, Bruera E (2012) The role of thalidomide and placebo for the treatment of cancer-related anorexia-cachexia symptoms: results of a double-blind placebo-controlled randomized study. J Palliat Med 15(10):1059–1064. CrossRefPubMedPubMedCentralGoogle Scholar
  165. 165.
    Mueller TC, Bachmann J, Prokopchuk O, Friess H, Martignoni ME (2016) Molecular pathways leading to loss of skeletal muscle mass in cancer cachexia--can findings from animal models be translated to humans? BMC Cancer 16:75. CrossRefPubMedPubMedCentralGoogle Scholar
  166. 166.
    Cohen S, Nathan JA, Goldberg AL (2015) Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov 14(1):58–74. CrossRefPubMedGoogle Scholar
  167. 167.
    Knight MI, Tester AM, McDonagh MB, Brown A, Cottrell J, Wang J, Hobman P, Cocks BG (2014) Milk-derived ribonuclease 5 preparations induce myogenic differentiation in vitro and muscle growth in vivo. J Dairy Sci 97(12):7325–7333. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Jian Yang
    • 1
    • 2
  • Richard Y. Cao
    • 1
    • 2
  • Qing Li
    • 1
    • 2
  • Fu Zhu
    • 1
    • 2
  1. 1.Zhongshan-Xuhui HospitalFudan UniversityShanghaiChina
  2. 2.Shanghai Clinical Research CenterChinese Academy of SciencesShanghaiChina

Personalised recommendations