The complex liaison between cachexia and tumor burden (Review)

De Lerma Barbaro,Andrea

doi:10.3892/or.2015.4164

The complex liaison between cachexia and tumor burden (Review)

Authors:
- Andrea De Lerma Barbaro
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Affiliations: Biomedical Research Division, Department of Theoretical and Applied Sciences, University of Insubria, Busto Arsizio, Varese, Italy
Published online on: July 31, 2015 https://doi.org/10.3892/or.2015.4164
Pages: 1635-1649

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Abstract

Cachexia is a wasting syndrome that afflicts end-stage cancer patients. Whereas a consensus statement for a definition of cachexia recently has been accomplished, a useful measurement for this condition at present is lacking. The aim of the present review is to discuss the advantage of introducing the measurement of tumor burden for a better overall evaluation of cachexia. Our suggestion ensues from a somewhat novel perspective in the field of infectious disease research where a careful measurement of the pathogen load, between i.e. different host genotypes, leads to the definition of the concept of tolerance to the infectious insult. Indeed tolerance concurs, together the more classical resistance, in maintaining the host reproductive fitness or health state. Noticeably a similar reasoning may apply to tumor biology as well. Whereas the extent of cachexia increases with tumor burden, the relationship between these two correlates of tumor progression fluctuates in a broad range. We have selected from the literature studies in the rodent model where significant variation in the course of the wasting illness during cancer was observed and quantitatively assessed comparing experimental groups marked by different genotype, drug treatment, diet or gender. These studies may be further classified in two categories: the former where the experimental condition associated to milder cachexia is accompanied to a lesser tumor burden, the latter where the inhibition of cachexia results disentangled from the tumor burden, that is the whole number of cancer cells results unchanged or even, paradoxically, is increased. In addition we survey, even in the context of human malignancy, the significance and feasibility of plotting quantitative estimates of cachexia against the whole tumor burden. Ultimately, the principal endeavor of introducing the measurement of tumor burden, in both experimental and clinical oncology, may be to achieve a better assessment of the inter-individual variation in the host vulnerability to cancer cachexia.

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1	Tisdale MJ: Mechanisms of cancer cachexia. Physiol Rev. 89:381–410. 2009. View Article : Google Scholar : PubMed/NCBI
2	Fearon KC, Glass DJ and Guttridge DC: Cancer cachexia: Mediators, signaling, and metabolic pathways. Cell Metab. 16:153–166. 2012. View Article : Google Scholar : PubMed/NCBI
3	Argilés JM, Busquets S, Stemmler B and López-Soriano FJ: Cancer cachexia: Understanding the molecular basis. Nat Rev Cancer. 14:754–762. 2014. View Article : Google Scholar : PubMed/NCBI
4	Ali S and Garcia JM: Sarcopenia, cachexia and aging: Diagnosis, mechanisms and therapeutic options - a mini-review. Gerontology. 60:294–305. 2014. View Article : Google Scholar : PubMed/NCBI
5	Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, Jatoi A, Loprinzi C, MacDonald N, Mantovani G, et al: Definition and classification of cancer cachexia: An international consensus. Lancet Oncol. 12:489–495. 2011. View Article : Google Scholar : PubMed/NCBI
6	Argilés JM, López-Soriano FJ, Toledo M, Betancourt A, Serpe R and Busquets S: The cachexia score (CASCO): A new tool for staging cachectic cancer patients. J Cachexia Sarcopenia Muscle. 2:87–93. 2011. View Article : Google Scholar : PubMed/NCBI
7	Windsor JA and Hill GL: Risk factors for postoperative pneumonia. The importance of protein depletion. Ann Surg. 208:209–214. 1988. View Article : Google Scholar : PubMed/NCBI
8	Tian M, Nishijima Y, Asp ML, Stout MB, Reiser PJ and Belury MA: Cardiac alterations in cancer-induced cachexia in mice. Int J Oncol. 37:347–353. 2010.PubMed/NCBI
9	Damrauer JS, Stadler ME, Acharyya S, Baldwin AS, Couch ME and Guttridge DC: Chemotherapy-induced muscle wasting: Association with NF-κB and cancer cachexia. Basic Appl Myol. 18:139–148. 2008.
10	Sakai H, Sagara A, Arakawa K, Sugiyama R, Hirosaki A, Takase K, Jo A, Sato K, Chiba Y, Yamazaki M, et al: Mechanisms of cisplatin-induced muscle atrophy. Toxicol Appl Pharmacol. 278:190–199. 2014. View Article : Google Scholar : PubMed/NCBI
11	Bachmann J, Heiligensetzer M, Krakowski-Roosen H, Büchler MW, Friess H and Martignoni ME: Cachexia worsens prognosis in patients with resectable pancreatic cancer. J Gastrointest Surg. 12:1193–1201. 2008. View Article : Google Scholar : PubMed/NCBI
12	Onesti JK and Guttridge DC: Inflammation based regulation of cancer cachexia. Biomed Res Int. 2014:1684072014. View Article : Google Scholar : PubMed/NCBI
13	Hotamisligil GS: The role of TNFalpha and TNF receptors in obesity and insulin resistance. J Intern Med. 245:621–625. 1999. View Article : Google Scholar : PubMed/NCBI
14	Heinrich PC, Behrmann I, Haan S, Hermanns HM, Müller-Newen G and Schaper F: Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem J. 374:1–20. 2003. View Article : Google Scholar : PubMed/NCBI
15	Schakman O, Kalista S, Barbé C, Loumaye A and Thissen JP: Glucocorticoid-induced skeletal muscle atrophy. Int J Biochem Cell Biol. 45:2163–2172. 2013. View Article : Google Scholar : PubMed/NCBI
16	Watchorn TM, Waddell I, Dowidar N and Ross JA: Proteolysis-inducing factor regulates hepatic gene expression via the transcription factors NF-(kappa)B and STAT3. FASEB J. 15:562–564. 2001.PubMed/NCBI
17	Deans DA, Wigmore SJ, Gilmour H, Tisdale MJ, Fearon KC and Ross JA: Expression of the proteolysis-inducing factor core peptide mRNA is upregulated in both tumour and adjacent normal tissue in gastro-oesophageal malignancy. Br J Cancer. 94:731–736. 2006.PubMed/NCBI
18	Han HQ, Zhou X, Mitch WE and Goldberg AL: Myostatin/activin pathway antagonism: Molecular basis and therapeutic potential. Int J Biochem Cell Biol. 45:2333–2347. 2013. View Article : Google Scholar : PubMed/NCBI
19	Zimmers TA, Davies MV, Koniaris LG, Haynes P, Esquela AF, Tomkinson KN, McPherron AC, Wolfman NM and Lee SJ: Induction of cachexia in mice by systemically administered myostatin. Science. 296:1486–1488. 2002. View Article : Google Scholar : PubMed/NCBI
20	Elkina Y, von Haehling S, Anker SD and Springer J: The role of myostatin in muscle wasting: An overview. J Cachexia Sarcopenia Muscle. 2:143–151. 2011. View Article : Google Scholar : PubMed/NCBI
21	Martin L, Birdsell L, Macdonald N, Reiman T, Clandinin MT, McCargar LJ, Murphy R, Ghosh S, Sawyer MB and Baracos VE: Cancer cachexia in the age of obesity: Skeletal muscle depletion is a powerful prognostic factor, independent of body mass index. J Clin Oncol. 31:1539–1547. 2013. View Article : Google Scholar : PubMed/NCBI
22	Egerman MA and Glass DJ: Signaling pathways controlling skeletal muscle mass. Crit Rev Biochem Mol Biol. 49:59–68. 2014. View Article : Google Scholar :
23	Nagy V and Dikic I: Ubiquitin ligase complexes: From substrate selectivity to conjugational specificity. Biol Chem. 391:163–169. 2010. View Article : Google Scholar
24	Baird TD and Wek RC: Eukaryotic initiation factor 2 phosphorylation and translational control in metabolism. Adv Nutr. 3:307–321. 2012. View Article : Google Scholar : PubMed/NCBI
25	Lecker SH, Jagoe RT, Gilbert A, Gomes M, Baracos V, Bailey J, Price SR, Mitch WE and Goldberg AL: Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J. 18:39–51. 2004. View Article : Google Scholar : PubMed/NCBI
26	Petruzzelli M, Schweiger M, Schreiber R, Campos-Olivas R, Tsoli M, Allen J, Swarbrick M, Rose-John S, Rincon M, Robertson G, et al: A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab. 20:433–447. 2014. View Article : Google Scholar : PubMed/NCBI
27	Bosaeus I, Daneryd P, Svanberg E and Lundholm K: Dietary intake and resting energy expenditure in relation to weight loss in unselected cancer patients. Int J Cancer. 93:380–383. 2001. View Article : Google Scholar : PubMed/NCBI
28	Tisdale MJ: Molecular pathways leading to cancer cachexia. Physiology (Bethesda). 20:340–348. 2005. View Article : Google Scholar
29	Hyltander A, Drott C, Körner U, Sandstrom R and Lundholm K: Elevated energy expenditure in cancer patients with solid tumours. Eur J Cancer. 27:9–15. 1991. View Article : Google Scholar : PubMed/NCBI
30	Cantor JR and Sabatini DM: Cancer cell metabolism: One hallmark, many faces. Cancer Discov. 2:881–898. 2012. View Article : Google Scholar : PubMed/NCBI
31	Wise DR and Thompson CB: Glutamine addiction: A new therapeutic target in cancer. Trends Biochem Sci. 35:427–433. 2010. View Article : Google Scholar : PubMed/NCBI
32	Delano MJ and Moldawer LL: The origins of cachexia in acute and chronic inflammatory diseases. Nutr Clin Pract. 21:68–81. 2006. View Article : Google Scholar : PubMed/NCBI
33	Rousset S, Alves-Guerra MC, Mozo J, Miroux B, Cassard-Doulcier AM, Bouillaud F and Ricquier D: The biology of mitochondrial uncoupling proteins. Diabetes. 53(Suppl 1): S130–S135. 2004. View Article : Google Scholar : PubMed/NCBI
34	Bing C, Russell ST, Beckett EE, Collins P, Taylor S, Barraclough R, Tisdale MJ and Williams G: Expression of uncoupling proteins-1, -2 and -3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor. Br J Cancer. 86:612–618. 2002. View Article : Google Scholar : PubMed/NCBI
35	Thair SA, Walley KR, Nakada TA, McConechy MK, Boyd JH, Wellman H and Russell JA: A single nucleotide polymorphism in NF-κB inducing kinase is associated with mortality in septic shock. J Immunol. 186:2321–2328. 2011. View Article : Google Scholar : PubMed/NCBI
36	Tan BH, Ross JA, Kaasa S, Skorpen F and Fearon KC; European Palliative Care Research Collaborative: Identification of possible genetic polymorphisms involved in cancer cachexia: A systematic review. J Genet. 90:165–177. 2011. View Article : Google Scholar : PubMed/NCBI
37	Schneider DS and Ayres JS: Two ways to survive infection: What resistance and tolerance can teach us about treating infectious diseases. Nat Rev Immunol. 8:889–895. 2008. View Article : Google Scholar : PubMed/NCBI
38	Råberg L, Graham AL and Read AF: Decomposing health: Tolerance and resistance to parasites in animals. Philos Trans R Soc Lond B Biol Sci. 364:37–49. 2009. View Article : Google Scholar :
39	Li C, Corraliza I and Langhorne J: A defect in interleukin-10 leads to enhanced malarial disease in Plasmodium chabaudi chabaudi infection in mice. Infect Immun. 67:4435–4442. 1999.PubMed/NCBI
40	Medzhitov R, Schneider DS and Soares MP: Disease tolerance as a defense strategy. Science. 335:936–941. 2012. View Article : Google Scholar : PubMed/NCBI
41	De Lerma Barbaro A, Perletti G, Bonapace IM and Monti E: Inflammatory cues acting on the adult intestinal stem cells and the early onset of cancer (Review). Int J Oncol. 45:959–968. 2014.PubMed/NCBI
42	Wu ZH and Shi Y: When ubiquitin meets NF-κB: A trove for anticancer drug development. Curr Pharm Des. 19:3263–3275. 2013. View Article : Google Scholar :
43	Karin M, Cao Y, Greten FR and Li ZW: NF-kappaB in cancer: From innocent bystander to major culprit. Nat Rev Cancer. 2:301–310. 2002. View Article : Google Scholar : PubMed/NCBI
44	Cai D, Frantz JD, Tawa NE Jr, Melendez PA, Oh BC, Lidov HG, Hasselgren PO, Frontera WR, Lee J, Glass DJ, et al: IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell. 119:285–298. 2004. View Article : Google Scholar : PubMed/NCBI
45	Hunter RB, Stevenson E, Koncarevic A, Mitchell-Felton H, Essig DA and Kandarian SC; SC: Activation of an alternative NF-kappaB pathway in skeletal muscle during disuse atrophy. FASEB J. 16:529–538. 2002. View Article : Google Scholar : PubMed/NCBI
46	Penner CG, Gang G, Wray C, Fischer JE and Hasselgren PO: The transcription factors NF-kappab and AP-1 are differentially regulated in skeletal muscle during sepsis. Biochem Biophys Res Commun. 281:1331–1336. 2001. View Article : Google Scholar : PubMed/NCBI
47	Wyke SM, Russell ST and Tisdale MJ: Induction of proteasome expression in skeletal muscle is attenuated by inhibitors of NF-kappaB activation. Br J Cancer. 91:1742–1750. 2004.PubMed/NCBI
48	Wang H, Lai YJ, Chan YL, Li TL and Wu CJ: Epigallocatechin-3-gallate effectively attenuates skeletal muscle atrophy caused by cancer cachexia. Cancer Lett. 305:40–49. 2011. View Article : Google Scholar : PubMed/NCBI
49	Yang Q, Wan L, Zhou Z, Li Y, Yu Q, Liu L, Li B and Guo C: Parthenolide from Parthenium integrifolium reduces tumor burden and alleviate cachexia symptoms in the murine CT-26 model of colorectal carcinoma. Phytomedicine. 20:992–998. 2013. View Article : Google Scholar : PubMed/NCBI
50	Crawford LJ, Walker B and Irvine AE: Proteasome inhibitors in cancer therapy. J Cell Commun Signal. 5:101–110. 2011. View Article : Google Scholar : PubMed/NCBI
51	Beck SA, Smith KL and Tisdale MJ: Anticachectic and antitumor effect of eicosapentaenoic acid and its effect on protein turnover. Cancer Res. 51:6089–6093. 1991.PubMed/NCBI
52	Whitehouse AS, Smith HJ, Drake JL and Tisdale MJ: Mechanism of attenuation of skeletal muscle protein catabolism in cancer cachexia by eicosapentaenoic acid. Cancer Res. 61:3604–3609. 2001.PubMed/NCBI
53	Benny Klimek ME, Aydogdu T, Link MJ, Pons M, Koniaris LG and Zimmers TA: Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia. Biochem Biophys Res Commun. 391:1548–1554. 2010. View Article : Google Scholar
54	Marchal JA, Lopez GJ, Peran M, Comino A, Delgado JR, García-García JA, Conde V, Aranda FM, Rivas C, Esteban M, et al: The impact of PKR activation: from neurodegeneration to cancer. FASEB J. 28:1965–1974. 2014. View Article : Google Scholar : PubMed/NCBI
55	Eley HL and Tisdale MJ: Skeletal muscle atrophy, a link between depression of protein synthesis and increase in degradation. J Biol Chem. 282:7087–7097. 2007. View Article : Google Scholar : PubMed/NCBI
56	Eley HL, Russell ST and Tisdale MJ: Role of the dsRNA-dependent protein kinase (PKR) in the attenuation of protein loss from muscle by insulin and insulin-like growth factor-I (IGF-I). Mol Cell Biochem. 313:63–69. 2008. View Article : Google Scholar : PubMed/NCBI
57	Eley HL, Russell ST and Tisdale MJ: Attenuation of muscle atrophy in a murine model of cachexia by inhibition of the dsRNA-dependent protein kinase. Br J Cancer. 96:1216–1222. 2007. View Article : Google Scholar : PubMed/NCBI
58	Eley HL, Russell ST and Tisdale MJ: Effect of branched-chain amino acids on muscle atrophy in cancer cachexia. Biochem J. 407:113–120. 2007. View Article : Google Scholar : PubMed/NCBI
59	Davis TW, Zweifel BS, O'Neal JM, Heuvelman DM, Abegg AL, Hendrich TO and Masferrer JL: Inhibition of cyclooxygenase-2 by celecoxib reverses tumor-induced wasting. J Pharmacol Exp Ther. 308:929–934. 2004. View Article : Google Scholar : PubMed/NCBI
60	Hyde CA and Missailidis S: Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis. Int Immunopharmacol. 9:701–715. 2009. View Article : Google Scholar : PubMed/NCBI
61	Roth E: Immune and cell modulation by amino acids. Clin Nutr. 26:535–544. 2007. View Article : Google Scholar : PubMed/NCBI
62	Ham DJ, Murphy KT, Chee A, Lynch GS and Koopman R: Glycine administration attenuates skeletal muscle wasting in a mouse model of cancer cachexia. Clin Nutr. 33:448–458. 2014. View Article : Google Scholar
63	Zhou X, Wang JL, Lu J, Song Y, Kwak KS, Jiao Q, Rosenfeld R, Chen Q, Boone T, Simonet WS, et al: Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell. 142:531–543. 2010. View Article : Google Scholar : PubMed/NCBI
64	Gallot YS, Durieux AC, Castells J, Desgeorges MM, Vernus B, Plantureux L, Rémond D, Jahnke VE, Lefai E, Dardevet D, et al: Myostatin gene inactivation prevents skeletal muscle wasting in cancer. Cancer Res. 74:7344–7356. 2014. View Article : Google Scholar : PubMed/NCBI
65	Ruas JL, White JP, Rao RR, Kleiner S, Brannan KT, Harrison BC, Greene NP, Wu J, Estall JL, Irving BA, et al: A PGC-1α isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell. 151:1319–1331. 2012. View Article : Google Scholar : PubMed/NCBI
66	Braun TP, Grossberg AJ, Krasnow SM, Levasseur PR, Szumowski M, Zhu XX, Maxson JE, Knoll JG, Barnes AP and Marks DL: Cancer- and endotoxin-induced cachexia require intact glucocorticoid signaling in skeletal muscle. FASEB J. 27:3572–3582. 2013. View Article : Google Scholar : PubMed/NCBI
67	Kadmiel M and Cidlowski JA: Glucocorticoid receptor signaling in health and disease. Trends Pharmacol Sci. 34:518–530. 2013. View Article : Google Scholar : PubMed/NCBI
68	Schakman O, Kalista S, Barbé C, Loumaye A and Thissen JP: Glucocorticoid-induced skeletal muscle atrophy. Int J Biochem Cell Biol. 45:2163–2172. 2013. View Article : Google Scholar : PubMed/NCBI
69	Das SK, Eder S, Schauer S, Diwoky C, Temmel H, Guertl B, Gorkiewicz G, Tamilarasan KP, Kumari P, Trauner M, et al: Adipose triglyceride lipase contributes to cancer-associated cachexia. Science. 333:233–238. 2011. View Article : Google Scholar : PubMed/NCBI
70	Kir S, White JP, Kleiner S, Kazak L, Cohen P, Baracos VE and Spiegelman BM: Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature. 513:100–104. 2014. View Article : Google Scholar : PubMed/NCBI
71	Hendifar A, Yang D, Lenz F, Lurje G, Pohl A, Lenz C, Ning Y, Zhang W and Lenz HJ: Gender disparities in metastatic colorectal cancer survival. Clin Cancer Res. 15:6391–6397. 2009. View Article : Google Scholar : PubMed/NCBI
72	Koo JH, Jalaludin B, Wong SK, Kneebone A, Connor SJ and Leong RW: Improved survival in young women with colorectal cancer. Am J Gastroenterol. 103:1488–1495. 2008. View Article : Google Scholar : PubMed/NCBI
73	al-Azzawi F and Wahab M: Estrogen and colon cancer: Current issues. Climacteric. 5:3–14. 2002. View Article : Google Scholar : PubMed/NCBI
74	Cosper PF and Leinwand LA: Cancer causes cardiac atrophy and autophagy in a sexually dimorphic manner. Cancer Res. 71:1710–1720. 2011. View Article : Google Scholar :
75	Sandri M: Protein breakdown in muscle wasting: Role of autophagy-lysosome and ubiquitin-proteasome. Int J Biochem Cell Biol. 45:2121–2129. 2013. View Article : Google Scholar : PubMed/NCBI
76	Strassmann G, Masui Y, Chizzonite R and Fong M: Mechanisms of experimental cancer cachexia. Local involvement of IL-1 in colon-26 tumor. J Immunol. 150:2341–2345. 1993.PubMed/NCBI
77	Piccinini AM and Midwood KS: DAMPening inflammation by modulating TLR signalling. Mediators Inflamm. 2010:6723952010.PubMed/NCBI
78	Cannon TY, Guttridge D, Dahlman J, George JR, Lai V, Shores C, Buzková P and Couch ME: The effect of altered Toll-like receptor 4 signaling on cancer cachexia. Arch Otolaryngol Head Neck Surg. 133:1263–1269. 2007. View Article : Google Scholar : PubMed/NCBI
79	Vahle AK, Kerem A, Oztürk E, Bankfalvi A, Lang S and Brandau S: Optimization of an orthotopic murine model of head and neck squamous cell carcinoma in fully immunocompetent mice - role of toll-like-receptor 4 expressed on host cells. Cancer Lett. 317:199–206. 2012. View Article : Google Scholar
80	Di Marco S, Cammas A, Lian XJ, Kovacs EN, Ma JF, Hall DT, Mazroui R, Richardson J, Pelletier J and Gallouzi IE: The translation inhibitor pateamine A prevents cachexia-induced muscle wasting in mice. Nat Commun. 3:8962012. View Article : Google Scholar : PubMed/NCBI
81	Kuznetsov G, Xu Q, Rudolph-Owen L, Tendyke K, Liu J, Towle M, Zhao N, Marsh J, Agoulnik S, Twine N, et al: Potent in vitro and in vivo anticancer activities of des-methyl, des-amino pateamine A, a synthetic analogue of marine natural product pateamine A. Mol Cancer Ther. 8:1250–1260. 2009. View Article : Google Scholar : PubMed/NCBI
82	Buck M and Chojkier M: Muscle wasting and dedifferentiation induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants. EMBO J. 15:1753–1765. 1996.PubMed/NCBI
83	Hall DT, Ma JF, Marco SD and Gallouzi IE: Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia. Aging (Albany NY). 3:702–715. 2011.
84	Buchan JR and Parker R: Eukaryotic stress granules: The ins and outs of translation. Mol Cell. 36:932–941. 2009. View Article : Google Scholar
85	Pretto F, Ghilardi C, Moschetta M, Bassi A, Rovida A, Scarlato V, Talamini L, Fiordaliso F, Bisighini C, Damia G, et al: Sunitinib prevents cachexia and prolongs survival of mice bearing renal cancer by restraining STAT3 and MuRF-1 activation in muscle. Oncotarget. 6:3043–3054. 2015.
86	Bonetto A, Aydogdu T, Jin X, Zhang Z, Zhan R, Puzis L, Koniaris LG and Zimmers TA: JAK/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia. Am J Physiol Endocrinol Metab. 303:E410–E421. 2012. View Article : Google Scholar : PubMed/NCBI
87	Gonzalez MC, Pastore CA, Orlandi SP and Heymsfield SB: Obesity paradox in cancer: New insights provided by body composition. Am J Clin Nutr. 99:999–1005. 2014. View Article : Google Scholar : PubMed/NCBI
88	Monitto CL, Berkowitz D, Lee KM, Pin S, Li D, Breslow M, O'Malley B and Schiller M: Differential gene expression in a murine model of cancer cachexia. Am J Physiol Endocrinol Metab. 281:E289–E297. 2001.PubMed/NCBI
89	Robert F, Mills JR, Agenor A, Wang D, DiMarco S, Cencic R, Tremblay ML, Gallouzi IE, Hekimi S, Wing SS, et al: Targeting protein synthesis in a Myc/mTOR-driven model of anorexia-cachexia syndrome delays its onset and prolongs survival. Cancer Res. 72:747–756. 2012. View Article : Google Scholar
90	Cuenca AG, Cuenca AL, Winfield RD, Joiner DN, Gentile L, Delano MJ, Kelly-Scumpia KM, Scumpia PO, Matheny MK, Scarpace PJ, et al: Novel role for tumor-induced expansion of myeloid-derived cells in cancer cachexia. J Immunol. 192:6111–6119. 2014. View Article : Google Scholar : PubMed/NCBI
91	Baltgalvis KA, Berger FG, Pena MM, Davis JM, Muga SJ and Carson JA: Interleukin-6 and cachexia in Apc^Min/+ mice. Am J Physiol Regul Integr Comp Physiol. 294:R393–R401. 2008. View Article : Google Scholar
92	Velázquez KT, Enos RT, Narsale AA, Puppa MJ, Davis JM, Murphy EA and Carson JA: Quercetin supplementation attenuates the progression of cancer cachexia in Apc^Min/+ mice. J Nutr. 144:868–875. 2014. View Article : Google Scholar
93	Lyons SK: Advances in imaging mouse tumour models in vivo. J Pathol. 205:194–205. 2005. View Article : Google Scholar : PubMed/NCBI
94	Jain M, Nilsson R, Sharma S, Madhusudhan N, Kitami T, Souza AL, Kafri R, Kirschner MW, Clish CB and Mootha VK: Metabolite profiling identifies a key role for glycine in rapid cancer cell proliferation. Science. 336:1040–1044. 2012. View Article : Google Scholar : PubMed/NCBI
95	Rose ML, Madren J, Bunzendahl H and Thurman RG: Dietary glycine inhibits the growth of B16 melanoma tumors in mice. Carcinogenesis. 20:793–798. 1999. View Article : Google Scholar : PubMed/NCBI
96	Liu Y, Cheng H, Zhou Y, Zhu Y, Bian R, Chen Y, Li C, Ma Q, Zheng Q, Zhang Y, et al: Myostatin induces mitochondrial metabolic alteration and typical apoptosis in cancer cells. Cell Death Dis. 4:e4942013. View Article : Google Scholar : PubMed/NCBI
97	Stratton MR, Campbell PJ and Futreal PA: The cancer genome. Nature. 458:719–724. 2009. View Article : Google Scholar : PubMed/NCBI