{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:12:33Z","timestamp":1790244753379,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2017,5,5]],"date-time":"2017-05-05T00:00:00Z","timestamp":1493942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The gastrointestinal hormone ghrelin reduces energy expenditure and stimulates food intake. Ghrelin analogs are a possible treatment against cancer anorexia-cachexia syndrome (CACS). This study aimed to investigate whether oral treatment with the non-peptidergic ghrelin receptor agonist HM01 counteracts CACS in colon-26 (C26) tumor-bearing mice. The C26 tumor model is characterized by pronounced body weight (BW) loss and muscle wasting in the absence of severe anorexia. We analyzed the time course of BW loss, body composition, muscle mass, bone mineral density, and the cytokines interleukin-6 (IL-6) and macrophage-inhibitory cytokine-1 (MIC-1). Moreover, we measured the expression of the muscle degradation markers muscle RING-finger-protein-1 (MuRF-1) and muscle atrophy F-box (MAFbx). After tumor inoculation, MIC-1 levels increased earlier than IL-6 and both cytokines were elevated before MuRF-1\/MAFbx expression increased. Oral HM01 treatment increased BW, fat mass, and neuronal hypothalamic activity in healthy mice. In tumor-bearing mice, HM01 increased food intake, BW, fat mass, muscle mass, and bone mineral density while it decreased energy expenditure. These effects appeared to be independent of IL-6, MIC-1, MuRF-1 or MAFbx, which were not affected by HM01. Therefore, HM01 counteracts cachectic body weight loss under inflammatory conditions and is a promising compound for the treatment of cancer cachexia in the absence of severe anorexia.<\/jats:p>","DOI":"10.3390\/ijms18050986","type":"journal-article","created":{"date-parts":[[2017,5,5]],"date-time":"2017-05-05T10:31:08Z","timestamp":1493980268000},"page":"986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Oral Treatment with the Ghrelin Receptor Agonist HM01 Attenuates Cachexia in Mice Bearing Colon-26 (C26) Tumors"],"prefix":"10.3390","volume":"18","author":[{"given":"Fabienne","family":"Villars","sequence":"first","affiliation":[{"name":"Institute of Veterinary Physiology, University of Zurich, 8057 Zurich, Switzerland"},{"name":"Zurich Center for Human Integrative Physiology, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Pietra","sequence":"additional","affiliation":[{"name":"Helsinn Healthcare SA, 6912 Pazzallo\u2013Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Giuliano","sequence":"additional","affiliation":[{"name":"Helsinn Healthcare SA, 6912 Pazzallo\u2013Lugano, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5056-8548","authenticated-orcid":false,"given":"Thomas","family":"Lutz","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology, University of Zurich, 8057 Zurich, Switzerland"},{"name":"Zurich Center for Human Integrative Physiology, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2448-2222","authenticated-orcid":false,"given":"Thomas","family":"Riediger","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology, University of Zurich, 8057 Zurich, Switzerland"},{"name":"Zurich Center for Human Integrative Physiology, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.clnu.2008.06.013","article-title":"Cachexia: A new definition","volume":"27","author":"Evans","year":"2008","journal-title":"Clin. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S48","DOI":"10.1038\/sj.ijo.0801911","article-title":"Cytokines and feeding","volume":"25","year":"2001","journal-title":"Int. J. Obes. Relat. Metab. Disord."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/S0959-8049(97)10090-9","article-title":"Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies?","volume":"34","author":"Andreyev","year":"1998","journal-title":"Eur. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nrc3829","article-title":"Cancer cachexia: Understanding the molecular basis","volume":"14","author":"Busquets","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nrclinonc.2012.209","article-title":"Understanding the mechanisms and treatment options in cancer cachexia","volume":"10","author":"Fearon","year":"2013","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8500","DOI":"10.1200\/JCO.2005.01.8010","article-title":"Systematic review of the treatment of cancer-associated anorexia and weight loss (Structured abstract)","volume":"23","author":"Yavuzsen","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1001\/archinte.1997.00440300118010","article-title":"Clinical adrenal insufficiency in patients receiving megestrol therapy","volume":"157","author":"Subramanian","year":"1997","journal-title":"Arch. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1001\/archinte.1997.00440360053005","article-title":"Glucocorticoidlike activity of megestrol. A summary of Food and Drug Administration experience and a review of the literature","volume":"157","author":"Mann","year":"1997","journal-title":"Arch. Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4325","DOI":"10.1210\/endo.141.11.7873","article-title":"The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion","volume":"141","author":"Wren","year":"2000","journal-title":"Endocrinology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1073\/pnas.0305930101","article-title":"Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor","volume":"101","author":"Sun","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/45230","article-title":"Ghrelin is a growth-hormone-releasing acylated peptide from stomach","volume":"402","author":"Kojima","year":"1999","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2044-5040-1-4","article-title":"Regulation of skeletal muscle growth by the IGF1-Akt\/PKB pathway: Insights from genetic models","volume":"1","author":"Schiaffino","year":"2011","journal-title":"Skelet. Muscle"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/B978-0-12-410473-0.00003-9","article-title":"The Role of Ghrelin in Anorexia-Cachexia Syndromes","volume":"92","author":"Guillory","year":"2013","journal-title":"Vitam. Horm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/35038090","article-title":"Ghrelin induces adiposity in rodents","volume":"407","author":"Smiley","year":"2000","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1017\/S0029665112000778","article-title":"The receptive function of hypothalamic and brainstem centres to hormonal and nutrient signals affecting energy balance","volume":"71","author":"Riediger","year":"2012","journal-title":"Proc. Nutr. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0169-328X(97)00071-5","article-title":"Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues","volume":"48","author":"Guan","year":"1997","journal-title":"Mol. Brain Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1046\/j.1365-2826.1999.00408.x","article-title":"GHRP-6-induced changes in electrical activity of single cells in the arcuate, ventromedial and periventricular nucleus neurones [correction of nuclei] of a hypothalamic slice preparation in vitro","volume":"11","author":"Hewson","year":"1999","journal-title":"J. Neuroendocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1046\/j.1365-2826.2000.00584.x","article-title":"Systemic administration of ghrelin induces Fos and Egr-1 proteins in the hypothalamic arcuate nucleus of fasted and fed rats","volume":"12","author":"Hewson","year":"2000","journal-title":"J. Neuroendocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1091\/mbc.e06-12-1162","article-title":"Canonical interaction of cyclin G associated kinase with adaptor protein 1 regulates lysosomal enzyme sorting","volume":"18","author":"Kametaka","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1053\/j.gastro.2006.01.041","article-title":"Therapeutic Action of Ghrelin in a Mouse Model of Colitis","volume":"130","author":"Chorny","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1164\/rccm.200604-511OC","article-title":"Ghrelin attenuates sepsis-induced acute lung injury and mortality in rats","volume":"176","author":"Wu","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0167-0115(03)00117-4","article-title":"Ghrelin, a novel growth hormone-releasing peptide, in the treatment of chronic heart failure","volume":"114","author":"Nagaya","year":"2003","journal-title":"Regul. Pept."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1002\/cncr.24917","article-title":"Effects by daily long term provision of ghrelin to unselected weight-losing cancer patients: A randomized double-blind study","volume":"116","author":"Lundholm","year":"2010","journal-title":"Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2832","DOI":"10.1210\/jc.2003-031768","article-title":"Ghrelin increases energy intake in cancer patients with impaired appetite: Acute, randomized, placebo-controlled trial","volume":"89","author":"Neary","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S1470-2045(15)00558-6","article-title":"Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): Results from two randomised, double-blind, phase 3 trials","volume":"17","author":"Temel","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chen, J.A., Splenser, A., Guillory, B., Luo, J., Mendiratta, M., Belinova, B., Halder, T., Zhang, G., Li, Y.P., and Garcia, J.M. (2015). Ghrelin prevents tumour- and cisplatin-induced muscle wasting: Characterization of multiple mechanisms involved. J. Cachexia Sarcopenia Muscle, 132\u2013143.","DOI":"10.1002\/jcsm.12023"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"R89","DOI":"10.1152\/ajpregu.00044.2016","article-title":"The ghrelin receptor agonist HM01 mimics the neuronal effects of ghrelin in the arcuate nucleus and attenuates anorexia-cachexia syndrome in tumor-bearing rats","volume":"311","author":"Borner","year":"2016","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1210\/en.2007-0016","article-title":"Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia","volume":"148","author":"DeBoer","year":"2007","journal-title":"Endocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0006-291X(02)03028-0","article-title":"Anti-cachectic effect of ghrelin in nude mice bearing human melanoma cells","volume":"301","author":"Hanada","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1007\/s00520-013-1800-0","article-title":"Effect of ghrelin and anamorelin (ONO-7643), a selective ghrelin receptor agonist, on tumor growth in a lung cancer mouse xenograft model","volume":"21","author":"Northrup","year":"2013","journal-title":"Support. Care Cancer"},{"key":"ref_31","first-page":"1393","article-title":"Effects of ghrelin on anorexia in tumor-bearing mice with eicosanoid-related cachexia","volume":"28","author":"Wang","year":"2006","journal-title":"Int. J. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1111\/nmo.12459","article-title":"New ghrelin agonist, HM01 alleviates constipation and L-dopa-delayed gastric emptying in 6-hydroxydopamine rat model of Parkinson\u2019s disease","volume":"26","author":"Karasawa","year":"2014","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Borner, T., Arnold, M., Ruud, J., Breit, S.N., Langhans, W., Lutz, T.A., Blomqvist, A., and Riediger, T. (2016). Anorexia-cachexia syndrome in hepatoma tumour-bearing rats requires the area postrema but not vagal afferents and is paralleled by increased MIC-1\/GDF15. J. Cachexia. Sarcopenia Muscle.","DOI":"10.1002\/jcsm.12169"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1002\/cne.21407","article-title":"Identification of rat brainstem neuronal structures activated during cancer-induced anorexia","volume":"504","author":"Ruud","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Aulino, P., Berardi, E., Cardillo, V.M., Rizzuto, E., Perniconi, B., Ramina, C., Padula, F., Spugnini, E.P., Baldi, A., and Faiola, F. (2010). Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse. BMC Cancer, 10.","DOI":"10.1186\/1471-2407-10-363"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s11914-013-0165-0","article-title":"Bone Mineral Density Deficits and Fractures in Survivors of Childhood Cancer","volume":"11","author":"Wilson","year":"2013","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0304-3940(02)00241-0","article-title":"Peripheral ghrelin selectively increases Fos expression in neuropeptide Y\u2014Synthesizing neurons in mouse hypothalamic arcuate nucleus","volume":"325","author":"Wang","year":"2002","journal-title":"Neurosci. Lett."},{"key":"ref_38","first-page":"31","article-title":"The Pentapeptide RM-131 Promotes Food Intake and Adiposity in Wildtype Mice but Not in Mice Lacking the Ghrelin Receptor","volume":"1","author":"Fischer","year":"2014","journal-title":"Front. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0304-3940(03)00789-4","article-title":"Centrally administered ghrelin suppresses sympathetic nerve activity in brown adipose tissue of rats","volume":"349","author":"Yasuda","year":"2003","journal-title":"Neurosci. Lett."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.regpep.2005.04.004","article-title":"Ghrelin regulates adiposity in white adipose tissue and UCP1 mRNA expression in brown adipose tissue in mice","volume":"130","author":"Tsubone","year":"2005","journal-title":"Regul. Pept."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2814","DOI":"10.1096\/fj.11-183632","article-title":"Ghrelin-induced adiposity is independent of orexigenic effects","volume":"25","author":"Heppner","year":"2011","journal-title":"FASEB J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1210\/me.2008-0432","article-title":"Ghrelin Induces Abdominal Obesity Via GHS-R-Dependent Lipid Retention","volume":"23","author":"Davies","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"ref_43","first-page":"2290","article-title":"Experimental cancer cachexia induced by transplantable colon 26 adenocarcinoma in mice","volume":"50","author":"Tanaka","year":"1990","journal-title":"Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s13539-014-0141-2","article-title":"Modeling human cancer cachexia in colon 26 tumor-bearing adult mice","volume":"5","author":"Talbert","year":"2014","journal-title":"J. Cachexia. Sarcopenia Muscle"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1172\/JCI115767","article-title":"Evidence for the involvement of interleukin 6 in experimental cancer cachexia","volume":"89","author":"Strassmann","year":"1992","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.peptides.2006.11.021","article-title":"Central infusion of the melanocortin receptor antagonist agouti-related peptide (AgRP(83\u2013132)) prevents cachexia-related symptoms induced by radiation and colon-26 tumors in mice","volume":"28","author":"Joppa","year":"2007","journal-title":"Peptides"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/jcsm.12008","article-title":"Differences in food intake of tumour-bearing cachectic mice are associated with hypothalamic serotonin signalling","volume":"6","author":"Dwarkasing","year":"2015","journal-title":"J. Cachexia. Sarcopenia Muscle"},{"key":"ref_48","first-page":"533","article-title":"Importance of functional and metabolic impairments in the characterization of the C-26 murine model of cancer cachexia","volume":"5","author":"Murphy","year":"2012","journal-title":"Dis. Model. Mech."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.cmet.2014.06.011","article-title":"A Switch from White to Brown Fat Increases Energy Expenditure in Cancer-Associated Cachexia","volume":"20","author":"Petruzzelli","year":"2014","journal-title":"Cell Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.bbi.2010.12.010","article-title":"Cancer induces inflammation and depressive-like behavior in the mouse: Modulation by social housing","volume":"25","author":"Lamkin","year":"2011","journal-title":"Brain. Behav. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1097\/MCO.0b013e32833a5577","article-title":"Glucose metabolism in cancer cells","volume":"13","author":"Annibaldi","year":"2010","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1210\/jc.2004-1788","article-title":"Active Ghrelin Levels and Active to Total Ghrelin Ratio in Cancer-Induced Cachexia","volume":"90","author":"Garcia","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.1210\/endo.142.8.8324","article-title":"Reversal of Cancer Anorexia by Blockade of Central Melanocortin Receptors in Rats","volume":"142","author":"Wisse","year":"2001","journal-title":"Endocrinology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1159\/000076042","article-title":"Agonist-Specific Coupling of Growth Hormone Secretagogue Receptor Type 1a to Different Intracellular Signaling Systems","volume":"79","author":"Carreira","year":"2004","journal-title":"Neuroendocrinology"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Guntur, A.R., and Rosen, C.J. (2013). IGF-1 regulation of key signaling pathways in bone. Bonekey Rep., 2.","DOI":"10.1038\/bonekey.2013.171"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1038\/nm1677","article-title":"Tumor-induced anorexia and weight loss are mediated by the TGF-\u03b2 superfamily cytokine MIC-1","volume":"13","author":"Johnen","year":"2007","journal-title":"Nat. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4951","DOI":"10.1523\/JNEUROSCI.14-08-04951.1994","article-title":"Systemic interleukin-1 induces early and late patterns of c-fos mRNA expression in brain","volume":"14","author":"Brady","year":"1994","journal-title":"J. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/0361-9230(94)00217-O","article-title":"Anatomic patterns of FOS immunostaining in rat brain following systemic endotoxin administration","volume":"36","author":"Sagar","year":"1995","journal-title":"Brain Res. Bull."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1210\/endo.139.5.6005","article-title":"Cytokine regulation of the rat proopiomelanocortin gene expression in AtT-20 cells","volume":"139","author":"Katahira","year":"1998","journal-title":"Endocrinology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11815","DOI":"10.1523\/JNEUROSCI.2234-10.2010","article-title":"Agrp Neurons Mediate Sirt1\u2019s Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity","volume":"30","author":"Dietrich","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"136","DOI":"10.4103\/0973-1075.73644","article-title":"Treatment of cachexia in oncology","volume":"16","author":"Tazi","year":"2010","journal-title":"Indian J. Palliat. Care"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/sj.bjc.6604148","article-title":"Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia\/cachexia: A randomised, placebo-controlled, double-blind, double-crossover study","volume":"98","author":"Strasser","year":"2008","journal-title":"Br. J. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.1007\/s00520-016-3144-z","article-title":"Anamorelin (ONO-7643) in Japanese patients with non-small cell lung cancer and cachexia: Results of a randomized phase 2 trial","volume":"24","author":"Takayama","year":"2016","journal-title":"Support. Care Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/jso.2930310402","article-title":"Tumor measurement in the nude mouse","volume":"31","author":"Euhus","year":"1986","journal-title":"J. Surg. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"11619","DOI":"10.1021\/ac403061n","article-title":"Multiplexed Target Detection Using DNA-Binding Dye Chemistry in Droplet Digital PCR","volume":"85","author":"McDermott","year":"2013","journal-title":"Anal. Chem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/5\/986\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:34:42Z","timestamp":1760207682000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/5\/986"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,5]]},"references-count":66,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2017,5]]}},"alternative-id":["ijms18050986"],"URL":"https:\/\/doi.org\/10.3390\/ijms18050986","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,5]]}}}