title: A non-human primate model of radiation-induced cachexia.
abstract: Cachexia, or muscle wasting, is a serious health threat to victims of radiological accidents or patients receiving radiotherapy. Here, we propose a non-human primate (NHP) radiation-induced cachexia model based on clinical and molecular pathology findings. NHP exposed to potentially lethal partial-body irradiation developed symptoms of cachexia such as body weight loss in a time- and dose-dependent manner. Severe body weight loss as high as 20-25% was observed which was refractory to nutritional intervention. Radiographic imaging indicated that cachectic NHP lost as much as 50% of skeletal muscle. Histological analysis of muscle tissues showed abnormalities such as presence of central nuclei, inflammation, fatty replacement of skeletal muscle, and muscle fiber degeneration. Biochemical parameters such as hemoglobin and albumin levels decreased after radiation exposure. Levels of FBXO32 (Atrogin-1), ActRIIB and myostatin were significantly changed in the irradiated cachectic NHP compared to the non-irradiated NHP. Our data suggest NHP that have been exposed to high dose radiation manifest cachexia-like symptoms in a time- and dose-dependent manner. This model provides a unique opportunity to study the mechanism of radiation-induced cachexia and will aid in efficacy studies of mitigators of this disease.
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201 USA 10 South Pine Street, MSTF Room 604, Baltimore, MD 21201 USA.
authors.forename: Wanchang
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201 USA 10 South Pine Street, MSTF Room 604, Baltimore, MD 21201 USA.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Bennett
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201 USA 10 South Pine Street, MSTF Room 604, Baltimore, MD 21201 USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201 USA 10 South Pine Street, MSTF Room 604, Baltimore, MD 21201 USA.
authors.forename: Kory R
authors.initials: KR
authors.lastname: Barrow
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201 USA 10 South Pine Street, MSTF Room 604, Baltimore, MD 21201 USA.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Kearney
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201 USA 10 South Pine Street, MSTF Room 604, Baltimore, MD 21201 USA.
authors.forename: Kim G
authors.initials: KG
authors.lastname: Hankey
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201 USA 10 South Pine Street, MSTF Room 604, Baltimore, MD 21201 USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Taylor-Howell
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201 USA 10 South Pine Street, MSTF Room 604, Baltimore, MD 21201 USA.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Gibbs
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201 USA 10 South Pine Street, MSTF Room 604, Baltimore, MD 21201 USA.
authors.forename: Cassandra P
authors.initials: CP
authors.lastname: Smith
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland, 21201 USA 10 South Pine Street, MSTF Room 604, Baltimore, MD 21201 USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: MacVittie
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000009:adverse effects*; D005786:Gene Expression Regulation; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D009133:Muscular Atrophy / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D055435:Myostatin / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D013997:Time Factors; D015431:Weight Loss / Q000528:radiation effects*
chemical_list: D006454:Hemoglobins; D055435:Myostatin; D012709:Serum Albumin; D044843:SKP Cullin F-Box Protein Ligases; D030301:Activin Receptors, Type II