Cancer cachexia and anabolic interventions: a case report

Dillon, E. Lichar; Basra, Gurjot; Horstman, Astrid M.; Casperson, Shanon; Randolph, Kathleen M.; Durham, William J.; Urban, Randall J.; Diaz-Arrastia, Concepcion; Levine, Lyuba; Hatch, Sandra S.; Willis, Maurice; Richardson, Gwyn; Sheffield‐Moore, Melinda

doi:10.1007/s13539-012-0066-6

Cited by 31 publications

(30 citation statements)

References 58 publications

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“…Despite evidence of the androgen-induced improvement of muscle wasting and anorexia, androgen replacement therapy is not a standard treatment for cancer cachexia (25)(26)(27). Testosterone may be a viable therapeutic option for cancer cachexia.…”

Section: Discussionmentioning

confidence: 99%

Prevention of body weight loss and sarcopenia by a novel selective androgen receptor modulator in cancer cachexia models

et al. 2017

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Abstract. Cancer cachexia is a syndrome that impairs the quality of life and overall survival of patients, and thus the effectiveness of anticancer agents. There are no effective therapies for cancer cachexia due to the complexity of the syndrome, and insufficient knowledge of its pathogenesis results in difficulty establishing appropriate animal models. Previously, promising results have been obtained in clinical trials using novel agents including the ghrelin receptor agonist anamorelin, and the selective androgen receptor modulator (SARM) enobosarm to treat cachexia in patients with cancer. The present study examined the pharmacological effects of SARM-2f, a novel non-steroidal small molecule SARM, in animal models. SARM-2f increased body and skeletal muscle weight without significantly increasing the weight of the seminal vesicles or prostates of the castrated male rats. In the mice with tumor necrosis factor α-induced cachexia, SARM-2f and TP restored body weight, carcass weight, and food consumption rate. In the C26 and G361 cancer cachexia animal models, body and carcass weight, lean body mass, and the weight of the levator ani muscle were increased by SARM-2f and TP treatments. Tissue selectivity of SARM-2f was also observed in these animal models. The results demonstrate the anabolic effects of SARM-2f in a cytokine-induced cachexia model and other cancer cachexia models, and suggest that SARM-2f may be a novel therapeutic option for cachexia in patients with cancer. IntroductionCancer cachexia is defined as a multifactorial disorder associated with an ongoing loss of skeletal muscle mass with or without loss of fat mass, which leads to a progressive functional impairment that cannot be fully reversed with conventional nutritional supplementation (1). The symptoms appear in up to 80% of patients with cancer and account for at least 20% of cancer-associated deaths (1,2). Cancer cachexia has been reported to be caused by nutritional deficiencies, metabolic disorders, and inflammatory disorders (3-6). Presently, however, there is no approved therapy for the treatment or prevention of cancer cachexia. Therefore, an effective therapy for cancer cachexia is an unmet medical need. There are several potential therapeutic approaches for cancer cachexia (7-10). Androgen is a steroid hormone with multiple physiological functions including promotion of growth hormone release, appetite stimulation, anabolic actions, stimulatory effects on the central nervous system (CNS), and regulation of energy homeostasis. Low plasma androgen levels are often observed in patients with terminal cancer (11,12). Therefore, androgen-based treatments might be a potential therapy for cancer cachexia. However, testosterone replacement therapy has unavoidable side effects such as myocardial infarction, heart failure, stroke, depression, and aggression (13,14).In a previous study, we reported the 4-(pyrrolidin-1-yl) benzonitrile derivative as a selective androgen receptor modulator (SARM)-1c (15). Unlike testosterone, SARM-1c exhibited an...

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Section: Discussionmentioning

confidence: 99%

Prevention of body weight loss and sarcopenia by a novel selective androgen receptor modulator in cancer cachexia models

et al. 2017

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“…A 48-year-old Caucasian female with recurrent cervical cancer was administered with whey protein (10 g thrice daily) and a weekly intramuscular injection of testosterone enanthate before and during the standard-of-care (SOC) chemotherapy. As a result of the combination therapy, improvement of lean body mass, physical activity, and overall quality of life was observed (Dillon et al 2012). The protective effect of whey protein hydrolysate against oxidative damage on rat pheochromocytoma PC12 cells was studied.…”

Section: Anticancermentioning

confidence: 99%

Emerging trends in nutraceutical applications of whey protein and its derivatives

Patel

2015

J Food Sci Technol

125

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The looming food insecurity demands the utilization of nutrient-rich residues from food industries as valueadded products. Whey, a dairy industry waste has been characterized to be excellent nourishment with an array of bioactive components. Whey protein comprises 20 % of total milk protein and it is rich in branched and essential amino acids, functional peptides, antioxidants and immunoglobulins. It confers benefits against a wide range of metabolic diseases such as cardiovascular complications, hypertension, obesity, diabetes, cancer and phenylketonuria. The protein has been validated to boost recovery from resistance exercise-injuries, stimulate gut physiology and protect skin against detrimental radiations. Apart from health invigoration, whey protein has proved its suitability as fat replacer and emulsifier. Further, its edible and antimicrobial packaging potential renders its highly desirable in food as well as pharmaceutical sectors. Considering the enormous nutraceutical worth of whey protein, this review emphasizes on its established and emerging biological roles. Present and future scopes in food processing and dietary supplement formulation are discussed. Associated hurdles are identified and how technical advancement might augment its applications are explored. This review is expected to provide valuable insight on whey protein-fortified functional foods, associated technical hurdles and scopes of improvement.

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“…In the instance of cancer cachexia approximately 50% of patients suffer with cachexia (muscle atrophy), which alone accounts for 25% of all cancer deaths [12][13][14]. The regulation of skeletal muscle mass is reliant on the balance between hypertrophy (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…A potential clinical intervention for promoting a positive net balance in the favour of protein synthesis is Testosterone (T) administration [15,16]. T replacement therapy has been observed to increase muscle strength and mass in various clinical populations including patients with AIDS, COPD and sarcopenia [12,[17][18][19][20]. However a limited number of studies have investigated the role of T in skeletal muscle hypertrophy and atrophy [21][22][23] at the cellular level.…”

Section: Introductionmentioning

confidence: 99%