Theophylline is able to partially revert cachexia in tumour-bearing rats

Oliván, Mireia; Springer, Jochen; Busquets, Sı́lvia; Tschirner, Anika; Figueras, Maite; Toledo, Míriam; Fontes-Oliveira, Cibely C.; Genovese, Maria Inês; Silva, Paula Ventura da; Sette, Angelica; López‐Soriano, Francisco J.; Anker, Stefan D.; Argilés, Josep Μ.

doi:10.1186/1743-7075-9-76

Cited by 18 publications

(14 citation statements)

References 34 publications

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“…We also found an increase in the expression of autophagy genes in skeletal muscle, corroborating previous clinical evidence that this pathway of catabolism is a key contributor to lean tissue loss 42. In addition to skeletal muscle, cardiac muscle is often profoundly catabolic and functionally compromised by cancer cachexia 43, 44, 45. Cardiac dysfunction is independently associated with substantial morbidity and mortality in cachexia, and its mechanistic underpinnings are therefore an important topic of investigation.…”

Section: Discussionsupporting

confidence: 87%

“…42 In addition to skeletal muscle, cardiac muscle is often profoundly catabolic and functionally compromised by cancer cachexia. [43][44][45] Cardiac dysfunction is independently associated with substantial morbidity and mortality in cachexia, and its mechanistic underpinnings are therefore an important topic of investigation. Cardiac muscle catabolism in cachexia has previously been linked to induction of autophagy and variably to expression of atrophy-associated ubiquitin ligases.…”

Section: Discussionmentioning

confidence: 99%

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Establishment and characterization of a novel murine model of pancreatic cancer cachexia

Michaelis

Zhu

Burfeind

et al. 2017

J cachexia sarcopenia muscle

110

161

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BackgroundCachexia is a complex metabolic and behavioural syndrome lacking effective therapies. Pancreatic ductal adenocarcinoma (PDAC) is one of the most important conditions associated with cachexia, with >80% of PDAC patients suffering from the condition. To establish the cardinal features of a murine model of PDAC‐associated cachexia, we characterized the effects of implanting a pancreatic tumour cell line from a syngeneic C57BL/6 KRASG12D P53R172H Pdx‐Cre+/+ (KPC) mouse.MethodsMale and female C57BL/6 mice were inoculated subcutaneously, intraperitoneally, or orthotopically with KPC tumour cells. We performed rigorous phenotypic, metabolic, and behavioural analysis of animals over the course of tumour development.ResultsAll routes of administration produced rapidly growing tumours histologically consistent with moderate to poorly differentiated PDAC. The phenotype of this model was dependent on route of administration, with orthotopic and intraperitoneal implantation inducing more severe cachexia than subcutaneous implantation. KPC tumour growth decreased food intake, decreased adiposity and lean body mass, and decreased locomotor activity. Muscle catabolism was observed in both skeletal and cardiac muscles, but the dominant catabolic pathway differed between these tissues. The wasting syndrome in this model was accompanied by hypothalamic inflammation, progressively decreasing brown and white adipose tissue uncoupling protein 1 (Ucp1) expression, and increased peripheral inflammation. Haematological and endocrine abnormalities included neutrophil‐dominant leukocytosis and anaemia, and decreased serum testosterone.ConclusionsSyngeneic KPC allografts are a robust model for studying cachexia, which recapitulate key features of the PDAC disease process and induce a wide array of cachexia manifestations. This model is therefore ideally suited for future studies exploring the physiological systems involved in cachexia and for preclinical studies of novel therapies.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Establishment and characterization of a novel murine model of pancreatic cancer cachexia

Michaelis

Zhu

Burfeind

et al. 2017

J cachexia sarcopenia muscle

110

161

View full text Add to dashboard Cite

show abstract

“…As with skeletal muscle, the cardiac muscle is an important target in cancer cachexia and the loss of body weight is often accompanied by wasting of cardiac muscle . Identical observations were made in laboratory rodents bearing cachexia‐inducing tumours, where cardiac atrophy is frequently observed . In the mouse colon‐26 cancer cachexia model, cardiac alterations include marked fibrosis, disrupted myocardial ultrastructure and altered composition of contractile proteins (e.g.…”

Section: Cancer Cachexiamentioning

confidence: 99%

Cancer cachexia and its pathophysiology: links with sarcopenia, anorexia and asthenia

Silva

Santos

Silva

et al. 2020

J cachexia sarcopenia muscle

218

191

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Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass, along with adipose tissue wasting, systemic inflammation and other metabolic abnormalities leading to functional impairment. Cancer cachexia has long been recognized as a direct cause of complications in cancer patients, reducing quality of life and worsening disease outcomes. Some related conditions, like sarcopenia (age‐related muscle wasting), anorexia (appetite loss) and asthenia (reduced muscular strength and fatigue), share some key features with cancer cachexia, such as weakness and systemic inflammation. Understanding the interplay and the differences between these conditions is critical to advance basic and translational research in this field, improving the accuracy of diagnosis and contributing to finally achieve effective therapies for affected patients.

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“…Cancer is associated with severe heart alterations. Indeed, tumours implanted in experimental animals result in a decrease of the heart weight [ 53 , 54 ], accompanied by functional cardiac changes, similar to those found in congestive heart failure. According to Schünemann et al “cancer fatigue syndrome reflects clinically non-overt heart failure,” clearly attributing a main role for heart abnormalities in the fatigue of cancer patient [ 55 ].…”

Section: Heartmentioning

confidence: 99%

Nonmuscle Tissues Contribution to Cancer Cachexia

Argilés

Stemmler²,

López‐Soriano

et al. 2015

Mediators of Inflammation

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Cachexia is a syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting, and inflammation, being often associated with anorexia. In spite of the fact that muscle tissue represents more than 40% of body weight and seems to be the main tissue involved in the wasting that occurs during cachexia, recent developments suggest that tissues/organs such as adipose (both brown and white), brain, liver, gut, and heart are directly involved in the cachectic process and may be responsible for muscle wasting. This suggests that cachexia is indeed a multiorgan syndrome. Bearing all this in mind, the aim of the present review is to examine the impact of nonmuscle tissues in cancer cachexia.

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Theophylline is able to partially revert cachexia in tumour-bearing rats

Cited by 18 publications

References 34 publications

Establishment and characterization of a novel murine model of pancreatic cancer cachexia

Establishment and characterization of a novel murine model of pancreatic cancer cachexia

Cancer cachexia and its pathophysiology: links with sarcopenia, anorexia and asthenia

Nonmuscle Tissues Contribution to Cancer Cachexia

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