Role of Activin A and Myostatin in Human Cancer Cachexia

Loumaye, Audrey; Barsy, Marie de; Nachit, Maxime; Lause, Pascale; Frateur, L.; Maanen, Aline Van; Tréfois, Pierre; Gruson, Damien; Thissen, Jean‐Paul

doi:10.1210/jc.2014-4318

Cited by 171 publications

(198 citation statements)

References 41 publications

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“…This observation is consistent with our previous study, showing an association between cancer cachexia and low circulating Myostatin 15. Although Myostatin is doubtless an inhibitor of skeletal muscle mass development, its role in muscle atrophy remains unclear.…”

Section: Discussionsupporting

confidence: 93%

“…In addition, in an animal model of cancer cachexia, ActA inhibition reverses the cachexia phenotype together with an increased survival, without any effect on tumour mass 8. Moreover, we highlighted previously that cachexia is associated with high levels of ActA 15. These data suggest that high levels of ActA may affect survival by decreasing skeletal muscle mass or quality associated with loss of functional capacity.…”

Section: Discussionmentioning

confidence: 55%

“…Supporting this hypothesis, we observed that both low muscularity and ActA are significantly associated with poor prognosis in our patients, particularly those with lung cancer. In other hand, ActA levels were negatively correlated with SMD,15 a marker of muscle quality, which was also associated with poor prognosis in our population. Interestingly, excepted nature tumour, all other parameters highlighted as prognostic factors, such as low albumin levels and decrease of functional capacity, are linked to skeletal muscle loss.…”

Section: Discussionmentioning

confidence: 66%

“…At baseline, deceased patients had a lower body mass index (24 kg/m 2 vs. 25 kg/m 2 , P = 0.026) and had lost more body weight (5.4% vs. 2.4%, P = 0.019) than alive patients. Moreover, deceased patients had more severe anorexia (SNAQ score: deceased vs. alive patients: 146, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 vs. 168, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20; P = 0.005), more symptoms (QLQ‐C30: deceased vs. alive patients: 33 2–66 vs. 15 6–69 ; P < 0.0001), a poorer quality of life (QLQ‐C30: deceased vs. alive patients: 58 16–100 vs. 66 0–100 ; P = 0.002) and a lower functional capacity (QLQ‐C30: deceased vs. alive patients: 64 18–97 vs. 82 33–100 ; P < 0.0001 and ECOG; P < 0.0001) than alive patients.…”

Section: Resultsmentioning

confidence: 99%

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Circulating Activin A predicts survival in cancer patients

Loumaye

Barsy

Nachit

et al. 2017

J cachexia sarcopenia muscle

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BackgroundSeveral experimental evidences pinpoint the possible role of Activin A (ActA) as a driver of cancer cachexia. Supporting this hypothesis, we showed recently that human cancer cachexia is associated with high ActA levels. Moreover, ActA levels were correlated with body weight loss and skeletal muscle density, two prognostic factors in cancer patients. Our goal was therefore to investigate the value of ActA to predict survival in cancer patients.MethodsPatients with colorectal or lung cancer were prospectively enrolled at the time of diagnosis or relapse between January 2012 and March 2014. At baseline, patients had clinical, nutritional, and functional assessment. Body composition and skeletal muscle density were measured by CT scan, and plasma ActA concentrations were determined. Overall survival (OS) was analysed since inclusion to 24 months later.ResultsSurvival data were available for 149 patients out of 152. Patients with high ActA (≥408 pg/mL) had lower OS than those with low levels, regardless the type of cancer (OS in colorectal cancer, 50% vs. 79%, P < 0.05; and in lung cancer, 27% vs. 67%, P = 0.001). The multivariable analysis confirmed the prognostic value of ActA independently of tumour stage or inflammatory markers, particularly in lung cancer. Low muscularity was also an independent prognostic factor.ConclusionsOur study demonstrates that high ActA level is an independent prognosis factor of survival in cancer patients. More than a basic marker of the severity of the neoplastic disease or of the inflammatory process, ActA seems to influence survival by contributing to the development of cachexia and loss of skeletal muscle mass.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 66%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Circulating Activin A predicts survival in cancer patients

Loumaye

Barsy

Nachit

et al. 2017

J cachexia sarcopenia muscle

Self Cite

View full text Add to dashboard Cite

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“…In particular, treatment with ghrelin and parathyroid hormone-related protein (PTHrP) alleviates anorexia in receptor B (ActR2B), whose antagonism potently reverses cancer-induced cachexia (Xia & Schneyer 2009, Zhou et al 2010. Interestingly, circulating serum levels of ActA, which has been demonstrated to be secreted by cancer cells, are elevated in cancer cachectic patients (Zhou et al 2010, Loumaye et al 2015. Mechanistically, myostatin and activins trigger skeletal muscle protein breakdown by upregulating MuRF1 and MAFbx/Atrogin1, as well as decreasing protein synthesis via inhibition of the Akt/ mTOR pathway (Chen et al 2014, Gallot et al 2014.…”

Section: Molecular Mechanisms Of Skeletal Muscle Wastingmentioning

confidence: 99%

Molecular and neuroendocrine mechanisms of cancer cachexia

Mendes

Pimentel

Costa

et al. 2015

Journal of Endocrinology

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Cancer and its morbidities, such as cancer cachexia, constitute a major public health problem. Although cancer cachexia has afflicted humanity for centuries, its underlying multifactorial and complex physiopathology has hindered the understanding of its mechanism. During the last few decades we have witnessed a dramatic increase in the understanding of cancer cachexia pathophysiology. Anorexia and muscle and adipose tissue wasting are the main features of cancer cachexia. These apparently independent symptoms have humoral factors secreted by the tumor as a common cause. Importantly, the hypothalamus has emerged as an organ that senses the peripheral signals emanating from the tumoral environment, and not only elicits anorexia but also contributes to the development of muscle and adipose tissue loss. Herein, we review the roles of factors secreted by the tumor and its effects on the hypothalamus, muscle and adipose tissue, as well as highlighting the key targets that are being exploited for cancer cachexia treatment.

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Cancer Cachexia

Eid¹,

Njeim²,

Khuri³

et al. 2022

Holland‐Frei Cancer Medicine

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Overview Cachexia is a systemic wasting syndrome of progressive muscle and, usually, adipose loss, multi‐organ dysfunction, and wide metabolic derangement, often exacerbated by anorexia and diminished nutritional intake. More than half of all cancer patients develop cachexia, which directly causes profound morbidity and substantially reduced survival. New large‐scale high‐dimensional clinical and experimental studies are revealing unexpected ground truths that cachexia frequently occurs in early stages of many cancers; has several distinct clinical phenotypes; increases complications of and reduces response to cancer‐directed therapies. More precise tools for early assessment, diagnosis, and multi‐modal interventions, including quantitative image‐based body composition analysis, molecular biomarkers, and new targeted therapeutics are in advanced development. These advances, with rapidly expanding basic research into causal molecular mechanisms, are transforming our fundamental understanding of this complex disease as being integral with cancer biology, treatment response, and patient outcomes.

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Role of Activin A and Myostatin in Human Cancer Cachexia

Cited by 171 publications

References 41 publications

Circulating Activin A predicts survival in cancer patients

Circulating Activin A predicts survival in cancer patients

Molecular and neuroendocrine mechanisms of cancer cachexia

Cancer Cachexia

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