Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia

Klimek, Margaret E. Benny; Aydogdu, Tufan; Link, Majik; Pons, Marianne; Koniaris, Leonidas G.; Zimmers, Teresa A.

doi:10.1016/j.bbrc.2009.12.123

Cited by 204 publications

(136 citation statements)

References 36 publications

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“…In effect, myostatin is a skeletal muscle-specific secreted peptide that essentially modulates myoblast proliferation and thus muscle mass/strength . Preclinical trials using myostatin loss or inhibition have been effective in ameliorating symptoms of weakness in several animal Klimek et al 2010;Bogdanovich et al 2002;Lee and McPherron 2001;Liu et al 2008;Morrison et al 2009;Murphy et al 2010;Qiao et al 2009;Siriett et al 2006;Tsuchida 2008;Wagner et al 2008;Zhu et al 2007). In humans, myostatin inhibitors, such as MYO-029, have an adequate safety margin and are able to improve the muscle strength/function or muscle contractile properties in some patients with muscular dystrophy (Krivickas et al 2009;Wagner et al 2008).…”

Section: Discussionmentioning

confidence: 99%

“…Myostatin loss or inhibition has proven effective in ameliorating symptoms of weakness in several animal models of muscle injury, atrophy and disease (Benny Klimek et al 2010;Bogdanovich et al 2002;Lee and McPherron 2001;Liu et al 2008;Morrison et al 2009;Murphy et al 2010;Qiao et al 2009;Siriett et al 2006;Tsuchida 2008;Wagner et al 2008;Zhu et al 2007). Myostatin inhibition, as well as variations in the MSTN gene, can also have functional consequences in humans.…”

Section: Introductionmentioning

confidence: 99%

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Association of the K153R polymorphism in the myostatin gene and extreme longevity

Garatachea

Pinós

Cámara

et al. 2013

AGE

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The myostatin (MSTN) gene is a candidate to influence extreme longevity owing to its role in modulating muscle mass and sarcopenia and especially in inhibiting the main nutrient-sensing pathway involved in longevity, i.e. mammalian target of rapamycin. We compared allele/genotype distributions of the exonic MSTN variants K153R (rs1805086), E164K (rs35781413), I225T and P198A, in Spanish centenarians (cases, n=156; 132 women, age range 100-111 years) and younger adults (controls, n=384; 167 women, age <50 years). No subject of either group carried a mutant allele of the E164K, I225T or AGE (2013) 35:2445-2454 DOI 10.1007 Antoni L. Andreu and Alejandro Lucia share senior authorship. P198A variation. The frequency of the variant R allele was significantly higher in centenarians (7.1 %) than in controls (2.7 %) (P=0.001). The odds ratio of being a centenarian if the subject had the R allele was 3.48 (95 % confidence interval 1.67-7.28, P=0.001), compared to the control group, after adjusting for sex. The results were replicated in an Italian cohort (centenarians, n=79 (40 women), age range 100-104 years; younger controls, n=316 (155 women), age <50 years), where a higher frequency of the R allele in centenarians (7.6 %) compared to controls (3.0 %) (P=0.004) was independently confirmed. Although more research is needed, the variant allele of the MSTN K153R polymorphism could be among the genetic contributors associated with exceptional longevity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of the K153R polymorphism in the myostatin gene and extreme longevity

Garatachea

Pinós

Cámara

et al. 2013

AGE

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“…But TSA treatment to tumor-bearing mice increased the expression level of follistatin without preserving or increasing skeletal muscle mass. These studies show that alteration of myostatin/follistatin axis is not sufficient to protect muscle mass specifically in cancer-induced cachexia [87][88][89]. Such findings point to the fact that the outcome of TSA treatment is not same under diverse clinical settings.…”

Section: Meloxicammentioning

confidence: 91%

Skeletal muscle atrophy: Potential therapeutic agents and their mechanisms of action

Dutt

Gupta

Dabur

et al. 2015

Pharmacological Research

143

112

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“…It has been suggested that eicosanoids also mediate inflammation in cancer cachexia [38][39][40] . There is considerable evidence that signaling through cytokines and myostatin/activin pathways has a role in cancer cachexia and anorexia [41][42][43] ( Figure 1). Numerous cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), IL-6, and interferon-gamma (IFN-γ), have been postulated to play a role in the etiology of cancer cachexia [44][45][46][47][48][49][50][51][52] .…”

Section: Inflammationmentioning

confidence: 99%

Cancer cachexia, mechanism and treatment

Aoyagi¹,

Terracina²,

Ali³

et al. 2015

WJGO

369

282

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It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responses to chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials.

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Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia

Cited by 204 publications

References 36 publications

Association of the K153R polymorphism in the myostatin gene and extreme longevity

Association of the K153R polymorphism in the myostatin gene and extreme longevity

Skeletal muscle atrophy: Potential therapeutic agents and their mechanisms of action

Cancer cachexia, mechanism and treatment

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