Understanding and Managing Cancer Cachexia

MacDonald, Neil; Easson, Alexandra; Mazurak, Vera C.; Dunn, Geoffrey P.; Baracos, Vickie E.

doi:10.1016/s1072-7515(03)00382-x

Cited by 174 publications

(104 citation statements)

References 163 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although cachexia has been described as ''a wasting syndrome involving loss of muscle and fat directly caused by tumor factors, or indirectly caused by an aberrant host response to tumor presence,'' thus indicating weight loss as the hallmark of cachexia, [7] a recent consensus definition has been proposed to include additional factors to diagnose the cachexia syndrome, such as involuntary weight loss, decreased muscle mass, anorexia, inflammation, and biochemical alterations. [8] Systemic inflammation is closely associated with cancer cachexia and could result from production of pro-inflammatory cytokines such as interleukin 1-beta (IL-1b), interleukin 6 (IL-6), tumor necrosis factor alpha (TNFa), and interferon gamma (IFNg).…”

Section: Introductionmentioning

confidence: 99%

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

et al. 2012

View full text Add to dashboard Cite

Background and Objective: In patients with advanced cancer, cachexia correlates with low performance status and poor quality of life. In addition, cachexia may be associated with reduced response to chemoradiotherapy and a poor prognosis in cancer patients. Nearly all forms of cachexia are closely associated with chronic inflammation and elevated levels of inflammatory and pro-inflammatory circulating factors, including C-reactive protein (CRP), which is considered a valid laboratory and clinical marker. Among the different pathways involved in the production of inflammatory cytokines and chemokines, the vitamin Dvitamin D receptor (VDR) axis plays a fundamental role.In this study, we explore the possible association between CRP and key factors pertaining to the vitamin D axis -in particular, VDR gene polymorphisms -in cancer patients with cachexia. Although certain tumor types are more commonly associated with cachexia, even within the same tumor type there are significant differences in the extent and duration of cachexia. Such variations may be due to polymorphisms of the VDR gene that could lead to cachexia-prone genotypes or to cachexia-resistant genotypes. Identification of such genotypes could be very helpful in the management of cancer patients. Methods: Forty-three cancer patients were recruited by the Nutritional Unit of the Prato Hospital. Data on age, gender, type of cancer, stage of cancer, and nutritional assessment, as well as transferrin, ferritin, albumin, and CRP levels, were collected. Genomic DNA was extracted from peripheral blood leukocytes and amplified by polymerase chain reaction. BsmI, ApaI, TaqI, and FokI polymorphisms of the VDR gene were investigated using the respective restriction enzymes. For the different VDR polymorphisms, the absence or presence of the restriction sites were designated with capital or small letters, respectively. For example, for the BsmI polymorphism, the presence of the undigested fragment identified the B allele, whereas the presence of the digested fragment identified the b allele. Results: Cancer patients with cachexia have higher CRP levels compared with non-cachectic cancer patients, independently from the genotype. In cachectic patients, the presence of specific VDR BsmI and TaqI alleles was associated with higher CRP levels. In particular, the VDR b and T alleles were more frequent in cachectic cancer patients with elevated CRP levels than in cachectic patients with normal CRP levels. Conclusion: From these results, we hypothesize that there is an association between BsmI and TaqI VDR gene polymorphisms and the cachectic syndrome. In particular, we propose that in cancer patients, the concomitance of b and T alleles with elevated CRP levels may represent an early clinical predictor for the development of a more aggressive form of cachexia.

show abstract

Section: Introductionmentioning

confidence: 99%

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Muscle loss has serious clinical consequences such as decline in functional status, increased disability risk and alteration of respiratory muscle function (2).…”

Section: Introductionmentioning

confidence: 99%

β-hydroxy-β-methylbutyrate (HMB) attenuates muscle and body weight loss in experimental cancer cachexia

Muscaritoli¹

2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. ß-hydroxy-ß-methylbutyrate (HMB), a leucine metabolite, improves muscle mass and function. This study aimed at evaluating the effects of HMB administration in an experimental in vivo model of cancer cachexia (CC). Wistar rats were randomized to receive standard or 4% HMBenriched chow. Rats from both groups were randomized to receive an i.p. inoculum of AH-130 cells (TB). All rats were weighed and sacrificed at day 24. Liver, heart and muscles were dissected and weighed. The protein levels of p-p70S6k, p-eIf2·, p-mTOR and p-4-EB-P1 were evaluated by Western blotting on gastrocnemius muscle (GSN). As expected, the growth of the AH-130 ascites hepatoma induced significant carcass weight and GSN muscle loss. HMB treatment significantly increased GSN and heart weight in controls (p=0.002 and p<0.001, respectively). In HMB-treated TB, body weight was not lost but significantly (p=0.003) increased, and GSN loss was significantly (p=0.04) attenuated with respect to TB. Phosphorylated eIF2· markedly decreased in TB-rats vs. C. Feeding the HMB-enriched diet resulted in decreased p-eIF2· levels in control animals, while no changes could be observed in the TB group. Phosphorylated p70S6K and phosphorylated mTOR were markedly increased by HMB treatment in controls and further increased in TB. Phosphorylated 4-EB-P1 was markedly increased in TB but substantially unaffected by HMB treatment. Administration of HMB attenuates body weight and muscle loss in experimental CC. Increased phosphorylation of key anabolic molecules suggests that these actions are mediated by improved protein anabolism in muscle.

show abstract

“…It has no agreed definition but represents the complex metabolic process that occurs in patients with these conditions. 1 Cachectic patients lose lean muscle mass as well as fat, unlike starvation where only fat stores are initially depleted. In addition, the muscle wasting of cachexia cannot be reversed by increased food intake alone.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the muscle wasting of cachexia cannot be reversed by increased food intake alone. 2,3 Weight loss is the symptom most commonly associated with cachexia but there are numerous other features (Table 1), 1 of which fatigue is an important one (70-100% of cancer patients). 4 Cancer cachexia is common.…”

Section: Introductionmentioning

confidence: 99%