Anorexia–Cachexia syndrome in cancer: implications of the ubiquitin–proteasome pathway

Camps, Carlos; Iranzo, Virginia Pardo; Bremnes, Roy M.; Sirera, Rafael

doi:10.1007/s00520-006-0097-7

Cited by 30 publications

(26 citation statements)

References 120 publications

(43 reference statements)

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“…The ubiquitin proteasome pathway is a major protein degradation pathway involved in cancer cachexia (Camps et al 2006;Lecker et al 1999). The E1, E2, and E3 ubiquitin conjugating enzymes work to polyubiquitinate proteins for degradation by the proteasome complex.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic analysis of cancer cachexia reveals distinct lipid and glucose alterations

O’Connell

Ardeshirpour

Asher³

et al. 2008

Metabolomics

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Cancer cachexia remains a challenging clinical problem with complex pathophysiology and unreliable diagnostic tools. A blood test to detect this metabolic derangement would aid in early treatment of these patients. A 1 H NMR-based metabolomics approach was used to determine the unique metabolic fingerprint of cachexia and to search for biomarkers in serum samples taken from an established murine model of cancer cachexia. Male CD2F1 mice received a subcutaneous flank injection of C26 adenocarcinoma cells to induce experimental cancer-related cachexia. Two molecular markers of muscle atrophy, upregulation of the E3 ubiquitin ligase Muscle Ring Finger 1 (MuRF1) and aberrant glycosylation of b-dystroglycan (b-DG), were used to confirm muscle wasting in the tumorbearing mice. Serum samples were collected for metabolomic analysis during the development of the cachexia: at baseline, when the tumor was palpable, and when the mice demonstrated cachexia. The unsupervised statistical analysis demonstrated a distinct metabolic profile with the onset of cachexia. The critical metabolic changes associated with cachexia included increased levels of very low density lipoprotein (VLDL) and low density lipoprotein (LDL), with decreased serum glucose levels. Regression analysis demonstrated a very high correlation of the presence of aberrant glycosylation of b-DG with the unique metabolic profile of cachexia. This study demonstrates for the first time that metabolomics has potential as a diagnostic tool in cancer cachexia, and in further elucidating simultaneous metabolic pathway alterations due to this syndrome. In addition, variations in VLDL and LDL deserve more investigation as surrogate serum biomarkers for cancer cachexia.

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Section: Discussionmentioning

confidence: 99%

Metabolomic analysis of cancer cachexia reveals distinct lipid and glucose alterations

O’Connell

Ardeshirpour

Asher³

et al. 2008

Metabolomics

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“…Aberrant immune system activity is a crucial aspect of the chronic systemic inflammation associated with CACS and it triggers a vicious cycle leading to further tumour growth and metastases. Although the interconnections between aberrant immune system activity and CACS are multifaceted, two specific pathways appear to be prominent; the ubiquitinproteasome pathway (Camps et al, 2006) and the vitamin D axis that includes vitamin D, the polymorphic vitamin D receptor (VDR), the vitamin D-binding protein (or Gc-protein) and its derivative, Gc protein-derived Macrophage Activating Factor (GcMAF), one of the most potent stimuli of the immune system (Strohle et al, 2010;Ruggiero and Pacini, 2011). As schematically illustrated in Fig.…”

Section: Introductionmentioning

confidence: 99%

Role of Angiotensin-Converting Enzyme and Vitamin D Receptor Gene Polymorphisms in Cancer Anorexia-Cachexia Syndrome

Fabris

Biagioni²,

Punzi

et al. 2012

American Journal of Immunology

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The ubiquitin-proteasome pathway is a crucial connection between aberrant immune system activation, systemic inflammation and Cancer Anorexia-Cachexia Syndrome (CACS), a syndrome that culminates in hyper-activation of the ubiquitin-proteasome pathway. Angiotensin directly up-regulates this pathway, while vitamin D down-regulates it indirectly through the insulin-like growth factor-1 pathway. We investigated the genetic predisposition towards CACS in a cancer population, examining Insertion/Deletion (I/D) polymorphism of angiotensin-converting enzyme gene and FokI and BsmI polymorphisms of vitamin D receptor gene. Sixty-two cancer patients were recruited and divided into three groups: primary cachectic (C1, n = 14; dysmetabolic body weight loss â¥5% in 6 months); secondary cachectic (C2, n = 34; similar weight loss, mechanic or iatrogenic origin); and non-cachectic (NC, n = 16). C2+NC were merged in the control group. The three groups showed significant differences in average prognostic inflammatory nutritional index (C1: 26.4Â±23.4; C2: 5.4Â±5.6; NC: 0.37Â±0.5), C-reactive protein serum levels (C1: 6.6Â±2.1; C2: 2.4Â±2.2; NC: 1.0Â±2.0 mg/dL), albumin serum levels (C1: 3.1Â±0.6; C2: 3.5Â±0.4; NC 3.7Â±0.6 g/dL), weight loss (C1: 22Â±8; C2: 15Â±6.7; NC 5Â±6%) and life expectancy (C1: 6.4Â±3.3; C2: 25Â±28; NC: 45Â±25 months). However, none of the chosen polymorphisms showed any statistically significant correlation with CACS. The complexity of the changes of the immune system in the chronic inflammation state associated with CACS is far greater than expected and further studies are required to identify genetic independent markers of progression toward CACS.

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“…Anorexia-cachexia syndrome affects up to 80% of patients with advanced cancer (Harman, 2009). This syndrome results in weight loss, anorexia, tissue wasting, weakness, impaired immune function and poor physical performance (Camps, Iranzo, Bremnes & Sirera, 2006;Esper & Harb, 2005;Laviano, Meguid, Inui, Muscaritoli, & Rossi-Fannelli, 2005). This, combined with anemia (which is often present), results in limitations in physical activities and the inhibition of protein synthesis.…”

Section: Anorexia-cachexia Syndromementioning

confidence: 99%

“…When anorexia is combined with cachexia: "it acts synergistically to impact on patients' morbidity, mortality and quality of life" (Laviano et al, 2005, p.159). According to the literature, 50% of patients express abnormalities of eating behavior at the time of initial diagnosis and in those with terminally ill cancer, the incidence increases to 65% (Camps et al, 2006Laviano et al, 2005. Patients with no weight loss at the initial cancer diagnosis had better survival rates, fewer treatment complications, and a better response to Artificial hydration at the end of life 14 chemotherapy than those with weight loss (Camps et al, 2006Laviano et al , 2005 present the optimal treatment is to cure the underlying cancer.…”

Section: Anorexia-cachexia Syndromementioning

confidence: 99%

“…When this is not possible, a number of approaches need to be considered. The expertise of dieticians, coupled with pharmacotherapies such as progestins, cannabinoids and corticosteroids are possibilities (Camps, Iranzo, Bremnes & Sirera, 2006;Esper & Harb, 2005;Harman, 2009;Laviano, Meguid, Inui, Muscaritoli, & Rossi-Fannelli, 2005). There is no cure for anorexia-cachexia syndrome, and the management is challenging.…”

Section: Anorexia-cachexia Syndromementioning

confidence: 99%

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Is there a place for artificial hydration in end of life care

Bourque¹

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The purpose of this project is to thoroughly explore research and best practice guidelines related to the administration of artificial hydration in end of life care for patients diagnosed with cancer. More specifically, this project will address the question: Is there a place for artificial hydration in end of life care? Upon reviewing the information included in subsequent sections, nurse practitioners will acquire the following: an appreciation of the historical context of hospice palliative care, a thorough understanding of the pathophysiology of the dying process, knowledge of the burdens and benefits of artificial hydration, an understanding of the psychosocial aspects of death and dying, knowledge of ethical principles in relation to end of life care, as well as tools to communicate effectively to patients and family members during one of the most critical phases of their life.Artificial hydration at the end of life 3 Acknowledgement

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Anorexia–Cachexia syndrome in cancer: implications of the ubiquitin–proteasome pathway

Cited by 30 publications

References 120 publications

Metabolomic analysis of cancer cachexia reveals distinct lipid and glucose alterations

Metabolomic analysis of cancer cachexia reveals distinct lipid and glucose alterations

Role of Angiotensin-Converting Enzyme and Vitamin D Receptor Gene Polymorphisms in Cancer Anorexia-Cachexia Syndrome

Is there a place for artificial hydration in end of life care

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