Protein-calorie undernutrition in hospitalized cancer patients

Nixon, Daniel W.; Heymsfield, Steven B.; Cohen, Alice E.; Kutner, Michael; Ansley, Joseph D.; Lawson, David H.; Rudman, Daniel

doi:10.1016/0002-9343(80)90254-5

Cited by 260 publications

(79 citation statements)

References 12 publications

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“…Clinical observations suggested that low albumin might indicate an unfavourable prognosis, especially in the near future (Nixon et al, 1980;Hill, 1987;Heys et al, 1992). Still, our flexible spline-based model showed the statistical significance of time-dependent changes in the effect of albumin, and detected the dramatic effect of low baseline albumin on NSCL mortality in the next 3 -4 months.…”

Section: Discussionmentioning

confidence: 68%

Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer

et al. 2010

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BACKGROUND: C-reactive protein (CRP) is gaining credibility as a prognostic factor in different cancers. Cox's proportional hazard (PH) model is usually used to assess prognostic factors. However, this model imposes a priori assumptions, which are rarely tested, that (1) the hazard ratio associated with each prognostic factor remains constant across the follow-up (PH assumption) and (2) the relationship between a continuous predictor and the logarithm of the mortality hazard is linear (linearity assumption). METHODS: We tested these two assumptions of the Cox's PH model for CRP, using a flexible statistical model, while adjusting for other known prognostic factors, in a cohort of 269 patients newly diagnosed with non-small cell lung cancer (NSCLC). RESULTS: In the Cox's PH model, high CRP increased the risk of death (HR ¼ 1.11 per each doubling of CRP value, 95% CI: 1.03 -1.20, P ¼ 0.008). However, both the PH assumption (P ¼ 0.033) and the linearity assumption (P ¼ 0.015) were rejected for CRP, measured at the initiation of chemotherapy, which kept its prognostic value for approximately 18 months. CONCLUSION: Our analysis shows that flexible modeling provides new insights regarding the value of CRP as a prognostic factor in NSCLC and that Cox's PH model underestimates early risks associated with high CRP.

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Section: Discussionmentioning

confidence: 68%

Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer

et al. 2010

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“…Although cancer cachexia is associated w-ith depletion of both adipose tissue and skeletal muscle mass. it is x-isceral protein and lean body mass depletion (as assessed by serum albumin concentration and creatinine-heijht index) rather than adipose depletion that haxe a w-orse prognostic impact (Nixon et al 1980). Peripheral muscle w asting may be due to increased muscle catabolism or decreased protein synthesis.…”

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confidence: 99%

Mechanism of muscle protein degradation induced by a cancer cachectic factor

Lorite

Thompson²,

Drake³

et al. 1998

Br J Cancer

121

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Summary A proteolysis-inducing factor (PIF) isolated from a cachexia-inducing murne tumour (MAC16) produced a decrease in body weight (1.6 g, P. 0.01 compared with control subjects) within 24 h after i.v. administration to non-tumour-bearing mice. Weight loss was associated with significant decreases in the weight of the spleen and soleus and gastrocnemius muscles. with no effect on the weight of the heart or kidney and with an increase in weight of the liver. Protein degradation in isolated soleus muscle was signfficantly increased in mice bearing the MAC16 tumour. To define which proteolytic pathways contribute to this increase, soleus muscles from mice bearing the MAC16 tumour and non-tumour-bearing animals administered PIF were incubated under conditions that modify different proteolytic systems. In mice bearing the MAC16 tumour, there were increases in both cathepsin B and L, and the Ca2--dependent lysosomal and ATP-dependent pathways were found to contribute to the increased proteolysis; whereas, in PIF-injected animals, there was activation only of the ATP-dependent pathway. Further studies in mice bearing the MAC16 tumour have provided evidence for increased levels of ubiquitin-conjugated proteins and increased mRNA levels for the 14 kDa ubiquitin carrier protein E2 and the C9 proteasome subunit in gastrocnemius muscle, suggesting activation of the ATP-ubiquitin-dependent proteolytic pathway. A monoclonal antibody to PIF attenuated the enhanced protein degradation in soleus muscle from mice bearing the MAC16 tumour, confirming that PIF is responsible for the loss of skeletal muscle in cachectic mice.

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“…More than 80% of hospitalised cancer patients show evidence of protein-energy undernutrition (Nixon et al, 1980) and cachexia is a major contributing factor to mortality in patients with malignant disease (Warren, 1932). Often, the side effects of ineffective antineoplastic therapy exacerbate the nutritional consequences of progressive tumour growth.…”

mentioning

confidence: 99%