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On the model of tumor growth of Guerin's carcinoma and experimental modeling of vitamin A provision the biochemical characteristics of tumor cachexia in animals with malignant tumors and different vitamin A provision status were studied. It is determined that tumor growth in the body, deprived of vitamin A, is characterized by negative nitrogen balance, decrease of glucose, free fatty acids and ketone bodies level in the blood serum, which indicates the increase of cancer cachexia.

Background: It is not clear why cardiac or renal cachexia in chronic diseases is associated with poor cardiovascular outcomes. Platelet reactivity predisposes to thromboembolic events in the setting of atherosclerotic cardiovascular disease, which is often present in patients with end-stage renal disease (ESRD)., Objectives: We hypothesized that ESRD patients with relative thrombocytosis (platelet count >300 × 10(3)/μL) have a higher mortality rate and that this association may be related to malnutrition-inflammation cachexia syndrome (MICS)., Design: We examined the associations of 3-mo-averaged platelet counts with markers of MICS and 6-y all-cause and cardiovascular mortality (2001-2007) in a cohort of 40,797 patients who were receiving maintenance hemodialysis., Results: The patients comprised 46% women and 34% African Americans, and 46% of the patients had diabetes. The 3-mo-averaged platelet count was 229 ± 78 × 10(3)/μL. In unadjusted and case-mix adjusted models, lower values of albumin, creatinine, protein intake, hemoglobin, and dialysis dose and a higher erythropoietin dose were associated with a higher platelet count. Compared with patients with a platelet count of between 150 and 200 × 10(3)/μL (reference), the all-cause (and cardiovascular) mortality rate with platelet counts between 300 and <350, between 350 and <400, and ≥400 ×10(3)/μL were 6% (and 7%), 17% (and 15%), and 24% (and 25%) higher (P < 0.05), respectively. The associations persisted after control for case-mix adjustment, but adjustment for MICS abolished them., Conclusions: Relative thrombocytosis is associated with a worse MICS profile, a lower dialysis dose, and higher all-cause and cardiovascular disease death risk in hemodialysis patients; and its all-cause and cardiovascular mortality predictability is accounted for by MICS. The role of platelet activation in cachexia-associated mortality warrants additional studies.

Background and Objective: Weight loss in patients with severe chronic obstructive pulmonary disease (COPD) is a prognostic bad factor. The objective of this study is to analyze the effectively of megestrol acetate (MA) to increase appetite of these patients., Patients and Methods: Randomized double blind placebo controlled trial to study the effect of 160 mg/bid of MA, for 8 weeks, on nutritional, functional, analytical and quality of life parameters, in 38 patients with severe COPD and body mass index (BMI) < 21 kg/m(2), or between 21-25 with involuntary weight loss of 5% in the last 3 months., Results: At 8 weeks, in the MA group the body weight increased (2.3 kg) with respect to the control group (0.1 kg) (p<0.04). MA improved significantly the triceps skin-fold thickness (p < 0.04), prealbumin (p<0.004), lymphocytes (p<0.0006), C3 (p<0.04), PCO(2) (p<0.007) and bicarbonate levels (p<0.008). MA did not increase the MRC and SGRQ scales, the distance of 6 MWT nor BODE index. The IL-6 and TNF alpha levels were not modified in the MA group, but leptin did increase (p<0.043). MA improved the sense of wellbeing (p<0.02) and the appetite (p<0.008), compared to the control group. Adverse effects were similar in both groups., Conclusions: MA safely increases the body weight and the appetite in severe COPD patients with weight loss. MA improves blood gases and nutritional parameters and the sense of wellbeing, but it does not improve the respiratory muscular function or exercise tolerance., (Copyright © 2010 Elsevier España, S.L. All rights reserved.)

Cachexia has plagued clinicians for centuries. Although all cachexia is related to malnutrition, cachexia associated with malignant diseases differs from starvation cachexia in that it is more recalcitrant to nutritional therapy. All cachexia responds to judicious nutritional support; however, cancer cachexia worsens autonomously as the disease advances and cannot be arrested or reversed by any known form of nutrition, hormonal, or pharmacologic therapy. Cachexia must be treated cautiously to avoid overfeeding syndrome, which may result in serious or dangerous complications or death., (2011 Elsevier Inc. All rights reserved.)

Aims: Treatment of cachexia requires pharmacological intervention which, in turn, requires knowledge of the mediators and processes. Cachexia markers that are specifically expressed in pancreatic cancer and secreted into the blood circulation have yet to be identified. The aim of our study was to investigate the serum protein profiles and protein alterations associated with cachexia and to identify potential disease protein biomarkers indicative for this syndrome., Main Methods: Serum samples from cachectic and non-cachectic patients undergoing pancreatic cancer (PaCa) surgery and controls were investigated by Surface Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS). The identity of detected discriminatory markers was determined by a combination of protein fractionation, chromatographic purification steps, gel electrophoresis, and mass spectrometry., Key Findings: Using Cu-IMAC array and CM-10 array based SELDI-TOF-MS. we identified eleven up- and four down-regulated proteins associated with cachexia. CiphergenExpress analysis revealed four disease-associated protein features (38559Da, 9138Da, 8925Da and 3358Da) that were elevated by a factor of 2.3, 1.7, 1.4 and 1.4, respectively. Zinc-α2-glycoprotein (ZAG), apolipoproteins apo C-II and apo C-III and glucagon-like peptide-1 (GLP-1) were identified as markers for PaCa-associated cachexia syndrome. ZAG levels were additionally evaluated in serum and tissue samples by ELISA and immunohistochemistry and the obtained data confirmed the SELDI-TOF-MS results., Significance: The identified proteins could be routinely and reliably measured in the serum of patients and provide an elegant non-invasive approach for early diagnosis of cachectic pancreatic cancer patients. Controlling ZAG and GLP-1 activity could be beneficial in the management of cancers and cachexia-induced conditions., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Cachexia, or weight loss despite adequate nutrition, significantly impairs quality of life and response to therapy in cancer patients. In cancer patients, skeletal muscle wasting, weight loss and mortality are all positively associated with increased serum cytokines, particularly Interleukin-6 (IL-6), and the presence of the acute phase response. Acute phase proteins, including fibrinogen and serum amyloid A (SAA) are synthesized by hepatocytes in response to IL-6 as part of the innate immune response. To gain insight into the relationships among these observations, we studied mice with moderate and severe Colon-26 (C26)-carcinoma cachexia., Methodology/principal Findings: Moderate and severe C26 cachexia was associated with high serum IL-6 and IL-6 family cytokines and highly similar patterns of skeletal muscle gene expression. The top canonical pathways up-regulated in both were the complement/coagulation cascade, proteasome, MAPK signaling, and the IL-6 and STAT3 pathways. Cachexia was associated with increased muscle pY705-STAT3 and increased STAT3 localization in myonuclei. STAT3 target genes, including SOCS3 mRNA and acute phase response proteins, were highly induced in cachectic muscle. IL-6 treatment and STAT3 activation both also induced fibrinogen in cultured C2C12 myotubes. Quantitation of muscle versus liver fibrinogen and SAA protein levels indicates that muscle contributes a large fraction of serum acute phase proteins in cancer., Conclusions/significance: These results suggest that the STAT3 transcriptome is a major mechanism for wasting in cancer. Through IL-6/STAT3 activation, skeletal muscle is induced to synthesize acute phase proteins, thus establishing a molecular link between the observations of high IL-6, increased acute phase response proteins and muscle wasting in cancer. These results suggest a mechanism by which STAT3 might causally influence muscle wasting by altering the profile of genes expressed and translated in muscle such that amino acids liberated by increased proteolysis in cachexia are synthesized into acute phase proteins and exported into the blood.

Muscle wasting that occurs with cancer cachexia is caused by an imbalance in the rates of muscle protein synthesis and degradation. The Apc(Min/+) mouse is a model of colorectal cancer that develops cachexia that is dependent on circulating IL-6. However, the IL-6 regulation of muscle protein turnover during the initiation and progression of cachexia in the Apc(Min/+) mouse is not known. Cachexia progression was studied in Apc(Min/+) mice that were either weight stable (WS) or had initial (≤5%), intermediate (6-19%), or extreme (≥20%) body weight loss. The initiation of cachexia reduced %MPS 19% and a further ∼50% with additional weight loss. Muscle IGF-1 mRNA expression and mTOR targets were suppressed with the progression of body weight loss, while muscle AMPK phosphorylation (Thr 172), AMPK activity, and raptor phosphorylation (Ser 792) were not increased with the initiation of weight loss, but were induced as cachexia progressed. ATP dependent protein degradation increased during the initiation and progression of cachexia. However, ATP independent protein degradation was not increased until cachexia had progressed beyond the initial phase. IL-6 receptor antibody administration prevented body weight loss and suppressed muscle protein degradation, without any effect on muscle %MPS or IGF-1 associated signaling. In summary, the %MPS reduction during the initiation of cachexia is associated with IGF-1/mTOR signaling repression, while muscle AMPK activation and activation of ATP independent protein degradation occur later in the progression of cachexia. IL-6 receptor antibody treatment blocked cachexia progression through the suppression of muscle protein degradation, while not rescuing the suppression of muscle protein synthesis. Attenuation of IL-6 signaling was effective in blocking the progression of cachexia, but not sufficient to reverse the process.

In individuals with advanced chronic kidney disease, secondary hyperparathyroidism is known to be associated with high turnover bone disease. Low serum parathyroid hormone (PTH) levels may not necessarily be because of hypodynamic bone, but could be another facet of the malnutrition-inflammation-cachexia syndrome (MICS). A recent 5-year cohort study in 748 stable hemodialysis outpatients showed that after the confounding effect by the MICS was removed, the moderately low levels of PTH in the 100 to 150 pg/mL range was associated with the greatest survival rate. Data from Japanese dialysis patients show similar survival advantages of having a lower PTH range. Low levels of serum PTH seem to be associated with markers of protein-energy wasting and inflammation, and this association may confound the relationship between serum PTH and alkaline phosphatase. PTH stimulates lipogenesis through influx of calcium into the adipocytes. PTH secretion is suppressed by interleukin-1 beta and interleukin-6, which are proinflammatory cytokines that are associated with poor outcome in dialysis patients. These cytokines inhibits PTH secretion in cultured parathyroid tissue slices. In this article, we review the association of a low serum PTH level with the MICS in patients with chronic kidney disease and suggest avoiding over-interpretation of low serum PTH level as an indicator of low turnover bone disease., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

We report on a patient suffering from chronic anorexia nervosa who in the course of treatment showed elevated high-sensitive troponin T, creatine kinase and most markedly N-terminal pro-brain natriuretic peptide (NT-proBNP). Elevated enzymes improved significantly throughout the course of treatment without cardiac specific medication but exceeded the normal range for weeks. Abnormally high myocardial enzymes and NT-proBNP in cachectic anorectic patients might resemble conditions of cardiac cachexia. A review of the available literature is provided. Further research is required to explain the pathophysiological meaning of the abnormal laboratory findings., (Copyright © 2011 S. Karger AG, Basel.)

Objective: To investigate whether the single nucleotide polymorphisms (SNPs) at -1082, -819 and -592 of interleukin-10 gene and its haplotype are associated with cachexia in patients with gastric cancer., Methods: Radioimmunoassay was used to examine the serum levels of IL-10 in 223 patients with gastric cancer. The single nucleotide polymorphisms (SNPs) of IL-10 gene -1082G/A, -819T/C and -592A/C were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)., Results: The serum levels of IL-10 were significantly higher in patients with cachexia than those without (P < 0.001). An increased frequency of -1082G allele was noted in patients with cachexia (P = 0.049). The frequencies of -1082AG and -819CC genotypes were elevated in patients with cachexia than those without (P = 0.036, 0.024). In a logistic regression analysis adjusted for actual weight, carcinoma location and stage, the -1082AG genotype was associated with an odds ratio of 1.989 (95%CI, 1.041 - 3.802, P = 0.037), and the -819CC genotype with an odds ratio of 3.393 (95%CI, 1.298 - 8.871, P = 0.013) for cachexia. Furthermore, haplotype analysis revealed that G1082C819C592 haplotype was associated with a significantly increased risk of cachexia (OR = 2.21; 95%CI, 1.14 - 4.30; P = 0.02)., Conclusion: Our results suggest that the gene haplotype of IL-10 contributes to the occurrence of cachexia in patients with gastric cancer in Chinese population.

Interleukin 6 (IL-6) has received significant attention for its regulatory role in muscle wasting during cachexia. This review examines the role of circulating IL-6 for decreasing muscle mass during cancer and emphasizes some of the indirect actions of IL-6 that may cause muscle wasting.

Background: Acute-phase response proteins (APRP), cytokines and hormones have been claimed to be an independent prognostic factor of malignancies, however the basis for their association with prognosis remains unexplained. We suggest that in colon malignancies, as similar to pancreatic and lung cancers, changes in APRP are associated with angiogenesis., Methods: C-reactive protein (CRP), albumin, IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, midkine, VEGF-A, VEGF-C, leptin, adiponectin, and ghrelin serum levels are studied in 126 colon cancer patients and 36 healthy subjects., Results: We found statistically significant difference and correlations between two groups. We found significantly higher serum CRP, IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, VEGF-A, VEGF-C and leptin concentrations in patients relative to controls (p < 0.001). We found lower levels of the serum albumin, midkine, adiponectin and ghrelin in patients compared to control subjects (p < 0.001)., Conclusions: Cachexia in patients with colon cancers is associated with changes in APRP, cytokines and hormone concentrations. These biomarkers and cachexia together have a direct relationship with accelerated angiogenesis. This may lead to a connection between the outcomes in malignancies and the biomarkers.

We investigated the association between esophageal cancer and cachexia-anorexia syndrome (CAS) of the alimentary tract and leptin, an adipocytokine crucial for body weight regulation, a modulator of inflammatory/immune response, implication of which in cancer and CAS development remains debatable. Circulating leptin was measured in 135 esophageal cancer patients (51 non-cachectic and 84 cachectic) and 83 controls (63 non-cachectic and 20 cachectic) and referred to cancer stage, CAS, and inflammatory and nutritional indices. Leptin was down-regulated in cancer patients and cachectic controls as compared to non-cachectic controls, with more pronounced hypoleptinemia in advanced cancers. Leptin correlated directly with BMI, TNF-alpha, albumin, and hemoglobin and indirectly with IL-6, IL-8, and hsCRP. The correlations, except for hsCRP, were more pronounced in females. BMI alone (females) and BMI and hsCRP (males) were independent predictors of leptin explaining over 60% of its variability. Following adjustment for BMI and gender, cancer-related CAS but not cancer itself negatively affected leptin. Leptin and BMI were independently associated with cancer-related and non-malignant CAS with diagnostic accuracy of 93% in identifying subjects with CAS. Pro-inflammatory, angiogenic and mitogenic properties of leptin do not seem to be important for esophageal cancer development but hypoleptinemia, independently from co-occurring reduction of adiposity, appears to be strongly associated with esophageal cancer-related CAS and non-malignant CAS of the alimentary tract., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background & Aims: Extensive loss of adipose tissue is a key feature of cancer cachexia. Advanced cancer patients also exhibit low plasma phospholipids. It is not known whether these processes coincide across the cancer trajectory nor has their relationship with survival been defined. Changes in adipose tissue mass and plasma phospholipids were characterized within 500days prior to death and prognostic significance assessed., Methods: Adipose tissue rate of change was determined in a retrospective cohort of patients who died of colorectal and lung cancers (n=108) and who underwent >2 computed tomography scans in the last 500days of life. Plasma phospholipid fatty acids were measured prospectively in a similar cohort of patients with metastatic cancer (n=72)., Results: Accelerated loss of adipose tissue begins at 7months from death reaching an average loss of 29% of total AT 2months from death. Plasma phospholipid fatty acids were 35% lower in patients closest to death versus those surviving >8months. Losses of phospholipid fatty acids and adipose tissue occur in tandem and are predictive of survival., Conclusions: Depletion of plasma phospholipids likely indicates a deficit of essential fatty acids in the periphery which may contribute to loss of adipose tissue., (Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Cytokines such as tumor necrosis factor-alpha (TNF) contribute to cardiac dysfunction in chronic heart failure (CHF). Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) are thought to reflect cardiac functional and structural damage., Methods and Results: To study the relationship between BNP, ANP, and TNF, these parameters were measured in fasting venous blood samples of 25 CHF patients (age 66+/-2 years, pVO(2) 17.4+/-2.1 mL/kg/min, NYHA class 2.8+/-0.2, all mean+/-SEM) and 8 healthy controls (age 71+/-2 years). Patients with CHF had higher plasma levels of BNP (p<0.05), ANP (p<0.05), norepinephrine (p<0.01), and echocardiographic left ventricular end-diastolic diameter (LVEDD, p<0.05) compared to controls, whereas TNF and epinephrine were not significantly different. There were significant correlations between natriuretic peptides and markers of inflammation and myocardial dysfunction in CHF patients: BNP vs. TNF (r=0.64, p=0.0006), vs. LVEDD (r=0.59, p=0.0025); ANP vs. TNF (r=0.60, p=0.0016), vs. LVEDD (r=0.65, p=0.0006); TNF vs. LVEDD (r=0.57, p=0.004). After adjustment for NYHA, creatinine clearance, and age TNF correlated with BNP (all p=0.01) and ANP (all p<0.002). The cachectic CHF patients (n=7,>6% weight loss) had the highest BNP (p<0.001 vs. controls, p<0.05 vs. non-cachectic CHF) and ANP levels (p=0.01 vs. controls). Concentrations of uric acid, epinephrine, and norepinephrine also correlated with ANP and BNP., Conclusion: In CHF, TNF is closely related to BNP and ANP (independently of CHF severity and ventricular dysfunction), particularly in patients with cardiac cachexia. TNF may causally contribute to intrinsic cardiac dysfunction thereby stimulating BNP and ANP secretion., (Crown Copyright (c) 2008. Published by Elsevier Ireland Ltd. All rights reserved.)

Background and Objective: Interleukin (IL)-10 is a pleiotropic cytokine that can both stimulate and suppress the immune response. Previous studies have reported that IL-10 production was significantly elevated in cachectic patients, and it has been confirmed that polymorphisms of the IL10 gene could influence its expression. Therefore, we designed this study to investigate whether polymorphisms of the IL10 gene were associated with cachexia in patients with low-third gastric cancer in a Chinese population., Methods: 190 patients with low-third gastric cancer were included in this study. The serum levels of IL-10 were measured by radioimmunoassay. The single nucleotide polymorphisms (SNPs) at positions -1082A/G, -819T/C, and -592A/C in the IL10 gene promoter were analyzed using polymerase chain reaction (PCR) restriction fragment length polymorphism (PCR-RFLP)., Results: The serum levels of IL-10 were significantly higher in patients with cachexia than in those without (Z = -10.66, p < 0.001). Single SNP analysis showed that the frequency of the IL10 -1082G allele was increased in patients with cachexia (p = 0.02). The -1082AG and -819CC genotypes were observed to be associated with an increased risk of cachexia. In a logistic regression analysis adjusted for actual weight and carcinoma stage, the -1082AG genotype was associated with an odds ratio (OR) of 2.45 (95% CI 1.21, 4.96; p = 0.01), and the -819CC genotype was associated with an OR of 3.70 (95% CI 1.20, 11.39; p = 0.02) for cachexia. Furthermore, haplotype analysis of the -1082A/G, -819T/C, and -592A/C SNPs revealed that at least five haplotypes (ATA, ACC, GCC, ACA, and ATC) were present in this Chinese population, and the -1082G/-819C/-592C (GCC) haplotype was associated with a significantly increased risk of cachexia as compared with the ATA haplotype (OR = 2.42; 95% CI 1.17, 5.00; p = 0.02)., Conclusion: Our results indicate that genetic polymorphisms of IL-10 may influence susceptibility to cachexia in patients with low-third gastric cancer in this Chinese population.

Background: Anorexia, cachexia, and insulin resistance are commonly seen in patients with cancer. Adipocyte-derived hormones or adipokines play a role in the regulation of appetite, body weight, and insulin sensitivity. However, their role in cancer-induced cachexia has not been well-established. The objective of this study was to determine the levels of adipokines and their relation to appetite, weight loss, insulin resistance, and other hormones in cancer cachexia., Methods: We measured adiponectin, resistin, and leptin plasma levels in 21 men with cancer cachexia, 24 noncachectic cancer subjects, and 25 noncancer controls matched by age, sex, and pre-illness body weight. Body weight change, appetite scores, insulin resistance assessed by homeostasis model assessment, and other cytokines and hormones were also measured. Differences between groups were measured by analysis of covariance. Relations between variables were examined by linear regression analyses., Results: Adiponectin levels were similarly elevated in cachectic and noncachectic cancer patients compared with noncancer controls. Leptin levels were significantly decreased in cancer cachexia and were directly associated with appetite and insulin resistance, explaining 37% and 19% of the variance seen in cancer patients, respectively. Resistin levels were not different between groups., Conclusions: Leptin may play a role in the increased insulin resistance seen in cancer patients. However, these patients are resistant to the orexigenic effects of hypoleptinemia. Other mechanisms besides weight loss are responsible for the increased adiponectin level seen in cancer patients. It is unlikely that resistin plays a major metabolic role in this setting.

This study investigated whether the single nucleotide polymorphisms (SNPs) and haplotypes of interleukin-10 (IL-10) were associated with cachexia in 223 Chinese patients with gastric cancer diagnosed by histopathological examination. Genomic DNA was extracted from peripheral blood leukocytes. The SNPs at positions -1082A/G, -819T/C, and -592A/C in the IL-10 gene promoter were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). No significant differences were found in the allele and genotype frequencies of -592A/C in patients with or without cachexia. Increased frequency of the -1082G allele was found in patients with cachexia (OR = 1.83, 95% CI, 1.00-3.33, p = 0.049). In a logistic regression analysis adjusted for body weight, carcinoma location, and stage, the -1082AG genotype was associated with an odds ratio of 1.989 (95% CI, 1.041-3.802, p = 0.037) for cachexia. The -819CC genotype was associated with an odds ratio of 3.393 (95% CI, 1.298-8.871, p = 0.013) for cachexia. Furthermore, haplotype analysis revealed that the G(1082)C(819)C(592) haplotype was associated with increased risk of cachexia as compared to the A(1082)T(819)A(592) haplotype (OR = 2.21; 95% CI, 1.14 - 4.30; p = 0.02). Our results suggest that genetic polymorphisms of IL-10 contribute to the susceptibility to cachexia in patients with gastric cancer in the Chinese population.

Objectives: To evaluate the prognostic potential of the modified Glasgow Prognostic Score (mGPS), known to reflect the degree of tumor-associated inflammation and cachexia, in patients with vulvar cancer., Study Design: We included 93 consecutive patients with vulvar cancer into our study. As previously published, the pre-therapeutic mGPS was calculated as follows: patients with elevated C-reactive protein (CRP) serum levels (>10 mg/L) and hypoalbuminaemia (<35 g/L) were allocated a score of 2, patients with elevated CRP serum levels without hypoalbuminaemia were allocated a score of 1, patients with normal CRP serum levels with or without hypoalbuminaemia were allocated a score of 0. The mGPS was correlated with clinico-pathological parameters. The association between mGPS and prognosis was evaluated by univariate and multivariate survival analysis., Results: Mean (SD) pretreatment CRP and albumin serum levels were 9.5 (9.6) mg/L and 41.4 (5.3) g/L, respectively. mGPS was associated with tumor stage (p=0.01), but not with lymph node involvement (p=0.4), histological grade (p=0.8), and patients' age (p=0.7). In univariate analyses, mGPS (p=0.006, p=0.001), tumor stage (p<0.001, p<0.001), lymph node involvement (p<0.001, p<0.001), and patients' age (p=0.04, p=0.007), but not histological grade (p=0.1, p=0.3) and year of surgery (1995-2001 vs. 2002-2008, p=0.7, p=0.3) were associated with disease-free and overall survival, respectively. In a multivariate analysis, tumor stage (p=0.01, p=0.02) and lymph node involvement (p<0.001, p=0.001), but not mGPS (p=0.7, p=0.8), patients' age (p=0.6, p=0.4), histological grade (p=0.2, p=0.1), and year of surgery (p=0.4, p=0.8) were associated with disease-free and overall survival, respectively., Conclusions: Despite being associated with prognosis in a univariate analysis, mGPS cannot be used as an independent inflammation-based predictor for survival in patients with vulvar cancer., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Adipocytokines are adipocyte-secreted hormones associated with some malignancies. It has been reported that the impaired response of adipocytokines to body weight loss may play a role in the pathogenesis of cancer-induced cachexia. We investigated the association between adipocytokines with squamous cell carcinoma of the esophagus (SCCE)., Methods: The levels of body mass index (BMI) and adiponectin, leptin, resistin, visfatin and C-peptide in the blood at diagnosis were measured in 117 SCCE patients and 117 age- and sex-matched controls. Logistic regression models were employed to estimate odds ratio. One-way analysis was performed to examine the prevalence of variables between two or more groups. A non-parametric Spearman correlation test was conducted to examine the associations between BMI and other variables., Results: Adiponectin and BMI levels were significantly lower, and resistin level was significantly higher in the patients on multivariate analysis (P = 0.01, <0.01 and <0.01 respectively). BMI gradually decreased with stage progression, and resistin level gradually increased with stage progression (P < 0.01 for both). The inverse correlation between BMI and adiponectin was comparatively strong in the controls, but was weak in the patients. Leptin showed comparatively strong correlation with BMI in the controls, but was weakly correlated in the patients. The correlation between BMI and resistin or C-peptide was demonstrated weakly only in the controls, and visfatin did not correlate with BMI., Conclusions: Resistin may be a biomarker for the progression of SCCE. In addition, the impaired responses to body weight loss of adiponectin and leptin in the patients with SCCE were suggested.

Goals of Work: Advanced tumor disease very often evokes excessive loss of body weight. Among others, fish oil or marine fatty acid ethyl esters were investigated for treatment of cancer cachexia with controversial results. In this study, a new formulation of marine fatty acids was investigated, the marine phospholipids, with more than 50% of phospholipid-bound fatty acids being eicosapentaenoic and docosahexaenoic acid., Materials and Methods: Thirty-one tumor patients with various tumor entities suffering from weight loss were asked to take marine phospholipids (1.5 g/day) as softgel capsules for a period of 6 weeks. Compliance, body weight, appetite, and quality of life as well as the fatty acid profile in plasma and blood cells were monitored; 17 patients could be analyzed., Main Results: Marine phospholipids were very well accepted; low-dose supplementation resulted in a significant increase of eicosapentaenoic and docosahexaenoic acid in plasma phospholipids; therefore, significantly reducing the n-6 to n-3 fatty acid ratio. A stabilization of body weight was achieved (median weight change of +0.6% after 6 weeks), while appetite and quality of life improved., Conclusions: These promising first results encourage further investigation of marine phospholipids in cancer care.

Interleukin (IL)-8 has been implicated in a wide range of diseases. The polymorphism of IL-8 gene, which may affect the production level of the cytokine, may be associated with cancer cachexia. To test this hypothesis, we investigated the potential influence of the polymorphisms of the IL-8 gene, -251 A/T and +781 C/T, on susceptibility to cachexia from patients with gastric cancer in a Chinese population, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). A significantly increased frequency of +781 T allele was noted in patients with cachexia (OR = 1.765, 95% CI: 1.192-2.615, P = 0.004). The +781 TT genotypes were observed to be associated with a significantly increased risk of cachexia (OR = 2.156, 95% CI: 1.056-4.400, P = 0.033), and the difference was enhanced beyond the level of statistical significance when logistic regression was applied (OR = 3.500, 95% CI: 1.406-8.710, P = 0.007). Haplotype analysis revealed that A(251)T(781) haplotype (defined by SNPs at positions -251 and +781) was associated with a significantly increased risk of cachexia as compared with the T(251)C(781) haplotype (OR = 1.69; 95% CI: 1.08-2.62; P = 0.022). These results suggest that the genetic polymorphisms of proinflammatory cytokine IL-8 may contribute to the pathogenesis of cachexia in gastric cancer patients.

We provide evidence that a factor other than the previously identified lipid mobilizing factor, zinc alpha-2 glycoprotein, promotes lipolysis in the MCA-induced sarcoma-bearing cachexia model. Cachexia is characterized by progressive loss of adipose tissue and skeletal muscle without a concurrent increase in food intake to restore lost tissue stores. We compared tumor-bearing ad lib fed (TB) animals to nontumor bearing ad lib fed (NTB) animals or nontumor-bearing pair-fed (PF) animals at various time points throughout development of tumor derived cachexia. Prior to cachexia, the TB animals lost more than 10 +/- 0.7% of their body fat before losing protein mass and decreasing their food intake. Fat loss occurred because adipocyte size, not number, was reduced. Increased turnover of palmitate and significantly higher serum triglyceride levels prior to cachexia were further indicators of an early loss of lipid from the adipocytes. Yet, circulating levels of norepinephrine, epinephrine, TNF-alpha, and zinc alpha-2 glycoprotein were not increased prior to the loss of fat mass. We provide evidence for a serum factor(s), other than zinc alpha-2 glycoprotein, that stimulates release of glycerol from 3T3-L1 adipocytes and promotes the loss of stored adipose lipid prior to the loss of lean body mass in this model.

Background: Cachexia contributes significantly to mortality in cancer patients; role of cytokines in inducing cachexia is an emerging view. Leptin, a homologous protein of cytokine family, is found to be decreased in serum with cachexia. The purpose of this study was to compare serum leptin levels of oral squamous cell carcinoma patients with that of control group and correlate it with body mass index., Method: Serum samples of 31 oral squamous cell carcinoma patients and that of 28 healthy individuals were subjected to evaluation of serum leptin levels (ng/ml) using enzyme-linked immunosorbent assay., Results: A significant reduction in leptin level of oral squamous cell carcinoma patients was observed. Definite correlation between body mass index and serum leptin and also between serum leptin levels of various histopathological variants of oral squamous cell carcinoma was observed., Conclusion: The results of this study suggest that evaluation of serum leptin level can provide status of cachexia in oral squamous cell carcinoma patients.

It is determined that endocrine factors can play role on cachexia in chronic obstructive pulmonary disease (COPD). High levels of ghrelin is reported in cachectic COPD cases but its' relation couldn't shown statistically. In our study, it is aimed to detect serum ghrelin levels in COPD, its' relation with proinflammatory cytokines and whether serum ghrelin is associated with cachexia. Sixty stable COPD patients and 15 healthy volunteers were included in the study. COPD patients were divided into two groups, cachectic and normal weight, according to their body mass index. Spirometric assessments were performed and serum tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6) and ghrelin levels were measured in all cases. When COPD patients were compared with control group; serum ghrelin levels were statistically lower, TNF-a and IL-6 levels were statistically higher in COPD group. For cachectic COPD patients; serum ghrelin levels were statistically lower and IL-6 levels were statistically higher, compared with normal weight COPD patients. Although, serum TNF-a levels were higher for cachectic COPD patients; these levels were not significant. Positive correlation between serum ghrelin levels and body mass index was detected in patients with COPD. As a result; it is thought that increased proinflammatory cytokines and decreased serum active ghrelin levels may contribute to the development of weight loss.

Plasma ghrelin was elevated in chronic heart failure (CHF) patients with cachexia. Obestatin, a sibling of ghrelin, opposes several actions of ghrelin. We, therefore, investigated plasma obestatin and ghrelin levels in patients with CHF. Total plasma ghrelin and obestatin levels were measured in 65 patients with CHF (22 with cardiac cachexia) and 15 controls. Ghrelin levels were significantly higher in patients with cachexia (1237.8+/-47.9 pg/ml) than those without cachexia (P=0.041) and controls (P<0.01). Obestatin levels correlated positively with ghrelin levels, and obestatin levels were significantly increased in patients with cachexia (282.3+/-13.0 pg/ml) than patients without cachexia and controls (both P<0.01). However, the ghrelin to obestatin ratios (4.5+/-0.2) were significantly lower in CHF patients with cachexia than controls (P<0.01). Ghrelin and ratio of ghrelin to obestatin were independent predictors of the development of cardiac cachexia. No association was found between ghrelin, obestatin and New York Heart Association functional class, brain natriuretic peptide. There was disturbance of circulating ghrelin and obestatin in the CHF patients especially those with cachexia, which may have a role in the pathogenesis of cardiac cachexia in CHF.

Background: Ghrelin is a growth hormone-releasing acylated peptide found to be an appetite stimulant and low levels of it are detected in cachexia. The aim of the present study was to investigate the plasma ghrelin levels in cancer patients with a low performance status and weight loss and compare them with those of healthy individuals without weight loss., Patients and Methods: Thirty patients (median age 65 years) with different malignancies, mainly pancreatic and gastric, and 27 healthy individuals (median age 62 years) were examined. The gender of both groups was well balanced. Plasma ghrelin was measured by a radioimmunoassay kit that uses a polyclonal antibody which recognizes the C-terminal of ghrelin., Results: There was a statistically significant difference in the plasma ghrelin levels of the patients vs. the controls, with the patients having much lower levels (p<0.001)., Conclusion: The notable reduction of ghrelin levels might be due to the severity and progression of the disease.

The discovery of ghrelin has resulted in the development of approaches to appetite, enabling a better understanding of the mechanisms regulating appetite through molecular analyses. Ghrelin is a 28-amino acid peptide that was isolated from the stomach only a decade ago, and has recently been investigated as a potential therapeutic endogenous agent. This peptide increases appetite, adjusts energy balance, suppresses inflammation, and enhances the release of growth hormone from the pituitary gland. Although many bioactive substances such as peptide YY, leptin, adiponectin and obestatin are involved in appetite control, ghrelin is the only known peptide to signal starvation information from a peripheral organ to the central nervous system, contributing to an increase in appetite. Clinical trials have revealed the effectiveness of ghrelin in increasing lean body mass and activity in cachectic patients. As shown in clinical research on humans and basic research using animal models, cachexia often occurs in response to excess release of proinflammatory cytokines and induces further appetite loss, which aggravates the physiological status of underlying diseases. Ghrelin functions as a protector against the vicious cycle of the cachectic paradigm through orexigenic, anabolic and anti-inflammatory effects, so administration of ghrelin may be able to improve quality of life in cachectic patients. We show here a significant role of ghrelin in the pathophysiology of cachectic diseases and the possibility of clinical applications.

Background: Cancer cachexia, a catabolic state characterized by weight loss, occurs frequently in patients with terminal-stage neoplastic diseases. Gastrointestinal hormones and cytokines may be associated with anorexia and wasting in cancer cachexia., Methods: This study aimed to examine the mechanism of anorexia in cachectic patients through a prospective investigation of plasma cytokines, ghrelin, and leptin in 16 cachectic patients with cancer of the digestive organs and 10 healthy volunteers., Results: Tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-1 receptor antagonist (IL-1Ra), and ghrelin levels were significantly higher in cachectic cancer patients than in the healthy volunteers, whereas leptin was significantly lower in the cachectic cancer patients. Plasma leptin levels and cytokine levels (TNF-alpha and IL-6) correlated significantly with body mass index (BMI), but plasma ghrelin levels did not correlate with BMI or with the grade of symptoms., Conclusion: Neither weight loss nor the grade of symptoms seemed to be directly associated with the increase in ghrelin levels. Hence, it is considered that the increase in ghrelin levels cannot simply be explained by an increase in ghrelin secretion, suggesting that other mechanisms, such as the decreased inactivation of ghrelin, may also play a role. Further studies are needed to clarify the mechanisms of the increase in ghrelin levels. Additionally, the changes in plasma cytokines (TNF-alpha and IL-6) and leptin in cachectic cancer patients suggest that these molecules may be useful markers for the evaluation of cancer cachexia.

Fentanyl is an opioid with high lipid solubility, suitable for intravenous, spinal, transmucosal and transdermal administration. The transdermal fentanyl patch has become widely used in the treatment of both malignant and non-malignant chronic pain. The absorption of fentanyl from the patch is governed by the surface area of the patch, by skin permeability and by local blood flow. The aim of this study is to find out whether absorption of fentanyl in cachectic patients with cancer-related pain is different from that of normal weight cancer patients. We recruited ten normal weight (mean body mass index (BMI) 23 kg/m(2)) and ten cachectic (mean BMI 16 kg/m(2)) cancer pain patients. A transdermal fentanyl patch with a dose approximately equianalgesic to the patients' previous opioid dose was administered to the upper arm of the patient for 3 days. Prior to patch application, the height, weight and BMI of the patient, as well as upper arm skin temperature, local sweating, thickness of skin fold and local blood flow were measured. Plasma fentanyl concentrations were analyzed from blood samples taken at baseline, 4, 24, 48 and 72 h. Plasma fentanyl concentrations adjusted to dose were significantly lower at 48 and 72 h in cachectic patients than normal weight patients. The cachectic patients had a significantly thinner upper arm skin fold, but no differences were found in local blood flow, sweating, or skin temperature. Absorption of transdermal fentanyl is impaired in cachectic patients compared with that of normal weight cancer pain patients.

Aims: Cardiac cachexia (CC) is a complication of chronic heart failure (CHF). Little is known about the mechanisms leading to CC. Adiponectin, leptin, and ghrelin are important regulators of energy metabolism and body weight. Previous studies of CHF and CC had great differences in body mass index (BMI) between cachectic and non-cachectic patients. To assess serum adiponectin, leptin, and ghrelin concentrations in cachectic and non-cachectic patients., Methods and Results: We conducted a case-control study in CHF patients matched for BMI. Cases (n = 33) were cachectic patients with unintentional weight loss of > or = 7.5% of the previous baseline weight. Controls (n = 33) had no history of weight loss and were individually matched with cases for age, sex, and BMI. Cachectic patients had significantly higher adiponectin levels than controls: 25.0 +/- 12.3 vs. 14.7 +/- 8.8 microg/mL (P = 0.002). Leptin concentration was lower in the cachectic group: 7.5 (IQR 4.0-10.8) vs. 8.0 (IQR 7.1-10.5) ng/mL. Differences in leptin lost significance once adjusted for fat mass. Adiponectin remained higher in cachectics after such adjustment. Ghrelin was not significantly different between groups. Adiponectin correlated positively with weight loss and BNP., Conclusion: Cachexia in CHF was associated with an increase in adiponectin, irrespective of BMI. This suggests a role of adiponectin in the wasting process of cachectic patients.

Background: Soft tissue sarcomas are rare tumors with a wide clinical spectrum. Prognostic factors for survival have been identified, but they have been focused in the characteristics of the tumor. Patient related variables have not usually been considered in previous analysis., Methods: We analyzed a group of 61 patients with soft tissue sarcomas. Tumor related variables and patient related ones were recorded. Overall and disease free survival were calculated according to the Kaplan and Meier method. Prognostic factors for survival were determined by the log-rank method for univariate analysis and the Cox method for multivariate analysis., Results: Clinical and demographic characteristics are comparable to those of previous reports. Adverse prognostic factors for overall survival in multivariate analysis were advanced stage, high tumor grade, irresecability, and serum albumin. Size, high surgical risk (ASA III-IV) and a low performance status (Karnofsky less than 70) were predictive of overall survival only in univariate analysis. For disease free survival, only high tumor grade had statistical significance., Conclusions: Besides the usual tumor related prognostic factors, such as grade and stage, patient related factors, such as performance status and surgical risk should be considered when predicting survival. Specifically, serum albumin was an independent prognostic factor for overall survival.

Background: Patients with renal insufficiency often suffer from cachexia and growth retardation due to low appetite and increased resting metabolic rate. The neuroendocrine hormone ghrelin, a growth hormone secretagogue, enhances food intake, but its role in the development of a cachectic state in renal insufficiency is unclear. Objective. The aim of our study was to investigate the plasma concentration of total ghrelin and other hormones involved in appetite regulation in children with preterminal chronic renal failure (CRF, n = 24), children undergoing dialysis (n = 19), children after renal transplantation (RTx, n = 59) and healthy controls (n = 10)., Results: Total ghrelin was significantly elevated in CRF patients (1370 +/- 182 pg/ml; mean +/- SEM) when compared to control subjects (682 +/- 106 pg/ml; P = 0.016) or patients following RTx (859 +/- 51 pg/ml; P = 0.002). Furthermore, a negative correlation between glomerular filtration rate and total ghrelin was observed in CRF and transplant recipients (r = 0.36, P = 0.0006). BMI SDS (standard deviation score) is lower in CRF patients compared to the other groups (P < 0.0001). Leptin, adiponectin, blood glucose, insulin, IGF-I, IGFBP-3 and growth hormone concentrations did not differ among groups., Conclusions: We observed elevated ghrelin levels in uraemic patients despite poor appetite, but the underlying reasons remain unclear. Normal ghrelin levels can be re-achieved following RTx.

Several biochemical pathways can lead to cancer cachexia, one of which involves the elevation of the cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interferon gamma (INF-gamma). It was suggested that TNF-alpha and INF-gamma genes polymorphisms may influence these cytokines serum levels, but published data are still controversial. The aim of our study was to assess the clinical significance of -308G/A TNF-alpha and +874A/T INF-gamma genes polymorphisms as well as TNF-alpha and INF-gamma serum levels in pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP) as regards to healthy volunteers. We studied 41 patients with pancreatic adenocarcinoma, 56 with chronic pancreatitis and 50 healthy volunteers. Peripheral venous blood samples were obtained from all patients for TNF-alpha and INF-gamma serum concentrations measurement. After DNA isolation TNF-alpha and INF-gamma genes polymorphisms have been studied using restriction fragment length polymorphism (RFLP) analysis. Plasma levels of TNF-alpha were significantly higher in PA patients (32.7 pg/ml) compared with CP patients (3.2 pg/ ml) and control group (<1.6 pg/ml; p<0.01). Similarly, plasma levels of INF-gamma in PA patients (12.7 pg/ml) were higher from those in CP and control group (<7.1 pg/ml; p<0.01). In contrast, there were no differences between CP patients and healthy volunteers in INF-gamma levels. We observed a trend toward a correlation between weight loss in PA patients and TNF-alpha serum level (p=0.02). The TNF-alpha and INF-gamma genotype distribution were similar in patients with PA, CP and control group. We have not observed any association between TNF-alpha and INF-gamma serum levels and their genes polymorphisms. Our results suggest that elevated TNF-alpha serum level may have clinical significance in the development of cachexia in PA patients. -308G/A TNF-alpha and +874A/T INF-gamma genes polymorphisms probably do not play important role in pancreatic diseases. Key words: pancreatic adenocarcinoma, tumor necrosis factor alpha, interferon gamma, cytokines, polymorphism.

Purpose: Adipocytokines are adipocyte-secreted hormones associated with some malignancies. We investigated the association of adipocytokines with gastric cancer., Methods: The levels of body mass index (BMI) and adiponectin, leptin, resistin, visfatin, and C-peptide in blood at diagnosis were measured in 156 gastric cancer patients and 156 age- and sex-matched controls. Logistic regression models were used to estimate odds ratio, and one-way analysis of variance was performed to examine the prevalence of each variable between 2 or more groups., Results: Adiponectin, C-peptide and BMI levels were significantly lower, and resistin and visfatin levels were significantly higher in the patients on multivariate analysis (P=0.0004, 0.0006, 0.0051, 0.0006 and 0.0013, respectively). In the controls, the inverse correlation between BMI and adiponectin was comparatively strong, but was weak in the patients. The correlation between BMI and leptin was strong in both the controls and the patients. The correlation between BMI and resistin or visfatin was not clear in either the patients or the controls. The correlation between BMI and C-peptide was not clear in the controls, but might be weak in the patients. Leptin, C-peptide and BMI levels gradually decreased with stage progression, and resistin and visfatin levels gradually increased with stage progression (P<0.0001 for all). Comparison between 38 patients with Stage I gastric cancer and the controls showed that adiponectin level tended to decrease in the patients (P=0.0582), and BMI level was not different between two groups (P=0.2480)., Conclusions: Resistin and visfatin may be good biomarkers of gastric cancer.

Introduction: Leptin, protein taking part in body mass regulation, might play a role in cancer cachexia development. The aim of the study was to measure leptin serum levels in cachectic, non-cachectic lung cancer patients, healthy controls and to correlate leptin concentration with nutritional status markers., Material and Methods: 40 lung cancer patients were enrolled into the study: 20 with cachexia, 20 without cachexia, and 10 healthy controls. Leptin serum concentration, body mass, BMI, arm circumference and skin triceps fold thickness were measured in each subject., Results: Serum leptin level in cachectic cancer patients was significantly lower than in non-cachectic and healthy controls. Leptin concentration correlated with body mass, arm circumference and skin triceps fold thickness., Conclusions: Cachectic lung cancer patients have significantly lower serum leptin concentrations than non-cachectic patients and healthy controls which may suggest, that leptin does not play an important role in cancer cachexia development. Leptin levels positively correlate with good nutritional status markers. Non-cachectic lung cancer patients have similar leptin serum levels as healthy controls.

Background: Muscle wasting and cachexia are common occurrences in patients with chronic obstructive pulmonary disease (COPD)., Objectives: The current study aimed to investigate markers of inflammation in the circulation and skeletal muscle that might be associated with development of muscle wasting., Methods: Three groups of patients with mild, moderate and severe COPD and matched healthy controls were recruited. Serum levels of C-reactive protein (CRP), high-sensitivity CRP (hs-CRP), IL-6, IL-8, TNF-alpha, cortisol, insulin-like growth factor 1 (IGF-1), leptin and ghrelin were analysed. Skeletal muscle inflammation was investigated microscopically using a panel of antibodies and standard staining for inflammatory cell infiltration., Results: All COPD patients were clinically stable, with no sign of inflammation and normal CRP values. Compared to controls, significantly increased hs-CRP levels were observed in all COPD patient groups. Significant rises in IL-6 levels were first observed in moderate COPD, while IL-8 levels were significantly elevated at the late severe stage. Circulating levels of TNF-alpha, cortisol, IGF-1, leptin and ghrelin were similar to control levels. No microscopic signs of skeletal muscle inflammation were observed., Conclusion: Our results identify hs-CRP as an early marker of inflammation that is significantly increased in the circulation even in mild COPD. Serum interleukin levels appear to be increased with disease progress. These changes were manifested in the absence of any clinical signs of disease exacerbation, evidence of skeletal muscle inflammation or hormonal changes.

Malnutrition is an important problem in patients with chronic obstructive pulmonary disease (COPD). It still remains unclear whether malnutrition contributes to poor pulmonary function through a loss of respiratory muscle mass, or if advanced disease and hypoxemia are the causes of weight loss and malnutrition in COPD patients. This study was made to examine the effects of malnutrition on pulmonary function tests (PFTs) in COPD patients. With this purpose 35 stable COPD patients were enrolled in this study. According to their body mass indexes, the subjects were divided in two groups (group 1: cachectic and group 2: non-cachectic). All subjects were performed PFTs, serum tumor necrosis factor-alpha (TNF-alpha) levels, resting energy expenditure (REE), nutrition parameters, and arterial blood gas tension. PFTs were impaired to a greater degree in cachectic than non-cachectic patients. Serum TNF-alpha levels and REE were higher in cachectic patients than in non-cachectic patients. Significant correlations were observed among PFTs, REE, and serum TNF-alpha level. Furthermore there was a significant correlation between serum albumin level and PFTs. This study demonstrated that cachexia had a negative effect on PFTs in patients with COPD. Additionally, our study showed that serum protein levels can affect airway function and diffusing capacity of lungs in COPD. Another result of this study was that; increased REE and serum TNF-alpha levels could contribute to weight loss in patients with COPD. Further studies are needed to demonstrate the effect of nutritional supplementation containing essential amino acids on PFTs in these patients.

The majority of patients with advanced cancer are recognised by impaired immune competence influenced by several factors, including the type and stage of the tumour and the presence of cachexia. Recently, a specific nutritional combination containing fish oil, specific oligosaccharide mixture, high protein content and leucine has been developed aimed to support the immune system of cancer patients in order to reduce the frequency and severity of (infectious) complications. In a recently modified animal model cachexia is induced by inoculation of C26 tumour cells in mice. In a pre-cachectic state, no effect was observed on contact hypersensitivity, a validated in vivo method to measure Th1-mediated immune function, after adding the individual nutritional ingredients to the diet of tumour-bearing mice. However, the complete mixture resulted in significantly improved Th1 immunity. Moreover, in a cachectic state, the complete mixture reduced plasma levels of pro-inflammatory cytokines and beneficially affected ex vivo immune function. Accordingly, the combination of the nutritional ingredients is required to obtain a synergistic effect, leading to a reduced inflammatory state and improved immune competence. From this, it can be concluded that the specific nutritional combination has potential as immune-supporting nutritional intervention to reduce the risk of (infectious) complications in cancer patients.

In the elderly diabetic patient, therapeutic decision is very delicate because of the psycho social pathological ground at this age. The emergence of new concepts of ageing and frailty made it possible to re-examine the plasma glucose goals and to build strategies of prevention and treatment adapted to the clinical and biological profiles of elderly subjects.

Aim: Cancer cachexia and malnutrition are very common in patients receiving palliative care. They cause a deterioration in the quality of life., Methods: We studied 144 patients (52 females, 92 males) admitted to our Palliative Care Unit. Anthropometric measurements, food and nutritional intake, and plasma levels of few serum proteins were determined. Basal metabolic rate (BMR) was calculated., Results: A body mass index (BMI) below 18.5 kg/m2 was observed in 23% of females and in 13% of males (P = NS). Twenty females (44%) and 52 males (63%) showed a weight loss of more than 10% over the 6-month period (P = 0.073). Ten females (19%) and 58 males (63%) had an arm muscle area (AMA) below the 5th percentile (P < 0.001), while 20 females (38%) and 21 males (23%) had an arm fat area (AFA) below the 5th percentile (P = 0.071). The daily calorie intake was below the BMR in 22 females (42%) and in 53 males (58%) (P = NS). Plasma levels of prealbumin, transferrin, and albumin were found below the normal range in more than 70% in both sexes., Conclusion: Protein energy malnutrition can be easily detected by anthropometric and laboratory indexes. The larger percentage of males with a reduction in lean body mass compared to females could signify an advantage for females since lean body mass is preserved for longer in them. Patients with advanced cancer receiving palliative care should thus be evaluated routinely to assess their nutritional status in order to plan an adequate nutritional program when appropriate.

The syndrome of cancer cachexia is accompanied by several alterations in lipid metabolism, and the liver is markedly affected. Previous studies showed that moderate exercise training may prevent liver fat accumulation through diminished delivery of lipids to the liver, increased hepatic oxidation and increased incorporation of triacylglycerol (TAG) into very low density lipoprotein (VLDL). Our aim was to examine the influence of moderate intensity training (8 weeks) upon TAG content, VLDL assembly and secretion, apolipoprotein B (apoB) and microsomal transfer protein (MTP) gene expression in the liver of cachectic tumour-bearing rats. Animals were randomly assigned to a sedentary control (SC), sedentary tumour-bearing (ST) or exercise-trained control (EC) or to an exercise trained tumour-bearing (ET) group. Trained rats ran on a treadmill (60% VO(2max)) for 60 min day(-1), 5 day week(-1), for 8 weeks. TAG content and the rate of VLDL secretion (followed for 3 h), as well as mRNA expression of apoB and MTP, and total cholesterol, VLDL-TAG, VLDL-cholesterol, high density lipoprotein cholesterol (HDL-cholesterol) and tumour weight were evaluated. VLDL-cholesterol showed a decrease in ST (p < 0.05) in relation to SC. Serum TAG, VLDL-TAG and tissue TAG content were all increased in ST (p < 0.01), when compared with SC. ST showed a lower rate of VLDL secretion (p < 0.05) and reduced expression of apoB (p < 0.001) and MTP (p < 0.001), when compared with SC. These parameters were restored to control values (p < 0.05) when the animals were submitted to the exercise training protocol. Tumour weight decreased 10-fold after training (p < 0.001). It is possible to affirm, therefore, that endurance training promoted the re-establishment of lipid metabolism in cachectic tumour-bearing animals, especially in relation to VLDL secretion and assembly., (Copyright 2008 John Wiley & Sons, Ltd.)

The cachexia-anorexia syndrome (CACS) is common and important implication of cancer. It occurs in 30% to 80% cancer patients. At the time of diagnosis of lung cancer CACS is not yet very important problem, but the weight loss increases with progression of the cancer. CACS is characterized by anorexia, weight loss, weakness, impaired immune system and metabolic dysfunction. Weight loss is a potent stimulus to food intake in normal humans. The persistence of anorexia in cancer patients, therefore, implies a failure of this adaptive feeding response. The weight loss in patients with CACS differs from that in simple starvation or anorexia nervosa. Most research effort has focused on the role of cytokines as mediators of CACS. The role of TNF-alpha, IL-1 and IL-6 in CACS development has been evaluated and confirmed in many research, but some investigators suggest that the changes in cytokines' levels could be the result rather than the cause of CACS. A few of the latest studies concentrate on the role of nuclear factor kappa B and prevention of CACS by its inhibitors. CACS is an independent predictor of shorter survival and increases the risk of treatment failure and toxicity.

Background: Inflammatory immune mechanisms are involved in the pathogenesis and progression of chronic heart failure (CHF), and also promote the development of generalised body wasting seen in this syndrome. We examined the activity of nuclear factor kappa-B (NF-kappaB), the major mediator of immune response, in peripheral blood mononuclear cells (PBMC) isolated from cachectic and non-cachectic patients with CHF., Methods: Using electromobility shift assay, NF-kappaB activity was assessed in nuclear fractions of PBMC isolated from 43 patients with systolic CHF (88% men, age: 64 years [median], left ventricular ejection fraction [LVEF]: 30%, ischaemic CHF aetiology: 79%, NYHA class [I/II/III/IV]: 2/21/19/1, 10 patients with cardiac cachexia) and 12 healthy adult subjects., Results: As compared to healthy controls, NF-kappaB activity in PBMC was increased in patients with CHF (P<0.05), in particular in those with severe CHF (NYHA class III-IV) (P<0.05). NF-kappaB activity in PBMC in CHF patients was not related either to age, sex, CHF aetiology, LVEF, or any clinical parameters reflecting disease severity (haemoglobin, LDL cholesterol, sodium and creatinine levels) (all P>0.1). Regardless of the severity of CHF expressed as NYHA class, patients with cardiac cachexia demonstrated significantly reduced NF-kappaB activity in PBMC as compared to both non-cachectic CHF patients (P<0.001) and healthy controls (P<0.05)., Conclusion: The activity of NF-kappaB system in peripheral immune cells is augmented in patients with advanced CHF, whereas it is diminished in those with cardiac cachexia. The significance of derangements within NF-kappaB system in PBMC for immune phenomena seen in cachectic and non-cachectic CHF patients remains further studies.

Progressive muscle wasting is a central feature of cancer-related cachexia and has been recognized as a determinant of poor prognosis and quality of life. However, until now, no easily assessable clinical marker exists that allows to predict or to track muscle wasting. The present study evaluated the potential of myoglobin (MG) plasma levels to indicate wasting of large locomotor muscles and, moreover, to reflect the loss of MG-rich fiber types, which are most relevant for daily performance. In 17 cancer-cachectic patients (weight loss 22%) and 27 age- and gender-matched healthy controls, we determined plasma levels of MG and creatine kinase (CK), maximal quadriceps muscle cross-sectional area (CSA) by magnetic resonance imaging, muscle morphology and fiber composition in biopsies from the vastus lateralis muscle, body cell mass (BCM) by impedance technique as well as maximal oxygen uptake (VO(2)max). In cachectic patients, plasma MG, muscle CSA, BCM, and VO(2)max were 30-35% below control levels. MG showed a significant positive correlation to total muscle CSA (r = 0.65, p < 0.001) and to the CSA fraction formed by type 1 and 2a fibers (r = 0.80, p < 0.001). However, when adjusted for body height and age by multiple regression, MG yielded a largely improved prediction of total CSA (multiple r = 0.83, p < 0.001) and of fiber type 1 and 2a CSA (multiple r = 0.89, p < 0.001). The correlations between CK and these muscle parameters were weaker, and elevated CK values were observed in 20% of control subjects despite a prior abstinence from exercise for 5 days. In conclusion, plasma MG, when adjusted for anthropometric parameters unaffected by weight, may be considered as a novel marker of muscle mass (CSA) indicating best the mass of MG-rich type 1 and 2a fibers as well as VO(2)max as an important functional readout. CK plasma levels appear to be less reliable because prolonged increases are observed in even subclinical myopathies or after exercise. Notably, cancer-related muscle wasting was not associated with increases in plasma MG or CK in this study.

Purpose: To clarify the potential of parathyroid hormone-related protein (PTHrP) and interleukin-6 (IL-6) as cachectic factors in a colon 26 model and the effects of capecitabine on cancer cachexia as determined by plasma levels of IL-6 and PTHrP and body weight loss., Methods: From two colon 26 sublines-cancer cachectic clone20 and non-cachectic clone5 plasma levels of PTHrP protein and mRNA expression levels in tumor tissues were compared. An IL-6 neutralizing antibody, a PTHrP neutralizing antibody, and capecitabine were administered into mice bearing clone20 and their anticachectic effects evaluated., Results: The plasma level of PTHrP protein in mice bearing clone20 was higher than that in mice bearing clone5. The expression level of PTHrP mRNA was 49-fold higher in tumor tissues of clone20 than of clone5, according to GeneChip analysis. PTHrP antibody as well as IL-6 antibody suppressed wasting of the body and gastrocnemius and adipose tissue weights. PTHrP antibody suppressed the induction of hypercalcemia but not hypoglycemia or elevation of IL-6, whereas IL-6 antibody suppressed the induction of hypoglycemia but not hypercalcemia or elevation of PTHrP. Capecitabine, a fluorinated pyrimidine anticancer agent, improved body wasting of mice bearing clone20 at a low dose with no reduction of tumor volume. Furthermore, capecitabine lowered the levels of PTHrP and IL-6 in plasma and suppressed hypoglycemia and hypercalcemia in this model. Capecitabine also showed anticachectic effects on cachexia in a cancer model induced by human cervical cancer cell line Y (also known as Yumoto)., Conclusions: PTHrP and IL-6 were found to be factors in the development of cachexia in a colon 26 cancer model, and capecitabine improved cancer cachexia by suppressing the plasma levels of IL-6 and PTHrP in colon 26 and Y cachectic models.

Aims: Adiponectin is a fat-derived hormone involved in the regulation of metabolism. Adiponectin concentration is inversely related to body weight and, in animals, causes weight loss. We, therefore, measured adiponectin concentration in patients with heart failure (HF) and cachexia., Methods and Results: Serum adiponectin concentrations were measured in three groups of patients with coronary artery disease (CAD): (i) HF, reduced left ventricular systolic function, and cachexia (n = 10); (ii) HF, reduced systolic function but no cachexia (n = 20); (iii) HF-controls-patients with CAD, no HF, and preserved systolic function (n = 10); and in a healthy control group (n = 7). Patients with HF and cachexia had higher concentrations of adiponectin [23.8 (10.2-37.2) microg/mL] than all other groups: HF-no cachexia 8.1 (0.5-16.6) microg/mL; CAD-controls 7.1 (0.4-13.5) microg/mL; and healthy controls 8.7 (2.5-16.8) microg/mL) (P < 0.05 for each comparison). Adiponectin correlated negatively with body mass index, percentage of body fat, waist circumference and insulin resistance, and positively with B-type natriuretic peptide (BNP) and tumour necrosis factor-alpha., Conclusion: Cachexia in HF is associated with an increase in adiponectin concentration. This may represent preservation of the physiological response to change in body fat but might also suggest that adiponectin plays a role in the pathogenesis of cachexia. The correlation between BNP and adiponectin also raises the possibility that the former might increase the secretion of the latter.