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PubMed1994

Is enteral nutrition a primary therapy in cancer patients?

At present, there is limited evidence for the role of enteral nutrition as a primary therapy in cancer patients. Cachexia commonly occurs in patients with advanced cancer. A consensus view from a large number of studies suggests that cachexia cannot be fully reversed by vigorous enteral nutritional support. A review is included of the available data on the effects of enteral nutritional support on the common indices of nutritional state and on the final outcome of patients receiving enteral nutrition in conjunction with radiotherapy or chemotherapy, or both. The 'nutritional' effects are probably limited because the duration of the nutritional support in most studies consists of a few weeks while malnutrition in the cancer patients often occurs over many months.

Enteral Nutrition↗

PubMed2004

NF-kappaB activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight.

BACKGROUND: Weight loss, mostly due to skeletal muscle atrophy, is a frequent and clinically relevant problem in patients with chronic obstructive pulmonary disease (COPD). The molecular mechanisms underlying this phenomenon are unclear. This study sought to investigate whether activation of the nuclear transcription factor NF-kappaB and upregulation of the inducible form of nitric oxide synthase (iNOS) occur in the skeletal muscle of patients with COPD and low body weight as potential molecular mechanisms leading to cachexia METHODS: NF-kappaB DNA binding activity was determined by electromobility shift assay and the immunoreactivity of its inhibitory subunit IkappaB-kappa and that of iNOS by Western blot analysis in biopsy specimens of the quadriceps femoris muscle of seven COPD patients with normal body mass index (BMI, 27.5 (1) kg/m(2)) and seven patients with low BMI (18.5 (1) kg/m(2)). RESULTS: Compared with patients with normal body weight, those with low BMI showed a 30% increase in NF-kappaB DNA binding activity, a lower expression of IkappaB-alpha (3.37 (0.47) IOD v 5.96 (0.75) IOD, p<0.05; mean difference 2.59; 95% CI -4.53 to -0.65) and higher iNOS expression (1.51 (0.29) IOD v 0.78 (0.11) IOD, p<0.05; mean difference 0.74; 95% CI 0.04 to 1.42). CONCLUSIONS: NF-kappaB activation and iNOS induction occur in skeletal muscle of COPD patients with low body weight. These changes might contribute to the molecular pathogenesis of cachexia in COPD.

Body Mass Index↗

PubMed2004

Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats.

Chronic arthritis induces hypermetabolism and cachexia. Ghrelin is a gastrointestinal hormone that has been proposed as a treatment to prevent cachexia. The aim of this work was to examine the effect of administration of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) to arthritic rats. Male Wistar rats were injected with Freund's adjuvant, and 15 days later arthritic and control rats were daily injected with GHRP-2 (100 microg/kg) or with saline for 8 days. Arthritis induced an increase in serum ghrelin (P < 0.01) and a decrease in serum concentrations of leptin (P < 0.01), whereas GHRP-2 administration increased serum concentrations of leptin. GHRP-2 increased food intake in control rats but not in arthritic rats. However, in arthritic rats GHRP-2 administration ameliorated the external symptoms of arthritis, as it decreased the arthritis score (10.4 +/- 0.8 vs. 13.42 +/- 0.47, P < 0.01) and the paw volume. In addition, circulating IL-6 and nitrites/nitrates were increased by arthritis, and GHRP-2 treatment decreased the serum IL-6 levels (P < 0.01). To elucidate whether GHRP-2 is able to modulate IL-6 release directly on immune cells, peritoneal macrophage cultures were incubated with GHRP-2 or ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue receptor. Both GHRP-2 (10(-7) M) and ghrelin (10(-7) M) prevented endotoxin-induced IL-6 and decreased nitrite/nitrate release from peritoneal macrophages in vitro. These data suggest that GHRP-2 administration has an anti-inflammatory effect in arthritic rats that seems to be mediated by ghrelin receptors directly on immune cells.

Adrenocorticotropic Hormone↗

PubMed2002

Proteolysis-inducing factor differentially influences transcriptional regulation in endothelial subtypes.

Proteolysis-inducing factor (PIF) is a novel sulfated glycoprotein initially identified as a protein capable of triggering muscle proteolysis during the process of cancer cachexia. Only skeletal muscle and liver exhibit substantial binding of PIF in adult tissue. Here, we demonstrate that PIF induces transcriptional regulation in both the liver endothelial cell line SK-HEP-1 and in human umbilical vein endothelial cells (HUVECs) but not in pulmonary artery endothelial cells. PIF differentially induces activation of nuclear factor-kappaB, resulting in the induction of proinflammatory cytokines [interleukin (IL)-8 and IL-6] and increased expression of the cell surface proteins intercellular adhesion molecule-1 and vascular cell adhesion molecule in SK-HEP-1 and HUVECs only. In addition, PIF induces the shedding of syndecans from the cell surface. Syndecans are involved in wound repair, metastasis of cancers, and embryonic development. These results suggest that PIF may play additional roles in the proinflammatory response observed in cancer cachexia but may also have a role without the cachectic process.

Blood Proteins↗

PubMed1991

Effects of recombinant IGF-I on protein and glucose metabolism in rTNF-infused lambs.

Achieving nitrogen accretion in patients with critical surgical illness or cancer cachexia is often not possible by the simple provision of calories and nitrogen. Cachexia may result from the metabolic derangements caused by release of inflammatory mediators such as tumor necrosis factor (TNF). We wished to determine whether recombinant human insulin-like growth factor I (rhIGF-I) preserves its protein-sparing effects in the face of high plasma TNF concentrations. Primed constant infusions of [15N]urea and [6-3H]glucose tracers were used to measure protein and glucose kinetics in fasted lambs. The lambs were divided into four groups: two groups received normal saline infusions of 480 min, and two groups received recombinant TNF (rTNF) infusions of 1 microgram.kg-1.h-1. During the last 300 min, one of the normal saline and one of the rTNF-infused groups were infused with rhIGF-I at a dose of 50 micrograms.kg-1.h-1. rTNF infusion resulted in the lambs becoming febrile and significantly increased plasma cortisol, glucagon, and insulin levels. rhIGF-I infusion in the control animals reduced the rate of loss of protein by 15% (P less than 0.01) and increased the rate of peripheral glucose clearance by 55% (P less than 0.01). rhIGF-I infusion in the rTNF-treated animals reduced the rate of net protein loss by 15% (P less than 0.01) and caused similar changes in glucose kinetics, as were observed in the control animals. We conclude that as rhIGF-I preserves its protein anabolic action in the face of high rTNF levels, further investigation into a possible clinical role for rhIGF-I in severe surgical illness is warranted.

Animals↗

PubMed1997

Altered energy balance and cytokine gene expression in a murine model of chronic infection with Toxoplasma gondii.

The temporal pattern of changes in energy balance and cytokine mRNA expression in spleen and brain were examined in a mouse model of infection with Toxoplasma gondii. During days 1-7 postinfection, food intake was unaltered, but energy expenditure was significantly increased, and this was associated with elevated tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-5, and interferon (IFN)-gamma. The hypermetabolic state persisted during subsequent anorexia, whose onset coincided with elevated IL-2, and at the end of the acute phase of cachexia, the dual anorexic and hypermetabolic states were associated with the cytokines examined: TNF-alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-gamma. In the chronic phase of the infection, the mice showed either partial weight recovery (gainers) or no weight regain (nongainers). The infected gainers, though still hypophagic, were no longer hypermetabolic, and their cytokine mRNA was no longer elevated, except for TNF-alpha and IL-10. In contrast, the infected nongainers continued to show both anoroxia and hypermetabolism, which were associated with elevations in all cytokines examined and particularly those of the TH2 profile (IL-4 and IL-5) and IL-6. Taken together, these studies reveal a distinct pattern of cytokine mRNA expression underlying 1) hypermetabolism vs. anorexia, 2) acute vs. chronic cachexia, and 3) stable weight loss vs. partial weight recovery.

Acute Disease↗

PubMed1998

Metabolic-cytokine responses to a second immunological challenge with LPS in mice with T. gondii infection.

Injection of 10 cysts of Toxoplasma gondii (Me49 strain) into Swiss Webster mice results in 1) an acute phase of infection lasting for 2-3 wk, characterized by weight loss, and 2) a chronic phase in which surviving mice show either partial weight recovery (Gainers) or persistent, although stable, cachexia (Nongainers). In response to a second immunological stimulation with lipopolysaccharide (LPS) in the chronic phase of the infection, it is shown that 1) the increase in energy expenditure was more prolonged in both groups of infected mice than in controls, 2) the intensity and duration of hypophagia were also differently affected with Nongainers > Gainers > controls, and 3) the infected mice had higher serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-10 and a lower ratio of IL-10 to TNF-alpha than controls. In contrast, serum IL-4 increased to the same level in all three groups. Evaluation of the permeability of the blood-brain barrier by intravenous injection of Evans blue revealed a marked staining in the brain of only the infected Nongainers. Taken together, these results indicate that, in mice with chronic toxoplasmosis, a second nonspecific challenge (with LPS) exacerbates the hypophagic and hypermetabolic states, the latter being associated with hyperresponsiveness in TNF-alpha and IL-10 production. Furthermore, the greater exacerbation of the hypophagic state in mice showing persistent cachexia may be due to a preexisting higher permeability of the blood-brain barrier, which would allow a greater access of plasma-borne cytokines and/or other neuroimmunologically active substances to the central nervous system.

Animals↗

PubMed1998

Role of IL-6 and TNF in thermoregulation and survival during sepsis in mice.

Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) have been implicated as key mediators in inflammation, morbidity, and mortality associated with sepsis. We examined the role of IL-6 and TNF-alpha signaling on hypothermia, fever, cachexia, anorexia, and survival during sepsis induced by cecal ligation and puncture (CLP) in male and female gene knockout mice. Male wild-type mice developed an initial hypothermia and subsequent fever during sepsis. Male IL-6 knockout mice did not develop fever; rather, they maintained a profound hypothermia during sepsis. Male TNF p55/p75 receptor (TNFR) knockout mice had attenuated hypothermia, but developed a virtually identical fever as wild-type mice. Cachexia did not differ between male wild-type and IL-6 or TNFR knockout mice, whereas anorexia was prolonged in IL-6 knockout mice. Due to the rapid lethality of sepsis in female mice, survival was the only variable we were able to statistically compare among female genotypes. Female wild-type mice had significantly decreased survival compared with male wild-type mice. Survival was significantly enhanced in male and female TNFR knockout mice compared with their wild-type controls. Lack of IL-6 did not affect male or female lethality. These data support the hypothesis that IL-6 is a key mediator of fever and food intake, whereas TNF is responsible for the initial hypothermia and lethality of sepsis in both sexes of mice. The enhanced lethality of CLP-treated female mice supports a role for sex steroids during sepsis.

Animals↗

PubMed1986

Different sensitivity of two Walker 256 carcinoma lines to cyclophosphamide: correlation with drug distribution, biotransformation and macromolecule binding.

Two closely related lines of the same Walker 256 carcinoma in Crl-CD/COBS rats, described as behaving differently as regards tumor growth and host reaction, show different chemotherapeutic sensitivity to cyclophosphamide (CPA). Line B, which induces early cachexia with marked anorexia, is only moderately sensitive to CPA, while line A, which causes mild anorexia and only terminal cachexia, shows marked responsiveness to CPA, cure being attained in 75% of animals treated with a single dose of 120 mg/kg and in 90-100% of those given 20 mg/kg every other day. Comparative studies in both tumor lines on the distribution of CPA in vivo and on its metabolism by the liver perfusion technique showed no appreciable differences between the two lines in the pharmacokinetics of the compound, but indicate a much greater metabolizing capacity of CPA in the Walker 256/A animals. In vitro metabolic and covalent binding studies confirm that the liver of the Walker 256/A group metabolizes and covalently binds twice as much CPA as the liver of the Walker 256/B group. Conversely to Walker B, microsomal preparations of the Walker tumor line A are able to metabolize CPA to intermediates which irreversibly bind to tissue macromolecules, suggesting an in situ activation of the compound in the sensitive Walker tumor.

Animals↗

PubMed2001

Roles of tumor necrosis factor-alpha receptor subtypes in the pathogenesis of the tristetraprolin-deficiency syndrome.

Tristetraprolin (TTP) is a member of the CCCH tandem zinc-finger class of proteins. It can bind to and destabilize mRNAs encoding tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Conversely, mice deficient in TTP develop a complex syndrome characterized by cachexia, myeloid hyperplasia, and joint and skin inflammation. Studies using anti-TNF-alpha neutralizing antibodies demonstrated that this syndrome, at least in part, is a consequence of the excess production of TNF-alpha in the absence of TTP. To evaluate the role played by each TNF-alpha receptor in the pathogenesis of this syndrome, mice were generated that were deficient in TTP and either or both of the known TNF-alpha receptors (TNFRs), type 1 (TNFR1) and type 2 (TNFR2). Mice deficient in TTP and TNFR1, or in TTP and both receptors, were protected from developing the TNF-alpha-induced cachexia and inflammation. In contrast, mice deficient in TNFR2 were more severely affected than mice deficient in TTP alone, suggesting that TNFR2 might play a protective role in the development of the syndrome. In cultured cells derived from these mice, apparent cooperation between the TNFRs was required to achieve normal TNF-alpha-induced expression of TTP, TNF-alpha, and GM-CSF mRNAs. Finally, the results showed that TNFR1 plays an important role in mediating TNF-alpha-induced changes in TNF-alpha and GM-CSF mRNA stability.

Animals↗

PubMed2002

Role of lipid peroxidation and antioxidant enzymes in omega 3 fatty acids induced suppression of breast cancer xenograft growth in mice.

BACKGROUND: Supplementing mice with high levels of dietary n-3 polyunsaturated fatty acids (PUFAs) increases the n-3 PUFAs in cell membranes, increases the susceptibility of the cells for lipid peroxidation (LPO) and decreases the growth rate of mammary and other tumors. However, the results of an earlier study indicated that a factor in addition to LPO was involved in the reduction in tumor growth in n-3 PUFAs fed mice. Athymic mice bearing MDA-MB-231 human breast carcinoma xenografts, were fed fish oil concentrate (FOC) or control diets, with and without supplemental Vitamin E (2000 IU /kg diet) and were sacrificed both before and after doxorubicin (DOX) treatment to evaluate factors involved in tumor growth suppression. RESULTS: Prior to DOX, basal LPO in the tumor of 3% FOC fed mice was slightly higher than in the control fed mice and was decreased in mice consuming FOC with vitamin E. Vitamin E suppressed the DOX induced increase in LPO in the tumors of control mice, however, vitamin E was not sufficient to suppress a DOX induced increase in LPO in the tumors of FOC fed mice. The mean growth rate of tumors of FOC fed mice was significantly less than the mean growth rate of the tumors of control mice. Multiple regression analyses indicated that suppression of glutathione peroxidase (GPX) activity by FOC prior to DOX therapy was more important than increased LPO as an explanation of tumor growth suppression. Tumor induced cachexia was decreased in mice consuming FOC. CONCLUSIONS: It appears that the increased sensitivity to DOX was related to an FOC induced reduction in GPX activity. FOC reduced tumor induced cachexia.

Journal Article↗

PubMed2003

Minireview: From anorexia to obesity--the yin and yang of body weight control.

Over the past decade, there has been a tremendous increase in the understanding of the molecular and neural mechanisms that control food intake and body weight. Yet eating disorders and cachexia are still common, and obesity cases are rising at alarming rates. Thus, despite recent progress, an increased understanding of the molecular and neural substrates that control body weight homeostasis is a major public health goal. In this review, we discuss the mechanisms by which metabolic signals interact with key behavioral, neuroendocrine, and autonomic regulatory regions of the central nervous system. Additionally, we offer a model in which hormones such as leptin and ghrelin interact with similar central nervous system circuits and engage them in such a way as to maintain an appropriate and tight regulation of body weight and food intake. Our model predicts that overstimulation or understimulation of these central pathways can result in obesity, anorexia, or cachexia.

Animals↗

PubMed2000

Insulin-like growth factor I reduces ubiquitin and ubiquitin-conjugating enzyme gene expression but does not inhibit muscle proteolysis in septic rats.

We examined the effect of insulin-like growth factor I (IGF-I), administered in vivo, on protein turnover rates and gene expression of the ubiquitin-proteasome proteolytic pathway in skeletal muscle of septic rats. Sepsis was induced by cecal ligation and puncture. Other rats were sham-operated. Miniosmotic pumps were implanted sc, and groups of rats received IGF-I (7 mg/kg x 24 h) or saline. Protein synthesis and breakdown rates were determined in incubated extensor digitorum longus muscles. Messenger RNA levels for ubiquitin and the ubiquitin-conjugating enzyme E2(14k) were determined by Northern blot analysis. Sepsis resulted in an approximately 30% reduction of muscle protein synthesis, and this effect of sepsis was blunted in rats treated with IGF-I. In contrast, IGF-I did not prevent the sepsis-induced increase in total and myofibrillar muscle protein breakdown. Ubiquitin and E2(14k) messenger RNA levels were increased several fold in muscle from septic rats, and this effect of sepsis was abolished in IGF-I treated rats. The results suggest that administration of IGF-I may improve sepsis-induced muscle cachexia by stimulating protein synthesis. However, because muscles were resistant to IGF-I, with regard to regulation of protein breakdown, the use of IGF-I to treat muscle cachexia during sepsis remains unclear. An additional important implication of the present study is that changes in messenger RNA levels for ubiquitin and the ubiquitin-conjugating enzyme E2(14k) do not always reflect changes in muscle protein breakdown rates.

Animals↗

PubMed2000

Cockayne syndrome and xeroderma pigmentosum.

OBJECTIVES: To review genetic variants of Cockayne syndrome (CS) and xeroderma pigmentosum (XP), autosomal recessive disorders of DNA repair that affect the nervous system, and to illustrate them by the first case of xeroderma pigmentosum-Cockayne syndrome (XP-CS) complex to undergo neuropathologic examination. METHODS: Published reports of clinical, pathologic, and molecular studies of CS, XP neurologic disease, and the XP-CS complex were reviewed, and a ninth case of XP-CS is summarized. RESULTS: CS is a multisystem disorder that causes both profound growth failure of the soma and brain and progressive cachexia, retinal, cochlear, and neurologic degeneration, with a leukodystrophy and demyelinating neuropathy without an increase in cancer. XP presents as extreme photosensitivity of the skin and eyes with a 1000-fold increased frequency of cutaneous basal and squamous cell carcinomas and melanomas and a small increase in nervous system neoplasms. Some 20% of patients with XP incur progressive degeneration of previously normally developed neurons resulting in cortical, basal ganglia, cerebellar, and spinal atrophy, cochlear degeneration, and a mixed distal axonal neuropathy. Cultured cells from patients with CS or XP are hypersensitive to killing by ultraviolet (UV) radiation. Both CS and most XP cells have defective DNA nucleotide excision repair of actively transcribing genes; in addition, XP cells have defective repair of the global genome. There are two complementation groups in CS and seven in XP. Patients with the XP-CS complex fall into three XP complementation groups. Despite their XP genotype, six of nine individuals with the XP-CS complex, including the boy we followed up to his death at age 6, had the typical clinically and pathologically severe CS phenotype. Cultured skin and blood cells had extreme sensitivity to killing by UV radiation, DNA repair was severely deficient, post-UV unscheduled DNA synthesis was reduced to less than 5%, and post-UV plasmid mutation frequency was increased. CONCLUSIONS: The paradoxical lack of parallelism of phenotype to genotype is unexplained in these disorders. Perhaps diverse mutations responsible for UV sensitivity and deficient DNA repair may also produce profound failure of brain and somatic growth, progressive cachexia and premature aging, and tissue-selective neurologic deterioration by their roles in regulation of transcription and repair of endogenous oxidative DNA damage.

Cockayne Syndrome↗

PubMed2004

Role of cytokines in regulating feeding behaviour.

Immune activation occurs in response to noxious stimuli such tissue injury, infection, inflammation and malignant neoplasia with the production of cytokines both in the circulation and the central nervous system (CNS). In addition to their fundamental immune functions, cytokines such as the interleukins (ILs), interferons (IFNs) and tumour necrosis factor-alpha also elicit significant pathophysiological effects on feeding behaviour and play prominent roles in the anorexia and cachexia syndrome often seen in chronic disease states. There is now compelling evidence that demonstrates that an important site of cytokine bioactivity is located within the hypothalamus where they appear to modulate appetite and energy homeostasis. Hypercytokinaemia has also been observed in the obese state where it has been proposed that they may play pivotal roles in mediating the detrimental components of the metabolic syndrome including insulin resistance, impaired glucose tolerance, hypertension. dyslipidaemia and increased cardiovascular risk. This review summarises these putative roles of various cytokines in the regulation of feeding in the setting of anorexia-cachexia and obesity.

Animals↗

PubMed2005

The emerging roles of leptin and ghrelin in cardiovascular physiology and pathophysiology.

Leptin and ghrelin are novel peptide hormones which are counter-regulatory in the central control of appetite. More recently, it has become clear that these hormones have a range of effects on the cardiovascular system. Leptin increases sympathetic activity, producing a pressor effect when acting on the central nervous system. However, leptin produces vasodilation by an endothelium-dependent mechanism peripherally. Ghrelin decreases sympathetic activity and has a depressor effect when acting on the central nervous system. Peripherally, ghrelin produces vasodilation by an endothelium-independent mechanism. Ghrelin improves left ventricular function and cardiac cachexia in heart failure. Leptin may contribute to cardiac cachexia, and to obesity-related cardiomyopathy by a variety of mechanisms. Leptin has pro-inflammatory, proliferative and calcification promoting effects in the vasculature. Ghrelin has recently been shown to be anti-inflammatory in the vasculature. Leptin may also produce a pro-thrombotic state through stimulation of platelet aggregation and inhibition of coagulation and fibrinolysis. The evidence for and against these effects as well as their pathophysiological significance in obesity hypertension, heart failure, atherosclerosis and thrombosis are discussed.

Animals↗

PubMed2001

Angiogenesis in the adipose tissue of tumor-bearing rabbits treated by cyclic plasma perfusion.

The mechanisms of cancer cachexia have not been elucidated. We previously reported that cyclic plasma perfusion using non-coated charcoal was effective in cancer cachexia. In the present study we investigated the angiogenic effect of cyclic plasma perfusion on adipose tissue. Twenty rabbits were divided into two groups, i.e., tumor-bearing rabbits subjected to cyclic plasma perfusion (n=10, PP group), and tumor-bearing rabbits subjected to sham-perfusion (n=10, SP group). The changes in body weight, total body fat, and expression of angiogenic factors were investigated. Loss of body weight and total body fat was significantly suppressed in the PP group. Apoptosis of adipocytes was seen in both groups only in the early stage of tumor bearing. Lipolytic activity in the PP group showed a lower ratio than that in the SP group. In the PP group, increased microvessel density and expression of vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) were seen at 40 days after transplantation. Similar findings were not seen in the SP group. These results suggest that cyclic plasma perfusion not only decreased lipolytic activity but induced angiogenesis in the adipose tissue.

Adipose Tissue↗

PubMedDate not supplied

Serum levels of tumor necrosis factor-alpha and nutritional status in pancreatic cancer patients.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine associated with cancer-related cachexia. In this study we evaluated serum levels of TNF-alpha in pancreatic cancer patients and investigated their relationships to cachexia. PATIENTS AND METHODS: Serum TNF-alpha levels were determined in 63 patients with pancreatic cancer using an enzyme immunoassay specific for human TNF-alpha. RESULTS: Serum TNF-alpha levels were detected in 36.5% of patients. Patients with metastatic disease showed significantly higher positive serum TNF-alpha rate compared to those with non-metastatic disease. Patients with detectable serum TNF-alpha levels had significantly lower body weight and body mass index, lower haematocrit and haemoglobin values, and lower serum total protein and albumin levels compared to those with undetectable TNF-alpha levels. Serum TNF-alpha levels were inversely correlated with body weight, body mass index, haematocrit, haemoglobin, and serum protein and albumin levels. CONCLUSIONS: TNF-alpha levels are detectable in the serum of pancreatic cancer patients, particularly in those with advanced disease, and these levels correlate with poor nutritional status.

Aged↗