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PubMed2004

[Leukaemia inhibitory factor (LIF): structure and biological activity].

Leukaemia inhibitory factor (LIF) is a multifunctional cytokine, which plays a role in growth-promotion and differentiation, regulates calcium and bone metabolism, induces acute phase proteins and causes cachexia in organisms with neoplastic disorders. Moreover, LIF participates in the induction of inflammation, and therefore represents an important pathogenic factor of many disorders. The multifunctional properties of LIF have become of special interest to investigators from different disciplines of medicine.

Acute-Phase Proteins↗
PubMed2004

Selenium is effective in inducing lymphocyte progression through cell cycle in cancer patients: potential mechanisms for its activity.

Epidemiologic evidence in humans suggests a role for selenium in reducing cancer incidence and mortality. The aim of the present study was that to assess the ability of selenium dioxide (SeO2) to enhance the lymphocyte progression through the cell cycle in patients with advanced (stage IV) cancer. Ten patients (mean age 51.9 years, range: 32-74; M/F ratio: 3/7) with tumors at different sites were included in the study. The addition into culture of SeO2 1.5 microM enhanced significantly the progression into S phase of PBMCs isolated from cancer patients, whilst no significant effect was observed on PBMCs isolated from controls. ROS levels were significantly higher, whereas GPx activity was significantly lower in cancer patients than controls. Serum levels of IL-6 and TNFalpha were significantly higher in cancer patients than controls. Our results show the ability of selenium to induce a progression of PBMCs from cancer patients into the cell cycle, which is an essential prerequisite for the physiological functioning of the immune system and thus positively influence the immune status of advanced cancer patients. The mechanism of action of selenium could be to downregulate the production and release of proinflammatory cytokines, which have a role in cancer progression and particularly in the onset of cachexia.

Adult↗
PubMedDate not supplied

Granulocyte/macrophage colony-stimulating factor and interleukin-4-induced dendritic cells.

BACKGROUND: We investigated whether GM-CSF/IL-4 is the most efficient cytokine combination for differentiating dendritic cells (DC) in terms of its ability to elicit an antitumor immune response. MATERIALS AND METHODS: Two experimental models were examined: C57BL/6 mice bearing MC38 cells and Balb/c mice bearing cachexia-inducible Colon-26 cells. After immunization with DC pulsed with whole tumor cell lysate, tumors were inoculated into the subcutis. RESULTS: C57BL/6 mice immunized with lysate-pulsed DC effectively rejected the MC38 challenge and detectable MC38-specific cytotoxic lymphocytes (CTL) were observed. However, even those groups immunized with lysate-pulsed DC exhibited no protective immunity against Colon-26 challenge in Balb/c mice. Unexpectedly, mice inoculated with lysate-unpulsed DC showed an acceleration of cachectic progression (p=0.031) compared to control mice. CONCLUSION: We speculate that GM-CSF/IL-4-induced DC promotes Th2-dominated immunity in Balb/c mice. Consideration might be given to which combination of cytokines is appropriate for the ex vivo differentiation of DC in tumor immunotherapy.

Animals↗
PubMedDate not supplied

New biochemical markers in chronic heart failure.

We investigated the plasma levels of tumour necrosis factor-alpha (TNF-alpha), leptin and insulin, and their relation to body mass index (BMI) in 80 male patients who presented with chronic heart failure (mean age: 47 +/- 4 years) at Tanta University Hospital. Plasma leptin, TNF-alpha and insulin were significantly increased and BMI significantly decreased in New York Heart Association classes III and IV patients. TNF-alpha, leptin and insulin were positively correlated, and TNF-alpha and BMI and leptin and BMI were negatively correlated in stages III and IV of heart failure. We conclude that cytokine neuroendocrine activation may form part of advanced stage heart failure. It may also be responsible for worsening cachexia, and can be used as a marker to determine disease severity.

Biomarkers↗
PubMed2004

[Surgical policy in complicated traumatic diaphragmatic hernias].

Rare variants of surgical policy in different terms after traumatic diaphragmatic hernias complicated with necrosis and perforation of gastric walls and abdominal part of esophagus, ulcerous gastric bleedings, empyema of pleura, enzymatic-gangrenous destruction of lung, cachexia are analyzed. Necessity of revision of diaphragm during surgery for diagnosis of it injuries is noted. In old diaphragmatic hernias and significant disposition of intraabdominal organs into pleural cavity thoracotomy or thoracophrenolaparotomy are recommended, in acute trauma when symptoms of abdominal injuries dominate laparotomy is expedient. In severe conditions minimal and organ-saving surgeries are recommended. Creation of "small stomach" from remains of its wall may be considered as alternative to traumatic gastrectomy.

Adult↗
PubMed2005

Plasmid-based growth hormone-releasing hormone supplementation and its applications.

A single dose of a plasmid expressing growth hormone-releasing hormone (GHRH) has been safely used in a number of animal species and applications to physiologically increase growth hormone and insulin-like growth factor-I for over a year. An array of constructs encoding for analogs of, or species-specific, GHRH has been tested to treat anemia and cachexia associated with cancer and its treatment, and renal failure, as well as to increase immune surveillance and animal welfare. The positive results obtained with plasmid-based GHRH in companion and farm animals may be translated to a number of human applications.

Anemia↗
PubMed2005

The cachectic mediator proteolysis inducing factor activates NF-kappaB and STAT3 in human Kupffer cells and monocytes.

A novel proteoglycan, proteolysis inducing factor (PIF), is capable of inducing muscle proteolysis during the process of cancer cachexia, and of inducing an acute phase response in human hepatocytes. We investigated whether PIF is able to activate pro-inflammatory pathways in human Kupffer cells, the resident macrophages of the liver, and in monocytes, resulting in the production of pro-inflammatory cytokines. Normal liver tissue was obtained from patients undergoing partial hepatectomy and Kupffer cells were isolated. Monocytes were isolated from peripheral blood. Following exposure to native PIF, pro-inflammatory cytokine production from Kupffer cells and monocytes was measured and the NF-kappaB and STAT3 transcriptional pathways were investigated using electrophoretic mobility shift assays. We demonstrate that PIF is able to activate the transcription factor NF-kappaB and NF-kappaB-inducible genes in human Kupffer cells, and in monocytes, resulting in the production of pro-inflammatory cytokines such as TNF-alpha, IL-8 and IL-6. PIF enhances the expression of the cell surface molecules LFA-1 and CD14 on macrophages. PIF also activates the transcription factor STAT3 in Kupffer cells. The pro-inflammatory effects of PIF, mediated via NF-kappaB and STAT3, are important in macrophage behaviour and may contribute to the inflammatory pro-cachectic process in the liver.

Acute-Phase Reaction↗
PubMed1992

Differential metastatic capacity of three AKR lymphoma variants.

The comprehension of tumour progression has advanced due to the use of various models, the most rewarding being probably the study of malignancy variants derived from the same tumour. In the present study the biological behaviours of three AKR lymphoma variants were compared. The three variants, TAU-33, TAU-38 and TAU-39, differed markedly in biological behaviour. The TAU-39 variant formed very large 'primary tumours', TAU-33 produced local growths of intermediate size, and TAU-38 formed small s.c. tumours. However, the metastatic potentials of the variants were inversely related to their ability to produce local tumours. According to various parameters (spread to organs, cachexia and mice mortality rate), the variant of highest metastatic potential was TAU-38, the one of intermediate ability TAU-33 and the TAU-39 had the least aggressive behaviour. A lack of difference in invasive capacity as well as a similar ranking of malignancy by both s.c. and i.v. inoculation indicate a differential behaviour in late metastasis phase. Tumour progression models may contribute to a better understanding of this threatening process and to testing of new treatment modalities suitable for cancer at different stages.

Animals↗
PubMed2005

[Ghrelin--role in energy homeostasis and glucose metabolism].

Ghrelin is a 28 aminoacids peptide secreted from the stomach that stimulates the release of growth hormone (GH) from the anterior pituitary cells and is the strongest orexigenic hormone discovered so far. Ghrelin seems to be involved in the pathogenesis of obesity, anorexia nervosa and cachexia. Furthermore, low levels of ghrelin are negatively correlated with the degree of insulin resistance, blood pressure and the prevalence of type 2 diabetes. The role of ghrelin in the energy homeostasis and carbohydrate metabolism is discussed.

Anorexia Nervosa↗
PubMed2005

[Effects of lactone I from Atractylodes macrocephala Koidz on cytokines and proteolysis-inducing factors in cachectic cancer patients].

OBJECTIVE: To observe the effect of lactone I from Atractylodes macrocephala Koidz (LAMK I) on the cytokines and proteolysis-inducing factors (PIF) in cachectic cancer patients. METHOD: Sixty-four cachectic cancer patients were randomized into two groups, namely LAMK I group and FOE (fish oil-enriched nutritional supplementation) treatment group. The appetite, body weight changes, mid-arm muscle circumference (MAMC), and KPS scores were recorded 3 and 7 weeks after the treatment. Immunohistochemistry was used to analyze the changes in the cytokines interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-alpha and Western blotting employed to examine the changes of PIF after the treatment. RESULTS: The patients' appetite and MAMC in LAMKI group was better than those of patients in FOE group, and the serum IL-1 and TNF-alpha levels and urine PIF level were significantly lower than those of FOE group. Body weight and serum IL-6 level were not significantly different between the two groups. CONCLUSION: Lactone I from Atractylodes macrocephala Koidz can be beneficial for treating cancer cachexia.

Adult↗
PubMed2005

[Peptides regulating food intake and body weight].

Regulation of food intake and body weight depends on direct and feedback signals from adipose tissue, alimentary canal and pancreas to the hypothalamus nuclei, where hunger and satiety centers are. During the last decade a few signaling molecules of peptide origin were discovered, which play an important role in the regulation of energy intake and energy expenditure as well as in obesity. So, adipocytes synthesize and express leptin, the product of Ob gene, a regulator of long-term food intake, in amounts proportional to the fat amount, while alimentary canal hormones are regulators of short-term food intake (from meal to meal). Some peptides decrease food intake as they promote satiety (anorexigenic signals), other peptides, contrary, increase food intake as they induce appetite (orexigenic signals). Disturbed equilibrium between the anorexigenic and orexigenic factors manifests as food intake disorders, increase in body weight and obesity or decrease in body weight, i.e. cachexia.

Adipocytes↗
PubMed1992

Tumour necrosis factor: roles in cancer pathophysiology.

Tumour necrosis factor (TNF) is a pleiotropic cytokine with activities that extend beyond its antitumour effect. There is now increasing evidence that TNF can be either constitutively produced or induced in human tumours. Tumour cells may also lead to TNF induction in normal cells. Experimental studies implicate TNF in processes that contribute to cancer progression. These range from stimulation of cancer growth and metastasis, to metabolic and haematological disturbances, e.g. cancer cachexia, anaemia, and hypercalcaemia. Future cancer therapies may therefore involve neutralisation of TNF activity in cancer patients.

Animals↗
PubMed1991

Anticachectic and antitumor effect of eicosapentaenoic acid and its effect on protein turnover.

The effect of the polyunsaturated fatty acids eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) on host body weight loss and tumor growth has been investigated in mice bearing a cachexia-inducing colon adenocarcinoma, the MAC16. EPA effectively inhibited both host weight loss and tumor growth rate in a dose-related manner with optimal effects being observed at a dose level of 1.25 to 2.5 g/kg. At these concentrations host body weight was effectively maintained, and there was a delay in the progression of growth of the tumor, such that overall survival was approximately doubled in EPA-treated animals, using the criteria dictated by the United Kingdom Coordinating Committee for the welfare of animals with neoplasms. Even when tumor growth resumed, weight loss did not occur. Animals bearing the MAC16 tumor showed a decreased protein synthesis and an increased degradation in skeletal muscle. Treatment with EPA significantly reduced protein degradation without an effect on protein synthesis. The effect of GLA on both host body weight loss and tumor growth was much less pronounced than that of EPA, with an effect only being seen at a dose of 5 g/kg, at which some toxicity was observed. In vitro studies showed that while EPA was effective in inhibiting tumor-induced lipolysis, GLA was ineffective in this respect. However, prostaglandin E1, which is formed from GLA in vivo, showed partial reversal of tumor-induced lipolysis and probably accounted for the anticachectic effect of GLA. These results suggest that EPA as the pure fatty acid should be considered for clinical investigation as both an anticachectic and antitumor agent, since prior work has shown that the other major component of fish oil docosahexaenoic acid is without pharmacological activity in this system.

Animals↗
PubMed1977

Virus-induced animal model of osteosarcoma in the rat: Morphologic and biochemical studies.

Osteosarcomas were produced by the intratibial inoculation of New Zealand black rats with Moloney sarcoma virus (MSV) at 1 day and 4 days of age. Radiographic evidence of osteosarcoma development was first demonstrated at 10 to 15 days postinoculation in both groups. Subsequent radiographic and light and electron microscopic evaluation of tumor-bearing rats demonstrated that osteosarcomas in rats inoculated at Day 4 of age were more osteoproliferative osteosarcomas than those in rats inoculated on Day 1. Rats inoculated at 4 days of age lived longer, had more slowly growing osteosarcomas, and developed a consistent tumor-associated cachexia compared to tumor-bearing rats inoculated at Day 1. Both groups of rats had a 93% metastasis rate involving either sublumbar lymph nodes, lungs, or both. Tumor-bearing rats inoculated at 4 days of age had consistent elevations in both urinary hydroxyproline excretion (HOP/CR) and serum alkaline phosphatase levels, and in serum calcium levels at some time points. The high tumor incidence after a short latent period and the morphologic and biochemical similarities between the MSV-induced murine osteosarcoma and the osteosarcoma in human beings makes this discrete tumor and a valuable animal model for the evaluation of new therapeutic regimens.

Animals↗
PubMed1991

[Complement behavior in rats bearing Yoshida tumors subjected to treatment with gonadotropin and PGE2].

The haemolytic activity of the total Complement (CH50) and the fractions C3 and C4 were assayed in rats transplanted with Yoshida's tumor and then treated with hCG, LH-FSH and PGE2. A relevant increase, only concerning the values of the CH50 and C3 fraction, was observed in all animals in the early days after the transplantation, probably due to a sort of stress "by transplantation". Afterwards, hCG and PGE2 induced an increase in CH50 and C3 values, but not in the C4 fraction. Treatment with LH and FSH led to a very slight increase in the CH50 and C3. In the following days, as a consequence of the cachexia, a progressive reduction of the values of the Complement was observed in all animals. Those treated with hCG also showed a little increase of survival. The authors suggest that the increase in CH50 and C3 fraction induced by the treatment with hCG and PGE2 could be an expression of increase of the aspecific humoral immunity, as a compensatory mechanism of the cell-mediated immunological depression which occurs during neoplasias.

Animals↗
PubMed1990

Total parenteral nutrition in a neonatal llama.

Total parenteral nutrition reversed cachexia, dehydration, and electrolyte abnormalities in a neonatal llama suffering from prolonged diarrhea. Complications were not observed during the 8 days that IV-administered fluids and nutritional support were provided.

Animals↗
PubMed1990

Cachectic effects of recombinant human tumor necrosis factor in rats.

Treatment of rats with either intermittent bolus i.v. injections or continuous i.v. infusions of the same sublethal daily dose of tumor necrosis factor (TNF) results in decreased food intake and decreased nitrogen balance compared to saline-treated control rats. After 4 days of treatment, rats treated with intermittent bolus doses of TNF develop tolerance to the nutritional effects and consume normal amounts of food and have nitrogen balance similar to those of saline treated rats. Rats receiving the continuous infusion of TNF do not. Rats treated with both routes of TNF lose more weight than pair fed rats who eat the same mean amount as the continuous TNF treated group. In addition, 56% of rats receiving continuous infusion TNF die during the 8-day experimental period while rats receiving either intermittent bolus TNF or similar food intake (pair fed) do not. Body composition studies of rats that completed the 8 days of treatment indicate that rats receiving either continuous infusion or intermittent bolus TNF have increased percentages of body water and reduced percentages of body solid compared to saline treated control rats. Rats pair fed to the food intake of continuous TNF treated rats also had increased percentages of body water and reduced percentages of body solid, but changes were significantly less than those observed in continuous TNF infused rats. Continuous TNF infusion reduced total body nitrogen and potassium while pair feeding did not reduce potassium and reduced nitrogen to a lesser degree. Pair feeding and continuous TNF infusion reduced total body fat to a similar extent. Twice a day administration of TNF resulted in lesser changes in carcass water, solid, nitrogen, lipid, and potassium than continuous infusion of the same dose of TNF. The results indicate that continuous infusion of TNF can produce anorexia, weight loss, edema, loss of body protein, lipid and cell mass, and lethality which is markedly ameliorated with bolus doses of TNF. The findings are consistent with the hypothesis that slow continuous secretion of sublethal amounts of TNF may mediate cancer cachexia.

Animals↗
PubMedDate not supplied

[Tumor necrosis factor alpha. Biological aspects].

Human Tumor Necrosis Factor-alpha (TNF-alpha) is a multifaceted cytokine mainly produced by activated monocytes or macrophages. Several recent studies have shown that TNF-alpha can exert a variety of in vitro and in vivo effects including: modulation of normal and malignant haemopoiesis, antineoplastic activity, activation of neutrophils, induction of IL-1 production, hyperpyrexia and induction of cachexia. Furthermore this cytokine is thought to play an important role in the pathogenesis of septic shock. The principal biochemical characteristics and biological activities of this cytokine will be here summarized.

Animals↗