Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cachexia”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,585 records · Page 88Linked to original sources

Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6.

Herbs as alternative cancer therapies have attracted a great deal of recent attention due to their low toxicity and costs. In this study, the antitumor activity and anticachectic effect of Coptidis rhizoma, an anti-inflammatory herb, were investigated in nude mice carrying a human esophageal cancer cell line YES-2, which constitutively secretes interleukin-6 (IL-6) and induces cachexia when injected into these mice. In this study, in vivo growth of YES-2 cells was not affected by an oral supplement containing the extract powder of C. rhizoma at a final concentration of 1% (CR supplement). However, in comparison with normal diet, CR supplement significantly attenuated weight loss of tumor-bearing mice without a change in food or water intake. Tumor IL-6 levels were significantly lower in mice treated with CR supplement than in control mice (P<0.001). Serum IL-6 was detectable in four (50%) of eight control mice; IL-6 was not detected in mice treated with CR supplement. We also confirmed that berberine (8-32 microM), a major component of C. rhizoma, dose-dependently inhibited secretion of IL-6 by YES-2 cells in vitro. Moreover, reverse transcription-PCR assay showed that treatment of YES-2 cells with berberine (8-32 microM) for 24 h reduced IL-6 mRNA expression. Our results suggest that C. rhizoma may have an anticachectic effect on esophageal cancer and an effect is associated with the ability of berberine to down-regulate tumor IL-6 production.

Administration, Oral↗

Comparative effects of beta2-adrenergic agonists on muscle waste associated with tumour growth.

The implantation of the Yoshida AH-130 ascites hepatoma (a fast growing tumour) to rats resulted in a dramatic loss of both white adipose tissue and muscle (skeletal and cardiac) mass. Administration of beta2-adrenergic agonists to tumour-bearing rats resulted in a partial recovery of skeletal muscle and heart mass. Treatment of the tumour-bearing animals with the different drugs (salbutamol, salmeterol and clenbuterol) did not influence tumour growth or food intake so it can be suggested that the effects were solely due to metabolic changes. In addition, while the three drugs had clear effects on gastrocnemius muscles, clenbuterol and salbutamol had also an effect on soleus, and salbutamol had a clear effect on cardiac muscle. It is suggested that any of the studied beta2-adrenergic agonists (but perhaps, particularly salmeterol) could be used clinically in the treatment of cancer cachexia.

Adipose Tissue↗

Protein turnover in skeletal muscle of tumour-bearing transgenic mice overexpressing the soluble TNF receptor-1.

The implantation of the Lewis lung carcinoma (a fast-growing mouse tumour that induces cachexia) to both wild-type and transgenic mice for the soluble TNF receptor type I protein (sTNF-R1) resulted in a considerable loss of carcass weight in both groups. However, while in the wild-type mice there was a loss of both fat and muscle, in the transgenic mice muscle waste was not affected to the same extent as in the wild-type group. Muscle waste in wild-type mice was accompanied by an increase in the fractional rate of protein degradation, while no changes were observed in protein synthesis. The result was a decreased rate of protein accumulation which accounted for the muscle weight loss observed as a result of the tumour burden. In contrast, transgenic mice did not have such low rates of protein accumulation after tumour implantation. The increase in protein degradation in the tumour-bearing transgenic mice was accompanied by a similar increase in protein synthesis which compensated for the loss of muscle protein by degradation. Both tumour-bearing groups showed an enhanced expression of ubiquitin and proteasome C8 subunit genes, all of them related to the activation of the ATP-dependent proteolytic system in skeletal muscle. It is suggested that TNF may, in part, be responsible for the loss of protein in skeletal muscle of tumour-bearing mice.

Animals↗

Different cytokines modulate ubiquitin gene expression in rat skeletal muscle.

Intravenous administration of different cytokines caused important changes in the expression of ubiquitin genes in skeletal muscle. Tumour necrosis factor-alpha caused a 2.2- and 1.9-fold increase in the expression of the 2.4 and 1.2 kb transcripts, respectively. Administration of interferon-gamma also caused a 2.2- and 1.8-fold increase in the 2.4 and 1.2 kb transcripts, respectively. While administration of leukaemia inhibitory factor and interleukin-6 resulted in no changes in ubiquitin gene expression, interleukin-1 administration also caused an increase in both ubiquitin gene transcripts (2.8- and 1.9-fold for the 2.4 and 1.2 kb transcripts, respectively). The results suggest that some of the cytokine effects on the ubiquitin system gene expression could be related to the enhanced skeletal muscle proteolysis found during cancer cachexia and other pathological states.

Animals↗

Acquired growth hormone resistance in patients with chronic heart failure: implications for therapy with growth hormone.

OBJECTIVES: We aimed to determine whether growth hormone (GH) resistance is present in patients with chronic heart failure (CHF) and whether it may be linked to the biochemical response to GH treatment. BACKGROUND: Acquired GH resistance is a feature of severe illness, in particular, cachexia. In patients with CHF, the response to GH therapy appears to be variable. METHODS: Biochemical markers of the GH-insulin-like growth factor-I (IGF-I) axis were compared in 21 cachectic patients with CHF, 51 noncachectic patients and 26 healthy control subjects. In separate studies, the predictive value of baseline biochemical variables for the IGF-I response to GH treatment was analyzed. RESULTS: Cachectic patients showed an increase of total GH and immunologically intact GH (p < or = 0.0002) and a decrease of GH-binding protein (BP) (p = 0.005), IGF-BP3 (p = 0.01) and IGF-I (p = 0.06), compared with noncachectic patients. Similar changes were found when the cachectic group was compared with the control group. No differences were found between noncachectic patients and control subjects. Levels of GH-BP correlated with the IGF-I/GH ratio in all subgroups (all p < or = 0.002). Baseline GH-BP levels were related to the increase of IGF-I levels in response to GH treatment in patients with CHF after 24 h (r = 0.83, p = 0.005; n = 9; study 2), 44 days (r = 0.52, p = 0.007; n = 25; study 3) and 96 days (r = 0.54, p = 0.006; n = 24; study 3). CONCLUSIONS: Most cachectic and some noncachectic patients with CHF show features of acquired GH resistance. The principal predictors of the biochemical features of GH resistance and of the poor biochemical response to short-term and longer-term GH treatment are GH-BP plasma levels. The presence of GH resistance is potentially a major factor determining the response to GH therapy in patients with CHF.

Biomarkers↗

Reduction of insulin-like growth factor-I expression in the skeletal muscle of noncachectic patients with chronic heart failure.

OBJECTIVES: We sought to assess the role of insulin-like growth factor-I (IGF-I) in muscle wasting in chronic heart failure (CHF), serum concentrations and local muscular IGF-I expression were determined in patients with severe CHF. BACKGROUND: Chronic heart failure is associated with progressive muscle atrophy, leading to cardiac cachexia. Skeletal muscle disuse and inflammatory activation with elevated cytokine levels have been implicated; however, the pathomechanism involved remains largely unknown. METHODS: Serum levels of IGF-I were measured by competitive solid phase immunoassay in 47 patients with severe CHF (left ventricular ejection fraction < or =30%) and 15 age-matched healthy subjects (HS). Insulin-like growth factor-I and IGF-I receptor expression were assessed in vastus lateralis biopsies by real-time PCR and Western blot analysis. RESULTS: Although serum IGF-I was not significantly different (175 +/- 10 ng/ml in CHF vs. 170 +/- 12 ng/ml in HS, p = NS), local muscle IGF-I mRNA expression was reduced by 52% in CHF (6.7 +/- 0.4 vs. 14.0 +/- 0.9 arbitrary units in HS, p < 0.001). This was accompanied by an increase in IGF-I receptor mRNA expression (86.8 +/- 5.4 in CHF vs. 23.1 +/- 1.8 arbitrary units in HS, p < 0.001). Local IGF-I expression was significantly correlated with muscle cross-sectional area (R = 0.75, p = 0.01). Chronic heart failure patients with a body mass index of < 25 kg/m(2) showed signs of peripheral growth hormone (GH) resistance, as indicated by elevated serum GH, and reduced IGF-I levels. CONCLUSIONS: In CHF patients, muscle IGF-I expression is considerably reduced in the presence of normal serum IGF-I levels, possibly contributing to early loss of muscle mass. These findings are consistent with a potential role of IGF-I for skeletal muscle atrophy in CHF.

Body Mass Index↗

Changes in somatotropic axis response and body composition during growth hormone administration in progressive cachectic parasitism.

A multistage protozoan parasitic disease was used as a cachexia model to study the effects of daily administration of bovine growth hormone (GH) on endocrine and body composition changes of young calves from the onset of the acute phase response (APR). Male calves averaging 127.5 +/- 2.0 kg body weight were assigned to control, ad libitum fed, noninfected (C); ad libitum fed, infected (250,000 oocysts Sarcocystis cruzi, per os, I); noninfected, pair-fed (PF) to matched I-treatment calves and these respective same treatments in calves injected daily with GH (USDA-bGH-B1), 12.5 mg/calf/day, im) designated as CGH, IGH and PFGH. GH injections were initiated on Day 20 postinfection (PI), 3 to 4 d before the onset of clinical signs of APR, and continued to Day 56 PI, at which time animals were euthanized for tissue collections. Abrupt increases in rectal temperature commensurate with up to 70% reduction in voluntary feed intake were observed in I and IGH beginning 23-25 d PI. For the trial period between Days 20 and 56 PI, average daily carcass protein gains were 123, 52, 109, 124, 48, and 67 g/d and average daily carcass fat gains were 85, 11, 43, 71, -23, and 29 g/d for C, I, PF, CGH, IGH, and PFGH, respectively. Effects of GH were significant for fat accretion and plasma urea depression. Rectus femoris was highly refractory to catabolic effects of infection while psoas major was significantly catabolized during infection. Plasma concentrations of insulin-like growth factor-I (IGF-I) increased significantly in all GH-treated calves between Day 20 and 23 PI. Plasma IGF-I declined well below Day 20 values in all infected calves from the onset of the APR through the end of the study. The decrease in plasma IGF-I concentrations in I and IG was highly correlated with the magnitude of the fever response. Hepatic mRNA for GH receptor and IGF-I was decreased in infected calves. Hepatic microsomal membrane binding of 125I-GH did not differ between groups. The data suggest that effects of GH and parasitism on tissue metabolism during disease may vary among different specific tissue pools. The data demonstrate that daily GH administration in young calves does not prevent lean tissue losses and may accelerate fat depletion associated with cachectic parasitism. Furthermore, the onset of APR overrode the capacity for GH to maintain elevated plasma concentrations of IGF-I, an effect not readily explained through changes of GH-receptor binding.

Acute-Phase Reaction↗

Role of cytokines in AIDS wasting.

There is now a large literature implicating cytokines in the development of wasting and cachexia commonly observed in a variety of pathophysiologic conditions. In the acquired immunodeficiency syndrome (AIDS), cytokines elicited by primary and secondary infections seem to exert subtle and sustained effects on behavioral, hormonal, and metabolic axes, and their combined effects on appetite and metabolism have been postulated to drive wasting. However, correlations of increased blood levels of a particular cytokine with wasting in AIDS have not been consistent observations, perhaps because cytokines act principally as paracrine and autocrine hormones, as well as indirectly by activating other systems. A better understanding of the mechanisms underlying the catabolic effects of cytokines in clearly needed if more efficacious strategies are to be developed for the prevention and treatment of wasting in AIDS. In this review we first examine the interacting factors contributing to the AIDS wasting syndrome. We then analyze the complex and overlapping role of cytokines in the pathophysiology of this condition, and put forward a number of hypotheses to explain some of the most important features of this syndrome.

Cachexia↗

Interventional nutrition for the cancer patient.

Dogs and cats with cancer have significant alterations in carbohydrate, protein, and fat metabolism, which can result in cancer cachexia and subsequently can decrease quality of life, reduce response to therapy, and shorten survival time. Nutritional modulation may be beneficial in the treatment of cancer patients to reverse these metabolic alterations. There is evidence that foods relatively low in simple carbohydrates with moderate amounts of high-quality protein, fiber, and fat (especially fats of the omega-3 fatty acid series) are beneficial for pets with cancer. In addition, certain supplemental nutrients may have potential to reduce the risk of developing cancer, or the growth and metastases of established malignant disease. Nutritional intervention can be a powerful tool for controlling malignant disease and for reducing toxicity associated with chemotherapy and radiation therapy.

Animals↗

Interventional nutrition for cardiac disease.

Animals with cardiac disease can have a variety of nutritional alterations for which interventional nutrition can be beneficial. Deviation from optimal body weight, both obesity and cachexia, is a common problem in cardiac patients and adversely affects the animal. Methods for maintaining optimal weight are important for good quality of life in dogs and cats with cardiac disease. Providing proper diets to prevent excess intake of sodium and chloride also is important, but severe salt restriction may not be necessary until later stages of disease. Certain nutrient deficiencies may play a role in the pathogenesis or complications of cardiac disease, but nutrients also may have effects on cardiac disease which are above and beyond their nutritional effects (nutritional pharmacology). Supplementation of nutrients such as taurine, carnitine, coenzyme Q10, and omega-3 polyunsaturated fatty acids may have benefits in dogs or cats with cardiac disease through a number of different mechanisms. By addressing each of these areas maintaining optimal weight, avoiding nutritional deficiencies and excesses, and providing the benefits of nutritional pharmacology, optimal patient management can be achieved.

Animals↗

Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARgamma coactivator-1.

Cachexia is a chronic state of negative energy balance and muscle wasting that is a severe complication of cancer and chronic infection. While cytokines such as IL-1alpha, IL-1beta, and TNFalpha can mediate cachectic states, how these molecules affect energy expenditure is unknown. We show here that many cytokines activate the transcriptional PPAR gamma coactivator-1 (PGC-1) through phosphorylation by p38 kinase, resulting in stabilization and activation of PGC-1 protein. Cytokine or lipopolysaccharide (LPS)-induced activation of PGC-1 in cultured muscle cells or muscle in vivo causes increased respiration and expression of genes linked to mitochondrial uncoupling and energy expenditure. These data illustrate a direct thermogenic action of cytokines and p38 MAP kinase through the transcriptional coactivator PGC-1.

Animals↗

4-{(2R)-[3-Aminopropionylamido]-3-(2,4-dichlorophenyl)propionyl}-1-{2-[(2-thienyl)ethylaminomethyl]phenyl}piperazine as a potent and selective melanocortin-4 receptor antagonist--design, synthesis, and characterization.

Recent studies have demonstrated that melanocortin-4 receptor (MC4R) antagonists can prevent weight loss in tumor-bearing mice, which indicates clinical usage for the treatment of cachexia. In our efforts to develop potent and selective antagonists of the human MC4R, we designed piperazinebenzylamines bearing a 2,4-dichlorophenylalanine, by utilizing information derived from structure--activity relationships of MC4R agonists and mutagenesis results of the MC4R and peptide ligands. On the basis of known MC4R agonists such 6, we successfully synthesized potent MC4R antagonists exemplified by 10, which possesses a K(i) value of 1.8 nM in binding affinity. 10 does not stimulate cAMP release in HEK 293 cells expressing the human MC4 receptor at 10 microM concentration. It was demonstrated by Schild analysis that 10 was a competitive functional antagonist with a pA(2) value of 7.9 in the inhibition of alpha-MSH-stimulated cAMP accumulation. 10 also penetrated into the brain when dosed intravenously in rats.

Animals↗

A candidate for cancer gene therapy: MIP-1 alpha gene transfer to an adenocarcinoma cell line reduced tumorigenicity and induced protective immunity in immunocompetent mice.

PURPOSE: To evaluate the possibility of cancer gene therapy by the gene delivery of chemokine, the effects of human macrophage inflammatory protein 1 alpha (hu-MIP-1 alpha), murine-macrophage inflammatory protein 1 alpha (mu-MIP-1 alpha), and human-interleukin 8 (hu-IL-8) on tumor progression and immunization were studied. METHODS: Cachexia-inducing and highly tumorigenic adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid, hu-MIP-1 alpha, mu-MIP-1 alpha, or hu-IL-8 expression vector. The production of hu-MIP-1 alpha reached > 1.5 ng/ml in vitro when transfectant cells were cultured at a cell density of 2 x 10(5) cells in 7 ml for 3 days. Immunocompetent BALB/c mice were inoculated into the footpad with the tumor cells, and then primary tumor growth, morphological analyses, and tumor immunogenicity were studied. RESULTS: The secretion of hu-MIP-1 alpha, mu-MIP-1 alpha, and hu-IL-8 did not affect the growth rate in vitro. Reduced tumorigenicities in vivo were observed in transfected cells with hu-MIP-1 alpha and mu-MIP-1 alpha. Morphologic observation of the site of inoculation of cells transfected with hu-MIP-1 alpha showed infiltration of macrophages and neutrophils on the 5th day after the inoculation. Mice that had rejected cells transfected with hu-MIP-1 alpha gene were immune to a subsequent challenge with the parental cells. CONCLUSIONS: The rejection of the cells depends on cytolysis and generates potent and long lasting antitumor immunity. These data suggest that tumor cells transfected with the MIP-1 alpha gene might be useful as an effective therapy for the treatment of certain tumors.

Adenocarcinoma↗

Human MCAF gene transfer enhances the metastatic capacity of a mouse cachectic adenocarcinoma cell line in vivo.

PURPOSE: To evaluate the effect of monocyte chemotactic and activating factor (MCAF/MCP-1/JE) on tumor progression and metastasis. METHODS: Cachexia-inducing adenocarcinoma cells (cell line colon 26, clone 20) were transfected with either a control plasmid or MCAF expression vector. Spontaneous lung metastases were determined in mouse. RESULTS: The production of MCAF reached 0.4 ng/ml in vitro when transfectant cells were cultured at a cell density of 5 x 10(4) cells/ml for 3 days. Transfection of MCAF expression vector did not affect the growth rate in vitro. Also, after MCAF-transfection, the size of tumors after intra-footpad inoculation was similar to that of the parental cells. When the primary tumors were resected on the 10th day after inoculation, the incidence of spontaneous lung metastasis was less than 20% in both cells. The number of endothelial cells in the primary tumor rapidly increased from the 10th to the 14th day after inoculation, as revealed by immunohistochemical staining. In accordance with enhanced angiogenesis, the incidence rates of spontaneous metastasis increased when the primary tumors were resected on the 14th day after inoculation. Moreover, the spontaneous lung metastases were augmented in the animals injected with MCAF-transfectants compared to those injected with parental cells with a concomitant increase of angiogenesis. CONCLUSIONS: These results suggest that MCAF may augment the metastastic potential by modulating tumor associated angiogenesis.

Adenocarcinoma↗

Induction of apoptosis by a cachectic-factor in murine myotubes and inhibition by eicosapentaenoic acid.

Treatment of C(2)C(12) myotubes with a tumour-derived proteolysis-inducing factor (PIF) at concentrations between 1 and 10 nM was shown to stimulate the activity of the apoptotic initiator caspases-8 and -9 and the apoptotic effector caspases-2, -3 and -6. This increased caspase activity was attenuated in myotubes pretreated with 50 microM eicosapentaenoic acid (EPA). At least part of the increase in caspase activity may be related to the increased proteasome proteolytic activity, since a caspase-3 inhibitor completely attenuated the PIF-induced increase in 'chymotrypsin-like' enzyme activity, the predominant proteolytic activity of the proteasome. However, Western blot analysis showed that PIF induced an increase in expression of the active form of caspase-3, which was also attenuated by EPA. Further Western blot analysis showed PIF increased the cytosolic content of cytochrome c, as well as expression of the pro-apoptotic protein bax but not the anti-apoptotic protein bcl-2, which were both attenuated by 50 microM EPA. Induction of apoptosis by PIF in murine myotubes was confirmed by an increase in free nucleasomes formation and increased DNA fragmentation evidenced by a nucleasomal ladder typical of apoptotic cells. This process was again inhibited by pre-incubation with EPA. These results suggest that in addition to activating the proteasome, PIF induces apoptosis in C(2)C(12) myotubes, possibly through the common intermediate arachidonic acid. Both of these processes would contribute to the loss of skeletal muscle in cancer cachexia.

Animals↗

[From starving to life-threatening nutrition--the history of an intestinal pseudoobstruction].

It is the story of a 70-year-old lady, who suffered from chronic intestinal pseudoobstruction since her adolescence. In the early 90ies progressive cachexia developed. In 1994 parenteral nutrition was begun via a port-à-cath-system with good success in the first years. Later, various complications occurred: thrombotic events, several catheter-related infections with various bacterial strains, an endocarditis of the aortic valve, which was replaced by a bioprosthesis, and finally a relapsing endocarditis of this artificial valve with a life-threatening paravalvular abscess and regurgitation. She also survived this second heart surgery and is currently under parenteral nutrition again, with a more than uncertain future.

Aged↗

Treatment of pure red cell aplasia and autoimmune haemolytic anaemia in chronic lymphocytic leukaemia with Campath-1H.

A patient with chronic lymphocytic leukaemia (CLL) progressive on fludarabine therapy and life-threatening anaemia related to immune haemolysis and pure red cell aplasia was treated with Campath-1H. The patient had sustained complete remission of both CLL and anaemia, but died of recurrent sepsis and cachexia 10 months after completion of the treatment. Campath-1H (alemtuzumab), a humanised anti-CD52 monoclonal antibody, is a potent therapeutic agent against advanced CLL and immune cytopenias. It could be indicated in the treatment of severe immune complications of CLL unresponsive to corticosteroids. Prolonged immunosuppression is a serious side-effect leading to severe infectious complication.

Aged↗

Interleukin-4 receptor-directed cytotoxin therapy of AIDS-associated Kaposi's sarcoma tumors in xenograft model.

The elusive and enigmatic origin of AIDS-associated Kaposi's sarcoma (AIDS-KS) makes it a complex tumor and therefore difficult to treat. Here we demonstrate that AIDS-KS cells express surface interleukin-4 (IL-4) receptors, and that IL-4 toxin (IL-4(38-37)-PE38KDEL) is specifically cytotoxic to these cells. Intratumoral, intraperitoneal and intravenous administration of IL-4 toxin in nude mice with established subcutaneous AIDS-KS tumors caused considerable anti-tumor activity in a dose-dependent manner, with highest dose producing durable complete responses. Metabolic changes, including cachexia and lymphopenia, induced by KS tumors were prevented by IL-4 toxin treatment. This report establishes IL-4(38-37)-PE38KDEL as an experimental therapeutic agent for the treatment of AIDS-KS.

ADP Ribose Transferases↗