Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy newly diagnosed Caucasian male patients with head and neck squamous cell carcinomas (HNSCC) were included in the study. All patients were less than 80 years of age, with no cachexia or auto-immune disease, and they were not taking immuno-active medications. Monocytes from these patients were cultured in vitro and supplemented with autologous serum under ex vivo conditions or cultured with serum-free medium. Comparison was made to monocytes from 59 patients with benign HN diseases. Similar physical activity levels prior to testing as well as a minimum stress load were ensured in both groups. Increased monocyte supernatant levels were determined under ex vivo conditions of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha, but not of interleukin-12 (IL-12) with endotoxin stimulated monocytes of HNSCC patients compared to control conditions. Increased monokine levels were not present with mononuclear cell cultures stimulated with a T-cell general stimulatory agent or with purified monocytes not specifically stimulated. With endotoxin-stimulated monocytes under in vitro conditions, an increased supernatant was shown for TNF-alpha, but not IL-6. With serum from the different patients cultured with monocytes employed from a healthy control, no difference between the groups was shown in the IL-6 and TNF-alpha response to endotoxin stimulation. The differences in IL-1 beta and TNF-alpha, but not IL-6 levels were differentiated statistically from the smoking and alcohol histories of the patients. These findings suggest that the function of monocytes in general, and thus possibly all mononuclear phagocyte system cells in HNSCC patients, are altered.
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PMID:Ex vivo interleukin (IL)-1 beta, IL-6, IL-12 and tumor necrosis factor-alpha responsiveness with monocytes from patients with head and neck carcinoma. 1039 1

Some paraneoplastic syndromes as fever, cachexia, loss of weight or hepatic dysfunction, are relatively frequent in patients affected by a renal cell carcinoma (RCC). However their pathogeny has been unknown until a short time ago. The advances in immunology have permitted to identify the interleukin-6 as the responsible for these changes. In spite of our better knowledge, the treatment of these paraneoplastic syndromes, when persist after the removal of the tumor, continues being a challenge. We present the case of a patient with a renal cell carcinoma that began as a feverish syndrome, developing thereinafter a hepatic dysfunction or Stauffer's syndrome. The paraneoplastic symptoms persisted after removal of the tumor. No response to the administered treatment has been observed. The patient died two months after the surgery.
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PMID:[Etiopathogenesis and management of paraneoplastic fever and Stauffer syndrome in renal carcinoma]. 1039 62

A new model of cachexia is described in which muscle protein metabolism related to the ubiquitin-proteasome pathway was investigated. Cloning of the colon-26 tumor produced a cell line, termed R-1, which induced cytokine (noninterleukin-1beta, interleukin-6 and tumor necrosis factor-alpha)-independent cachexia. Implantation of R-1 cells in mice elicited significant (20-30%) weight loss and decreased blood glucose by 70%, and adipose tissue levels declined by 95% and muscle weights decreased by 20-25%. Food intake was unaffected. The decrease in muscle weight reflected a decline in insoluble, but not soluble, muscle protein that was associated with a significant increase in net protein degradation. The rate of ubiquitin conjugation of proteins was significantly elevated in muscles of cachectic mice. Furthermore, the proteasome inhibitor lactacystin blocked the increase in protein breakdown but had no significant effect on proteolysis. Several markers of the ubiquitin-proteasome pathway, E2(14k) mRNA and E2(14k) protein and ubiquitin-protein conjugates, were not elevated. Future investigations with this new model should gain further insights into the mechanisms of cachexia and provide a background to evaluate novel and more efficacious therapies.
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PMID:A new model of cancer cachexia: contribution of the ubiquitin-proteasome pathway. 1044 30

Impaired hematopoiesis and dysregulated cytokine expression have important implications for cancer in the elderly. In aged people, hematopoiesis is dysregulated and becomes paradoxically down-modulated under periods of increased hematopoietic demand. This down-modulation may explain, at least in part, the increased incidence of anemia in the elderly, although the cause of anemia can usually be identified in these patients and frequently reversed with targeted therapy. An age-associated decrease in the expression of interleukin-2 may contribute to impaired cellular immunity. Additionally, the increased interleukin-6 production frequently found in the elderly may participate in promoting the survival and proliferation of malignant myeloma and in inducing resistance by myeloma cells to therapies that act through apoptosis. Dysregulation of the expression of these and other cytokines may be a mechanism contributing to age-related impairment of the hematopoietic response, the genesis and therapeutic resistance of specific malignancies, and cancer cachexia.
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PMID:Hematopoiesis and cytokines. Relevance to cancer and aging. 1068 71

Cancer-induced cachexia is a common manifestation observed in patients with malignancies. Elevated levels of circulating glucocorticoids and interleukin-6 (IL-6) have been observed in cancer patients with cachexia and are implicated as major mediators in this process. The purpose of this study was to investigate the role of circulating glucocorticoid levels as primary mediators in cancer-induced cachexia. We evaluated whether inhibition of glucocorticoids with the receptor antagonist RU-486 could abrogate the detrimental wasting of muscle and adipose tissues seen in a well-characterized murine tumor-induced cachexia model. Mice (12/group) were randomized to control, tumor-bearing, control + vehicle, or tumor-bearing + glucocorticoid receptor antagonist groups. Circulating serum glucocorticoid and IL-6 levels were measured in addition to multiple body composition parameters, such as total body weight, lean body mass, and adipose content. The results of this study indicate a significant physiological alteration in the tumor-bearing host that causes severe and detrimental changes in body composition parameters. Regression analysis demonstrated a significant correlation between increased circulating glucocorticoid levels and alterations in body composition parameters. These observed defects were not abrogated with the administration of a glucocorticoid receptor antagonist. We therefore conclude that the untoward effects of tumor-induced cachexia are not mediated primarily by the peripheral effects of high circulating glucocorticoid levels but may involve a complex interaction with IL-6.
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PMID:Glucocorticoid blockade does not abrogate tumor-induced cachexia. 1069 76

Renal cell carcinoma (RCC) has been shown to be immunologically more labile than other types of cancer. In this study, we examined tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) production of peripheral blood monocytes in 38 RCC patients. Monocytes were isolated from peripheral blood mononuclear cells by adherence to a plastic dish and cultured with lipopolysaccharide for 24 hours. The culture supernatant was obtained, and the production of TNF alpha, IL-1 beta and IL-6 was measured by ELISA. As a result, TNF alpha and IL-1 beta production was significantly higher in the high stage patients compared to the control subjects and low stage patients. When the patients were divided according to serum C-reactive protein (CRP), TNF alpha, IL-1 beta and IL-6 production was significantly higher in the CRP-positive patients compared to the control subjects and the CRP-negative patients. Overexpression of these cytokines may therefore induce a hypermetabolic status that may be a cause of malnutrition and cancer cachexia.
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PMID:TNF alpha, IL-1 beta and IL-6 production by peripheral blood monocytes in patients with renal cell carcinoma. 1076 74

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.
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PMID:Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on esophageal cancer cells that produce interleukin 6. 1094 May 6

Treatment of advanced or recurrent breast cancer with medroxyprogesterone acetate (MPA) shows high response rates and the accessory effects of appetite stimulation, improvement in performance status (PS) and bone marrow protection. In recent years, interleukin-6 (IL-6) has been reported to cause cachexia. In this study, to clarify the significance of IL-6 in advanced or recurrent breast cancer, the relationship between the IL-6 level and clinical findings or effect of MPA was investigated. Sixty-five patients with recurrent or advanced breast cancer participated in a prospective study. The age of patients ranged from 28 to 79 years with an average age of 51.3 years. IL-6 level was investigated in these patients dosed with 800 mg/day of MPA and in 17 postoperative nonrecurrent patients. Serum MPA level was measured by high-performance liquid chromatography and IL-6 level was measured prior to MPA administration, 4 weeks (in 59 cases) and 12 weeks (in 32 patients) after MPA administration by ELISA. Serum IL-6 level was significantly higher in recurrent cases, especially in those with visceral metastasis. Further, in patients for whom MPA therapy was effective, the IL-6 level prior to the treatment was clearly low. The IL-6 level was significantly increased after 4 weeks. However, response to MPA was significantly higher and PS was improved in those cases demonstrating less increased IL-6 levels after 4 weeks. In addition, the effect of MPA was significantly related to a higher serum concentration of MPA-positive ER, and longer disease-free interval, although there was no significant predictive factor for the clinical effect of MPA therapy in multivariate analysis. In conclusion, MPA therapy was effective in cases demonstrating a low IL-6 level and less increased IL-6 levels after 4 weeks. PS was improved in those cases in which the degree of IL-6 increase was suppressed by MPA, and many such cases showed low IL-6 levels prior to MPA therapy. Furthermore, PS was improved even in nonresponders to MPA. Therefore, it is suggested that MPA therapy might be useful in treating recurrent breast cancer, and its benefits might be mediated by IL-6.
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PMID:An analysis of serum interleukin-6 levels to predict benefits of medroxyprogesterone acetate in advanced or recurrent breast cancer. 1097 Nov 77

The cachexia-anorexia syndrome occurs in chronic pathophysiologic processes including cancer, infection with human immunodeficiency virus, bacterial and parasitic diseases, inflammatory bowel disease, liver disease, obstructive pulmonary disease, cardiovascular disease, and rheumatoid arthritis. Cachexia makes an organism susceptible to secondary pathologies and can result in death. Cachexia-anorexia may result from pain, depression or anxiety, hypogeusia and hyposmia, taste and food aversions, chronic nausea, vomiting, early satiety, malfunction of the gastrointestinal system (delayed digestion, malabsorption, gastric stasis and associated delayed emptying, and/or atrophic changes of the mucosa), metabolic shifts, cytokine action, production of substances by tumor cells, and/or iatrogenic causes such as chemotherapy and radiotherapy. The cachexia-anorexia syndrome also involves metabolic and immune changes (mediated by either the pathophysiologic process, i.e., tumor, or host-derived chemical factors, e.g., peptides, neurotransmitters, cytokines, and lipid-mobilizing factors) and is associated with hypertriacylglycerolemia, lipolysis, and acceleration of protein turnover. These changes result in the loss of fat mass and body protein. Increased resting energy expenditure in weight-losing cachectic patients can occur despite the reduced dietary intake, indicating a systemic dysregulation of host metabolism. During cachexia, the organism is maintained in a constant negative energy balance. This can rarely be explained by the actual energy and substrate demands by tumors in patients with cancer. Overall, the cachectic profile is significantly different than that observed during starvation. Cachexia may result not only from anorexia and a decreased caloric intake but also from malabsorption and losses from the body (ulcers, hemorrhage, effusions). In any case, the major deficit of a cachectic organism is a negative energy balance. Cytokines are proposed to participate in the development and/or progression of cachexia-anorexia; interleukin-1, interleukin-6 (and its subfamily members such as ciliary neurotrophic factor and leukemia inhibitory factor), interferon-gamma, tumor necrosis factor-alpha, and brain-derived neurotrophic factor have been associated with various cachectic conditions. Controversy has focused on the requirement of increased cytokine concentrations in the circulation or other body fluids (e.g., cerebrospinal fluid) to demonstrate cytokine involvement in cachexia-anorexia. Cytokines, however, also act in paracrine, autocrine, and intracrine manners, activities that cannot be detected in the circulation. In fact, paracrine interactions represent a predominant cytokine mode of action within organs, including the brain. Data show that cytokines may be involved in cachectic-anorectic processes by being produced and by acting locally in specific brain regions. Brain synthesis of cytokines has been shown in peripheral models of cancer, peripheral inflammation, and during peripheral cytokine administration; these data support a role for brain cytokines as mediators of neurologic and neuropsychiatric manifestations of disease and in the brain-to-peripheral communication (e.g., through the autonomic nervous system). Brain mechanisms that merit significant attention in the cachexia-anorexia syndrome are those that result from interactions among cytokines, peptides/neuropeptides, and neurotransmitters. These interactions could result in additive, synergistic, or antagonistic activities and can involve modifications of transducing molecules and intracellular mediators. Thus, the data show that the cachexia-anorexia syndrome is multifactorial, and understanding the interactions between peripheral and brain mechanisms is pivotal to characterizing the underlying integrative pathophysiology of this disorder.
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PMID:Central nervous system mechanisms contributing to the cachexia-anorexia syndrome. 1105 8

Patients with cancer often undergo a specific loss of skeletal muscle mass, while the visceral protein reserves are preserved. This condition known as cachexia reduces the quality of life and eventually results in death through erosion of the respiratory muscles. Nutritional supplementation or appetite stimulants are unable to restore the loss of lean body mass, since protein catabolism is increased mainly as a result of the activation of the ATP-ubiquitin-dependent proteolytic pathway. Several mediators have been proposed. An enhanced protein degradation is seen in skeletal muscle of mice administered tumour necrosis factor (TNF), which appears to be mediated by oxidative stress. There is some evidence that this may be a direct effect and is associated with an increase in total cellular-ubiquitin-conjugated muscle proteins. Another cytokine, interleukin-6 (IL-6), may play a role in muscle wasting in certain animal tumours, possibly through both lysosomal (cathepsin) and non-lysosomal (proteasome) pathways. A tumour product, proteolysis-inducing factor (PIF) is produced by cachexia-inducing murine and human tumours and initiates muscle protein degradation directly through activation of the proteasome pathway. The action of PIF is blocked by eicosapentaenoic acid (EPA), which has been shown to attenuate the development of cachexia in pancreatic cancer patients. When combined with nutritional supplementation EPA leads to accumulation of lean body mass and prolongs survival. Further knowledge on the biochemical mechanisms of muscle protein catabolism will aid the development of effective therapy for cachexia.
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PMID:Loss of skeletal muscle in cancer: biochemical mechanisms. 1117 57


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