Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006625 (cachexia)
 5,650 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is, at present, considerable interest in the possible role for the proinflammatory cytokines, tumor necrosis factor-alpha, interleukin-1, interleukin-6, and interferon-gamma in the pathogenesis of cancer cachexia. Indirect evidence for such a role is based on the observation that chronic administration of many of these cytokines, either alone or in combination, can reproduce the myriad of host responses seen in experimental and human cancer cachexia. Elevated plasma levels of tumor necrosis factor-alpha, interleukin-2, and interferon-gamma have rarely been detected in patients or experimental animals with cancer, although interleukin-6 levels appear to correlate with tumor progression in animal models. The strongest evidence for a causal role for cytokines has come from rodent studies in which tumor-bearing animals have been passively immunized with antibodies directed against individual cytokines. Several groups have shown modest but significant improvements in food intake and lean tissue retention with antibodies directed against tumor necrosis factor-alpha, interleukin-1, interleukin-6, and interferon-gamma. However, there has been no consistent finding that one cytokine is universally involved in cancer cachexia in histologically distinct tumor models. One ominous finding in several tumor models has been that the endogenous production of cytokines appears to support tumor growth. Such findings raise the intriguing possibility that these cytokines, although contributors to tissue wasting and anorexia, may also serve the tumor as either direct or indirect cell growth factors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of cytokines in cancer cachexia. 128 23

To ascertain anorexigenic effect of toxohormone-L, a polypeptide extracted and purified from ascites of patients with hepatoma were infused into the rat third cerebroventricle. Food intake decreased on the first day after infusion of an optimum dose of 10.0 micrograms (p less than 0.05). The suppressive effect on feeding was linearly dose dependent (p less than 0.05). Meal size and latency to the first meal decreased in the 12-h dark period, and the first and the second 4-h cumulative blocks after infusion of a 10.0 micrograms dose (p less than 0.01 for each). The suppressive effects on total food intake and meal size were completely recovered within 24 h after infusion. Neither postprandial intermeal interval nor eating speed was affected. Periprandial drinking, a ratio of water intake to food intake, was not affected after infusion of 5.0 and 10.0 micrograms toxohormone-L. Infusion of a 10.0 micrograms dose showed no effect on ambulation. These findings suggest that anorexia and cachexia produced in cancer patients may essentially be due to the suppressive effect of toxohormone-L on food intake.
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PMID:Anorexia induced by toxohormone-L isolated from ascites fluid of patients with hepatoma. 132 17

We have previously shown that spontaneous physical exercise can delay the onset of experimental anorexia and cachexia and retard tumour growth and we now report the effects on the energy metabolism in skeletal muscle. Exercising tumour-bearing animals (TBE) had an increased maximal capacity for oxygen uptake expressed as Vmax of the cytochrome c oxidase compared with their tumour-bearing sedentary controls (TBS) [mean (S.E.) 289.9 (30.7) vs. 141.6 (11.0); P less than 0.05] but an unchanged Km value. The TBS animals had a depressed Vmax as compared with non-tumour-bearing sedentary controls (CS) [141.6 (11.0) vs. 210.1 (15.1); P less than 0.05]. Most of the purine nucleotides in the 'glycolytic' anterior tibial muscle were significantly altered in the TBE animals compared with the TBS animals, but in the mainly 'oxidative' soleus muscle only the level of inosine monophosphate (IMP) was changed. The results indicate that physical exercise can normalise the oxidative capacity and improve the energy state in skeletal muscle in the tumour-bearing host.
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PMID:Cytochrome c oxidase and purine nucleotides in skeletal muscle in tumour-bearing exercising rats. 132 6

Tumor necrosis factor is a cytokine that participates in the mediation of numerous diseases associated with inflammation, cachexia, shock, and tissue injury. Early studies of the biology of TNF delineated its hormonal actions as well as its systemic toxicity. More recent investigations have drawn attention to its paracrine actions that predominate when it is produced locally in the brain or vital organs. For instance, when compartmentalized production of TNF occurs in the central nervous system it directly mediates fever, anorexia, and altered whole-body metabolism. Since these changes are mediated within the neural network they occur independently of simultaneously sampled serum TNF levels. These paracrine actions of TNF have implications for diseases associated with production of TNF in tissues (e.g. HIV cerebritis, multiple sclerosis, cerebral malaria and cancer), because they may differ markedly from the hormone like-actions associated with systemic release. Since TNF may be beneficial in some diseases yet injurious in others, both the hormonal and paracrine actions must be precisely defined in order to formulate novel treatment strategies based on either enhancing its useful effects, or suppressing toxicity.
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PMID:Tumor necrosis factor in metabolism of disease: hormonal actions versus local tissue effects. 134 May 27

To determine whether the location of tumour growth influences host cytokine and metabolic responses, experimental subcutaneous (SQ) and liver (LIV) tumours were compared in Buffalo rats. An LIV tumour that was only 1 +/- 1% (P < 0.05 versus SQ) of body weight produced similar anorexia, weight loss, acute phase response, and systemic cytokine responses as are SQ tumour that was 10 +/- 2% of body weight. Neither tumour-bearing group had abnormal liver function tests or evidence of obstructive biliary pathology. Tumour necrosis factor (TNF) was detected by western analysis in both tumour as well as histologically normal liver remote from the tumour in the LIV group but not in livers of animals in freely fed and SQ groups. The proximity of the tumour to competent tissue macrophage populations, such as hepatic Kupffer cells, may be sufficient to induce cachexia. Hence, tumour location may be as important as tumour burden in determining the host's response to cancer.
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PMID:Tumour location influences local cytokine production and host metabolism. 134 Dec 37

Anorexia and cachexia are major problems in patients with cancer. Such measures as anti-cancer therapy, dietary counselling or hyperalimentation are not very successful in reversing this phenomenon in the vast majority of cancer patients. Thus, several drugs have been evaluated as agents to ameliorate cancer-associated anorexia/cachexia. Cyproheptadine is an antiserotonergic drug which appears to cause slight appetite stimulation in patients. A randomised clinical trial, however, was unable to demonstrate any weight gain from this agent. Corticosteroids are frequently used in clinical practice for appetite stimulation in patients with advanced malignancies. Supporting this practice, 4 randomised clinical trials showed that corticosteroid medications can stimulate the appetites of advanced cancer patients. However, these studies were not able to show any substantial nonfluid weight gain in treated patients. Megestrol acetate is a progestational agent which appears to be a relatively potent appetite stimulant. Randomised studies in advanced cancer patients have shown both substantial appetite stimulation and improvement in the nonfluid bodyweights of patients receiving this drug. Preliminary evidence also suggests that this drug has antiemetic properties. Several clinical studies are currently ongoing to determine the effect of various doses of megestrol acetate in patients with cancer. Efforts are also ongoing to evaluate both anabolic steroids and hydrazine sulfate as drugs for the treatment of patients with cancer anorexia/cachexia. The preliminary nature of these investigations, however, precludes recommendations for the use of either of these latter 2 drugs in routine clinical practice.
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PMID:Cancer-associated anorexia and cachexia. Implications for drug therapy. 137 16

The cancer-related cachexia/anorexia syndrome is not well understood. It is related to several factors like metabolic changes, tumor types, and disease extent and is frequently accompanied by decreased performance status. An important aspect of anorexia is the psychosocial problem: the patient is unable to join the family for meals precisely when he or she most needs familial support. Several randomized studies have shown that megestrol acetate, possibly in a dose-dependent fashion, can improve appetite and lead to weight gain. This effect seems to be most prevalent in patients with breast cancer and also occurs in the absence of a tumor response. We have retrospectively analyzed 176 patients with cancer types other than breast cancer who received only palliative treatment. The patients were treated with megestrol acetate (160 mg tid) because they complained of anorexia. After 10 days of treatment, megestrol acetate was continued only in those patients whose appetite and/or general well-being improved. Fifty-seven patients (32%) experienced such an improvement and asked for continuation of therapy. Many basic questions are still unanswered; nonetheless, from a practical clinical view it seems worthwhile to offer anorectic patients a chance to improve, especially since side effects of megestrol acetate are absent or mild, and the distinction between responders and nonresponders can be made by 10 days of treatment.
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PMID:Cachexia and cancer: a clinician's view. 138 53

Anorexia and cachexia frequently complicate the late stages of malignancy and may be a prominent feature of early disease. The resulting weight loss often becomes a major focus of concern for the patient and the family and may significantly add to the morbidity and mortality of cancer. Factors which contribute to the wasting syndrome include the effects of the tumour, effects of chemotherapy, abnormalities of carbohydrate, fat and protein metabolism and the cytokine response. Administration of total parenteral nutrition (TPN) is an important method of addressing malnutrition, particularly in patients with nonfunctioning gastrointestinal tracts. A critical review of the TPN cancer literature is provided along with a discussion of new approaches and future directions in the nutritional support of patients with malignant disease, such as anabolic agents, hydrazine sulfate and megestrol.
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PMID:Protein calorie malnutrition and cancer therapy. 141 97

Cachexia occurs in the majority of cancer patients before death. It is the result of major metabolic changes produced by tumor-released substances as well as by cytokines and some endogenous peptides. The most significant clinical manifestation is profound anorexia. Aggressive parenteral nutrition has not been able to increase patient survival or produce any significant symptomatic improvement. Recent research, therefore, has focused on drugs that might result in symptomatic improvement, even if no significant nutritional changes are detected. Corticosteroids have been shown to increase appetite for a brief period of time, but they do not appear to improve caloric intake or nutritional status. In addition to appetite stimulation, corticosteroids also improve a number of other symptoms transiently. Progestational drugs have been found in a number of studies to increase appetite, caloric intake, and nutritional status. The most effective type and dose of progestational drugs have not been clearly established. Cyproheptadine, hydrazine sulfate, and cannabinoids have all been suggested to have beneficial effects on appetite; their effectiveness, however, needs to be confirmed in prospective, controlled trials. Some of these trials are currently under way. Current data suggest that megestrol acetate or other progestational agents could be useful--because of effects on not only appetite but also overall nutritional status--in patients who have profound anorexia as the main manifestation of cachexia, provided expected survival can be measured in weeks or months. In patients with shorter expected survival or those who have problems tolerating progestational drugs, a brief course of corticosteroids may provide short-term symptomatic effects. Future studies should focus on (1) improving understanding of both the pathophysiology of cancer cachexia and the interaction of some of the major syndromes of terminal cancer--e.g., pain, cachexia, and cognitive failure--and (2) characterizing the symptomatic effects of different drugs more completely.
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PMID:Clinical management of anorexia and cachexia in patients with advanced cancer. 146 26

A placebo-controlled, randomized trial assessed the activity, tolerance, and degree of weight gain and anorexia of two doses of megestrol acetate in patients with advanced cancer and cachexia. Patients received either low-dose (480 mg/day) or high-dose (960 mg/day) megestrol acetate or placebo for 8 weeks. As of March 1991, 91 patients had been randomized; 65 patients were evaluable. Median initial weight loss in all patients ranged from 13 to 16%. Further weight loss was seen in 13 of 17 patients in the placebo group, compared with 10 of 27 and 6 of 21 in the low- and high-dose megestrol acetate groups, respectively. Eight of 27 patients in the low-dose-group and 9 of 21 in the high-dose group gained weight, with a median of 3 and 4 kg, respectively. Beneficial effects of megestrol acetate were seen in 63 and 71% of the low- and high-dose groups, respectively, compared with 24% of the placebo group. Side effects of megestrol acetate were mild. No correlation between megestrol acetate dosage and weight gain was found, but there was a tendency for increased weight in more patients taking high-dose megestrol acetate.
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PMID:Risks and benefits of various therapies for cancer anorexia. 146 27


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