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At least 883 records · Page 49Linked to original sources
PubMed2003

Cancer-related cachexia and oxidative stress: beyond current therapeutic options.

Cancer-related anorexia/cachexia syndrome is a complex phenomenon in which metabolic abnormalities, proinflammatory cytokines produced by the host immune system, circulating tumor-derived catabolic factors, decreased food intake and probably additional unknown factors all play different roles. This review examines the mechanisms of cancer-related anorexia/cachexia syndrome and the mainstays of its management. The two major options for pharmacological therapy have been progestational agents and corticosteroids. Agents currently under investigation are nonsteroidal anti-inflammatory drugs, N-3 fatty acids, branched-chain amino acids and thalidomide. On the basis of several previously published studies and clinical experience, an innovative treatment approach, which consists of an integrated nutritional and pharmacological treatment, has been developed. This approach, based upon multiple components each targeted at different factors involved, may be effective in both improving objective clinical symptoms, such as lean body mass, and subjective symptoms such as quality of life. A Phase II study has been initiated and Phase III study designed.

Animals↗
PubMed2006

High concentrations of organochlorines in a patient with kidney cancer and anorexia-cachexia syndrome.

PURPOSE: To determine persistent organic pollutants in adipose tissue in a patient with kidney cancer. METHODS: Adipose tissue was sampled from the abdominal wall during autopsy of a 75-year old man who had died from a kidney cancer. The concentrations of polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyltrichloroethane (DDE), hexachlorobenzene (HCB), chlordanes and tetrabromodiphenyl ether (TeBDE) were determined on lipid basis. For comparison results from 29 male population based subjects aged 70-80 years were used. RESULTS: All concentrations except for TeBDE were very high in the patient; sum of PCBs 18 808 ng/g fat (median for controls 997), DDE 14 183 (median for controls 751), HCB 424 (median for controls 46), and sum of chlordanes 2 389 (median for controls 62). The patient lost weight from 80 kg to 48 kg when he died, which may have contributed wholly or partly to the very high concentrations of organochlorines. CONCLUSION: Changes in weight must be recorded in cancer patients and the concentrations of persistent organic pollutants should be normalized to weight. The concentrations in this patient were 10- to almost 40-times higher than in the controls. Such very high concentrations may give clinical symptoms in the final stage of a wasting cancer patient.

Adipose Tissue↗
PubMed2006

Cachexia--induced cerebellar degeneration: involvement of serum TNF and MCP-1 in the course of experimental neoplastic disease.

Cerebellar degeneration may be recognized as a remote effect of a growing tumor. We have analysed serum concentrations of tumor necrosis factor-alpha (TNF-alpha), macrophage chemoattractant protein-1 (MCP-1), thyroxine and insulin to elucidate the pathomechanism which may be of importance for the development of central degeneration in cachectic Morris hepatoma bearing rats. Serum TNF-alpha and MCP-1 levels were evaluated by means of the ELISA system, while thyroxine and insulin were estimated by radioimmunoassay. Microscopic examination using hematoxylin-eosin, Nissl and Klüver-Barrera staining revealed an atrophy in the cerebellum, homogenization changes of Purkinje cells and decreased cell density of the granular layer. In the Morris hepatoma bearing animals serum MCP-1 content was elevated while TNF-alpha, thyroxine and insulin concentrations were decreased. This study has demonstrated that circulating TNF-alpha and MCP-1, together with decreased levels of insulin and thyroxine accompany and may produce a milieu of factors involved in mechanisms of the development of cerebellar degeneration in cachectic hepatoma bearing rats.

Animals↗
PubMed1994

Megestrol acetate in patients with AIDS-related cachexia.

OBJECTIVES: To compare the effects of oral suspensions of megestrol acetate, 800 mg/d, and placebo on body weight in patients with acquired immunodeficiency syndrome (AIDS)-related weight loss. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Outpatient community and university patient care setting. PATIENTS: Consecutive patients with AIDS who had substantial weight loss and anorexia were enrolled. Of 271 patients, 270 and 195 were evaluable for safety and efficacy, respectively. INTERVENTIONS: Patients were randomly assigned to receive placebo or megestrol acetate (100 mg, 400 mg, or 800 mg) daily for 12 weeks. MAIN OUTCOME MEASURES: The primary efficacy criterion was weight gain. Patients were evaluated at 4-week intervals for changes in weight and body composition, caloric intake, sense of well-being, toxic effects, and appetite. RESULTS: For evaluable patients receiving 800 mg of megestrol acetate per day, 64.2% gained 2.27 kg (5 pounds) or more compared with 21.4% of patients receiving placebo (P < 0.001). An intent-to-treat analysis showed significant differences (P = 0.002) between those receiving placebo and those receiving 800 mg of megestrol acetate for the number of patients who gained 2.27 kg (5 pounds) or more (8 of 32 [25%] compared with 38 of 61 [62.3%], respectively). Compared with patients receiving placebo at the time of maximum weight change, evaluable patients receiving megestrol acetate, 800 mg/d, reported improvement in overall well-being and had an increase in mean weight gain (-0.725 compared with 3.54 kg [-1.6 compared with +7.8 pounds]; P < 0.001), lean body mass (-0.772 compared with +1.14 kg [-1.7 compared with +2.5 pounds]; P < 0.001), appetite grade (P < 0.001), and caloric intake (-107 compared with +645.6 calories/d; P = 0.001). CONCLUSIONS: In patients with AIDS-related weight loss, megestrol acetate can stimulate appetite, food intake, and statistically significant weight gain that is associated with a patient-reported improvement in an overall sense of well-being.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Beneficial response to megoestrol acetate in AIDS-related cachexia and a possible megoestrol withdrawal-associated syndrome?

A man with AIDS is described in whom a profound weight loss was converted into a weight gain by treatment with megoestrol acetate, a synthetic progesterone. His appetite improved and was accompanied by a feeling of improved well-being. Following abrupt discontinuation of the drug, there was a significant but transient depression of mood and appetite associated with loss of energy; it is suggested that this complex of symptoms might represent a megoestrol acetate withdrawal-associated syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Is increased IL-1 beta mRNA expression in spleen of tumor-bearing mice relevant to cancer cachexia?

Using C3H/He mice bearing MH-134 tumor cells, cytokine inductions of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) were determined in spleens by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Levels of IL-1 beta were significantly (p<0.05) increased in the spleens of tumor-bearing mice compared with those of freely fed control animals. In contrast, no significant increase of other cytokine mRNAs was observed. In addition, constitutive levels of IL-1 beta mRNA were present in spleens of tumor-bearing mice during the experimental period. These results suggest that the over-expression of IL-1 beta mRNA was relevant to clinical manifestations of cancer-burden states.

Animals↗