Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proteolysis-inducing factor is a putative mediator of cancer-associated weight loss. The goal of this study was to examine for the first time: (i) its prevalence in patients with metastatic gastric/esophageal cancer; and (ii) whether it possibly correlated with weight loss and anorexia and whether it predicted tumor response and patient survival. This study recruited 41 patients as part of a phase II therapeutic, chemotherapy protocol for patients with metastatic gastric/esophageal cancer. Patient eligibility criteria were designed to select a group of patients who would tolerate treatment with the drugs capecitabine and oxaliplatin. Urine for assaying the proteolysis-inducing factor was obtained at registration and then 6 weeks later. Patients completed the FACT-E questionnaire every 6 weeks and had their weights checked at the same interval. Patients were followed prospectively for tumor response and patient survival. Twenty-three (56%) patients had the proteolysis-inducing factor in their urine at registration, and 18 (64%) had it at 6 weeks. There was no statistically significant correlation between the presence of the proteolysis-inducing factor and weight loss or between its presence and anorexia. Moreover, there was no evidence that the presence of the proteolysis-inducing factor in urine was able to predict tumor response or patient survival. The proteolysis-inducing factor in urine does not appear to be tied to weight loss, anorexia, tumor response, or patient survival in the clinical setting of metastatic gastric/esophageal cancer.
 ...
PMID:The proteolysis-inducing factor: in search of its clinical relevance in patients with metastatic gastric/esophageal cancer. 1686 54

In cancer-related anorexia, body weight loss is paradoxically associated with reduced appetite, which is contrary to the situation during starvation, implying that the normal coupling of food intake to energy expenditure is disarranged. Here we examined brainstem mechanisms that may underlie suppression of food intake in a rat model of cancer anorexia. Cultured Morris 7777 hepatoma cells were injected subcutaneously in Buffalo rats, resulting in slowly growing tumor and reduced food intake and body weight loss after about 10 days. The brainstem was examined for induced expression of the transcription factors Fos and FosB as signs of neuronal activation. The results showed that anorexia and retarded body weight growth were associated with Fos protein expression in the area postrema, the general visceral region of the nucleus of the solitary tract, and the external lateral parabrachial nucleus, structures that also display Fos after peripheral administration of satiating or anorexigenic stimuli. The magnitude of the Fos expression was specifically related to the size of induced tumor, and not associated with weight loss per se, because it was not present in pair-fed or food-deprived rats. It also appeared to be independent of proinflammatory cytokines, as determined by the absence of increased cytokine levels in plasma and induced cytokine and cyclooxygenase expression in the brain. The findings thus provide evidence that cancer-associated anorexia and weight loss in this model is associated with activation of brainstem circuits involved in the suppression of food intake, and suggest that this occurs by inflammatory-independent mechanisms.
 ...
PMID:Identification of rat brainstem neuronal structures activated during cancer-induced anorexia. 1764 50

Anorexia and weight loss are part of the wasting syndrome of late-stage cancer, are a major cause of morbidity and mortality in cancer, and are thought to be cytokine mediated. Macrophage inhibitory cytokine-1 (MIC-1) is produced by many cancers. Examination of sera from individuals with advanced prostate cancer showed a direct relationship between MIC-1 abundance and cancer-associated weight loss. In mice with xenografted prostate tumors, elevated MIC-1 levels were also associated with marked weight, fat and lean tissue loss that was mediated by decreased food intake and was reversed by administration of antibody to MIC-1. Additionally, normal mice given systemic MIC-1 and transgenic mice overexpressing MIC-1 showed hypophagia and reduced body weight. MIC-1 mediates its effects by central mechanisms that implicate the hypothalamic transforming growth factor-beta receptor II, extracellular signal-regulated kinases 1 and 2, signal transducer and activator of transcription-3, neuropeptide Y and pro-opiomelanocortin. Thus, MIC-1 is a newly defined central regulator of appetite and a potential target for the treatment of both cancer anorexia and weight loss, as well as of obesity.
 ...
PMID:Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1. 1798 62

Chemotherapy treatment can lead to delayed gastric emptying, early satiety, anorexia, nausea and vomiting, described collectively as the cancer-associated dyspepsia syndrome (CADS). Administration of ghrelin (GHRL), an endogenous orexigenic peptide known to stimulate gastric motility, has been shown to reduce the symptoms of CADS induced in relevant animal models with the potent chemotherapeutic agent, cisplatin. We examined the effects in the rat of cisplatin (6 mg/kg i.p.) treatment on the expression of GHRL and ghrelin receptor (GHSR) mRNAs in the hypothalamus and the stomach at a time-point (2 days) when the effects of cisplatin are pronounced. In addition, plasma levels of GHRL (acylated and total including des-acyl GHRL) were measured and the effect on these levels of treatment with the synthetic glucocorticoid dexamethasone (2 mg/kg s.c. bd.) was investigated. Cisplatin increased GHSR mRNA expression in the stomach (67%) and hypothalamus (52%) but not GHRL mRNA expression and increased the percentage of acylated GHRL (7.03+/-1.35% vs. 11.38+/-2.40%) in the plasma. Dexamethasone reduced the plasma level of acylated GHRL and the percentage of acylated GHRL to values below those in animals treated with saline alone (7.03+/-1.35% vs. 2.60+/-0.49%). Our findings support the hypothesis that an adaptive upregulation of the ghrelin receptor may occur during cancer chemotherapy-associated dyspepsia. This may have a role in defensive responses to toxic challenges to the gut. In addition, our results provide preliminary evidence for glucocorticoid modulation of plasma ghrelin levels.
 ...
PMID:Adaptive upregulation of gastric and hypothalamic ghrelin receptors and increased plasma ghrelin in a model of cancer chemotherapy-induced dyspepsia. 1845 14

The cancer-associated anorexia/weight loss syndrome occurs in > 50% of patients with advanced cancer. Associated with negative quality of life and diminished survival, this syndrome carries a devastating impact on patients with cancer. To date, efforts to manage this syndrome effectively have fallen short. However, recent data with therapy that targets the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) appear promising. This article discusses some of the preliminary data that suggest that further study of anti-TNF- alpha is warranted. It also describes the study design of an ongoing North Central Cancer Treatment Group trial that is aimed at treating this syndrome with the agent infliximab.
 ...
PMID:Tumor Necrosis Factor-alpha as a Treatment Target for the Cancer Anorexia/Weight Loss Syndrome. 1862 48

PURPOSE The experience of patients with cancer often involves symptoms of fatigue, anorexia, depression, and dyspnea. METHODS We developed a set of standards through an iterative process of structured literature review and development and refinement of topic areas and standards and subjected recommendations to rating by a multidisciplinary expert panel. Results For fatigue, providers should screen patients at the initial visit, for newly identified advanced cancer, and at chemotherapy visits; assess for depression and insomnia in newly identified fatigue; and follow up after treatment for fatigue or a secondary cause. For anorexia, providers should screen at the initial visit for cancer affecting the oropharynx or gastrointestinal tract or advanced cancer, evaluate for associated symptoms, treat underlying causes, provide nutritional counseling for patients undergoing treatment that may affect nutritional intake, and follow up patients given appetite stimulants. For depression, providers should screen newly diagnosed patients, those started on chemotherapy or radiotherapy, those with newly identified advanced disease, and those expressing a desire for hastened death; document a treatment plan in diagnosed patients; and follow up response after treatment. For general dyspnea, providers should evaluate for causes of new or worsening dyspnea, treat or symptomatically manage underlying causes, follow up to evaluate treatment effectiveness, and offer opioids in advanced cancer when other treatments are unsuccessful. For dyspnea and malignant pleural effusions, providers should offer thoracentesis, follow up after thoracentesis, and offer pleurodesis or a drainage procedure for patients with reaccumulation and dyspnea. CONCLUSION These standards provide a framework for evidence-based screening, assessment, treatment, and follow-up for cancer-associated symptoms.
 ...
PMID:Evidence-based recommendations for cancer fatigue, anorexia, depression, and dyspnea. 1868 57

An outbreak of spontaneous Toxoplasma gondii infection on an Italian bird-farm is described. Small passerine birds (Serinus canaria, Carduelis chloris, Carduelis carduelis, Carduelis spinus, Carduelis cannabina, Pyrrhula pyrrhula) showed clinical signs consisting of anorexia, prostration, weight loss, diarrhoea and dyspnoea accompanied by a high mortality rate. Clinical, pathological, biological and serological investigations were performed. Characteristic lesions and Toxoplasma gondii specimens were identified in several tissues by histopathological examinations. The detection of antibodies against Toxoplasma gondii was constant in dead and sacrificed animals with macroscopic lesions. A therapy based on the administration of sulphadimethoxine and diaveridine was successful in limiting the mortality rate. Four months later some surviving birds developed ocular atrophy. Toxoplasma gondii cysts were observed in the brain and cerebral and ocular lesions described. Sera obtained from these animals were positive (>1:64) for antibodies against Toxoplasma gondii. The authors conclude with some observations on the spread of toxoplasmosis among cage birds.
 ...
PMID:Spontaneous toxoplasmosis in canaries (Serinus canaria) and other small passerine cage birds. 1876 19

The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemotherapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin agonist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluoruracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BALB/c female tumour-bearing mice were randomized to receive a solution containing: (a) placebo; (b) GHRP-2; (c) 5-FU; or (d) 5-FU+GHRP-2. Ten BALB/c no tumour-bearing mice received placebo solution. Food intake and survival were checked. Six hours after the drug injection the cumulative food intake was significantly increased in mice treated with the combination of 5-FU+GHRP-2 versus the 5-FU alone (P=0.0096). On day 3, the cumulative food intake of mice treated with GHRP-2, 5-FU and 5-FU+GHRP-2 significantly increased compared with naive and vehicle groups (P=0.0007, P=0.0038 and P=0.0166, respectively). The median survival time was longer in 5-FU+GHRP-2 treated mice than in those with 5-FU, although it was not significant (18 d versus 15.5 d, P=0.7). For the first time, we demonstrated that the addition of GHRP-2 to cytotoxic therapy with 5-FU improved appetite in tumour-bearing mice with anorexia/cachexia syndrome in early stage. These data suggest that GHRP-2 may improve the efficacy of therapy and the quality of life of cancer patients thank to the amelioration of their nutritional state.
 ...
PMID:Growth hormone releasing peptide 2 reverses anorexia associated with chemotherapy with 5-fluoruracil in colon cancer cell-bearing mice. 1900 43

To provide a systematic review on the clinical utility of anti-inflammatory polyunsaturated fatty acids (PUFAs) in cancer-associated anorexia-cachexia syndrome (ACS), clinical trials involving eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for the management of ACS were identified in the medical literature using MEDLINE (1966 to October 2006) and EMBASE (1980 to October 2006). Review Manager 4.1 was used to compare trials based on outcome measures of interest, including weight change, lean muscle mass change, survival, and quality of life (QoL). Seven randomized controlled trials (RCTs) were identified. Various outcome measures were used in each study. Variability in study populations, dose of EPA and DHA, and standardized scales did not allow for analysis using Review Manager 4.1. Therefore, trials were summarized based on their individual outcomes. Except for one trial showing a positive effect on weight, none of the trials found a clinically or statistically significant difference in outcome measures reviewed. EPA and DHA alone have not shown significant clinical effect in altering weight, lean muscle mass, survival, or QoL in patients with ACS associated with cancer.
 ...
PMID:Anorexia-cachexia syndrome: a systematic review of the role of dietary polyunsaturated Fatty acids in the management of symptoms, survival, and quality of life. 1950 Jul 21

Although it has been established that some acute phase responses present differently depending on whether a virus or bacteria activates the innate immune system, it has not yet been established whether fever and sickness behaviors, such as anorexia and lethargy, present differently. We therefore investigated the effects of administering lipopolysaccharide (LPS) and polyinosinic : polycytidylic acid (poly I:C) on body temperature, food intake, body mass, and activity (cage activity and wheel running). Male Sprague-Dawley rats were randomly assigned to receive an intraperitoneal injection of one of LPS (75 microg/kg or 250 microg/kg), poly I:C (3000 microg/kg or 4000 microg/kg), or saline. Administration of LPS or poly I:C induced fever, anorexia, and lethargy. Although voluntary wheel running and cage activity were both significantly reduced after administration of LPS or poly I:C, they were not affected equally. Indeed voluntary wheel running was decreased on average by approximately 30% more than cage activity regardless of the dose or type of mimetic administered. Our results indicate that poly I:C is less effective at inducing anorexia, lethargy, and fever in rats than is LPS, and that avoidance of exercise in animals and humans during infection is likely to be a more prominent feature of illness than is avoidance of routine daily activity.
 ...
PMID:Comparison of anorexia, lethargy, and fever induced by bacterial and viral mimetics in rats. 1929 62


<< Previous 1 2 3 4 5 6 7 8 9 Next >>