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Cachexia
Kinds of Cachexia Terms modified by Cachexia Selected AbstractsCachexia in MAC16 adenocarcinoma: suppression of hunger despite normal regulation of leptin, insulin and hypothalamic neuropeptide YJOURNAL OF NEUROCHEMISTRY, Issue 5 2001Chen Bing Weight loss normally stimulates hunger, through mechanisms that include falls in circulating leptin and insulin, leading to stimulation of hypothalamic neuropeptide Y (NPY). Here, we investigated the leptin, insulin and NPY to clarify why hunger is suppressed in mice with severe cachexia due to the MAC16 adenocarcinoma. MAC16-bearing mice progressively lost weight (19% below controls) and fat (,,61%) over 16 days after tumour transplantation, while total food intake fell by 10%. Pair-fed mice showed less wasting, with final weight being 9% and fat mass 25% below controls. Plasma leptin fell by 85% in MAC16 and 51% in pair-fed mice, in proportion to loss of fat. Plasma insulin was also reduced by 49% in MAC16 and 53% in pair-fed groups. Hypothalamic leptin receptor (OB-Rb) mRNA was significantly increased in both MAC16 (+ 223%) and pair-fed (+192%) mice. Hypothalamic NPY mRNA was also significantly raised in MAC16 (+152%) and pair-fed (+ 99%) groups, showing negative correlations with plasma leptin and insulin, and a positive association with OB-Rb mRNA. In MAC16-induced cachexia, leptin production and hypothalamic OB-Rb and NPY expression are regulated appropriately in response to fat depletion. Therefore, suppression of hunger is probably due to tumour products that inhibit NPY transport or release, or that interfere with neuronal targets downstream of NPY. [source] Estimation of serum leptin in oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2010Harshkant P. Gharote J Oral Pathol Med (2010) 39: 69,73 Background:, Cachexia contributes significantly to mortality in cancer patients; role of cytokines in inducing cachexia is an emerging view. Leptin, a homologous protein of cytokine family, is found to be decreased in serum with cachexia. The purpose of this study was to compare serum leptin levels of oral squamous cell carcinoma patients with that of control group and correlate it with body mass index. Method:, Serum samples of 31 oral squamous cell carcinoma patients and that of 28 healthy individuals were subjected to evaluation of serum leptin levels (ng/ml) using enzyme-linked immunosorbent assay. Results:, A significant reduction in leptin level of oral squamous cell carcinoma patients was observed. Definite correlation between body mass index and serum leptin and also between serum leptin levels of various histopathological variants of oral squamous cell carcinoma was observed. Conclusion:, The results of this study suggest that evaluation of serum leptin level can provide status of cachexia in oral squamous cell carcinoma patients. [source] Comparison of Animal Models for Head and Neck Cancer Cachexia,THE LARYNGOSCOPE, Issue 12 2007Trinitia Cannon MD Abstract Objectives/Hypothesis: Despite its negative impact on cancer patients, there are few animal models of cancer cachexia. Our hypothesis was that different human cell lines would variably induce cachexia. Study Design: Prospective animal study. Methods: We established two xenograft models in athymic mice and compared these with a cachexigenic cell line, the murine adenocarcinoma 16 (MAC16) cell line. Eight-week-old female, athymic mice were injected with human head and neck cell lines (JHU022, JHU012) and the MAC16 cell line. Body weight, food intake, body composition, leg weights, serum cytokines, and lipid mobilizing factor (LMF) were compared. Results: Mean food intake for all groups was equivalent. Mean percent change in body weight after 18 days was 18%, 19%, 12%, and 3% for control, JHU012, JHU022, and MAC16 experimental groups, respectively. Both JHU022- and MAC16-injected mice showed wasting even when tumor burden was low. In contrast, mice injected with JHU012 developed larger tumors yet lacked evidence of cachexia. These mice demonstrated loss of lean body mass but not fat mass. Serum cytokine levels for interleukin (IL)-1, and IL-1, were elevated in JHU022-bearing mice, whereas IL-1,, IL-6, interferon (IFN)-,, and tumor necrosis factor alpha (TNF)-, were elevated in MAC16-bearing mice. LMF was present in both the JHU022 and JHU012 cell lines. Conclusions: The JHU022 cell line caused more severe cachexia than the JHU012 cells, suggesting these cell lines may be used to further study cancer cachexia. IL-1, and IL-1, in the JHU022 model may be mediators of cachexia, whereas TNF-,, IFN-,, and IL-6 may be mediators in MAC16-induced cachexia. [source] Serum tumour necrosis factor-, levels in cancer patients are discontinuous and correlate with weight lossEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2000M. Bossola Tumour necrosis factor-, (TNF) has been regarded as a potential mediator of cancer cachexia. Assessment of TNF circulating levels in cancer patients and their correlation with weight loss has led to controversial results. We measured TNF circulating levels in 28 patients with gastrointestinal cancer and 29 controls with benign gastrointestinal diseases at different times (08.00 h, 14.00 h, 20.00 h) before operation. TNF activity was not detected in any of controls at any times. In cancer patients, TNF circulating levels were detectable in 18 cases (64·3%) and appeared to be discontinuous. TNF levels above the limit of detection were present in 15 patients (53·6%) at 08.00 h, in 14 (50%) at 014.00 h and in nine (32·1%) at 20.00 h. Mean TNF levels were 14·3 ± 4 pg mL,1 at 08.00 h, 16·7 ± 4·6 pg mL,1 at 14.00 h (P = 0·05) and 18·5 ± 10·2 pg mL,1 at 20.00 h (P < 0·05 vs. 08.00 h and 14.00 h). According to Spearman's analysis, the sum of TNF concentrations at the three times significantly correlated with the severity of weight loss (Spearman's correlation coefficient =,,0·420; P = 0·026). TNF concentrations were consistently and significantly higher in patients with severe weight loss than in those with moderate or light weight loss at 08.00 h (26·3 ± 8·3, 8·9 ± 4·2, 3·8 ± 2·1, respectively; P = 0·04 at one-way anova). TNF levels were higher in anorectic than in nonanorectic patients at any hour, but the differences were not statistically significant. The present study demonstrates that TNF is intermittently or discontinuously detectable in patients with gastrointestinal cancer and that its levels correlate with the severity of weight loss. [source] Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shuntEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Elena Mishchenko Abstract Clinical care of patients with polycythemia vera, essential thrombocythemia and myelofibrosis (MF) requires not only a broad understanding of general treatment principles but also familiarity with the management of hydroxyurea-refractory disease complications. The latter include progressive splenomegaly, symptomatic portal hypertension (e.g. ascites, variceal bleeding), pulmonary hypertension, bone pain, intractable pruritus, constitutional symptoms (e.g. fatigue, night sweats) and cachexia (i.e. loss of lean body mass, general ill health, poor appetite). Some of these symptoms are directly or indirectly related to extramedullary hematopoiesis (EMH) and others to proinflammatory cytokine excess. Results from recent clinical trials of JAK inhibitors suggest remarkable activity in MF-associated constitutional symptoms, cachexia, pruritus and hydroxyurea-refractory splenomegaly. Involved-field radiotherapy is best utilized in the setting of EMH-associated symptoms, including ascites, bone (extremity) pain and pulmonary hypertension. Splenectomy is indicated in the presence of drug-refractory splenomegaly and frequent red cell transfusion requirement. Transjugular intrahepatic portosystemic shunt is used to alleviate symptoms of portal hypertension. [source] Postradiation nasopharyngeal necrosis in the patients with nasopharyngeal carcinoma,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2009Yi-Jun Hua MD Abstract Background Radiation-induced nasopharyngeal necrosis is a consequential late effect in the patients with nasopharyngeal carcinoma (NPC). Patients with NPC who have been treated with high-dose radiotherapy are at risk of developing postradiation nasopharyngeal necrosis (PRNN). However, the analysis of PRNN with a significant cohort of patients has not been reported in English-language literature. In this study, we aimed to evaluate PRNN in 28 patients with NPC. Methods From June 2006 to December 2007, 28 patients were diagnosed with PRNN with pathologic evidence. Surgical procedure of endoscopy-guided debridement and systemic anti-inflammatory treatments were conducted for the patients. Their clinical features, treatment procedures, and outcomes were analyzed retrospectively. Results Clinical symptoms such as foul odor and headache were alleviated in all, 8 patients were cured of their PRNN, 9 patients with exposed internal carotid artery died of sudden nasopharyngeal massive bleeding, and 3 patients died of exhaustion (cachexia). Conclusion PRNN is an important consequential late effect of radiotherapy in the patients with NPC. Internal carotid artery erosion is a severe situation and acts as an independent prognostic factor for the patients. Diagnosis of PRNN could be made after ruling out the persistent-recurrent NPC proven by pathologic examination. Surgery is effective for improving the quality of life and for curing PRNN. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source] Cancer cachexia syndrome in head and neck cancer patients: Part II.HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 5 2007Pathophysiology Abstract Cancer cachexia is a morbid wasting syndrome common among patients with head and neck cancer. While its clinical manifestations have been well characterized, its pathophysiology remains complex. A comprehensive literature search on cancer cachexia was performed using the National Library of Medicine's PubMed. The Cochrane Library and Google search engine were also used. Recent evidence and new concepts on the pathophysiology of cancer cachexia are summarized. Targeted therapies are presented, and new concepts are highlighted. Cancer cachexia is characterized by complex, multilevel pathogenesis. It involves up-regulated tissue catabolism and impaired anabolism, release of tumor-derived catabolic factors and inflammatory cytokines, and neuroendocrine dysfunction. These culminate to create an energy-inefficient state characterized by wasting, chronic inflammation, neuroendocrine dysfunction, and anorexia. © 2007 Wiley Periodicals, Inc. Head Neck, 2007 [source] Cancer cachexia syndrome in head and neck cancer patients: Part I. Diagnosis, impact on quality of life and survival, and treatmentHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2007Marion Couch MD Abstract Background Cancer cachexia is a debilitating, wasting condition that affects many cancer patients, including those with head and neck cancer. The overall incidence of cancer cachexia is quite high for some types of cancer, and cachexia will be the main cause of death for more than 20% of all cancer patients. This syndrome uniquely challenges patients with head and neck cancer. This article outlines the diagnosis of cancer cachexia, reviews its impact on patient quality of life (QOL) and survival, and updates the reader on potential therapies that may suppress it. Methods A comprehensive literature search was performed using PubMed of the National Library of Medicine, which includes more than 15 million citations back to the 1950s. The Cochrane Library and Google search engine were used as well. Results This syndrome differs significantly from starvation, and thus accurate and timely diagnosis is essential. Nutritional therapy alone is insufficient. Current management strategies include corticosteroids and megesterol acetate, in conjunction with nutritional therapy. Future strategies may include nutraceuticals, omega-3 fatty acids, inflammatory antagonists, and other targeted treatments. Conclusions Because cancer cachexia differs significantly from starvation, nutritional supplementation must be used in conjunction with other anti-cachexia agents to reverse the chronic systemic inflammatory state and the effects of circulating tumor-derived factors seen in cachexia. Careful identification of patients at risk and those suffering from this syndrome will lead to better outcomes and treatments. Ultimately, more research is needed to better treat this devastating condition. © 2007 Wiley Periodicals, Inc. Head Neck, 2007 [source] Role of Chronic Infection and Inflammation in the Gastrointestinal Tract in the Etiology and Pathogenesis of Idiopathic ParkinsonismHELICOBACTER, Issue 4 2005Part 1: Eradication of Helicobacter in the Cachexia of Idiopathic Parkinsonism ABSTRACT Background., Neuronal damage in idiopathic parkinsonism may be in response to ubiquitous occult infection. Since peptic ulceration is prodromal, Helicobacter is a prime candidate. Aim., To consider the candidature of Helicobacter in parkinsonism with cachexia. Methods., We explore the relationship between being underweight and inflammatory products in 124 subjects with idiopathic parkinsonism and 195 controls, and present the first case-series evidence of efficacy of Helicobacter eradication, in parkinsonism advanced to the stage of cachexia. Results., Association of a low body mass index with circulating interleukin-6 was specific to parkinsonism (p = .002), unlike that with antibodies against Helicobacter vacuolating-toxin and cytotoxicity-associated gene product (p < .04). Marked reversibility in both cachexia and disability of idiopathic parkinsonism followed Helicobacter heilmannii eradication in one case, Helicobacter pylori eradication in another, follow-up being , 3.5 years. The latter presented with postprandial bloating, and persistent nausea: following eradication, radioisotope gastric-emptying returned towards normal, and upper abdominal symptoms regressed. Reversibility of their cachexia/disability contrasts with the outcome of anti- Helicobacter therapy where eradication repeatedly failed (one case), and in non- Helicobacter gastritis (three cases). Anti-parkinsonian medication remained constant. Intestinal absorption and barrier function were normal in all. Conclusion., Categorization, according to presence or absence of Helicobacter infection, was a useful therapeutic tool in late idiopathic parkinsonism. [source] Chylous effusions complicating lymphoma: a serious event with octreotide as a treatment optionHEMATOLOGICAL ONCOLOGY, Issue 2 2003J. Evans Abstract Chylous effusions have an identical appearance to milk and occur when the thoracic duct is blocked. Since chyle represents direct absorption of fat from the small intestine lacteals, it is rich in fat, calories, vitamins and immunoglobulins. Drainage of this milk-like fluid from any cavity (chest or abdomen) results in rapid weight loss and profound cachexia. The recognition of this milk-like fluid as chyle is urgent for the implementation of the correct treatment. In adults, lymphoma is one of the commonest malignancies to cause blockages in the thoracic duct. Once the diagnosis is made, conservative treatment with strict dietary adjustment often fails to prevent weight loss or resolve the underlying cause. Since the condition is uncommon, no guidelines exist. Many surgeons recommend early surgical intervention before the patient becomes too weak. Surgery may also fail. We report the case of a 62-year-old man with chylous effusions and a weight loss of 30,kg. The nature of the effusion was unrecognized for the first 16 weeks. Upon diagnosis, dietary adjustment was made and a lymphangiogram organized with a view to surgery. Literature searches revealed two cases in which somatostatin was used after surgical procedures failed. We therefore used octreotide (a synthetic analogue of somatostatin). We report complete resolution of the condition within 72,h leading to the resumption of a normal diet and discharge within 2 weeks. Copyright © 2003 John Wiley & Sons, Ltd. [source] The kidney disease wasting: Inflammation, oxidative stress, and diet-gene interactionHEMODIALYSIS INTERNATIONAL, Issue 4 2006Kamyar KALANTAR-ZADEH Abstract The 350,000 maintenance hemodialysis (MHD) patients in the United States have an unacceptably high mortality rate of >20%/year. Almost half of all deaths are assumed to be cardiovascular. Markers of kidney disease wasting (KDW) such as hypoalbuminemia, anorexia, body weight and fat loss, rather than traditional cardiovascular risk factors, appear to be the strongest predictors of early death in these patients. The KDW is closely related to oxidative stress (SOX). Such SOX markers as serum myeloperoxidase are associated with pro-inflammatory cytokines and poor survival in MHD patients. Identifying the conditions that modulate the KDW/SOX-axis may be the key to improving outcomes in MHD patients. Dysfunctional lipoproteins such as a higher ratio of the high-density lipoprotein inflammatory index (HII) may engender or aggravate the KDW, whereas functionally intact or larger lipoprotein pools, as in hypercholesterolemia and obesity, may mitigate the KDW in MHD patients. Hence, a reverse epidemiology or "bad-gone-good" phenomenon may be observed. Diet and gene and their complex interaction may lead to higher proportions of pro-inflammatory or oxidative lipoproteins such as HII, resulting in the aggravation of the SOX and inflammatory processes, endothelial dysfunction, and subsequent atherosclerotic cardiovascular disease and death in MHD patients. Understanding the factors that modulate the KDW/SOX complex and their associations with genetic polymorphism, nutrition, and outcomes in MHD patients may lead to developing more effective strategies to improve outcomes in this and the 20 to 30 million Americans with chronic disease states such as individuals with chronic heart failure, advanced age, malignancies, AIDS, or cachexia. [source] An adult with Prader-Willi syndrome and anorexia nervosa: A case reportINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 2 2001Debra Counts Abstract A 39-year-old man with Prader-Willi syndrome presents for evaluation of uncontrolled weight loss. Past history was significant for gastric bypass and prior episodes of intentional dieting. Family history was significant for an alcoholic father and two siblings with anorexia nervosa. The patient was unconcerned about his weight loss despite cachexia and did not want to stop dieting. This presentation of a restrictive eating pattern in a man with a syndrome usually associated with compulsive hyperphagia is the first known report © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 30: 231,233, 2001. [source] Review: Energy regulation and neuroendocrine,immune control in chronic inflammatory diseasesJOURNAL OF INTERNAL MEDICINE, Issue 6 2010R. H. Straub Abstract., Straub RH, Cutolo M, Buttgereit F, Pongratz G (University Hospital Regensburg, Regensburg, Germany; University of Genova, Genova, Italy; and Charité University Medicine Berlin, Berlin, Germany). Energy regulation and neuroendocrine,immune control in chronic inflammatory diseases (Review). J Intern Med 2010; 267:543,560. Energy regulation (EnR) is most important for homoeostatic regulation of physiological processes. Neuroendocrine pathways are involved in EnR. We can separate factors that provide energy-rich fuels to stores [parasympathetic nervous system (PSNS), insulin, insulin-like growth factor-1, oestrogens, androgens and osteocalcin] and those that provide energy-rich substrates to consumers [sympathetic nervous system (SNS), hypothalamic,pituitary,adrenal axis, thyroid hormones, glucagon and growth hormone]. In chronic inflammatory diseases (CIDs), balanced energy-rich fuel allocation to stores and consumers, normally aligned with circadian rhythms, is largely disturbed due to the vast fuel consumption of an activated immune system (up to 2000 kJ day,1). Proinflammatory cytokines such as tumour necrosis factor or interleukins 1, and 6, circulating activated immune cells and sensory nerve fibres signal immune activation to the rest of the body. This signal is an appeal for energy-rich fuels as regulators are switched on to supply energy-rich fuels (,energy appeal reaction'). During evolution, adequate EnR evolved to cope with nonlife-threatening diseases, not with CIDs (huge negative selection pressure and reduced reproduction). Thus, EnR is inadequate in CIDs leading to many abnormalities, including sickness behaviour, anorexia, hypovitaminosis D, cachexia, cachectic obesity, insulin resistance, hyperinsulinaemia, dyslipidaemia, fat deposits near inflamed tissue, hypoandrogenaemia, mild hypercortisolaemia, activation of the SNS (hypertension), CID-related anaemia and osteopenia. Many of these conditions can contribute to the metabolic syndrome. These signs and symptoms become comprehensible in the context of an exaggerated call for energy-rich fuels by the immune system. We propose that the presented pathophysiological framework may lead to new therapeutical approaches and to a better understanding of CID sequence. [source] Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failureJOURNAL OF INTERNAL MEDICINE, Issue 1 2006H. NØRRELUND Abstract. Objective., It is well known that chronic heart failure (CHF) is associated with insulin resistance and cachexia, but little is known about the underlying substrate metabolism. The present study was undertaken to identify disturbances of basal glucose, lipid and protein metabolism. Design., We studied eight nondiabetic patients with CHF (ejection fraction 30 ± 4%) and eight healthy controls. Protein metabolism (whole body and regional muscle fluxes) and total glucose turnover were isotopically assayed. Substrate oxidation were obtained by indirect calorimetry. The metabolic response to exercise was studied by bicycle ergometry exercise. Results., Our data confirm that CHF patients have a decreased lean body mass. CHF patients are characterised by (i) decreased glucose oxidation [glucose oxidation (mg kg,1 min,1): 1.25 ± 0.09 (patients) vs. 1.55 ± 0.09 (controls), P < 0.01] and muscle glucose uptake [a , v diffglucose (,mol L,1): ,10 ± 25 (patients) vs. 70 ± 22 (controls), P < 0.01], (ii) elevated levels of free fatty acids (FFA) [FFA (mmol L,1): 0.72 ± 0.05 (patients) vs. 0.48 ± 0.03 (controls), P < 0.01] and 3-hydroxybutyrate and signs of elevated fat oxidation and muscle fat utilization [a , v diffFFA (mmol L,1): 0.12 ± 0.02 (patients) vs. 0.05 ± 0.01 (controls), P < 0.05] and (iii) elevated protein turnover and protein breakdown [phenylalanine flux (,mol kg,1 h,1): 36.4 ± 1.5 (patients) vs. 29.6 ± 1.3 (controls), P < 0.01]. Patients had high circulating levels of noradrenaline, glucagon, and adiponectin, and low levels of ghrelin. We failed to observe any differences in metabolic responses between controls and patients during short-term exercise. Conclusions., In the basal fasting state patients with CHF are characterized by several metabolic abnormalities which may contribute to CHF pathophysiology and may provide a basis for targeted intervention. [source] Spontaneous pancreatic islet amyloidosis in 40 baboonsJOURNAL OF MEDICAL PRIMATOLOGY, Issue 2 2002G.B. Hubbard Spontaneous amyloidosis occurs in many nonhuman primate species but remains difficult to diagnose and treat. Nonhuman primates continue to offer promise as animal models in which to study amyloidosis in humans. Amyloidosis was not diagnosed clinically but was found histologically in four male and 36 female baboons. The baboons averaged 18 years of age at death (range, 7,28 years). Clinical signs, if present, were hyperglycemia and cachexia. Blood glucose values were elevated in 12 of 30 baboons with available clinical pathology data. Four baboons had been clinically diagnosed as diabetic and three were treated with insulin. Amyloid was found in the islets of Langerhans of the pancreas in 40 baboons; 35 baboons had amyloid only in the islets of Langerhans. Amyloid was found in nonislet tissue of baboons as follows: five, nonislet pancreas; four, intestine and adrenal; three, kidney; two, prostate and spleen; and one each, lymph node, liver, gall bladder, stomach, tongue, urinary bladder, and salivary gland. Sections of paraffin-embedded tissues were evaluated for amyloid with hematoxylin and eosin (HE) and congo red (CR) staining, and using immunohistochemistry for human islet amyloid polypeptide (IAPP), calcitonin gene-related peptide (CGRP), glucagon, pancreatic polypeptide (PP), somatostatin (SS), and porcine insulin. Islet amyloid was positive with HE in 40 baboons, with CR in 39 baboons, and with IAPP and CGRP in 35 baboons. IAPP and CGRP only stained islet amyloid. PP, SS, glucagon, and porcine insulin did not stain amyloid. Islet amyloidosis in the baboon appears to be difficult to diagnose clinically, age-related, and similar to islet amyloidosis in other species. The baboon may be a good model for the study of islet amyloidosis in humans. [source] Cachexia in MAC16 adenocarcinoma: suppression of hunger despite normal regulation of leptin, insulin and hypothalamic neuropeptide YJOURNAL OF NEUROCHEMISTRY, Issue 5 2001Chen Bing Weight loss normally stimulates hunger, through mechanisms that include falls in circulating leptin and insulin, leading to stimulation of hypothalamic neuropeptide Y (NPY). Here, we investigated the leptin, insulin and NPY to clarify why hunger is suppressed in mice with severe cachexia due to the MAC16 adenocarcinoma. MAC16-bearing mice progressively lost weight (19% below controls) and fat (,,61%) over 16 days after tumour transplantation, while total food intake fell by 10%. Pair-fed mice showed less wasting, with final weight being 9% and fat mass 25% below controls. Plasma leptin fell by 85% in MAC16 and 51% in pair-fed mice, in proportion to loss of fat. Plasma insulin was also reduced by 49% in MAC16 and 53% in pair-fed groups. Hypothalamic leptin receptor (OB-Rb) mRNA was significantly increased in both MAC16 (+ 223%) and pair-fed (+192%) mice. Hypothalamic NPY mRNA was also significantly raised in MAC16 (+152%) and pair-fed (+ 99%) groups, showing negative correlations with plasma leptin and insulin, and a positive association with OB-Rb mRNA. In MAC16-induced cachexia, leptin production and hypothalamic OB-Rb and NPY expression are regulated appropriately in response to fat depletion. Therefore, suppression of hunger is probably due to tumour products that inhibit NPY transport or release, or that interfere with neuronal targets downstream of NPY. [source] Estimation of serum leptin in oral squamous cell carcinomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 1 2010Harshkant P. Gharote J Oral Pathol Med (2010) 39: 69,73 Background:, Cachexia contributes significantly to mortality in cancer patients; role of cytokines in inducing cachexia is an emerging view. Leptin, a homologous protein of cytokine family, is found to be decreased in serum with cachexia. The purpose of this study was to compare serum leptin levels of oral squamous cell carcinoma patients with that of control group and correlate it with body mass index. Method:, Serum samples of 31 oral squamous cell carcinoma patients and that of 28 healthy individuals were subjected to evaluation of serum leptin levels (ng/ml) using enzyme-linked immunosorbent assay. Results:, A significant reduction in leptin level of oral squamous cell carcinoma patients was observed. Definite correlation between body mass index and serum leptin and also between serum leptin levels of various histopathological variants of oral squamous cell carcinoma was observed. Conclusion:, The results of this study suggest that evaluation of serum leptin level can provide status of cachexia in oral squamous cell carcinoma patients. [source] Review article: anorexia and cachexia in gastrointestinal cancerALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2005J. OCKENGA Summary In patients with gastrointestinal malignancies, i.e. cancers of the stomach, colon, liver, biliary tract or pancreas, progressive undernutrition can be regularly observed during the course of illness. Undernutrition significantly affects the patients' quality of life, morbidity and survival. Pathogenetically, two different causes are relevant in the development of undernutrition in patients with gastrointestinal cancer. One cause is reduced nutritional intake. This condition is referred to as anorexia and can be worsened by the side effects of cancer therapy. The other cause is the release of endogenous transmitters and/or other products of the tumour leading to the cachexia syndrome, which is characterized by loss of body weight, negative nitrogen balance and fatigue. Cancer anorexia and cancer cachexia may have synergistic negative effects in affecting the patients' status. In this review, current nutritional support strategies with respect to different clinically relevant situations are described. An algorithm of the treatment strategies, including dietetic counselling, oral supplements, enteral and parenteral nutritional support is given. One focus is the approach of nutrition-focused patient care, which shows promising results. In addition, the possibilities of pharmacological intervention are discussed. [source] Temporal events in the intravenous challenge model for experimental Candida albicans infections in female miceMYCOSES, Issue 3 2005Donna M. MacCallum Summary We characterized the intravenous (i.v.) challenge model for disseminated Candida albicans infection in female BALB/c and DBA/2 mice. Clearance of fungi from the bloodstream and appearance of fungi in tissues were measured at intervals after challenge with various doses of C. albicans. The wild-type isolate SC5314 and derived strains CAF2,1 and CAI-4 transformed with CIp10 were of equal virulence in the model. Variability in mouse survival times, kidney fungal burdens and cachexia was lowest when challenge inocula were within the range 104,105 CFU g,1 body weight in BALB/c mice, but brain fungal burdens and outcomes in DBA/2 mice were variable for all inocula tested. Critical times in the development of infections in optimally challenged BALB/c mice were at 5,10 h (bloodstream fully cleared of fungi), 24 h (start of exponential fungal growth in kidneys) and 48 h (50% of blood cultures become positive). Differential involvement of right and left kidneys occurred almost exclusively in mice challenged with <2 × 104 CFU g,1. We conclude that the i.v. challenge model in female BALB/c mice is now sufficiently well characterized to permit more refined experimentation in future virulence studies with C. albicans mutants. [source] Evidence based practice guidelines for the nutritional management of cancer cachexiaNUTRITION & DIETETICS, Issue 2006Judith D Bauer [source] Is Sanfilippo type B in your mind when you see adults with mental retardation and behavioral problems?,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2007Ute Moog Abstract Sanfilippo type B is an autosomal recessive mucopolysaccharidosis (MPS IIIB) caused by deficiency of N -acetyl-,- D -glucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulfate. It is characterized by neurologic degeneration, behavioral problems, and mental decline. Somatic features are relatively mild and patients with this disorder can reach late adulthood. It is the most common subtype of MPS in the Netherlands and probably underdiagnosed in adult persons with mental retardation (MR). In order to increase knowledge on the adult phenotype and natural history in Sanfilippo type B, we present the clinical data of 20 patients with this disorder. Sixteen of them were followed for one to three decades. Six died between 28 and 69 years of age, mainly from pneumonia and cachexia; the surviving patients were 18,63 years old. Apart from the youngest, they had lost mobility at 36,68 years. Most had developed physical problems, in particular in the 4th,6th decade of life: cardiac disease (cardiomyopathy, atrial fibrillations), arthritis, skin blistering, swallowing difficulties requiring feeding by a gastrostomy tube, and seizures. The course of the disease was dominated in most of them by challenging behavioral problems with restlessness, extreme screaming and hitting, difficult to prevent or to treat pharmaceutically. Even in absence of knowledge of the history of an elderly patient with MR, the presence of behavioral problems should prompt metabolic investigation for MPS. © 2007 Wiley-Liss, Inc. [source] Changes in the natural abundance of 13CO2/12CO2 in breath due to lipopolysacchride-induced acute phase responseRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 23 2009Daniel E. Butz The natural abundance of carbon-13 in blood proteins increases during the cachectic state and may be a biomarker for disease status. We hypothesized a corresponding drop in the relative abundance of 13C in breath CO2. Using the lipopolysacchride (LPS)-induced endotoxemia model of the acute cachectic state, we demonstrated that the acute phase response causes shifts in the stable isotopes of carbon in exhaled CO2 (13CO2/12CO2 delta value) shortly after administration of LPS while glucocorticoid treatment does not. Mice were injected with LPS and stable isotopes of blood amino acids and carbon in exhaled CO2 were monitored. An increase in the relative isotopic mass of serum alanine, proline and threonine was observed at 3,h after LPS injection. Breath delta values began dropping immediately after administration of LPS, and were 4,5 delta values lower than those of the control animals by 2.5,h after injection. A corresponding drop in delta value was not observed with dexamethasone treatment. Thus protein synthesis during the acute phase response probably caused the fractionation of stable isotopes observed in the plasma amino acids and in exhaled breath 13CO2 delta values. The exhaled breath 13CO2 delta value may be a valuable real-time biomarker of cachexia associated with an acute phase response due to endotoxemia. Copyright © 2009 John Wiley & Sons, Ltd. [source] Inhibitors of COX activity preserve muscle mass in mice bearing the Lewis lung carcinoma, but not the B16 melanomaRESEARCH IN NURSING & HEALTH, Issue 2 2006Erin Graves Abstract Tumor-induced skeletal muscle wasting (SMW) contributes to the fatigue and weakness experienced by persons with cancer cachexia. Tumor necrosis factor-alpha (TNFa) and cyclooxygenase (COX) activity have been implicated in SMW in some animal models of cancer cachexia. We report that indomethacin, a nonspecific inhibitor of COX, and NS398, a specific inhibitor of COX2, preserved muscle mass and reduced type 1 TNF receptors in muscles of mice bearing the Lewis lung carcinoma, but not in mice bearing the B16 melanoma. These data suggest that tumor-induced SMW can occur via a COX2-independent pathway. The COX2-dependent pathway may involve reducing the catabolic effects of TNFa in muscle. Further study is needed to understand the relationship between COX and SMW, and whether patients with cancer cachexia might benefit from COX inhibitors. © 2006 Wiley Periodicals, Inc. Res Nurs Health 29:87,97, 2006 [source] Comparison of Animal Models for Head and Neck Cancer Cachexia,THE LARYNGOSCOPE, Issue 12 2007Trinitia Cannon MD Abstract Objectives/Hypothesis: Despite its negative impact on cancer patients, there are few animal models of cancer cachexia. Our hypothesis was that different human cell lines would variably induce cachexia. Study Design: Prospective animal study. Methods: We established two xenograft models in athymic mice and compared these with a cachexigenic cell line, the murine adenocarcinoma 16 (MAC16) cell line. Eight-week-old female, athymic mice were injected with human head and neck cell lines (JHU022, JHU012) and the MAC16 cell line. Body weight, food intake, body composition, leg weights, serum cytokines, and lipid mobilizing factor (LMF) were compared. Results: Mean food intake for all groups was equivalent. Mean percent change in body weight after 18 days was 18%, 19%, 12%, and 3% for control, JHU012, JHU022, and MAC16 experimental groups, respectively. Both JHU022- and MAC16-injected mice showed wasting even when tumor burden was low. In contrast, mice injected with JHU012 developed larger tumors yet lacked evidence of cachexia. These mice demonstrated loss of lean body mass but not fat mass. Serum cytokine levels for interleukin (IL)-1, and IL-1, were elevated in JHU022-bearing mice, whereas IL-1,, IL-6, interferon (IFN)-,, and tumor necrosis factor alpha (TNF)-, were elevated in MAC16-bearing mice. LMF was present in both the JHU022 and JHU012 cell lines. Conclusions: The JHU022 cell line caused more severe cachexia than the JHU012 cells, suggesting these cell lines may be used to further study cancer cachexia. IL-1, and IL-1, in the JHU022 model may be mediators of cachexia, whereas TNF-,, IFN-,, and IL-6 may be mediators in MAC16-induced cachexia. [source] Bridging necrosis and reticulin bridging fibrosis induced by intrahepatic involvement of acute biphenotypic leukemia,APMIS, Issue 12 2006Case report A 47-year-old Japanese woman was diagnosed as having acute biphenotypic leukemia with association of t(9;22)(q34;q11). Cholestatic liver dysfunction arose, and she died of cachexia and intracranial hemorrhage. Autopsy showed unusual hepatic fibrosis. In the liver, bridging infiltration, bridging necrosis and bridging fibrosis by leukemic cells were seen. It seemed that the degree of fibrosis was associated with the number of aggregates of infiltrating leukemic cells. The fibrotic foci were predominantly composed of reticulin and collagen fibers, and distortion of the lobules was observed. Immunohistochemically, dense bundles of alpha-smooth muscle actin (ASMA)-positive stromal cells, namely activated hepatic stellate cells (HSCs), were observed in the immature fibrotic foci as well as along the sinusoids densely infiltrated by leukemic cells. No cells positive for TGF-,1 or PDGF-BB were identified. In conclusion, extensive intrahepatic involvement by neoplastic cells in adult acute biphenotypic leukemia may cause the unusual "disorganized" hepatic fibrosis. [source] Involution of thymus and lymphoid depletion in mice expressing the hTNF transgeneAPMIS, Issue 1 2004HEIDI GLOSLI Tumour necrosis factor (TNF) is involved in the pathogenesis of several diseases. In mice, human TNF signals only through p55, one of two murine TNF receptors. We here report a study of growth, viability and morphological alterations in transgenic mice expressing a low constitutive and tissue-restricted level of human TNF in vivo. The transgene was expressed solely in T cells. The transgenic mice showed a marked failure to thrive and a rapid cellular depletion in spleen and thymus. Slight fibrosis was seen in most tissues investigated, in addition to immature adipose tissue and irregular lymphocytic areas. Serum levels of hTNF were only slightly increased in the transgenic mice, enough, however, to cause an inflammatory reaction. All the symptoms were abrogated by an inhibitory hTNF antibody, demonstrating the essential role of hTNF in this phenotype. Transgenic mice constitute a multidimensional system allowing observation of disease processes over time in all tissues. The effects of hTNF were seen first and foremost in the lymphoid organs of the transgenic mice, verifying their cells as major targets at low levels of hTNF expression in the T-cell compartments. Chronic, low levels of TNF expression cause profound disturbances in lymphoid tissue development resulting in cachexia and premature death. [source] Adiponectin, ghrelin, and leptin in cancer cachexia in breast and colon cancer patientsCANCER, Issue 4 2006Ido Wolf M.D. Abstract BACKGROUND The hormone ghrelin and the adipocytokines leptin and adiponectin participate in body weight regulation. In response to weight loss, ghrelin and adiponectin levels increase and leptin decreases. Cancer cachexia is a complex metabolic state, characterized by loss of muscle mass and adipose tissue together with anorexia. The authors hypothesized that responses of these hormones may be attenuated in cancer cachexia. METHODS Fasting plasma ghrelin, adiponectin, and leptin levels, as well as weight loss, were determined in 40 cancer patients: 18 of them suffered from cancer-induced cachexia, and 22 served as a comparison group. Hormone levels were measured before administration of cancer therapy. RESULTS A similar distribution of age, gender, and diagnosis was observed in both study groups, but the cachectic patients had higher rates of metastatic disease and lower albumin levels. No significant correlation was observed between plasma adiponectin levels and weight loss. Mean plasma ghrelin levels were higher among cachectic compared with noncachectic patients. Notably, the association between ghrelin levels and weight loss was only modest, and in a third of the cachectic patients, ghrelin levels were equal to or lower than those in the noncachectic group. Plasma leptin levels showed gender-dependent associations, and significantly lower levels were found among cachectic women but not among cachectic men. CONCLUSIONS Results suggested a gender-dependent attenuation of expected physiologic responses to weight loss among cancer cachexia patients. Thus, impaired response of adiponectin, ghrelin, and leptin may play a role in the pathogenesis of cancer cachexia syndrome. Cancer 2006. © 2006 American Cancer Society. [source] Body composition and time course changes in regional distribution of fat and lean tissue in unselected cancer patients on palliative care,Correlations with food intake, metabolism, exercise capacity, and hormonesCANCER, Issue 10 2005Marita Fouladiun M.D. Abstract BACKGROUND Several investigations that yielded different results in terms of net changes in body composition of weight-losing cancer patients have been reported that employed a variety of methods based on fundamentally different technology. Most of those reports were cross-sectional, whereas to the authors' knowledge there is sparse information available on longitudinal follow-up measurements in relation to other independent methods for the assessment of metabolism and performance. METHODS For the current report, the authors evaluated time course changes in body composition (dual-energy X-ray absorptiometry) with measurements of whole body and regional distribution of fat and lean tissue in relation to food and dietary intake, host metabolism (indirect calorimetry), maximum exercise capacity (walking test), and circulating hormones in cancer patients who were receiving palliative care during 4,62 months of follow-up. The entire cohort comprised 311 patients, ages 68 years ± 3 years who were diagnosed with solid gastrointestinal tumors (84 colorectal tumors, 74 pancreatic tumors, 73 upper gastrointestinal tumors, 51 liver-biliary tumors, 3 breast tumors, 5 melanomas, and 21 other tumor types). RESULTS Decreased body weight was explained by loss of body fat, preferentially from the trunk, followed by leg tissue and arm tissue, respectively. Lean tissue (fat-free mass) was lost from arm tissue, whereas trunk and leg tissue compartments increased, all concomitant with declines in serum albumin, increased systemic inflammation (C-reactive protein, erythrocyte sedimentation rate), increased serum insulin, and elevated daily caloric intake; whereas serum insulin-like growth factor 1 (IGF-1), resting energy expenditure, and maximum exercise capacity remained unchanged in the same patients. Serum albumin levels (P < 0.001), whole body fat (P < 0.02), and caloric intake (P < 0.001) predicted survival, whereas lean tissue mass did not. Daily intake of fat and carbohydrate was more important for predicting survival than protein intake. Survival also was predicted by serum IGF-1, insulin, leptin, and ghrelin levels (P < 0.02 , P < 0.001). Serum insulin, leptin, and ghrelin (total) levels predicted body fat (P < 0.001), whereas IGF-1 and thyroid hormone levels (T3, free T3) predicted lean tissue mass (P < 0.01). Systemic inflammation primarily explained variation in lean tissue and secondarily explained loss in body fat. Depletion of lean arm tissue was related most to short survival compared with the depletion of lean leg and trunk tissue. CONCLUSIONS The current results demonstrated that body fat was lost more rapidly than lean tissue in progressive cancer cachexia, a phenomenon that was related highly to alterations in the levels of circulating classic hormones and food intake, including both caloric amount and diet composition. The results showed importance in the planning of efficient palliative treatment for cancer patients. Cancer 2005. © 2005 American Cancer Society. [source] Phase II study of high-dose fish oil capsules for patients with cancer-related cachexiaCANCER, Issue 3 2005A Cancer, Leukemia Group B study No abstract is available for this article. [source] Role of ,1-adrenoceptor in increased lipolysis in cancer cachexiaCANCER SCIENCE, Issue 7 2010Dong-xing Cao Increased production of hormone-sensitive lipase (HSL) protein has been demonstrated to be the major cause behind enhanced lipolysis in cancer cachexia. The mechanism governing this alteration is unknown and was presently investigated. This study was conducted to detect the expression of relevant receptors in the adipocytes of cancer cachexia patients, and to elucidate their implication in the increased lipolysis. Gene expressions of ,1-adrenoceptor (ADRB1), ,2-adrenoceptor (ADRB2), ,3-adrenoceptor (ADRB3), ,2C-adrenoceptor (ADRA2C), natriuretic peptide receptor A (NPRA), insulin receptor (INSR), and HSL were determined in adipose tissues of 34 patients by real-time PCR. Protein levels of ADRB1 and HSL were determined by western blot analysis. ,1-Adrenoceptor (ADRB1) was also detected by immunofluorescence staining. mRNA expressions of both ADRB1 and HSL were approximately 50% elevated selectively in the cachexia group, whereas mRNA levels of the other receptors were unchanged. ,1-Adrenoceptor (ADRB1) protein expression was 1.5-fold increased in cachexia as compared with the cancer controls, and 3-fold increased as compared with nonmalignant controls, and was confirmed as a membrane protein in adipocytes by immunofluorescence. Hormone-sensitive lipase (HSL) protein expression was 2,2.5-fold increased selectively in cachectic patients. There was a positive correlation between the protein expressions of ADRB1 and HSL. As much as approximately 50% of the variations in HSL protein expression could be explained by variations in ADRB1 protein expression. There was a link between ADRB1 protein level and lipolytic rate. Increased ADRB1 expression may account for some of the functional changes of HSL in patients with cancer cachexia. (Cancer Sci 2010) [source] | ||||||||||||||||||||||||||||||||||