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At least 217 records · Page 12Linked to original sources
PubMed1994

Development of cancer cachexia-like syndrome and adrenal tumors in inhibin-deficient mice.

Activins and inhibins, members of the type beta transforming growth factor superfamily of growth regulatory proteins, are produced in multiple tissues and affect diverse physiologic processes. Using embryonic stem cell technology, we previously demonstrated that inhibin can function as a gonadal tumor suppressor. In this study, we show that development of gonadal tumors is rapidly followed by a cancer cachexia-like wasting syndrome. Cachectic inhibin-deficient mice develop hepatocellular necrosis around the central vein and parietal cell depletion and mucosal atrophy in the glandular stomach, are anemic, and demonstrate severe weight loss. The liver pathology is consistent with studies demonstrating an effect of elevated activins on rat hepatocytes. In inhibin-deficient mice with tumors, activins are > 10-fold elevated in the serum and are likely causing some of the cachexia symptoms. In contrast, inhibin-deficient mice gonadectomized at an early age do not develop this wasting syndrome. However, these gonadectomized, inhibin-deficient mice eventually develop adrenal cortical sex steroidogenic tumors with nearly 100% penetrance, demonstrating that inhibin is also a tumor suppressor for the adrenal gland.

Activins↗
PubMed1996

Gastro-intestinal protein loss in elderly patients with cardiac cachexia.

Undernutrition resulting from chronic congestive heart failure (cardiac cachexia, CC) increases morbidity and mortality particularly in elderly people. The aetiology of CC is thought to be multifactorial. We have assessed the presence of gastro-intestinal protein loss in a group of patients with CC and a group of healthy age-and sex-matched controls. Gastro-intestinal protein loss was measured using the chromic chloride test in 29 patients with CC [mean age 76.1 (SD4.4) years] and 29 healthy controls [mean age 74.9 (SD 4.8) years]. The patients were undernourished in terms of anthropometric measurements compared to controls. The patients had a significantly lower mean ejection fraction [41.5(18.3)% vs. 65.5(2. 2)%] and higher mean pulmonary artery pressure [89.4(19.9)mmHg vs. 19.3(8.1) mmHg]. The recovery of radioactivity in a 5-day stool collection was similar in the two groups [patients vs. controls: 1. 0(0.7)% vs. 0.98(0.6)%, p=0.9]. These values are within the expected normal range. We conclude that gastro-intestinal protein loss is not a significant factor in the production of cardiac cachexia.

Aged↗
PubMed1980

An experimental model of cachexia induced by a xenografted human tumor.

A hypernephroma removed from a male patient who had lost 30 kg in weight in the 2 months preceding surgery was established in immunosuppressed CBA/Lac mice as a nonmetastasizing transplantable xenograft. The xenografted tumors, although comprising less than 5% of the total body weight of the mice, produced considerable weight loss (greater than 25%). A slight reduction in food intake of tumor-bearing mice was noted, but some animals bearing mouse or human tumors not inducing cachexia had equally low food intake without accompanying weight losses. No obvious defects in gastrointestinal histology or absorption were observed. The precise mechanism(s) producing the severe cachexia remains to be established.

Adenocarcinoma↗
PubMed1990

Controlled trial of megestrol acetate for the treatment of cancer anorexia and cachexia.

Preliminary information has suggested that megestrol acetate leads to appetite stimulation and nonfluid weight gain in patients with breast cancer, other cancers, and AIDS. Pursuant to this, we developed a randomized, double-blind, placebo-controlled trial of megestrol acetate in patients with cancer-associated anorexia and cachexia. We randomly assigned 133 eligible patients to receive 800 mg of megestrol acetate per day or a placebo. Patients assigned to megestrol acetate more frequently reported improved appetite (P = .003) and food intake (P = .009) when compared with patients receiving the placebo. A weight gain of 15 lb or more over baseline was seen in 11 of 67 (16%) patients receiving megestrol acetate compared with one of 66 (2%) given the placebo (P = .003). Patients receiving megestrol acetate reported significantly less nausea (13% vs. 38%; P = .001) and emesis (8% vs. 25%, P = .009). No clinically or statistically significant toxic reactions were ascribed to megestrol acetate, with the exception of mild edema. This study convincingly demonstrated that megestrol acetate can stimulate appetite and food intake in patients with anorexia and cachexia associated with cancer, leading to significant weight gain in a proportion of such patients.

Adult↗
PubMed1997

Journey from cachexia to obesity by TNF.

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine involved in the physiological and metabolic abnormalities found in cachectic states. Until very recently, it was inconceivable to think of TNF-alpha in obesity. However, recent studies have shown that TNF-alpha can also play a key role in obesity, the cytokine being overexpressed in adipose tissue of obese rodents and humans. The aim of this review is to reconcile the role of TNF-alpha in these two opposite metabolic situations: obesity and cachexia. It is suggested that TNF-alpha may have a key role in the control of body mass in normal weight-controlled situations and that abnormalities in either its production (during cachexia) or action (during obesity) are responsible for the lack of control of body weight.

Adipocytes↗
PubMed1998

Anticachectic efficacy of megestrol acetate at different doses and versus placebo in patients with neoplastic cachexia.

Anorexia and cachexia are present in the majority of patients with advanced-stage cancer. Several agents have been tested for their ability to reverse weight loss in these patients. Megestrol acetate has been demonstrated to improve appetite and weight, independent of tumor response, when used in the treatment of metastatic breast cancer. Several trials have studied the ability of megestrol acetate to stimulate weight gain in patients with non-hormone-sensitive tumors. One hundred fifty patients with a weight lost of more than 5% in the 3 previous months were randomized between double-blind megestrol acetate 160 mg daily (LMA), megestrol acetate 480 mg daily (HMA), or placebo (P). Weight, mid-arm circumference, triceps skinfold thickness (TST), performance status (Karnofsky index), and a quality-of-life status by seven linear analogic self-assessment scales were assessed before the start of treatment and at 4, 8, and 12 weeks thereafter. One hundred seven patients were assessable at 4 weeks, 79 at 8 weeks, and 64 at 12 weeks. Sixty-eight percent of patients treated with HMA increased their weights during their permanence on study, versus 37% and 38% of patients treated with P or LMA (p < 0.03). The mean weight gain after 12 weeks of treatment with HMA was 5.41 kg. A significant increase on TST was observed in the HMA group versus the LMA and P groups. There was no gain in performance status or quality of life in any group of treatment. The toxicity registered was mild. There were no thromboembolic events. This trial supports the efficacy of megestrol acetate at 480 mg/day in the treatment of cancer-related cachexia and anorexia, with mild toxicity. However, performance status and quality of life were not influenced by this treatment.

Aged↗
PubMed2000

Management of cancer cachexia.

The diagnosis of cancer has traditionally been associated with malnutrition and wasting. Oncology patients are at risk for nutrition-related problems because of the cancer itself, as well as the treatment prescribed. Clinical manifestations of cachexia include anorexia, weight loss, muscle wasting, and fatigue, resulting in poor performance status. Control of symptoms, such as anorexia, nausea and vomiting, and mucositis is imperative in the management of cancer cachexia. Current pharmacologic therapies, as well as complementary and alternative methods, are presented. The nurse plays a key role in ensuring that the nutritional needs of oncology patients are met.

Cachexia↗
PubMed2000

Cancer cachexia: from experimental models to patient management.

Cachexia is frequently associated with advanced or terminal cancer states, but it can also develop early during the course of neoplastic disease. This syndrome, which is characterized by body weight loss and negative nitrogen balance, significantly affects patient survival and quality of life. Studies on experimental models have shown that a complex interplay of different factors, such as anorexia, classical hormones, cytokines and other less well defined factors, concur in causing tissue wasting. On the basis of these results, it has been possible to prevent the onset of experimental cachexia by targeting therapeutic interventions at the underlying metabolic perturbations. Anticytokine treatments, either acting centrally or peripherally, have received particular attention, and are currently reaching the stage of clinical trials.

Animals↗
PubMed1988

Mouse cachexia induced by trehalose dimycolate from Nocardia asteroides.

Trehalose dimycolate (TDM) isolated from Nocardia asteroides induced in mice a severely wasted condition known as cachexia. Intraperitoneal injection of mice with five 10 micrograms doses of TDM in mineral oil at intervals of 2 d killed 90% of the animals within 26 d. Death followed a precipitous weight loss and an inflammatory process in the peritoneal cavity. When mice were injected intraperitoneally with a single 10 micrograms dose of TDM, 48 h later, they had begun to lose weight and exhibited extreme hypertriglyceridaemia and hypoglycaemia. Tumour necrosis factor (or cachectin) was detected in the plasma from animals injected with TDM. This cytokine released by mononuclear phagocytes may be involved in the induction of cachexia by TDM.

Animals↗
PubMed1992

Cachexia and graft-vs.-host-disease-type skin changes in keratin promoter-driven TNF alpha transgenic mice.

Tumor necrosis factor alpha (TNF alpha) orchestrates a wide range of effects that combat severe infections in animals. At lower levels, TNF alpha plays an important protective role in stimulating chemotaxis and antimicrobial activity of neutrophils, macrophages, and eosinophils. During chronic illness, TNF alpha secretion can be elevated markedly, giving rise to cachexia, hemorrhage, necrosis and, ultimately, death. Although TNF alpha may mediate many of its effects through macrophages, 30% of TNF alpha injected into animals concentrates in the skin. In recent years, it has been shown that keratinocytes can be induced to synthesize TNF alpha. To explore the role of TNF alpha synthesis in keratinocytes, we used a keratin-14 (K14) promoter to target human TNF alpha expression in the epidermis and other stratified squamous epithelia of transgenic mice. Most mice expressing the K14-TNF alpha transgene stopped gaining weight within 1 week postbirth, and exhibited retarded hair growth. In the skin, adipose production was profoundly inhibited, whereas signs of fibrosis and immune infiltration were evident in the dermis. Over time, the epidermis exhibited an increased stratum corneum, as signs of necrosis began to appear in the skin. Within 3-5 weeks, the mice displayed features characteristic of cachexia and necrosis. Our results suggest that TNF alpha expression by keratinocytes not only plays a role in inflammatory and graft-versus-host-disease-like responses in the skin, but also in other tissues, apparently by virtue of stratified squamous epithelial-derived TNF alpha entering the bloodstream. Our results have enabled the first evaluation of many of the effects of TNF alpha in transgenic animals.

Animals↗
PubMed1998

Increased hepatic nicotinamide N-methyltransferase activity as a marker of cancer cachexia in mice bearing colon 26 adenocarcinoma.

When a cachexigenic subclone (clone 20) of murine colon 26 adenocarcinoma was transplanted into female BALB/c mice, hepatic NNMT activity continued to increase until death in proportion to progressive carcass weight loss, a marker of cancer cachexia. On the other hand, noncachexigenic subclone (clone 5)-transplanted mice showed neither increase of NNMT activity nor carcass weight loss. Among cytostatic fluorinated pyrimidines, 5'-dFUrd could inhibit the increase of NNMT activity and prevent weight loss in mice bearing clone 20. On the other hand, 2'-dFUrd did not show these effects. 5-FUra and Tegafur inhibited the increase of NNMT activity at higher concentrations. These findings suggest that the levels of hepatic NNMT activity are closely associated with the degree of weight loss, and they appear to be a useful marker of cancer cachexia.

Adenocarcinoma↗
PubMed2000

NF-kappaB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia.

MyoD regulates skeletal muscle differentiation (SMD) and is essential for repair of damaged tissue. The transcription factor nuclear factor kappa B (NF-kappaB) is activated by the cytokine tumor necrosis factor (TNF), a mediator of skeletal muscle wasting in cachexia. Here, the role of NF-kappaB in cytokine-induced muscle degeneration was explored. In differentiating C2C12 myocytes, TNF-induced activation of NF-kappaB inhibited SMD by suppressing MyoD mRNA at the posttranscriptional level. In contrast, in differentiated myotubes, TNF plus interferon-gamma (IFN-gamma) signaling was required for NF-kappaB-dependent down-regulation of MyoD and dysfunction of skeletal myofibers. MyoD mRNA was also down-regulated by TNF and IFN-gamma expression in mouse muscle in vivo. These data elucidate a possible mechanism that may underlie the skeletal muscle decay in cachexia.

Animals↗
PubMed1985

A macrophage factor inhibits adipocyte gene expression: an in vitro model of cachexia.

Certain infections and malignancies in mammals cause the development of a condition known as cachexia in which the animal continues to lose weight, often while consuming an adequate diet. When macrophages are stimulated with an endotoxin, they produce a factor or factors, termed cachectin, that inhibits the activity of fat-producing (lipogenic) enzymes in cultured adipocytes. This effect may reflect one of the physiological bases for cachexia. In the present study, clones of complementary DNA from genes whose expression is increased during the differentiation of adipocytes were used to study the molecular basis of cachectin's actions. In the presence of cachectin, the expression of the corresponding genes was reversibly and specifically inhibited. Furthermore, when mature adipocytes were exposed to cachectin, the messenger RNA's of those genes diminished and rapidly approached the levels present before differentiation.

Actins↗
PubMed1998

Diabetic neuropathic cachexia: report of a recurrent case.

Diabetic neuropathic cachexia is an uncommon peripheral neuropathy associated with diabetes mellitus and characterised by profound weight loss and painful dysaesthesias over the limbs and trunk. The pathophysiological basis of this disorder remains unknown and there have been no published cases of recurrent episodes. A hispanic man who experienced two episodes of diabetic neuropathic cachexia over a seven year period is described.

Adult↗
PubMed1990

Insulin secretion in Walker 256 tumor cachexia.

The effect of cachexia on insulin secretion was examined in adult male rats. Isolated islets of Langerhans from Walker 256 tumor-bearing rats secreted less insulin by glucose stimuli as compared with the control group; this was accompanied by significant change in 45Ca2+ outflow rate. Reduced insulin secretion to glucose stimuli in tumor-bearing rats probably led to low insulinemia (one-third). These findings indicate that reduced insulin secretion is probably an important factor for the development of cachexia in Walker 256 tumor-bearing rats.

Animals↗
PubMed2001

Differential gene expression in a murine model of cancer cachexia.

Murine adenocarcinoma 16 (MAC16) tumors and cell lines induce cachexia in NMRI nude mice, whereas histologically similar MAC13 tumors do not. After confirming these findings in BALB/c nude mice, we demonstrated that this tissue wasting was not related to decreased food intake or increased total body oxidative metabolism. Previous studies have suggested that MAC16's cachexigenic properties may involve the production of tumor-specific factors. We therefore screened for genes having increased expression in the MAC16 compared with the MAC13 cell line by performing hybridization to a murine cDNA expression array, by generation and comparison of cDNA libraries from each cell line, and by PCR-based subtractive hybridization. Northern blot hybridization was performed to confirm differences in transcript expression. Transcripts encoding insulin-like growth factor binding protein-4, cathepsin B, ferritin light and heavy chain, endogenous long-terminal repeat sequences, and a viral envelope glycoprotein demonstrated increased expression in the MAC16 cell line. The roles of a number of these genes in known metabolic pathways identify them as potential participants in the induction of cachexia.

Adenocarcinoma↗
PubMed1982

Walker carcinoma 256: a model for studies on tumor-induced anorexia and cachexia.

Data on anorexia and cachexia induced by Walker carcinoma 256 in Sprague-Dawley rats were analyzed in order to standardize an experimental model using a statistical (nondeterministical) procedure for assessing the efficacy of potential orexigenic agents. This model was characterized by a mean survival time of 14 +/- 1 days and by food intake and body weight loss starting from day 6 after tumor implantation. The complex course of cachexia was characterized by reduction in the weight of gastrocnemius muscle and epididymal adipose tissue, taken as representative sites of loss of proteins and lipids.

Adipose Tissue↗