Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Moloney murine sarcoma virus (MoMuSV349) is produced by MuSV349 cells in at least eight-fold excess over the replication-competent helper virus. Less than 48-hours-old Balb/c mice inoculated intraperitoneally with supernatant from MuSV349 cells containing approximately 10(4) MuSV349 infectious units developed clinical symptoms, including severe generalized wasting, 15 to 20 days after inoculation. These infected mice became moribund 35 to 45 days after inoculation. Gross examination of the bodies revealed the presence of cutaneous and subcutaneous 0.2-cm to 1.5-cm macules, plaques, or nodules located predominantly on the ventral abdomen and legs. Nodules also were found in the spleen, liver, ovaries, testes, meninges, nerves, and skin. The nodules were semisoft, cystic, or solid and some expressed variable amounts of blood. Histologic examination of the macules, plaques, and nodules showed spindlelike cells intermingled with tortous, jagged vascular channels lined by plump and normal endothelial cells and unlined slitlike spaces filled with erythrocytes. These angiomatous lesions were infiltrated extensively with neutrophils, lymphocytes, macrophages, and some plasma cells. In some cases the lesions also included foci of densely packed eosinophils. These angiomatous lesions are clearly distinguishable from the fibrosarcomas induced by the myeloproliferative sarcoma virus (MPSV), and resemble the sarcomas induced in mice by Gz-MSV and Balb MSV, the sarcomas induced in rats by MPSV and Ha-MSV, and the acute generalized form of Kaposi's sarcoma (KS) associated with acquired immune deficiency syndrome (AIDS) in humans. Electron microscopy also revealed the presence of numerous extracellular type C virions and virions budding from the plasma membrane of endothelial and spindlelike cells. Erythrophagocytosis by the endothelial and spindlelike cells was demonstrated by light and electron microscopy. The widely disseminated lesions appear to have developed simultaneously as a consequence of viremia rather than metastasis.
 ...
PMID:Moloney murine sarcoma virus 349 induces Kaposi's sarcomalike lesions in Balb/c mice. 215 39

C57BL/6 mice bearing either a transplantable methylcholanthrene-induced sarcoma or Lewis lung adenocarcinoma were passively immunized every other day with a rabbit immunoglobulin fraction raised against murine cachectin/tumor necrosis factor-alpha. Mice bearing methylcholanthrene-induced sarcoma developed tumor-associated hypophagia that was attenuated by anticachectin immunoglobulin treatment. In the same tumor-bearing animals, anticachectin treatment also significantly reduced the extent of carcass protein and fat loss, and reduced tumor weight. Mice bearing Lewis lung adenocarcinoma did not develop significant anorexia or carcass lean tissue depletion as tumor growth progressed, but they lost carcass lipid. Treatment of Lewis lung adenocarcinoma bearing mice with anticachectin antibodies diminished the degree of carcass lipid depletion and prevented plasma hypertriglyceridemia. However, in both tumor models, anticachectin treatment did not affect either the development of anemia, hypoalbuminemia or the increase in serum amyloid P concentrations seen with increasing tumor burden. We conclude that an endogenous cachectin response, inhibitable by exogenously administered antibody, contributes to anorexia and to changes in body fat and protein metabolism in these tumor-bearing animals. Neutralizing endogenous cachectin production with antibodies offers the potential to reduce tissue wasting that is frequently associated with neoplastic disease, but it does not appear to affect all of the hematologic and acute phase responses in these murine tumor models.
 ...
PMID:Anticachectin/tumor necrosis factor-alpha antibodies attenuate development of cachexia in tumor models. 272 56

This study addressed the question of whether hypercorticism in tumor-bearing animals contributes to the wasting of body fat and lean body mass, particularly that of skeletal muscles. For this purpose, hydrocortisone-substituted nongrowing sarcoma-bearing and control C57BL/6J mice were used that were either adrenalectomized or sham-operated prior to experimentation. Adrenalectomy in itself did not alter food intake or body composition in normal animals. Tumor-bearing mice and pair-weighted control animals had elevated urinary excretion of corticosteroids compared with the urinary excretion in freely fed controls. The malignant tumor induced the well-recognized wasting in tumor-bearing animals, irrespective of the presence of the adrenal glands. Therefore, an elevated corticosteroid production did not account for the wasting of body fat, lean body mass, skeletal muscle proteins, or decreased RNA activity in quadriceps muscles from tumor-bearing animals, although such muscles were sensitive to physiologic doses of injected hydrocortisone (20 micrograms/day). Tyrosine aminotransferase (TAT) activity in liver tissue from tumor-bearing animals was higher than that induced by pharmacologic doses of hydrocortisone in normal animals. Physiologic doses of hydrocortisone induced hepatic TAT activity, but pair-weighed control animals with the same degree of hypercorticism as was found in tumor-bearing animals had normal TAT activity in liver tissue. Although hypercorticism is present in tumor-bearing animals, the results demonstrate that cancer cachexia can start and proceed independently of the adrenal glands. Therefore, adrenal hyperfunction is not the proximate cause for the development of experimental cancer cachexia induced by anorexia.
 ...
PMID:Tumor-host wasting not explained by adrenal hyperfunction in tumor-bearing animals. 289 Jul 87

Cancer cachexia is characterized by wasting of the lean tissue and profound changes in the body composition of the tumour host. These changes are partly explained by an inefficient energy production but other factors may also be important, such as deficiency of essential nutritional components. In the present study the changes of trace elements in serum and skeletal muscle were compared to those in tumour tissue during tumour progression in sarcoma--bearing rats. Trace element analysis was performed directly on serum specimens and frozen sections from skeletal muscle and tumour tissue. The samples were analysed by energy dispersive X-ray fluorescence spectrometry (EDXRF) without any other pre-treatment such as homogenization and extraction. In skeletal muscle an increased content of zinc was found during tumour progression. The iron concentration was unchanged, but since muscle wasting is part of the cachexia this means that iron was transferred to other compartments. Thus the iron content of serum was doubled and tumour tissue had a high concentration of iron. Selenium was below detection limits in skeletal muscle but well detectable in tumour tissue and it increased during tumour growth. Rubidium and potassium content correlated in all tissues (R:0.98) as did bromine and sodium (R:0.98). Copper behaved differently from the other trace elements and showed large variability. This was also true when tissue copper was individually correlated to all other trace elements in the same tissue.
 ...
PMID:Trace element changes in serum and skeletal muscle compared to tumour tissue in sarcoma-bearing rats. 297 76

This study evaluated whether altered insulin metabolism is a key factor behind weight loss during sarcoma growth in nongrowing mice (C57BL/6J). Fasted sarcoma-bearing mice had decreased blood glucose concentrations but unchanged levels of insulin, compared with those in pair-weighed and freely fed controls. During refeeding, insulin levels were inappropriately low for the degree of glycemia in sarcoma-bearing mice compared with those of pair-weighed and freely fed controls. Injections ip of glucose to tumor-bearing animals resulted in insulin levels comparable to postabsorptive values in healthy control animals, indicating that hypoinsulinemia in freely eating tumor-bearing animals was due to a reduced glycemic sensitivity for pancreatic insulin release. Insulin supplementation at doses [4 IU/100 g (body wt)] that increase body fat in normal animals could not protect the tumor-bearing host from progressive loss of body fat or lean tissues. Exogenous insulin in excess of endogenous insulin production did not stimulate tumor growth. Nitrogen and RNA-DNA content were significantly decreased in the quadriceps muscle of tumor-bearing mice. This reduction was independent of altered insulin levels and could not be prevented by exogenous insulin. The depressed capacity of protein synthesis in extensor digitorum longus (EDL) muscle could be entirely attributed to the state of malnutrition in tumor-bearing animals. The sensitivity and responsiveness of protein synthesis in EDL muscles to insulin were normal in tumor-bearing mice, regardless of whether exogenous insulin exerted its effect in vivo or in vitro. This study confirms insulin resistance for glucose metabolism in an experimental sarcoma animal model. Such changes are concluded to be secondary to anorexia and necessary to counteract hypoglycemia. In non-growing sarcoma-bearing mice, malnutrition and anorexia account entirely for depressed muscle protein synthesis, which is not explained by insulin resistance at the translational level. Insulin metabolism is not a key factor behind progression of wasting in sarcoma-bearing mice, but anorexia is.
 ...
PMID:Role of insulin in development of cancer cachexia in nongrowing sarcoma-bearing mice: special reference to muscle wasting. 355 91

In the present study we assessed the resting energy expenditure of 30 free-feeding control and methylcholanthrene-induced sarcoma-bearing rats prior to and following surgical removal of the tumor. Tumor-bearing rats demonstrated carcass wasting and massive tumor growth. The resting energy expenditure data in our model suggest that neither the presence and growth of a tumor nor its removal significantly change resting energy expenditure beyond the normal range for non-tumor-bearing rats. We suggest that in the partition of energy costs between host and tumor, both carry a similar input, proportional to their relative weight, into the total combined resting energy expenditure of host and tumor.
 ...
PMID:Resting energy expenditure of host and tumor is similar in rats with methylcholanthrene-induced sarcoma. 366 95

Brown adipose tissue plays a thermoregulatory role influencing energy balance in experimental animals and possibly also in humans. In the present study we have reevaluated whether brown adipose tissue may contribute to the development of cancer cachexia in non-growing mice bearing an isogeneic tumor. Interscapular brown adipose tissue mass decreased by 20% in freely-fed sarcoma-bearing mice housed at room temperature. Increased mitochondrial density and increased oxidation rate of acetate at low acetate concentrations were found in brown fat from sarcoma-bearing mice, while the oxidation capacity was unchanged compared with that of freely-fed controls. Metabolic and morphologic changes in brown fat from sarcoma-bearing mice were similar to those found in weight-paired controls, which had experienced the same loss of body weight as the tumor-bearing mice. Selective and non-selective B-receptor blockade and surgical removal of interscapular brown fat before tumor implantation did not influence the nutritional state of freely-fed tumor-bearing mice. Injections of noradrenaline caused a proportionately lower increase in oxygen uptake in tumor-bearing animals than in freely-fed controls. Exposure to cold (+5 degrees C) doubled food intake and led to hypertrophy of brown fat in both sarcoma-bearing mice and control animals. Tumor growth was lower although not statistically different in animals housed at +5 degrees C compared with animals housed at +25 degrees C. It is concluded that brown adipose tissue from sarcoma-bearing mice could not account quantitatively for the host wasting in tumor-bearing mice housed at room temperature.
 ...
PMID:Metabolic and morphologic changes in brown adipose tissue from non-growing mice with an isogeneic sarcoma. Evaluation with respect to development of cachexia. 369 34

Marked differences in cardiac associated morbidity and mortality have been reported between patients with and without malnutrition. Tumor-associated cachexia may impair heart function, which further aggravate host wasting and thereby create a vicious circle. The aim of this study was to evaluate to what extent a malignant tumor may influence heart function under well-defined experimental conditions. The perfused working rat heart was used as a model. Study groups of freely-fed sarcoma-bearing rats, starved and protein-calorie malnourished (PCM) non-tumor rats were compared to freely-fed control animals. All groups of malnourished animals (tumor-bearing, starved and PCM) lost significant amounts of body and heart mass compared to freely-fed controls. Loss of heart contractile mass in tumor-bearing rats and malnourished animals did not lead to impaired heart function in any respect. The rate of oxygen uptake was significantly higher under all experimental conditions in perfused hearts from tumor-bearing rats compared with hearts from starved, PCM and freely-fed control rats. Oxygen uptake per left ventricular work was significantly higher in tumor-bearing rats but significantly lower in starved and PCM rats compared with control animals. Norepinephrine at various concentrations (10(-9)-10(-5) mol/l) in the perfusate stimulated the contractility and the left ventricular peak pressure significantly more in hearts from malnourished animals compared with that of freely-fed controls. The results show that adaptive functional changes can be recorded in the isolated perfused rat heart from sarcoma-bearing rats and after a period of comparatively acute undernutrition in non-tumor rats. A malignant tumor or the associated malnutrition does not induce impaired pumping performance despite a reduction in contractile heart mass. Increased oxygen consumption in hearts from tumor-bearing animals may contribute to elevated energy expenditure in a cancer-bearing host.
 ...
PMID:Effects of tumor-load and malnutrition on myocardial function in the isolated working rat heart. 379 77

Morphometric data on left ventricular papillary muscle structures have been determined in tumor-induced malnutrition and related to the maximum activities of key enzymes for energy production in the whole myocardium. Adult, nongrowing mice with a syngeneic sarcoma were used to represent a condition of cancer associated host tissue wasting. Hearts from mice 11 days after tumor implantation showed atrophy and a significantly reduced amount of myofibrillar, soluble, and collagen proteins than hearts from control animals. The cross-sectional area of myocardial cells was 33% smaller in tumor-bearing mice (p less than 0.025), but the total number of capillaries and the residual interstitial volume were similar in the two groups. The total number of subcellular structures per cell, such as mitochondria, myofibrils, and myosin filaments per myofiber, were significantly lower in the tumor-bearing animals (p less than 0.025). Conversely, the proportion of myofibrils was higher (p less than 0.05) in tumor-bearing animals while the proportion of mitochondria was lower. Maximum activities (Vmax) of selected regulatory key enzymes for energy production (glycogenolytic, glycolytic, and mitochondrial) were not significantly altered in hearts from tumor-bearing mice. The results support the conclusion that myocardial functional capacity is better preserved than overall structural components would imply in tumor-host associated malnutrition, which is probably secondary to deprived food intake. Teleologically, this may be a means by which functional deterioration of the heart is minimized during the induction of malnutrition.
 ...
PMID:Ultrastructural changes and enzyme activities for energy production in hearts concomitant with tumor-associated malnutrition. 382 Oct 91

Changes in the cell population kinetics of the Balb/c mouse thymus were studied (a) during the growth of a syngeneic transplantable sarcoma and (b) following intraperitoneal injection of dexamethasone. The weight of the thymus fell briefly after tumour transplantation, then recovered with overshoot and eventually declined profoundly. After dexamethasone injection the weight of the thymus fell to roughly one-third of its normal value in 36 hr. Similar cytokinetic changes were observed in both sets of experiments; thymic wasting was accompanied by a small increase in thymocyte cell cycle time, a prolongation of the S-phase of the cycle, a marked decrease in the thymocyte cell production rate and a marked reduction in the growth fraction of the thymocyte population in the superficial cortex. It is suggested that thymic atrophy in tumour bearing animals may be a stress phenomenon.
 ...
PMID:Cytokinetic changes in the thymus of tumour-bearing and of dexamethasone-treated mice. 745 79


1 2 Next >>