Heterogeneous response of adipose tissue to cancer cachexia

Cancer cachexia causes disruption of lipid metabolism. Since it has been well established that the various adipose tissue depots demonstrate different responses to stimuli, we assessed the effect of cachexia on some biochemical and morphological parameters of adipocytes obtained from the mesenteric (MES), retroperitoneal (RPAT), and epididymal (EAT) adipose tissues of rats bearing Walker 256 carcinosarcoma, compared with controls. Relative weight and total fat content of tissues did not differ between tumor-bearing rats and controls, but fatty acid composition was modified by cachexia. Adipocyte dimensions were increased in MES and RPAT from tumor-bearing rats, but not in EAT, in relation to control. Ultrastructural alterations were observed in the adipocytes of tumor-bearing rat RPAT (membrane projections) and EAT (nuclear bodies)

Insulin and prostaglandins as signals between tumor and the host immune system

The development of malignant tissue in vivo is partially favored by the immunosuppression that occurs in cancer patients. However, the signals between tumor and immune tissues remain to be identified. We present evidence that prostaglandins may act as one of these signals by a direct action on cells of the immune system, or by inhibition of insulin secretion which in turn suppresses immune function, or both

Metabolism of glucose, glutamine and pyruvate in lymphocytes from Walker 256 tumor bearing rats

This study examined the effect of Walker 256 tumor growth in vivo on the metabolism of glucose, glutamine and pyruvate in lymphocytes. A comparison between the metabolism of Walker 256 tumor cells obtained in vivo with that of lymphocytes was also carried out. Lymphocytes and tumor cells were isolated and incubated for 1 h for the following measurements: lactate production from glucose (5.6 mM) and pyruvate (3 mM), glutamate and aspartate formation from glutamine (3 mM) and decarboxylation of [U-14C]-glucose, [U-14C]-glutamine, [1-14C]-pyruvate and [3-14C]-pyruvate. The presence of the tumor increased lactate production (2.7-fold from glucose and 2-fold from pyruvate), decarboxylation of [U-14C]-glucose (3.7-fold) and [1-14C]-pyruvate (4.4-fold) and the formation of aspartate (6.3-fold) and glutamate (4.6-fold) from glutamine. The conversion of glucose to lactate and CO2 was higher in tumor cells as compared to lymphocytes. Tumor cells also showed a higher production of glutamate and an 8-fold increased decarboxylation rate of [U-14C]-glutamine in tumor cells, which was more active than that of lymphocytes even from tumor-bearing rats. Tumor growth stimulated glucose and glutamine metabolism in lymphocytes; however, the importance of this fact for the function of these cells remains to be elucidated

Thoracic lymph node metastasis and carcinomatous lymphangitis after inoculation of Walker 256 tumor through the trachea

1. Experimental models of carcinomatous lymphangitis have not been described. This is an important clinical entity which usually results in the patients' death, although its natural history is still controversial. This study was undertaken to investigate whether the pattern of lung involvement after Walker 256 tumor inoculation through the trachea is a good model of carcinomatous lymphangitis. 2. Fifty male Wistar rats were inoculated through the trachea with 2.5 x 10(6) Walker 256 tumor cells and killed in groups of 5 animals each at 6 h and on days 1, 3, 7, 14, 21, 28, 35, 45, and 60 of the experiment. The lungs and thoracic lymph nodes were examined by light microscopy. 3. There were no tumors in the 25 animals killed before the 21st day of the experiment. The remaining 25 rats were sacrificed after 3 weeks of the experiment; 52 per cent of them displayed thoracic lymph node metastases, and 40 per cent developed a mild carcinomatous lymphangitis. The lung involvement did not correlate with respiratory distress, tumor dissemination or additional histological abnormalities. 4. We conclude that invasion of the lung is possible after intratracheal tumor cell inoculation, and that spreading follows a lymphatic pattern. This finding establishes this approach as a viable experimental model of carcinomatous lymphangitis. New approaches to increase the intensity and frequency of lung involvement, as well as the development of respiratory distress should be pursued in order to improve the efficiency of this model

Efeitos da nutriçäo parenteral sobre o desenvolvimento tumoral: aspectos experimentais / Effects of parenteral nutrition on tumor growth: experimental aspects

Persistem as controvérsias quanto ao impacto da nutriçäo parenteral sobre o desenvolvimento do câncer, em eventual detrimento do hospedeiro. Nessa linha de preocupaçöes os autores estudaram o desenvolvimento do carcinossarcoma de Walker 256 implantado em ratos Wistar submetidos a modelo de nutriçäo parenteral (NP). Foram utilizados 35 ratos adultos, distribuídos aleatoriamente em três grupos: grupo OT (11), de ratos portadores do tumor e alimentados por via oral por 14 dias; grupo PC (14), de animais controles submetidos a NP por sete dias; grupo PT (10), de animais portadores de tumor e submetidos a NP por sete dias após o implante tumoral. A soluçäo utilizada no esquema de NP continha 15% de glicose e 3% de aminoácidos, além dos micronutrientes essenciais à manutençäo do animal. Diariamente eram determinados o peso corpóreo do animal e o peso do tumor OT e PT), claculando-se o peso da carcaça pela diferença entre os dois valores referidos. os animais do grupo PC sofrem perda de peso corpóreo nos três primeiros dias da NP, estabilizando-se em seguida, ao passo que os ratos do grupo PT perdem peso inicialmente, mas começam a recuperá-lo após o 3§ dia. Essa diferença deve-se ao peso da massa tumoral em expansäo no grupo PT, uma vez que a evoluçäo do peso da carcaça do grupo PT aproxima-se muito da curva do peso corpóreo do grupo PC. O peso do tumor näo difere substancialmente entre os grupos que receberam dieta oral ou nutriçäo parenteral, em particular quando se utiliza a relaçäo peso do tumor/peso da carcaça. Esses resultados sugerem que o uso da nutriçäo parenteral näo beneficia o desenvolvimento tumoral, em detrimento do hospedeiro

Effects of aspirin-like drugs on Walker 256 tumor growth and cachexia in rats

Several studies have shown the relationship between prostaglandins (PGs) and cell proliferation. Some PGs may trigger cell dibision or are involved in this process. This a=study analyzes the effect of PG biosyntheseis inhibitors on tumor growth in vivo and cachexia in Walker 256 tumor-bearing rats. Indomethacin markedly inhibited tumor growth (95.5% while ibuprofen and aspirin reduced tumor growth by 73.9% and 59.4%, respectively. In addition, all drug-treated rats partially recovered body weight and food intake as compared to the saline-treated group. These findings suggest that PG synthesis inhibitors improve cancer cachexia

Effect of diets with different protein levels on the growth of walker 256 carcinosarcoma in rats

1. The effect of different nutritional situations on the growth of experimental Walker 256 carcinosarcoma was investigated in rats. Fifty adult male Wistar rats were randomly assigned to three groups: group NN received standard chow throughout the experiment; group DD initiaslly received an isocaloric protein-free diet, and some of the animals in this group (DN) were fed normal chow from the 34 th to The 53 rd day of the study. 2. On the 42 and day of the experimentas all animals were incolulated subcutaneously in the flank with 2.5 to 3.0 x 10*5 viable Walker 256 carcinosarcoma dells and tumor growth and rat body weight were monitored daily thereafter. 3. Significantly greater tumor growth was detected in well-nourished (group NNT) as compared with malnourished animals (group DDT), but not protein-depleted-refed (group NNT) as compared with malnourished animals (group DDT), but not in protein-depleted-refed (group DNT) animals, whose tumor growth was not significantly different from that of constantly malnourished (group DDT) rats. 4. Comparasion of tumor weight and of the tumor weight/carcass weight (TW/CW) ratio showed no significant difference between malnourished and malnourished/ refed animals, whereas well-nourishedd animals showed higher tumor weight and TW/CW ratios. 5. TW/CW curves for malnourished rats were parallel to those for malnourished/refed rats. TW/CW curves for constantly malnourished rats differed from those for well-nourished rats during the first observation period but ther was no difference during the second week of tumor growth. 6. although the protein-free diet inhibited tumor growth and refeeding enhanced it, carcass weight increased at the same rate, and therefore no change was observed in the TW/CW ratio. We conclude that nutritional rehabilitation should be considered for tumor-bearing hosts because the advantage in body weight for the host outweighs that for the tumor