ADAM12 is highly expressed in carcinoma-associated stroma and is required for mouse prostate tumor progression.

The interaction between stromal cells and tumor cells is emerging as a critical aspect of tumor progression. Yet there is a paucity of molecular markers for cells participating in such interactions, and only few genes are known to play a critical role in this process. Here, we describe the identification of ADAM12 (a disintegrin and metalloprotease 12) as a novel marker for a subpopulation of stromal cells that are adjacent to epithelial tumor cells in three mouse carcinoma models (models for prostate, breast and colon cancer). Moreover, we show that ADAM12 is essential for tumor development and progression in the W10 mouse model for prostate cancer. These results suggest that ADAM12 might be a useful marker for stromal cells in mouse tumors that are likely to participate in stromal/tumor cell crosstalk, and that ADAM12 is a potential target for design of drugs that prevent carcinoma growth.

Reduction of liver mass due to malnutrition in rats. Correlation with emaciation of animals and size of organs not inserted in the portal system.

We studied the effects of protein-energy malnutrition on the liver morphology of rats as compared to animal emaciation and to reduction in size of the organs not irrigated by splanchnic blood such as kidneys and spleen. The animals were divided into two groups, one of them fed ad libitum rate (N = 10) and the other (N = 14) receiving water but no food for 7 days, and the changes in animal weight, liver, kidney and spleen mass were determined. DNA and the protein/DNA ratio, as well as hepatocyte size, were determined in liver tissue. The liver decreased in mass (27.14%) at a significantly higher proportion (p < 0.05) when compared to body emaciation (19.22%). Similar to the reduction in body weight, the masses of kidneys and spleen were reduced by 18.68% and 24.28%, respectively. The reduction in liver mass occurred due to hypoplasia and atrophy, i.e., a decrease in hepatocyte number and size, respectively. We conclude that there is a preferential consumption of liver protein in protein-energy malnutrition which is suggested to result from the additive action of the effects of overall consumption of organic reserves due to malnutrition proper and to the reduction of the hepatotrophic stimulus.

Enhancement of liver size by stimulation of intact rat liver with exogenous hepatotrophic factors.

In mammals, liver size is related to animal body weight at the 2.5 to 3% proportion, a ratio mediated by the afflux of hepatotrophic factors. Formulas capable of modifying this ratio have been developed in previous studies on the rat, with enhancement of liver size brought about by intraperitoneal (portal) infusion of exogenous factors such as glucose, amino acids, insulin, glucagon, vitamins, electrolytes, and triiodothyronine. However, the efficacy of these formulations was accompanied by increased animal mortality (PARRA et al.). The present study, which was carried out with small methodological modifications on a larger number of rats using daily intraperitoneal injections of a solution of exogenous hepatotrophic factors (40 ml/kg) for seven days, confirms the previous findings, with a 114.16 +/- 7.90% enhancement of liver size beyond the expected value for the body weight of the animal. However, the problem of animal mortality was not fully resolved.

[Prevention of peritoneal adhesion formation with a combination of carboxymethyl-cellulose and papain: experimental study]. / Prevenção da formação de aderências peritoneais pela associação carboximetilcelulose-papaína: estudo experimental.

The inhibitory action of sodium carboxymethylcellulose (CMC) and papain (PP) in peritoneal adhesions formation, were studied in Wistar rats. After ether anesthesia and a midline laparotomy incision, the right parietal peritoneum was pinched with a fine hemostat and the pinched peritoneal fold was then ligated. This maneuver was repeated thrice creating four point as if they were little "polyps" with a standardized size. Before closing the incision, it was deposited on the four points of each animal the following substances: group A--saline solution; group B--CMC 2%; group C--PP 0.4% in distilled water; group D--CMC 2% + PP 0.2%; group E--CMC 2% + PP 0.4%. After ten days, the rats were sacrificed and classified according to the number of "points" that showed adhesions with the abdominal structures. There was a statistically significant decrease in the incidence of adhesions only in the group E (CMC + PP 0.4%).

[Dose-dependence of the carboxymethylcellulose-papain combination in the prevention of peritoneal adhesions. Study in rats]. / Dose-dependência da associação carboximetilcelulose-papaína na prevenção de aderências peritoneais. Estudo em ratos.

The action of a low volume (one drop) of sodium carboxymethylcellulose (CMC)-papain (PP) association gel to prevent peritoneal adhesions were studied in female Wistar rats. After ether anesthesia and a midline laparotomy incision, the right parietal peritoneum was pinched with a fine hemostat and the pinched peritoneal fold was then ligated. This maneuver was repeated thrice creating four points as if they were little "polyps" with a standardized size. Before closing the incision it was deposited on each point 0.05 ml (one drop) of CMC 2% (group A) or CMC + PP 0.4% (group B), with a total volume of 0.2 ml. These groups were compared with another similar group (group C) of a previous research, in which was used 7 ml/kg of body weight of CMC + PP 0.4% (1.5 ml by animal). Statistically significance was not noticed between groups A and B but it was noticed between these two groups (A and B) and group C (p < 0.001 and p < 0.01, respectively). It was concluded that the lowest effective volume (between 0.2 and 1.5 ml/animal) which can allow the desired effect is to be determined in order to diminish the quantity of substance to be deposited in the abdominal cavity.