Fibrinogen E fragment selectively disrupts the vasculature and inhibits the growth of tumours in a syngeneic murine model.

We recently demonstrated that a fragment of human fibrinogen, fibrinogen E fragment, inhibits the migration and differentiation of human endothelial cells in vitro. Here we show that it exerts similar effects on murine endothelial cells in vitro, and selectively disrupts tumour endothelium in vivo, causing widespread intravascular thrombosis and retarding the growth of CT26 tumours in a syngeneic murine model.

Observations on the adrenocortical structure of the female brush-tailed possum (Trichosurus vulpecula) and locations of cell division.

Twenty mature female possums (Trichosurus vulpecula) were captured at the Harry Waring Marsupial Reserve, some 30 km south of Perth in Western Australia, and injected simultaneously with tritiated thymidine in order to label dividing cells within the adrenal gland. The conservation status of the possum precluded killing all animals and adrenal glands were removed and examined histologically and autoradiographically in four experimental groups, timed for 1 hr, 1 week, and 2, 3, and 7 weeks following the injection. In two of the groups [untreated and FSH-1 (injected with an urogonadotrophin)] the left gland was obtained by unilateral adrenalectomy, whereas in the other two groups (ACTH and FSH-2, of pituitary origin) the animals were killed at the specified intervals. The precise location of labeled adrenocytes with time was measured in autoradiogrammes of adrenal sections. The labeled cells were counted and the distance from the outer connective-tissue capsule was measured with a MOP-Videoplan, calibrated for distance. The widths of the various cortical zones and the medulla were also estimated. The study focused primarily on the "Special Zone" (SZ) which is unique to the adrenals of the mature female possum. The only effect of hormonal treatments discerned was a slight hypertrophic effect of porcine FSH on the size of the SZ. Labeled cells indicative of cell division were found randomly distributed throughout the SZ, as well as in the cortex and occasionally, the medulla. Time series analysis gave no evidence of the progressive centripetal movement of cells within the SZ and our data are thus not consistent with the "Cell Migration Theory" concerning the differentiation of adrenocytes and accord instead with the "Zonal Theory" proposed to account for the maintenance of the classical zones in the eutherian adrenal cortex.

The pituitary in cirrhosis: ultrastructure, growth hormone, and prolactin concentrations.

Micronodular cirrhosis was induced in male SUAH substrain Wistar rats by combined phenobarbitone and carbon tetrachloride treatment. Both pituitary and serum concentrations of growth hormone were significantly reduced in cirrhotic rats compared with age-related untreated rats or those treated only with phenobarbitone. Ultrastructurally growth hormone-secreting cells (somatotrophs) of pituitaries of cirrhotic rats appeared relatively inactive, having few hormone-containing granules, sparse rough endoplasmic reticulum, and small nuclei with areas of condensed chromatin. The cells themselves were smaller than similar cells of untreated rats with a reduced cytoplasmic area. In addition immunocytochemistry of pituitaries at light microscope level, using sheep anti-rat growth hormone antibody, showed that somatotrophs of cirrhotic rats were more heteromorphic and disorganized than those in controls. There was marked development of the folliculo-stellate cell system in pituitaries of cirrhotic rats, the cells were enlarged with distinct golgi, and numerous microvilli were projecting into dilated follicular lumena.

Sex-steroid receptors in the diethylnitrosamine model of hepatocarcinogenesis: modifications by gonadal ablation and steroid replacement therapy.

The results of this study confirm our previous report of increased androgen receptor expression in livers of female SUAH Wistar rats during development of liver tumours induced by diethylnitrosamine (DENA). In adult female rats not treated with DENA, removal of the ovary increased liver androgen receptor levels but testosterone did not further enhance the androgen receptor status of ovariectomized rats. In normal adult males the testis and/or testosterone maintained high levels of androgen receptors but oestrogen reduced them in castrated rats. Oestrogen receptor levels were not significantly changed in either males or females by gonadectomy. Treatment of female rats with DENA for 10 and 16 weeks increased liver androgen receptors but oestrogen receptors were only reduced by 16 weeks of DENA treatment, whether the rats were intact or ovariectomized. Concentrations of liver androgen receptors were increased in intact and castrated male rats by 10 and 16 weeks of DENA treatment, an increase not seen in the previous experiments. Oestrogen appeared to inhibit both the increases in liver androgen receptor expression and liver tumour development in rats treated with the weakly carcinogenic dose of 10 weeks of DENA. However, the full carcinogenic dose of 16 weeks of DENA increased liver androgen receptors and decreased oestrogen receptors in female rats regardless of sex-steroid status. Development of malignant hepatocellular carcinoma (HCC) was associated with both an increase in liver androgen receptors and a decrease in oestrogen receptors. Maintenance of relatively high levels of liver oestrogen receptors appeared to protect the liver against development of HCC.