We have developed two different models of tumor angiogenesis by human brain tumors: one being tube formation by bovine aortic endothelial (BAE) cells cocultured with tumor cells in vitro, and other being in vivo angiogenesis in mice when tumor cells are transplanted into the dorsal sac. We investigated whether tube formation could be induced in BAE cells in type I collagen gel when these cells were cocultured with seven human glioma cell lines. Four of the seven glioma cell lines, which had high levels of basic fibroblast growth factor (bFGF) mRNA, induced tube formation by BAE cells. The tube formation was blocked by coadministration of anti-bFGF antibody. In in vivo model system of tumor angiogenesis in mice, these four cell lines were highly angiogenic. In contrast, with the other three glioma cell lines, which had poor expression of bFGF, BAE cells showed no apparent tube formation. These three cell lines did not efficiently develop capillary networks in mice. The results demonstrated a correlative relationship in the tubulogenesis of BAE cells, bFGF mRNA levels and angiogenesis in mice.The present study with two model systems of tumor angiogenesis suggests that the angiogenesis of some human glioma cell lines is mediated by bFGF, possibly via paracrine control. (J.

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Ingestion of a high-fat (HF) diet is known to enhance bile acid (BA) secretion, but precise information about the BA molecular species is lacking, especially information on the conjugated BAs in enterohepatic circulation. As cholesterol is the precursor of BAs, we analyzed alterations of the entire BA metabolic pathway in response to a HF diet without the addition of cholesterol and BA in the diet. Additionally, we evaluated the relationships between BA metabolism and some disorders, such as plasma transaminase activities and glucose intolerance induced by the HF diet. Acclimated WKAH/HkmSlc male rats (3 wk old) were divided into two groups fed a control or the HF diet for 22 wk. Fasting blood glucose was measured during the experimental period, and an intraperitoneal glucose tolerance test was performed at week 21. As a result, ingestion of the HF diet selectively increased the concentration of taurocholic acid in the bile and small intestinal contents as well as deoxycholic acid in the large intestinal contents and feces. These results indicated a selective increase of 12a-hydroxylated BA concentrations in response to the HF diet. Moreover, fecal 12a-hydroxylated BA concentration was positively correlated with cumulative energy intake, visceral adipose tissue weight, and glucose intolerance. The present study suggests that fecal 12a-hydroxylated BA is a non-invasive marker that can detect the early phase of glucose intolerance.

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In this study, we examined whether human glioma cells are angiogenic in a model using human microvascular endothelial cells, and also which factor is responsible for the glioma‐dependent angiogenesis. Tubular morphogenesis in type I collagen gel by human microvascular endothelial cells was stimulated in the presence of 10 and 100 ng/ml of vascular endothelial growth factor (VEGF), 10 ng/ml basic fihroblast growth factor (bFGF) and 10 ng/ml of interleukin‐8 (IL‐8). Tube formation of the microvascular endothelial cells was assayed in the glioma cell lines IN157 and IN301, co‐cultured using the double chamber method. IN301 cells had much higher levels of VEGF, bFGF and transforming growth factor‐(mRNA than IN157 cells, whereas the two had similar levels of transforming growth factor‐Alfa mRNA. By contrast, IN157 cells had much higher levels of IL‐8 mRNA than IN301 cells. IN301‐dependent tubular morphogenesis was inhibited by anti‐VEGF or anti‐bFGF antibody, and the inhibition was almost complete when anti‐VEGF and anti‐bFGF antibodies were present. On the other hand, IN157‐dependent tubular morphogenesis was inhibited by anti‐IL‐8 antibody, but not by anti‐VEGF or anti‐bFGF antibodies. These findings demonstrated dual paracrine controls of tumor angiogenesis by human glioma cells. One is mediated through VEGF and/or bFGF, and the other, through IL‐8.