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.

Metalloproteinases, inhibitors of metalloproteinases, plasminogen activators, inhibitors of plasminogen activators and cathepsins are thought to be involved in invasion by tumor cells. Glioblastoma multiforme is highly malignant and extremely refractory to therapy. One reason is because of its highly invasive nature within the nervous system. However, it remains unclear how invasion/dissemination of glioblastoma multiforme proceeds. In this study, we attempted to determine which proteinases were responsible for the invasion activity of human glioma cell lines in vitro. Nine human glioma cell lines (NHG1, NHG2, IN157, IN301, IN500, U251, U343, T98G and CCF-STTG1) derived from patients with glioma were grown in culture and used. We compared the invasion activity of glioma cell lines in a Matrigel invasion assay system, and formulated the activity as invasion index (%). Among the nine cell lines, IN157, IN500 and U343 showed less than 10% invasion activity (low group); NHGI, IN301 and CCF-STTG1 showed 10-25% activity (intermediate group); NHG2, U251 and T98G showed more than 30% activity (high group). Addition of an inhibitor of metalloproteinases, TIMP-1, to the assay system was found to significantly inhibit invasion activity of T98G cells (P < 0.01). Northern blot analysis demonstrated expression of urokinase-type plasminogen activator (uPA), tissue-type PA (tPA) and PA inhibitor-1 (PAI-1) in some of the above cell lines. Cellular levels of PAs and their inhibitor mRNA, however, appeared not to be correlated with invasion activity in most glioma cell lines except for CCF-STTG1. Expression of 72 kDa type IV collagenase (MMP-2) was much lower in IN157, IN500 and U343 than other cell lines, whereas expression of TIMP-1 was much higher in IN500 than in other cell lines. Zymographic activity was found to be comparable to MMP-2 mRNA levels in all cell lines except for CCF-STTG1. Type IV collagenolytic activity was also comparable to invasion activity in nine cell lines. These observations suggest the role of type IV collagenase and its inhibitors in determining capacity for invasion by human gliomas. However, a comprehensive analysis both in vitro and in vivo is required to confirm the role for this enzyme in glioma cell invasiveness.

Summary Multidrug resistance phenotypes in human tumours are associated with the overexpression of the 170 kDa P-glycoprotein encoded by the multidrug resistance 1 (MDRI) gene, and also with that of the non-P-glycoprotein-mediated multidrug resistance gene, MRP, which encodes a 190 kDa membrane ATPbinding protein. We Cancer, 58, 860-864, 1994). In this study, we investigated whether chemosensitising agents of P-glycoprotein-mediated multidrug resistance such as verapamil, a biscoclaurine alkaloid (cepharanthine), and a dihydropyridine analogue (NIK250) could also reverse

One hundred thirty-six strains of wood-rot fungi (74 strains, 66 species of 19 genera, and 62 unidentified strains) were screened for the dibenzo-p-dioxin (DD) decreasing activity. It was observed that 20% of additional DD (1 Wmol) disappeared in the cultures of eight strains belonging to four genera (Aleurodiscus (one strain), Ceriporia (one strain), Phanerochaete (one strain), Phlebia (five strains)) and four unidentified strains. These 12 fungal strains were used for the examination of the degradation of [U-14 C]2,7-dichlorodibenzo-p-dioxin (2,7-diCDD). The fungi unidentified strain MZ-227, Phlebia sp. MG-60 and Phlebia lindtneri showed higher cumulative 14 CO 2 evolution rates than the other nine fungi. MZ-227, Phlebia sp. MG-60, and P. lindtneri converted 250 nmol of 2,7-diCDD to 196, 155 and 149 nmol of 14 CO 2 , respectively, during a 30-day incubation period ß