Antiangiogenic drugs for chemotherapy of bladder tumours.

Background: Bladder cancers have different angiogenic pathways distinguishing not only papillary from solid tumours, but even papillary superficial from papillary invasive ones, thus representing selective targets for antiangiogenic drugs.

Methods: The bacterial wall component tecogalan, inhibiting basic fibroblast growth factor (bFGF), the fumagillin derivative TNP-470, inhibiting vascular endothelial growth factor (VEGF), the distamycin A derivative PNU153429, and the tetracycline minocycline were administered to nude mice injected with the human bladder cancer cell lines 639V, causing bFGF-expressing papillary superficial tumours, or T24, causing VEGF-expressing papillary invasive tumours.

Results: Tecogalan had no effect even on 639V tumour growth, where bFGF was unaffected.

Tumor and metastasis suppression by the human RNASET2 gene.

The region 6q27 from human chromosome 6 has been reported to contain one or more tumor suppressor genes on the basis of cytogenetic, molecular and functional studies. We have recently carried out a detailed analysis of a candidate gene from 6q27 to evaluate its putative role as a tumor suppressor gene involved in ovarian cancer pathogenesis. The RNASET2 gene was shown to behave as a class II tumor suppressor and abolish the tumorigenic potential of an ovarian cancer-derived cell line.

Tumor-host interaction mediates the regression of BK virus-induced vascular tumors in mice: involvement of transforming growth factor-beta1.

Several sexually transmitted viruses have been associated with the development of Kaposi's sarcoma (KS), a highly vascularized multi-focal neoplasm, characterized by the presence of spindle-shaped and endothelial cells, fibroblasts and macrophages. As BK virus (BKV) sequences were found in 100% of primary KS and 75% of KS cell lines, we established an experimental model to test whether BKV may be involved in the pathogenesis of KS. For this purpose, we transformed primary and spontaneously immortalized murine endothelial cells with BKV or with a plasmid containing BKV early region, which encodes BKV T antigen.

Inhibition of HIV-1 Tat activity correlates with down-regulation of bcl-2 and results in reduction of angiogenesis and oncogenicity.

The Tat protein of the human immunodeficiency virus type 1 promotes survival and growth and inhibits apoptosis of different cell types. These effects of Tat are attributed to the induction of bcl-2 gene expression. In this study we show that the blocking of both intracellular and extracellular Tat correlates with a decrease of bcl-2 transcripts, leading in vitro to a lower growth rate and attenuation of the transformed phenotype and in vivo to a reduced angiogenic and oncogenic activity of Tat-expressing cells.