Involvement of angiopoietins in cancer progression in association with cancer cell--fibroblast interaction.

PURPOSE: The role of angiopoietins (ANGs) in cancer progression is a new field of research. We examined the patterns of expression of ANGs in human renal cancer tissues (n =12) and investigated their roles in cancer progression in vitro and in vivo. METHODS AND RESULTS: In normal renal tissue, the expression of ANG-1 was apparent in the glomerular capillaries and podocytes as well as in the endothelial cells of vessels, whereas we observed no expression of ANG-2. In contrast, in tumor tissue, dense, diffuse expression of ANG-1 was apparent in the fibroblasts, but not in the cancer cells. Intense ANG-2 expression was observed in the cancer cells themselves as well as in the endothelial cells, where its expression was restricted to small vessels or neoplastic capillaries and not mature vessels. Secondly, we investigated the influence of fibroblasts on the production of angiopoietins in cancer cells, using the human renal cancer cell lines SN12 and SN-PM6 and a human dermal fibroblast cell line (HDF). We examined the in vitro production of angiopoietins in these cell lines, in either monoculture of each cell line or co-culture of cancer cells and fibroblasts. Immunohistochemical study demonstrated marked production of ANG-1 in fibroblasts and ANG-2 expression in cancer cells when we performed co-culture, but no expression of either in each monoculture. Western blot analysis confirmed these results, showing marked expression of ANGs in co-cultured cells, but not in each monoculture. CONCLUSION: Fibroblasts may influence cancer progression by promoting neoplastic angiogenesis, and ANGs are profoundly involved in this process through their association with the carcinoma cell-fibroblast interaction.

[Complete avulsion of ureter caused by abdominal blunt injury: a case report].

A 21-year-old woman who had been injured in a traffic accident appeared with abdominal pain and macroscopic hematuria. Computed tomography (CT) performed 6 hours after the injury showed extravasation of contrast medium in the right retroperitoneal space. Retrograde pyelography (RP) showed the interruption of right ureter at the site of ureteropelvic junction. We performed an abdominal operation 15 hours after the injury under the diagnosis of right ureteral avulsion. We observed a completely separated right ureter at the ureteropelvic junction, and performed an end to end anastomosis. The patient was discharged three weeks after surgery, and has not had any problems for three years.

The activation of caspase-3 and DNA fragmentation in B cells phagocytosed by macrophages.

Apoptotic signaling of mammalian cells involves two pathways: the death receptor and mitochondrial pathways. In this in vivo study, we investigated apoptotic signaling of B cells in mouse germinal centers (GCs) of gut-associated lymphoid tissues (GALTs) using transmission electron microscopy (TEM), terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL), immunofluorescence of members of caspase family and cFLIP(L), and caspase activity assay. It was very difficult to ultrastructurally differentiate B cells undergoing apoptosis from B cells differentiating into memory cells or plasma cells among B cells constituting GCs. Isolated B cells in GCs showed no active form of caspase-3 or TUNEL immunoreactivity, but expressed cFLIP(L). Contrary to isolated B cells, apoptotic B cells phagocytosed by macrophages exhibited immunoreactivity of the active form of caspase-3 and TUNEL, but lacked the cFLIP(L) expression. The caspase activity assay in GALTs clearly showed intense activity of caspase-3, caspase-9, and caspace-8 that was high in order. Therefore, the death receptor pathway accompanying the increased activity of caspase-3 and caspase-8 may be blocked by the expression of cFLIP(L) in B cells of GALTs. Moreover, both the activation of caspase-3 and DNA fragmentation first occur only when B cells are phagocytosed by macrophages.