Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent.

Endothelial cell migration is an essential aspect of tumor angiogenesis. Rac1 activity is needed for cell migration in vitro implying a requirement for this molecule in angiogenesis in vivo. However, a precise role for Rac1 in tumor angiogenesis has never been addressed. Here we show that depletion of endothelial Rac1 expression in adult mice, unexpectedly, has no effect on tumor growth or tumor angiogenesis. In addition, repression of Rac1 expression does not inhibit VEGF-mediated angiogenesis in vivo or ex vivo, nor does it affect chemotactic migratory responses to VEGF in 3-dimensions. In contrast, the requirement for Rac1 in tumor growth and angiogenesis becomes important when endothelial beta3-integrin levels are reduced or absent: the enhanced tumor growth, tumor angiogenesis and VEGF-mediated responses in beta3-null mice are all Rac1-dependent. These data indicate that in the presence of alphavbeta3-integrin Rac1 is not required for tumor angiogenesis.

Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors.

Inhibitors of alpha(v)beta(3) and alpha(v)beta(5) integrin have entered clinical trials as antiangiogenic agents for cancer treatment but generally have been unsuccessful. Here we present in vivo evidence that low (nanomolar) concentrations of RGD-mimetic alpha(v)beta(3) and alpha(v)beta(5) inhibitors can paradoxically stimulate tumor growth and tumor angiogenesis. We show that low concentrations of these inhibitors promote VEGF-mediated angiogenesis by altering alpha(v)beta(3) integrin and vascular endothelial growth factor receptor-2 trafficking, thereby promoting endothelial cell migration to VEGF. The proangiogenic effects of low concentrations of RGD-mimetic integrin inhibitors could compromise their efficacy as anticancer agents and have major implications for the use of RGD-mimetic compounds in humans.

Use of Petrifilm™ 3M to Assess Coliform Numbers on Lamb Carcasses.

Petrifilm™ (6410) was used directly on lamb carcasses to enumerate coliforms. Ten sampling locations (sites) on 30 carcasses were sampled at each of four separate meat processing establishments (works). The coliform counts obtained by this technique were statistically analyzed using analysis of variance (ANOVA) to select the optimum sampling sites on the carcass and to assess the contamination of the carcass by gut flora at a particular establishment. There was a large variation between sites and between works. In general, works 3 and 4 produced cleaner carcasses than works 2, which in turn was cleaner than works 1. Since works 1, 2 and 4 used conventional dressing techniques and works 3 used the inverted dressing method, the coliform counts found at works 3 and 4 are achievable regardless of dressing technique. The coliform bacteria were most concentrated around the posterior pelvic rim and least prevalent at the carcass extremities. The posterior pelvic rim (sites 3 and 4) had higher (P<0.05) coliform counts than the exterior ventral flank area (sites 5, 6, 7 and 8), which in turn had higher (P<0.05) counts than the proximal hind and proximal fore limbs (sites 1, 2, 9 and 10) across all works. With in-line routine testing it is recommended that the majority of carcasses sampled should give coliform counts of less than 50 colony forming units (CFU)/20 cm2 for sites 4 and 8.