Thrombin up-regulated Twist mRNA and protein in all seven cell lines. Down-regulation of Twist in B16F10 tumor cell lines led to a similar to 3-fold decrease in tumor growth on a chorioallantoic membrane assay and similar to 2-fold decrease in syngencic mice. Angiogenesis was decreased similar to 45% and 36%, respectively. The effect of Twist on angiogenesis was further

examined and compared with the effect of thrombin. In studies using a Twist-inducible plasmid, several identical vascular growth factors and receptors were up-regulated similar to 2- to 3-fold in tumor cells as well as human umbilical vascular endothelial LBH589 cells by both Twist as well as thrombin (vascular endothelial growth factor, KDR, Ang-2, matrix metalloproteinase 1, GRO-alpha, and CD31). Thrombin-induced endothelial cell chemotaxis and Matrigel endothelial cell tubule formation were similarly regulated by Twist. Thus, thrombin up-regulates Twist, which is required for thrombin-induced angiogenesis as measured by endothelial cell migration, Matrigel tubule formation, and tumor angiogenesis.”
“FZR1, an activator of the anaphase-promoting complex/cyclosome (APC/C), is recognized for its roles in the mitotic cell cycle. To examine its meiotic function in females we generated an oocyte-specific

knockout of the Fzr1 gene (Fzr1(Delta/Delta)). The total number of fully grown oocytes enclosed in cumulus complexes was 35-40% lower in oocytes from Fzr1(Delta/Delta).

Ro-3306 mice and there was a commensurate rise in denuded, meiotically advanced and/or fragmented oocytes. The ability of Fzr1(Delta/Delta) oocytes to remain prophase I/germinal vesicle (GV) arrested in vitro was also compromised, despite the addition of the phosphodiesterase milrinone. Meiotic competency of smaller diameter oocytes was also accelerated by Fzr1 loss. Cyclin B1 levels were elevated similar to 5-fold in Fzr1(Delta/Delta) oocytes, whereas securin and CDC25B, two other APC/C(FZR1) substrates, were unchanged. Cyclin B1 overexpression can mimic the effects of Fzr1 loss on GV arrest and here we show that cyclin B1 knockdown in Fzr1(Delta/Delta) oocytes affects the timing of meiotic Roscovitine mouse resumption. Therefore, the effects of Fzr1 loss are mediated, at least in part, by raised cyclin B1. Thus, APC/C(FZR1) activity is required to repress cyclin B1 levels in oocytes during prophase I arrest in the ovary, thereby maintaining meiotic quiescence until hormonal cues trigger resumption.”
“Case: A 65-year-old male who was previously in good health presented to his primary care physician with increasing fatigue over several months. He was found to be anemic (hemoglobin 7.5 mg/dL) and neutropenic (absolute neutrophil count 1000/mu L). Further laboratory investigation showed an elevated erythropoietin level and normal iron stores.