Flexible heteroarotinoid (Flex-Het) SHetA2 inhibits angiogenesis in vitro and in vivo

Flexible heteroarotinoids (Flex-Hets) compounds regulate growth, differentiation and apoptosis in cancer cells. The hypothesis of this study was that the lead Flex-Het, SHetA2, inhibits angiogenesis by blocking cytokine release from cancer cells. SHetA2 altered secretion of thrombospondin-4 (TSP-4), vascular endothelial growth factor A (VEGF) and fibroblast growth factor (bFGF) proteins from normal and cancerous ovarian and renal cultures. Thymidine phosphorylase (TP) expression was inhibited in cancer, but not normal cultures. Endothelial tube formation was stimulated by conditioned media from cancer but not normal cultures, and SHetA2 reduced secretion of this angiogenic activity. SHetA2 directly inhibited endothelial cell tube formation and proliferation through G1 cell cycle arrest, but not apoptosis. Recombinant TP reversed SHetA2 anti-angiogenic activity. SHetA2 inhibition of in vivo angiogenesis was observed in Caki-1 renal cancer xenografts. In conclusion, SHetA2 inhibits angiogenesis through alteration of angiogenic factor secretion by cancer cells and through direct effects on endothelial cells

Critical-Sized Bone Defects: Sequence and Planning.

Bone defects associated with open fractures require a careful approach and planning. At initial presentation, an emergent irrigation and debridement is required. Immediate definitive fixation is frequently safe, with the exception of those injuries that normally require staged management or very severe type IIIB and IIIC injuries. Traumatic wounds that can be approximated primarily should be closed at the time of initial presentation. Wounds that cannot be closed should have a negative pressure wound therapy dressing applied. The need for subsequent debridements remains a clinical judgment, but all nonviable tissue should be removed before definitive coverage. Cefazolin remains the standard of care for all open fractures, and type III injuries also require gram-negative coverage. Both induced membrane technique with staged bone grafting and distraction osteogenesis are excellent options for bony reconstruction. Soft tissue coverage within 1 week of injury seems critical