RESUMO
The use of acellular dermal matrices (ADMs) in breast reconstruction is a controversial topic. Recent literature has investigated the effects of ADM sterilization on infectious complications, although with varying conclusions. Previous work by our group showed no difference between aseptic and sterilized products immediately out of the package. In this study, we investigate the microbiologic profiles of these agents after implantation. METHODS: In this prospective study, we cultured samples of ADM previously implanted during the first stage of tissue expander-based immediate breast reconstruction. A 1 cm2 sample was excised during the stage II expander-implant exchange procedure, and samples were incubated for 48 hours in tryptic soy broth. Samples with growth were further cultured on tryptic soy broth and blood agar plates. Patient records were also analyzed, to determine if ADM sterilization and microbial growth were correlated with infectious complications. RESULTS: In total, 51 samples of ADM were collected from 32 patients. Six samples were from aseptic ADM (AlloDerm), 27 samples were from ADM sterilized to 10-3 (AlloDerm Ready-to-Use), and 18 samples were from products sterilized to 10-6 (AlloMax). No samples demonstrated bacterial growth. Only 5 patients experienced postoperative complications, of whom only 1 patient was infectious in nature. We failed to demonstrate a statistically significant correlation between sterility and postoperative complications. CONCLUSIONS: Our findings showed no difference in microbial presence and clinical outcomes when comparing ADM sterility. Furthermore, no samples demonstrated growth in culture. Our study brings into question the necessity for terminal sterilization in these products.
RESUMO
The present study sought to determine the anti-tumor effects of OXA-11, a potent, novel small-molecule amino pyrimidine inhibitor (1.2 pM biochemical IC(50)) of focal adhesion kinase (FAK). In studies of cancer cell lines, OXA-11 inhibited FAK phosphorylation at phospho-tyrosine 397 with a mechanistic IC(50) of 1 nM in TOV21G tumor cells, which translated into functional suppression of proliferation in 3-dimensional culture with an EC(50) of 9 nM. Studies of OXA-11 activity in TOV21G tumor-cell xenografts in mice revealed a pharmacodynamic EC(50) of 1.8 nM, indicative of mechanistic inhibition of pFAK [Y397] in these tumors. OXA-11 inhibited TOV21G tumor growth in a dose-dependent manner and also potentiated effects of cisplatin on tumor cell proliferation and apoptosis in vitro and on tumor growth in mice. Studies of pancreatic neuroendocrine tumors in RIP-Tag2 transgenic mice revealed OXA-11 suppression of pFAK [Y397] and pFAK [Y861] in tumors and liver. OXA-11 given daily from age 14 to 17 weeks reduced tumor vascularity, invasion, and when given together with the anti-VEGFR-2 antibody DC101 reduced the incidence, abundance, and size of liver metastases. Liver micrometastases were found in 100 % of mice treated with vehicle, 84 % of mice treated with OXA-11, and 79 % of mice treated with DC101 (19-24 mice per group). In contrast, liver micrometastases were found in only 52 % of 21 mice treated with OXA-11 plus DC101, and those present were significantly smaller and less numerous. Together, these findings indicate that OXA-11 is a potent and selective inhibitor of FAK phosphorylation in vitro and in vivo. OXA-11 slows tumor growth, potentiates the anti-tumor actions of cisplatin and--when combined with VEGFR-2 blockade--reduces metastasis of pancreatic neuroendocrine tumors in RIP-Tag2 mice.
