Abstract: INTRODUCTION: To report a case of increases in vancomycin concentrations without additional vancomycin doses being given. CASE STUDY: A 64 year-old morbidly obese female received three total doses of vancomycin for surgical prophylaxis and for ventilator-associated pneumonia. Subsequent vancomycin concentrations from the patient's central venous catheter (CVC) demonstrated increasing drug levels from 27.1 to 45.9mcg/mL despite no additional vancomycin being given and proper line flushing prior to sample collection. There is no clear explanation for the increase in the patient's vancomycin concentration. Drug leaching from the CVC, enterohepatic recycling, drug redistribution from adipose or other tissues, and assay cross-reactivity with other medications are all potential explanations for the increased vancomycin concentrations. CONCLUSION: This case report describes an unexplained increase in vancomycin concentrations and reinforces both the fallibility of laboratory testing and that unusual circumstances do occur. Several potential causes are hypothesised with CVC drug leaching being the most likely. Nurses and other healthcare providers with similar scenarios should consider a peripheral blood sample to rule out the potential for CVC drug leaching as a possible explanation.

Abstract: Glioblastoma multiforme is a common malignant brain tumor that portends extremely poor patient survival. Recent studies reveal that glioma stem-like cells (GSC) are responsible for glioblastoma multiforme escape from chemo-radiotherapy and mediators of tumor relapse. Previous studies suggest that AEG-1 (MTDH), an oncogene upregulated in most types of cancers, including glioblastoma multiforme, plays a focal role linking multiple signaling pathways in tumorigenesis. We now report a crucial role of AEG-1 in glioma stem cell biology. Primary glioblastoma multiforme cells were isolated from tumor specimens and cultured as neurospheres. Using the surface marker CD133, negative and positive cells were separated as nonstem and stem populations by cell sorting. Tissue samples and low passage cells were characterized and compared with normal controls. Functional biological assays were performed to measure stemness, self-renewal, differentiation, adhesion, protein-protein interactions, and cell signaling. AEG-1 was upregulated in all glioblastoma multiforme neurospheres compared with normal neural stem cells. Expression of AEG-1 was strongly associated with stem cell markers CD133 and SOX2. AEG-1 facilitated beta-catenin translocation into the nucleus by forming a complex with LEF1 and beta-catenin, subsequently activating Wnt signaling downstream genes. Through an AEG-1/Akt/GSK3beta signaling axis, AEG-1 controlled phosphorylation levels of beta-catenin that stabilized the protein. IMPLICATIONS: This study discovers a previously unrecognized role of AEG-1 in GSC biology and supports the significance of this gene as a potential therapeutic target for glioblastoma multiforme. Mol Cancer Res; 15(2); 225-33. (c)2016 AACR.