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We have recently shown that Matrigel-filled chambers containing fibroblast growth factor-2 (FGF2) and placed around an epigastric pedicle in the mouse were highly adipogenic. Contact of this construct with pre-existing tissue or a free adipose graft was required. To further investigate the mechanisms underpinning formation of new adipose tissue, we seeded these chambers with human adipose biopsies and human adipose-derived cell populations in severe combined immunodeficient mice and assessed the origin of the resultant adipose tissue after 6 weeks using species-specific probes. The tissues were negative for human-specific vimentin labeling, suggesting that the fat originates from the murine host rather than the human graft. This was supported by the strong presence of mouse-specific Cot-1 deoxyribonucleic acid labeling, and the absence of human Cot-1 labeling in the new fat. Even chambers seeded with FGF2/Matrigel containing cultured human stromal-vascular fraction (SVF) labeled strongly only for human vimentin in cells that did not have a mature adipocyte phenotype; the newly formed fat tissue was negative for human vimentin. These findings indicate that grafts placed in the chamber have an inductive function for neo-adipogenesis, rather than supplying adipocyte-precursor cells to generate the new fat tissue, and preliminary observations implicate the SVF in producing inductive factors. This surprising finding opens the door for refinement of current adipose tissue–engineering approaches. [ABSTRACT FROM AUTHOR]

Oxaliplatin is a medically-important platinum-based drug for treating advanced colorectal cancer, but its clinical pharmacokinetics and biotransformation are not well understood. We report the development of a reliable sample preparation procedure and a specific HPLC-ICP-MS assay for oxaliplatin and its putative active biotransformation product Pt(R,R-diaminocyclohexane)Cl2 [Pt(DACH)Cl2], and their application to the analysis of the plasma of patients undergoing a standard 2 h infusion of oxaliplatin. HPLC conditions were identified for separating intact oxaliplatin and Pt(DACH)Cl2 that were compatible with on-line detection by ICP-MS. Plasma samples were processed immediately after collection by methanol deproteinization, then stored under conditions in which the analytes of interest were stable. The linearity of calibration curves (R2 = 0.9974), intra- and inter-assay accuracy (101–107%) and precision (3.30–7.12%, n = 5), drug recovery (95–108%), and short- and long-term stability were adequate to quantify oxaliplatin. Clinical application of the assay showed that intact oxaliplatin was the major active platinum species in the plasma of colorectal cancer patients given oxaliplatin. Pt(DACH)Cl2 was undetectable in patient samples despite the HPLC-ICP-MS assay having a limit of detection of 5 nM (1.9 ppb) for this platinum species. [ABSTRACT FROM AUTHOR]