2 resultados para Ischemia modified albumin
em Duke University
Resumo:
OBJECT: Chordoma cells can generate solid-like tumors in xenograft models that express some molecular characteristics of the parent tumor, including positivity for brachyury and cytokeratins. However, there is a dearth of molecular markers that relate to chordoma tumor growth, as well as the cell lines needed to advance treatment. The objective in this study was to isolate a novel primary chordoma cell source and analyze the characteristics of tumor growth in a mouse xenograft model for comparison with the established U-CH1 and U-CH2b cell lines. METHODS: Primary cells from a sacral chordoma, called "DVC-4," were cultured alongside U-CH1 and U-CH2b cells for more than 20 passages and characterized for expression of CD24 and brachyury. While brachyury is believed essential for driving tumor formation, CD24 is associated with healthy nucleus pulposus cells. Each cell type was subcutaneously implanted in NOD/SCID/IL2Rγ(null) mice. The percentage of solid tumors formed, time to maximum tumor size, and immunostaining scores for CD24 and brachyury (intensity scores of 0-3, heterogeneity scores of 0-1) were reported and evaluated to test differences across groups. RESULTS: The DVC-4 cells retained chordoma-like morphology in culture and exhibited CD24 and brachyury expression profiles in vitro that were similar to those for U-CH1 and U-CH2b. Both U-CH1 and DVC-4 cells grew tumors at rates that were faster than those for U-CH2b cells. Gross tumor developed at nearly every site (95%) injected with U-CH1 and at most sites (75%) injected with DVC-4. In contrast, U-CH2b cells produced grossly visible tumors in less than 50% of injected sites. Brachyury staining was similar among tumors derived from all 3 cell types and was intensely positive (scores of 2-3) in a majority of tissue sections. In contrast, differences in the pattern and intensity of staining for CD24 were noted among the 3 types of cell-derived tumors (p < 0.05, chi-square test), with evidence of intense and uniform staining in a majority of U-CH1 tumor sections (score of 3) and more than half of the DVC-4 tumor sections (scores of 2-3). In contrast, a majority of sections from U-CH2b cells stained modestly for CD24 (scores of 1-2) with a predominantly heterogeneous staining pattern. CONCLUSIONS: This is the first report on xenografts generated from U-CH2b cells in which a low tumorigenicity was discovered despite evidence of chordoma-like characteristics in vitro. For tumors derived from a primary chordoma cell and U-CH1 cell line, similarly intense staining for CD24 was observed, which may correspond to their similar potential to grow tumors. In contrast, U-CH2b tumors stained less intensely for CD24. These results emphasize that many markers, including CD24, may be useful in distinguishing among chordoma cell types and their tumorigenicity in vivo.
Resumo:
PURPOSE: Long-term intraocular pressure reduction by glaucoma drainage devices (GDDs) is often limited by the fibrotic capsule that forms around them. Prior work demonstrates that modifying a GDD with a porous membrane promotes a vascularized and more permeable capsule. This work examines the in vitro fluid dynamics of the Ahmed valve after enclosing the outflow tract with a porous membrane of expanded polytetrafluoroethylene (ePTFE). MATERIALS AND METHODS: The control and modified Ahmed implants (termed porous retrofitted implant with modified enclosure or PRIME-Ahmed) were submerged in saline and gelatin and perfused in a system that monitored flow (Q) and pressure (P). Flow rates of 1-50 μl/min were applied and steady state pressure recorded. Resistance was calculated by dividing pressure by flow. RESULTS: Modifying the Ahmed valve implant outflow with expanded ePTFE increased pressure and resistance. Pressure at a flow of 2 μl/min was increased in the PRIME-Ahmed (11.6 ± 1.5 mm Hg) relative to the control implant (6.5 ± 1.2 mm Hg). Resistance at a flow of 2 μl/min was increased in the PRIME-Ahmed (5.8 ± 0.8 mm Hg/μl/min) when compared to the control implant (3.2 ± 0.6 mm Hg/μl/min). CONCLUSIONS: Modifying the outflow tract of the Ahmed valve with a porous membrane adds resistance that decreases with increasing flow. The Ahmed valve implant behaves as a variable resistor. It is partially open at low pressures and provides reduced resistance at physiologic flow rates.