Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

P-glycoprotein (P-gp) is an important multidrug resistance (MDR) regulator for leukemia to mediate its development and thus can be considered as a powerful reference for the diagnosis of MDR. The detection of P-gp is of vital significance and has attracted considerable concerns. In this study, we proposed a surface-enhanced Raman scattering (SERS) method for the evaluation of P-gp expression levels in leukemia cell lines. Basically, we utilized an aqueous phase sandwich-type immunoassay to analyze the expression of P-gp. First, anti-CD45-decorated magnetic beads (MBs) and P-gp antibody-decorated SERS probes were fabricated. CD45 is a common protein expressed in all leukemia cells. As a result, a sandwich immunocomplex can be formed by the MBs, P-gp-overexpressed leukemia cells, and SERS probes. The expression level of P-gp determines the amount of SERS probes that can be captured. Consequently, the SERS intensity of the immunocomplex can be used to evaluate the expression level of P-gp. In a typical procedure, we measured the P-gp expression of an MDR leukemia cell line (K562/ADM) as well as unprocessed whole-blood samples. The SERS intensity of K562/ADM cells was highly correlated with the extent of MDR or the incubation time of adriamycin (which is an MDR inducing drug). In addition, the SERS intensity of the refractory/relapsing group was about sixfolds of that of the control group ( P < 0.01). These results demonstrated that the proposed method holds excellent sensitivity, specificity, reliability, and application potential in assessing both cultured cells and clinical samples. With these outstanding features, we anticipated that such a SERS-based method could be very helpful for the clinical diagnosis of early-stage MDR in leukemia.
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PMID:Evaluation of Multidrug Resistance of Leukemia Using Surface-Enhanced Raman Scattering Method for Clinical Applications. 2999 49

Human culture-expanded mesenchymal stromal cells (MSC) are being considered for multiple therapeutic applications because of their regenerative and anti-inflammatory properties. Although a large number of MSC can be propagated from a small initial sample, several lines of evidence indicate that MSC lose their immunosuppressive and regenerative potency aftaer multiple passages. In this report, we use the FACSCAP Lyoplate proteomic analysis system to detect changes in cell surface protein expression of CD45- /CD31- /CD34- /CD73+ /CD105+ stromal cells in unpassaged bone marrow (BM) and through 10 serial culture passages. We provide for the first time a detailed characterization of native unpassaged BM MSC (0.08% of BM mononuclear cells) as well as the changes that occur during the initial expansion. Adipogenic and osteogenic differentiative potential was determined though the serial passages and correlated with immunophenotypic changes and senescence. Among the most prominent were striking decreases in Fas ligand, CD98, CD205, and CD106, accompanied by a gain in the expression of CD49c, CD63, CD98, and class 1 and class 2 major histocompatibility complex (MHC) molecules. Other molecules that are down-modulated with later passage include CD24, CD54, CD59, CD243/P-glycoprotein, and CD273/PD-L2. Early senescence, as defined by the loss of replicative capacity occurring with the loss of differentiative capacity, increase in CDKN2A p16, and increased time to confluence, was accompanied by loss of the motility-associated metalloproteinase CD10 and the proliferation-associated transferrin receptor CD71. Among the strongest statistical associations were loss of MAC-inhibitory protein/CD59, loss of ICAM-1/CD54, and increase in CDKN2A as a function of increasing passage, as well as increased CD10 expression with adipogenic and osteogenic capacities. The data provide a clear set of markers that can be used to assess MSC quality. We suggest that clinically relevant numbers of highly functional low passage MSC can be manufactured starting with large quantities of BM, which are readily available from cadaveric organ donors.
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PMID:Proteomic Profiling of Native Unpassaged and Culture-Expanded Mesenchymal Stromal Cells (MSC). 3021 67


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