The aim of this study was to investigate the influence of folylpolyglutamyl synthetase (FPGS) activity on the cellular pharmacology of the classical antifolates raltitrexed and methotrexate (MTX) using two human leukemia cell lines, CCRF-CEM and CCRF-CEM:RC2Tomudex. Cell growth inhibition and drug-induced inhibition of de novo thymidylate and purine biosynthesis were used as measures of the cel...

Human APOBEC3G inhibits the replication of Vif-deficient HIV-1 by hypermutating nascent viral cDNA (reviewed in [1– 3]). Zheng and colleagues recently reported that the HIV-1 restriction activity of APOBEC3G requires a cellular co-factor [4]. Their conclusion depended on three critical observations: i) CEM-T4 cells support the replication of Vif-deficient HIV-1, ii) CEM-T4 cells express restric...

The central amygdala (Ce), particularly its medial sector (CeM), is the main output station of the amygdala for conditioned fear responses. However, there is uncertainty regarding the nature of CeM control over conditioned fear. The present study aimed to clarify this question using unit recordings in rats. Fear conditioning caused most CeM neurons to increase their conditioned stimulus (CS) re...

P-glycoprotein (Pgp) mediates drug accumulation defects in malignant cells in vitro. It confers resistance to multiple drugs including paclitaxel, an agent useful in treating malignancies including acute leukemia. Pgp-mediated drug resistance appears to be due to primary active drug-transport as well as other effects on membrane permeability, but the relative contribution of each is unclear. Fl...

We have shown that a glycoprotein(s) with a molecular weight of —180,000 exists on the surface of cultured lymphoblasts selected for resistance to vinblastine (VLB) (CEM/VLB100). The amount of this glycoprotein, which is barely detectable on the VLB-sensitive cells (GEM), appears to be related in part to the degree of resistance, up to -270-fold. Exposure of cells to Pronase for 45 to 60 min ...

The administration of CycloSaligenyl 3'-azido-2',3'-dideoxythymidine monophosphate (CycloSal-AZTMP) to CEM cells resulted in a concentration- and time-dependent conversion to the 5'-monophosphate (AZTMP), 5'-diphosphate (AZTDP), and 5'-triphosphate (AZTTP) derivatives. High ratios of AZTMP/AZTTP were found in the CEM cell cultures treated with CycloSal-AZTMP. The intracellular T(1/2) of AZTTP i...

Multidrug resistance is a major obstacle to the success of cancer chemotherapy. The multidrug resistance-associated protein (MRP) has been shown to confer multidrug resistance. To study MRP gene expression at the transcriptional level, we have fused the MRP gene promoter with the luciferase reporter gene and studied its regulation. Cotransfection of MRP promoter constructs with p53 expression p...

Abstract This paper describes the collaborative project between National Research Council of Canada (NRC) and Centro Español de Metrología (CEM) for construction comparison high temperature fixed points (HTFPs). A hybrid-type crucible that uses piston method filling has been jointly developed. series 12 point blackbodies (HTFPBBs) have constructed, including Cu, Ru-C, Ir-C, Re-C WC-C covering r...

Reverse-phase microarray assays using phospho-specific antibodies (RPPA) can directly measure levels of phosphorylated protein isoforms. In the current study, lysates from parental and multidrug resistant (MDR) CEM leukemia cells were spotted onto reverse-phase protein microarrays and probed with a panel of phospho-antibodies to ERK, PCK and Akt pathways. In particular, the Akt pathway is consi...

In vivo efficacy testing of monoclonal antibody-based drugs specific for human leukemias is hampered by the paucity of suitable animal models, due in part to the inability of many anti-human monoclonal antibodies to cross-react with antigens expressed in animal tissues or cells. Moreover, human leukemic cells have proven difficult to establish in immunosuppressed mice except as solid tumors. We...