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Metabolism of MPTP by cytochrome P4502D6 and the demonstration of 2D6 mRNA in human foetal and adult brain by in situ hybridization.
It is demonstrated that MPTP N-demethylation, a detoxification pathway, is catalysed by cytochrome P450 CYP2D6 and up to 40% of the hepatic metabolism is mediated by this enzyme, indicating that 2D6-mediated detoxification will occur in target cells. Expand
Functional co-expression of CYP2D6 and human NADPH-cytochrome P450 reductase in Escherichia coli.
The polymorphic human CYP2D6 has been co-expressed with human NADPH-cytochrome P450 oxidoreductase in Escherichia coli in order to generate a functional recombinant monooxygenase system for the study of xenobiotic metabolism, and intact E. coli cells, even in the absence of exogenous NADPH, were able to metabolize bufuralol at rates almost as high as those measured in membranes. Expand
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a substrate of cytochrome P450 2D6: allosteric effects of NADPH-cytochrome P450 reductase.
Observations show that NADPH-cytochrome P450 reductase has an allosteric effect on the active site of cyto chrome P450 2D6 that affects the binding of some substrates but not others. Expand
The Role of Extracellular Spacer Regions in the Optimal Design of Chimeric Immune Receptors: Evaluation of Four Different scFvs and Antigens
Results show that a spacer is not necessary for optimal activity of CIRs but that the optimal design varies, and interestingly, mapping of the scFV epitopes has revealed that the anti-CEA scFv binds close to the amino-terminal of CEA, which is easily accessible to the CIR. Expand
Frequency of regulatory T cells in renal cell carcinoma patients and investigation of correlation with survival
The early follow up data show an association between higher peripheral blood regulatory T-cell count and adverse overall survival and provide impetus to further investigate modulation of TReg activity in RCC patients as part of therapy. Expand
Functional high level expression of cytochrome P450 CYP2D6 using baculoviral expression systems.
Cytochrome P-450 CYP2D6 plays a central role in the metabolism of many widely used therapeutic drugs including beta-adrenergic antagonists, antiarrhythmics, and tricyclic antidepressants. RecombinantExpand
O6-Methylguanine-DNA methyltransferase inactivation and chemotherapy.
Tissue- and tumour-specific approaches to the modulation of MGMT together with other DNA repair functions and in combination with immuno- or radiotherapy are promising strategies to improve alkylating agent therapy. Expand
The Optimal Antigen Response of Chimeric Antigen Receptors Harboring the CD3ζ Transmembrane Domain Is Dependent upon Incorporation of the Receptor into the Endogenous TCR/CD3 Complex
Results indicate that CARs containing the CD3ζ transmembrane domain can form a complex with the endogenous TCR that may be beneficial for optimal T cell activation. Expand
Building better chimeric antigen receptors for adoptive T cell therapy.
A structural overview of CAR development is provided and possible reasons for conflicting results are identified in the hope that this information will inspire future rational design strategies for optimal tumour targeting using CARs. Expand
Targeted immunotherapy of cancer with CAR T cells: achievements and challenges
This review will summarize the concept of CAR-based immunotherapy and recent clinical trial activity and will further discuss some of the likely future challenges facing CAR-modified T cell therapies. Expand