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Stem and progenitor cell-mediated tumor selective gene therapy
It is demonstrated that neural and mesenchymal stem cells can deliver therapeutic genes to elicit a significant antitumor response in animal models of intracranial glioma, medulloblastoma, melanoma brain metastasis, disseminated neuroblastoma and breast cancer lung metastasis. Expand
Efficacy of topoisomerase I inhibitors, topotecan and irinotecan, administered at low dose levels in protracted schedules to mice bearing xenografts of human tumors
Results indicate that low-dose protracted schedules of daily administration of these topoisomerase I inhibitors is either equi-effective or more efficacious than more intense shorter schedules of administration reported previously. Expand
Crystal structure of human carboxylesterase 1 complexed with the Alzheimer's drug tacrine: from binding promiscuity to selective inhibition.
HCE1's promiscuous action on distinct substrates is enhanced by its ability to interact with ligands in multiple orientations at once, and this structure is used to identify tacrine derivatives that act as low-micromolar inhibitors of hCE1 and may provide new avenues for treating narcotic abuse and cholesterol-related diseases. Expand
The anticancer prodrug CPT-11 is a potent inhibitor of acetylcholinesterase but is rapidly catalyzed to SN-38 by butyrylcholinesterase.
Modeling of CPT-11 within the predicted active site of AcChE and BuChE corroborated experimental results indicating that, although the drug was oriented correctly for activation, the constraints dictated by the active site gorge were such that C PT-11 would be unlikely to be activated by AcE. Expand
P53 mutation and MDM2 amplification frequency in pediatric rhabdomyosarcoma tumors and cell lines.
The response to treatment of patients with tumors wild- type for p53 and without MDM2 amplification was quite varied, indicating that expression of a wild-type p53 gene at diagnosis cannot always facilitate a favorable outcome. Expand
Carboxylesterase-mediated sensitization of human tumor cells to CPT-11 cannot override ABCG2-mediated drug resistance.
It is indicated that overexpression of ABCG2 in vivo would probably overcome any increased drug activation that might be achieved by gene delivery or antibody-directed enzyme prodrug therapy methods using rCE. Expand
Altered catalytic activity of and DNA cleavage by DNA topoisomerase II from human leukemic cells selected for resistance to VM-26.
The data support the hypothesis that the simultaneous development of resistance to the cytotoxic effects of several classes of natural product anticancer drugs, after exposure to only one of these agents, is due to an alteration in topoisomerase II or in a factor modulating its activity. Expand
Structural insights into CPT-11 activation by mammalian carboxylesterases
The crystallographic observation of a leaving group bound on the surface of rCE supports the 'back door' product exit site proposed for the acetylcholinesterases. Expand
Overexpression of a rabbit liver carboxylesterase sensitizes human tumor cells to CPT-11.
CPT-11 [7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin ] is a prodrug that is converted to the active metabolite SN-38 by carboxylesterases. In its active form, the drug inhibitsExpand
Comparison of activation of CPT-11 by rabbit and human carboxylesterases for use in enzyme/prodrug therapy.
Rabbit carboxylesterase/CPT-11 may be a useful enzyme/prodrug combination for activating the prodrug 7-ethyl-10-[4-(1-piper-idino)-1- piperidino]carbonyloxycamptothe cin (CPT -11). Expand