UNIGE document Scientific Article
previous document  unige:19540  next document
add to browser collection
Title

Synergetic bitherapy in mice with xenografts of human prostate cancer using a methional mimic (METLICO) and an aldehyde dehydrogenase 3 inhibitor (MATE): systemic intraperitoneal (IP) and targeted intra-tumoral (IT) administration

Authors
Hiltbrand, E.
Fournet, G.
Giliberto, J-P
Paret, M-J
Chantepie, J.
Gore, J.
Reichert, U.
show hidden authors show all authors [1 - 11]
Published in Current Medicinal Chemistry. 2009, vol. 16, no. 10, p. 1184-1191
Abstract An intraperitoneal (IP) monotherapy in nu/nu mice with subcutaneous xenografts of a human prostate epithelial cancer cell line:DU145 was undertaken with an aldehyde dehydrogenase 3 inhibitor MATE, that is a potent apoptogen on (DU145) in culture but not on their human prostate epithelial normal counterparts [13] . Tumour growth was slowed down but treatment had to be done 5days/week. To try to potentiate the action of MATE in vivo, a bitherapy was undertaken based on the synergetic apoptotic effect that had been observed previously in culture on DU145 treated with a methional mimic METLICO and DIMATE, an inhibitor of ALDH1 and ALDH3 [19]. The bitherapy with METLICO/MATE administered IP was as effective as the monotherapy with MATE alone by IP, but at a 2-fold lower dose of MATE and at a dose of METLICO that had no growth-inhibitory effect as a monotherapy . Hence there was definite synergism with bitherapy. To try to increase the efficacy of bitherapy, it was administered by the intra-tumoral (IT) route using the recently developed 20-bars-pressurized microinjection system from CERMA [16, 17]. IT administration of the bitherapy was indeed more effective than that by IP as regards tumour volumes are concerned. Histopathological analysis of IT-treated tumours confirmed that there were many necrotized zones but intact cells were still present. Approaches for treating a wider zone of tumour tissue by IT-bitherapy are discussed.
Keywords Aldehyde Dehydrogenase/*antagonists & inhibitorsAldehydes/administration & dosage/*chemistry/therapeutic useAnimals*BiomimeticsCombined Modality TherapyDrug Delivery SystemsEnzyme Inhibitors/administration & dosage/chemistry/*therapeutic useFemaleHumansInjections, IntralesionalInjections, IntraperitonealMaleMiceMice, NudeMolecular StructureMorpholines/chemistry/*therapeutic useProstatic Neoplasms/*drug therapy/pathologyQuinazolines/chemistry/*therapeutic useTumor Burden
Identifiers
PMID: 19355878
Full text
This document has no fulltext available yet, but you can contact its author by using the form below.
Structures
Citation
(ISO format)
HILTBRAND, E. et al. Synergetic bitherapy in mice with xenografts of human prostate cancer using a methional mimic (METLICO) and an aldehyde dehydrogenase 3 inhibitor (MATE): systemic intraperitoneal (IP) and targeted intra-tumoral (IT) administration. In: Current Medicinal Chemistry, 2009, vol. 16, n° 10, p. 1184-1191. https://archive-ouverte.unige.ch/unige:19540

143 hits

0 download

Update

Deposited on : 2012-04-23

Export document
Format :
Citation style :