title: Effects of in vitro exposure of Echinococcus multilocularis metacestodes to cytostatic drugs on in vivo growth and proliferation of the parasite.
abstract: The cytostatic drugs Vincristine (VCR), Navelbine (NAV), and Methotrexate (MTX) were evaluated for their growth inhibitory potential against metacestodes of Echinococcus multilocularis (Em) by in vitro and in vivo assays. In vitro cultures of E. multilocularis were exposed to IC 90, IC 80, and IC 5 concentrations of VCR, NAV, or MTX for 1 week, then parasite tissue cultures were kept for 1 week without drug exposure in vitro, and thereafter, metacestode tissues were injected intra-peritoneally into Meriones unguiculatus. Metacestode growth was monitored for several months post-infection (p.i.) by body weight control, magnetic resonance imaging (MRI), and autopsy at 5 months p.i. Weight monitoring of infected M. unguiculatus did not provide conclusive evidence for Em-metacestode growth, while MRI could detect growing Em-metacestode in the MTX-treated group at 8 weeks (p.i.), whereas metacestodes exposed to VCR and NAV were at 17 weeks (p.i.) detectable. MRI disclosed progressive and massive growth of Em-metacestode in the VCR- and MTX-exposed groups, while the NAV-pretreated Em-metacestodes' volume did not exceed 4 cm(3). At autopsy, Em-metacestodes of less than 4 cm(3) were found in infected M. unguiculatus, which was not detected by MRI. In summary, the cytostatic drugs Methotrexate, Navelbine, and Vincristine--as applied in the present work--did not show parasitocidal or clear parasitostatic effects on metacestodes of E. multilocularis. While parasite growth in vivo was inhibited in NAV- and VCR-pretreated Em-metacestodes, MTX pretreatment seemed to enhance parasite proliferation. Magnetic resonance imaging appears suitable to monitor in vivo the effects of drugs on growth progression and regression only of larger Em-metacestode tissues.
authors.affiliation: Institute for Tropical Medicine, University Clinics of Tübingen, Wilhelmstrasse. 27, 72074, Tübingen, Germany.
authors.forename: Cora
authors.initials: C
authors.lastname: Hübner
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiehr
authors.forename: Lars
authors.initials: L
authors.lastname: Kocherscheidt
authors.forename: Hans
authors.initials: H
authors.lastname: Wehrl
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
authors.forename: Andreas
authors.initials: A
authors.lastname: Schmid
authors.forename: Peter
authors.initials: P
authors.lastname: Kern
authors.forename: Peter T
authors.initials: PT
authors.lastname: Soboslay
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001344:Autopsy; D001835:Body Weight; D054697:Cytostatic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004443:Echinococcosis / Q000469:parasitology / Q000473:pathology; D048210:Echinococcus multilocularis / Q000187:drug effects* / Q000254:growth & development*; D005260:Female; D005849:Gerbillinae / Q000469:parasitology; D008279:Magnetic Resonance Imaging; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D014747:Vinblastine / Q000031:analogs & derivatives / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology; D000077235:Vinorelbine
chemical_list: D000871:Anthelmintics; D054697:Cytostatic Agents; D014750:Vincristine; D014747:Vinblastine; D000077235:Vinorelbine; D008727:Methotrexate
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