Imatinib has a fatal impact on morphology, pairing stability and survival of adult Schistosoma mansoni in vitro

Beckmann, Svenja; Grevelding, Christoph G.

doi:10.1016/j.ijpara.2010.01.007

Cited by 83 publications

(114 citation statements)

References 22 publications

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“…Co-immunoprecipitation experiments confirmed direct interactions between both kinases (13). First database analyses comparing SmTK6 with two recently detected Abl kinases from schistosomes suggested that SmTK6 may represent an Src-/Abl-like hybrid kinase (18).…”

mentioning

confidence: 55%

Characterization of the Src/Abl Hybrid Kinase SmTK6 of Schistosoma mansoni

Beckmann

Hahnel

Cailliau

et al. 2011

Journal of Biological Chemistry

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Background: SmTK6 was identified as interaction partner of SmTK4. Results: SmTK6 is a Src/Abl hybrid kinase and interacts also with the uncommon SmVKR1 and SmTK3. Conclusion: SmTK6 is suggested to be part of a complex of receptors, Syk and Src kinases, which are involved in gonad development. Significance: SmTK6 represents an Abl kinase progenitor, for which a function in reproduction could be assigned.

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confidence: 55%

Characterization of the Src/Abl Hybrid Kinase SmTK6 of Schistosoma mansoni

Beckmann

Hahnel

Cailliau

et al. 2011

Journal of Biological Chemistry

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“…vitro and in prevention of fibrosis in vivo in a mouse model of schistosomiasis (9,15), showed a significant increase in release of AP (Fig. 3) and PGI (Fig.…”

Section: Resultsmentioning

confidence: 95%

“…The widespread use and availability of these drugs in most regions of endemicity and their relatively low toxicity make them attractive new anticestode drugs. Imatinib, a tyrosine kinase inhibitor, has been previously demonstrated to have activity in vitro against Schistosoma mansoni, which encodes a tyrosine kinase in its genome (9,15). This drug has also been reported to have activity against the filarial parasite Brugia malayi (S. Bennuru, Laboratory of Parasitic Diseases, NIAID, personal communication).…”

Section: Discussionmentioning

confidence: 99%

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Quantitative Screening for Anticestode Drugs Based on Changes in Baseline Enzyme Secretion by Taenia crassiceps

Mahanty

Madrid²,

Nash

2013

Antimicrob Agents Chemother

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Neurocysticercosis (NCC), an infection of the brain with the larval stage of the Taenia solium tapeworm, is responsible for an estimated one-third of adult-onset epilepsy cases in regions of the world where it is endemic. Currently, anthelmintic drugs used for treatment of NCC are only partially effective, and there is, therefore, a pressing need for new therapeutic agents. Discovery of new anthelmintics with activity against T. solium has been limited by the lack of suitable sensitive assays that allow highthroughput screening. Using an in vitro culture system with Taenia crassiceps metacestodes, we demonstrate that changes in secretion of parasite-associated alkaline phosphatase (AP) and phosphoglucose isomerase (PGI) can be used to detect and quantify anthelmintic effects of praziquantel (PZQ), a drug with activity against T. solium. We applied two enzyme release assays to screen for anti-T. crassiceps activity in nonconventional antiparasitic drugs and demonstrate that nitazoxanide and artesunate induced release of both AP and PGI in differing time-and dose-related patterns. Furthermore, imatinib, a tyrosine kinase inhibitor previously reported to have parasiticidal activity against Schistosoma mansoni, also induced release of both AP and PGI in a dose-dependent manner, similar in pattern to that observed with the other anthelmintics. We also evaluated release of ATP into cyst supernatants as an indicator of drug effects but did not see any differences between treated and untreated cysts. These data provide the basis for rapid and quantitative screening assays for testing for anthelmintic activity in candidate anticestode agents.

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“…By this latter approach, which has been termed "piggy-backing" (Dissous & Grevelding 2011), anti-cancer drugs, such as imatinib, that target protein kinases, can be used as lead compounds for treating schistosomes since they express orthologues of the target proteins. Indeed, imatinib has been shown to kill adult schistosomes in vitro and, prior to parasite death, the drug affects morphology and causes separation of worm couples (Beckmann & Grevelding 2010). Our approach is similar, since we propose to consider schistosomes themselves as cancerous growths: they have an intense metabolic activity and a high rate of cell division (for the production of eggs by female worms) that is outside the control of the host.…”

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confidence: 99%