Doxycycline and its quaternary ammonium derivative for adjuvant therapies of chondrosarcoma View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-09

AUTHORS

Imen Miladi, Magali Vivier, Marie-Mélanie Dauplat, Morgane Chatard, Sophie Besse, Aurélien Vidal, Karine Chassain, Betty Jean, Christiane Forestier, Jean-Michel Chezal, Francoise Rédini, Francoise Degoul, Elisabeth Miot-Noirault

ABSTRACT

PURPOSE: This study was conducted during the development of innovative treatment targeting the microenvironment of chondrosarcoma. In this context, MMP inhibitors were conjugated with a quaternary ammonium (QA) function as a targeting ligand to proteoglycans of chondrosarcoma extracellular matrix. Here we report the proof of concept of this strategy applied to the MMP13 inhibitor, doxycycline (Dox). METHODS: A quaternary ammonium derivative of the MMP13 inhibitor doxycycline (QA-Dox) was synthesized, and its anticancer activity was evaluated in the Swarm rat chondrosarcoma (SRC) model compared with the parent drug doxycycline, in vitro and in vivo. In vivo, dox and QA-Dox efficiency was assessed at equimolar doses according to a q4dx4 schedule by monitoring tumour volume by MRI and PG-targeted scintigraphy. Molecular mechanism (MMP13 expression, proteoglycan level) and histology studies were performed on tumours. RESULTS: The link of QA targeting function to Dox maintained the MMP13 inhibitory activity in vitro. Interestingly, the bacteriostatic activity was lost. SRC cells incubated with both drugs were blocked in S and G2 M phases. Tumour growth inhibition (confirmed by histology) was observed for both Dox and QA-Dox. Undesirable blood effects (leukocyte decrease) were reduced when Dox was targeted to tumour tissue using the QA function. CONCLUSIONS: In the SRC model, the MMP13 inhibitor Dox and its QA derivative are promising as adjuvant therapies for chondrosarcoma management. More... »

PAGES

517-526

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00280-017-3377-7

DOI

http://dx.doi.org/10.1007/s00280-017-3377-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1090666210

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28707014


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

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curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s00280-017-3377-7'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s00280-017-3377-7'

Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00280-017-3377-7'


 

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292 rdf:type schema:Organization
 




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