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Author Notes:

Address correspondence to this author at the Department of Pediatrics, Laval University, Québec, QC, Canada; Tel: (418) 656-4141; Fax: (418) 654-2753; E-mail: deepak.kamnasaran@crchul.ulaval.ca

We thank Dr. Kam Kamnasaran for comments on this manuscript; Dr. Manjit Rana for technical assistance; Drs. Michael Bobola (University of Washington, USA), and Chris Jones (Institute for Cancer Research, UK) for providing all cell lines used in this study.

The authors have none to declare.

Subject:

Research Funding:

This work is supported by a Doctorate Scholarship to NFA from FRSQ, and grants to DK from the CHUQ Foundation, Fondation des étoiles, Canadian Foundation for Innovation, Laval University Faculty of Medicine Foundation, Natural Sciences and Engineering Research Council, and Fonds de la recherche en santé du Québec, and to HCJ from the National Institutes of Health. DK is a FRSQ scholar.

Keywords:

  • Pediatric astrocytomas
  • apoptosis
  • drug discovery
  • gene expression
  • microtubules
  • molecular therapeutics

Investigation of Targetin, a Microtubule Binding Agent which Regresses the Growth of Pediatric High and Low Grade Gliomas.

Tools:

Journal Title:

Journal of Pediatric Oncology Nursing

Volume:

Volume 1

Publisher:

, Pages 32-40

Type of Work:

Article | Final Publisher PDF

Abstract:

BACKGROUND: Pediatric gliomas, the most common solid childhood neoplasm, manifest unique molecular signatures that distinguish them from adult gliomas. Unfortunately, most studies have focused on adult gliomas and extrapolate the findings to treat pediatric gliomas. In this study, we assessed the efficacy of Targetin, a folate conjugated analogue of Noscapine, on the treatment of pediatric low and high grade gliomas. METHOD: An assortment of standard cancer assays were used with different drug doses and experimental durations. RESULTS: We found that pediatric glioma cells are more susceptible to lower doses of Targetin than parental Noscapine. Targetin functions by disrupting the microtubule network, and can likewise perturb DNA synthesis, delay the cellular transition within the S and G2M cell cycle phases, diminish anchorage independent growth and the migratory/invasiveness of pediatric glioma cells. Moreover, Targetin impairs the expression of several regulators of cancer progression belonging to prominent signalling pathways in pediatric gliomas; including Platelet Derived Growth Factor alpha and some members of the Mitogen Activated Protein Kinase cascade. CONCLUSION: Targetin has an excellent anti-neoplastic profile and functions to modulate the expression of several genes belonging to key cancer progression pathways in pediatric gliomas. Collectively, findings from this study highlight the usefulness of Targetin for the treatment of pediatric high and low grade gliomas.

Copyright information:

© 2013 Pharma Professional Services

This is an Open Access work distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/).

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