title: Investigation of Targetin, a Microtubule Binding Agent which Regresses the Growth of Pediatric High and Low Grade Gliomas.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Laval University, Québec, Québec, G1V 4G2, Canada.
authors.forename: Norbert F
authors.initials: NF
authors.lastname: Ajeawung
authors.affiliation: Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Harish C
authors.initials: HC
authors.lastname: Joshi
authors.affiliation: Department of Pediatrics, Laval University, Québec, Québec, G1V 4G2, Canada.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kamnasaran
keywords: Pediatric astrocytomas; apoptosis; drug discovery; gene expression; microtubules; molecular therapeutics
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