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RHPS4 G-Quadruplex Ligand Induces Anti-Proliferative Effects in Brain Tumor Cells

Background Telomeric 3′ overhangs can fold into a four-stranded DNA structure termed G-quadruplex (G4), a formation which inhibits telomerase. As telomerase activation is crucial for telomere maintenance in most cancer cells, several classes of G4 ligands have been designed to directly disrupt telomeric structure. Methods We exposed brain tumor cells to the G4 ligand ...

Pediatric high-grade glioma: identification of poly(ADP-ribose) polymerase as a potential therapeutic target

Pediatric high-grade gliomas (World Health Organization grades III and IV astrocytomas) remain tumors with a very poor prognosis for which novel therapeutic strategies are needed. Poly(ADP-ribose) polymerase (PARP) is known to have multiple functions in tumors, including single-strand DNA repair and induction of caspase-independent apoptosis. PARP has been suggested as a ...

CD105 (Endoglin) exerts prognostic effects via its role in the microvascular niche of paediatric high grade glioma

Paediatric high grade glioma (pHGG) (World Health Organisation astrocytoma grades III and IV) remains poor prognosis tumours, with a median survival of only 15 months following diagnosis. Current investigation of anti-angiogenic strategies has focused on adult glioblastoma multiforme (GBM) with phase III trials targeting vascular endothelial growth factor continuing. In this study ...

Recapitulation of Tumor Heterogeneity and Molecular Signatures in a 3D Brain Cancer Model with Decreased Sensitivity to Histone Deacetylase Inhibition

Introduction Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated using the 3D Rotary Cell Culture System (RCCS). Methods CNS cancer cell lines were grown in conventional 2D cultures and the RCCS and ...

Adjuvant Chemotherapy for Brain Tumors Delivered via a Novel Intra-Cavity Moldable Polymer Matrix

IntroductionPolymer-based delivery systems offer innovative intra-cavity administration of drugs, with the potential to better target micro-deposits of cancer cells in brain parenchyma beyond the resected cavity. Here we evaluate clinical utility, toxicity and sustained drug release capability of a novel formulation of poly(lactic-co-glycolic acid) (PLGA)/poly(ethylene glycol) ...


POLYMER PASTE DELIVERED INTERSTITIALLY Toby W.A. Gould, Cheryl V. Rahman, Stuart J. Smith, David A. Barrett, Kevin M. Shakesheff, Richard G. Grundy, and Ruman Rahman; University of Nottingham, Nottingham


Stuart J. Smith, Ruman Rahman, Cheryl Rahman, Jennifer Barrow, Donald Macarthur, Felicity Rose, and Richard G. Grundy; University of Nottingham, Nottingham, United Kingdom INTRODUCTION: We present a novel