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View the Table of Contents for the February 2008 issue of Molecular Cancer Therapeutics
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Among children with refractory neuroblastoma novel strategies are needed to improve survival. High vascular density within neuroblastoma is associated with advanced disease. Beaudry and colleagues carried out dual targeting of neuroblastoma tumor cells and tumor endothelium with ZD6474, a small molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 (VEGFR2) and RET. ZD6474 inhibited the phosphorylation of RET in neuroblastoma cells and decreased the viability of neuroblastoma cell lines. In xenografts, ZD6474 potently inhibited tumor growth. Immunohistochemical analysis demonstrated that ZD6474 treatment led to inhibition of VEGFR2 signaling and marked endothelial cell apoptosis. Dual targeting of tumor cells and vasculature may improve outcomes.
Peng et al. Page 432 Due to the lack of high-affinity targeting ligands, molecular imaging of α4β1 integrin is much less explored than that of integrins αvβ3 and αvβ5. Peng and colleagues described the use of LLP2A-Cy5.5 conjugate as an in vivo optical imaging probe in a human lymphoma xenograft model. This univalent LLP2A-Cy5.5 conjugate retained the binding activity and specificity to α4β1 integrin as shown by cell binding assays using α4β1-positive Molt-4 T-leukemia cells. This study demonstrated that the combinatorial chemical library-derived peptidomimetic LLP2A can be easily developed into an optical imaging probe for noninvasively monitoring of activated α4β1 integrin in vivo.
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