Research Toward a Cure
Oliveira, S., et al.
A novel method to quantify IRDye® 800CW fluorescent antibody probes ex vivo in tissue distribution studies
Eur J Nucl Med Mol Imaging Research (2):50 (2012) doi:10.1186/2191-219X-2-50
The authors describe a new method for biodistribution analysis of infrared (IR) fluorescent antibody probes used for in vivo imaging. Cetuximab (Erbitux) was conjugated to the IRDye 800CW fluorophore (LI COR Biosciences) and 89Zirconium, and injected into nude mice bearing A431 tumor xenografts. After PET imaging and optical imaging with the IVIS Lumina system, organs and tumors were collected. Half was used for radioactivity measurements of probe uptake. The remaining tissue was homogenized, for quantification of the IR fluorescent probe (Odyssey Imager) and extrapolation from a calibration curve. IR fluorescent and gamma ray quantification yielded comparable results (15.07±3.66% and 13.92±2.59% injected dose per gram of tissue (% ID/g), respectively). With this method, tissue distribution of IR fluorescent probes can now be very accurately measured. The method should be useful for preclinical development of IR fluorescent probes for optical molecular imaging and possible clinical translation.
Silverman, A., et al.
A Galectin-3-Dependent Pathway Upregulates Interleukin-6 in the Microenvironment of Human Neuroblastomas
Cancer Research (2):2228-38 (2012) doi: 10.1158/0008-5472.CAN-11-2165
Soluble growth factors in the tumor microenvironment, such as Interleukin-6 (IL-6), play a key role in cancer initiation and progression. In neuroblastoma, IL-6 is not produced by tumor cells but rather by stromal cells such as monocytes and bone marrow mesenchymal stem cells (BMMSC). This study demonstrates that production of IL-6 by BMMSCs is stimulated by galectin-3 binding protein (Gal-3BP), which is secreted by neuroblastoma cells. Quantitative IR fluorescent Western blots (Odyssey Imager), immunofluorescent microscopy, and immunohistochemistry were used to investigate the role of Gal-3BP in IL-6 regulation. The results indicated that Gal-3, which is present in BMMSCs, is required for Gal-3BP to upregulate expression of IL-6. Quantitative Westerns showed that Gal-3BP signals through the Ras/MEK/ERK pathway. Immunohistochemistry of human neuroblastoma tumor samples showed that Gal-3BP was present in tumor cells and the extracellular matrix. The authors suggest that malignant cells may use this mechanism to upregulation IL-6 production by stromal cells.
Roller, D.G., et al.
Synthetic Lethal Screening with Small-Molecule Inhibitors Provides a Pathway to Rational Combination Therapies for Melanoma
Mol Cancer Ther 11:2505-2515 (Nov 2012)
Yadav, V., et al.
Reactivation of Mitogen-activated Protein Kinase (MAPK) Pathway by FGF Receptor 3 (FGFR3)/Ras Mediates Resistance to Vemurafenib in Human B-RAF V600E Mutant Melanoma
J Biol Chem 287:28087-28098 (Aug 2012)