Documents Page

Cho et al. Noninvasive near-infrared (NIR) fluorescence imaging is a promising technique for the intraoperative assessment of solid tumor removal. We incorporated a lipophilic NIR probe, 1,1′-dioctadecyltetramethyl indotricarbocyanine iodide (DiR), in poly(ethylene glycol)-b-poly(ɛcaprolactone) (PEG-b-PCL) micelles, resulting in DiR solubilization in water, occupying nanoscopic PEG-b-PCL micelles. DiR in a self quenched
or nonquenched state showed different kinetics of release from PEG-b-PCL micelles in vitro; however, both obtained high tumor delineation (tumor-to-muscle ratio of 30–43 from collected organs). These results suggest that PEG-b-PCL micelles with DiR are a promising nanosized imaging agent that will provide a basis for enhanced surgical guidance via NIR visualization of tumors.

Leystra et al.
Aberrations in the phosphoinositide 3-kinase (PI3K) signaling pathway play a key role in the pathogenesis of numerous cancers by altering cellular growth, metabolism, proliferation, and apoptosis. Mutations in the catalytic domain of PI3K that generate a dominantly active kinase are commonly found in human colorectal cancers and have been thought to drive tumor progression but not initiation. However, the effects of constitutively activated PI3K upon the intestinal mucosa have not been previously studied in animal models. Here, we show that the expression of a dominantly active form of the PI3K protein in the mouse intestine results in hyperplasia and advanced neoplasia. Mice expressing constitutively active PI3K in the epithelial cells of the distal small bowel and colon rapidly developed invasive adenocarcinomas in the colon that spread into the mesentery and adjacent organs. The histologic characteristics of these tumors were strikingly similar to invasive mucinous colon cancers in humans. Interestingly, these tumors formed without a benign polypoid intermediary, consistent with the lack of aberrant WNT signaling observed. Together, our findings indicate a noncanonical mechanism of colon tumor initiation that is mediated through activation of PI3K. This unique model has the potential to further our understanding of human disease and facilitate the development of therapeutics through pharmacologic screening and biomarker identification.