Timothy J Triche — Page 2

PubMed2002

cDNA microarray analysis of global gene expression in sarcomas.

Sequencing of the human genome and rapidly evolving microarray technology have combined to provide investigators with the ability to analyze individual tumors and groups of tumors for global patterns of gene expression. Few of these types of studies have been performed on rhabdomyosarcomas and osteogenic sarcomas, including cell lines and animal models. Groups of expressed genes that may characterize rhabdomyosarcomas and their subgroups and separate them from other types of tumors have been identified. More specifically, genes involved in myogenesis or the inhibition of myogenesis have been identified, as have genes that may play a role in metastatic activity in osteogenic sarcomas. Also, a study documenting the consistent and specific gene expression profile of gastrointestinal stromal tumors has been published. While the data regarding gene expression patterns in sarcomas is accruing, numerous investigators are working on developing and enhancing bioinformatic skills and tools such that the vast amount of data can be converted into knowledge regarding biology, therapeutic responsiveness or resistance, and prognosis.

Gene Expression Profiling↗

PubMedDate not supplied

A nanoparticle-based model delivery system to guide the rational design of gene delivery to the liver. 2. In vitro and in vivo uptake results.

In Part 1 of our work (1), four nanoparticles were synthesized specifically for the purpose of identifying design constraints to guide next generation gene delivery to the liver. The four nanoparticles are Gal-50 and Gal-140 (galactosylated 50 and 140 nm nanoparticles) and MeO-50 and MeO-140 (methoxy-terminated 50 and 140 nm nanoparticles). All four particles have the same surface charge, and Gal-50 and Gal-140 have the same surface galactose density (ca. 25-30 pmol/cm2). Here, the hepatocyte uptake in vitro and hepatic distribution in vivo of these four nanoparticles is investigated. With freshly isolated hepatocytes, Gal-50 nanoparticles are taken up to a greater extent than are MeO-50, and both 50 nm beads are taken up to a much greater extent than either of the 140 nm nanoparticles. In mice, about 90% of the in vivo dose of Gal-140 nanoparticles is found within the liver 20 min after tail-vein injection. TEM and immunohistochemistry images confirm that Gal-140 nanoparticles are primarily internalized by Kupffer cells, though isolated examples of a few Gal-140 in hepatocytes are also observed. Gal-50 nanoparticles are overwhelmingly found in vesicles throughout the cytoplasm of hepatocytes, with only isolated examples of Kupffer cell uptake 20 min after tail vein injections in mice. Despite similar surface charge and ligand density, 50 nm nanoparticles are primarily found in hepatocytes while 140 nm nanoparticles are primarily observed in Kupffer cells. These results clearly show that slightly anionic, galactose-PEGylated nanoparticles with 25-30 pmol/cm2 galactose should be about 50 nm in diameter to preferentially target hepatocytes while they should be about 140 nm in diameter to selectively target Kupffer cells.

Animals↗