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1) caTissue or similar product. 2) caTissue or similar product pathology imaging tools to be developed by TBPT. 3) caTissue or similar product. 4) Combination of custom, ad-hoc software and manual processes. 5) Proprietary, platform-dependent software, a wide variety of non-caBIG-compatible software packages: Solexa Mapper, Mosaic, 454 Mapper, Velvet Mapper, Solid Mapper (uses a non-standard sequence representation model), Mac. 6) Combination of custom, ad-hoc software and manual processes. 7) Manual process. 8) Combination of custom, ad-hoc software and manual processes. 9) Manual process. This should not be a manual process, but almost always is, or it is of low quality.)

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Nanoparticle Delivery System

This is a scenario based on finding a nanoparticle delivery system to target a drug which in its free form causes significant side effects. Sorafenib is a Raf kinase inhibitor that disrupts the key Ras/Raf/MEK/ERK cellular pathway that is up-regulated in renal cell carcinoma, glioblastoma multiforme (GBM), and stomach cancer. The drug has significant side effects and a scientist hypothesizes that nanoparticle-assisted targeted delivery of the drug will reduce the required dosing and its side effects.

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The physical characteristics have been determined. These include size, zeta potential, and the relevant IC50. In a cell adhesion assay, the 10 of 19 effect of multivalency on IC50 is also measured. Selectivity was also demonstrated in a receptor-binding assay and it is also shown that the ?v ?3-targeted NP is not rapidly cleared from the target tissue. Previous studies have shown this particle to be highly stable, to have no measurable toxicity and to specifically target tumor associated vasculature in GBM when conjugated to GFP. Furthermore the particle has been used as an imaging agent when conjugated with Gd3+ or Indium2+. The ?v ?3-targeted NPsorafenib is synthesized. Sorafenib absorption characteristics are available and the concentration of the drug in the system is determined via spectroscopy methods. Other physical properties are characterized.

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Nanoparticle Delivery System B

This is Scenario 12 the Nanoparticle Delivery System scenario extended. The scientist investigates what data sets are available for in vivo use of the drug. A breast cancer xenograph subcutaneous model is found and cell lines from this system are also available. However, toxicity data for the drug in animal models are not publicly available. The scientist contacts the drug manufacturer and begins in vitro testing. PK/PD in vitro tests, including drug uptake, toxicity and effectiveness, are performed in the model system cell lines, and related and control cell lines by comparing the effects of drug alone, nanoparticle alone, and the combination. Next is in vivo testing with three established animal tumor models. The drug alone, nanoparticle alone, and the combination are administered and tumor size (and other parameters) are monitored. Finally efficacy, dosing, and side effects of the current dosing protocol are compared with targeted nanoparticle delivery of sorafenib.

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