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McMillin, Douglas

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McMillin

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Douglas

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McMillin, Douglas
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    High-throughput approaches to discover novel immunomodulatory agents for cancer
    (Landes Bioscience, 2012) McMillin, Douglas; Mitsiades, Constantine
    The clinical success of immunomodulatory thalidomide derivatives has renewed the general interest in immunomodulatory anticancer compounds and prompted us to develop a high-throughput system to quantify immune effector-cell activity. We documented that the interaction between cancer cells, their stroma, anticancer agents and cells from the innate system are critical for determining the response of tumors to immunomodulatory strategies.
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    Stem Cell Implants for Cancer Therapy: TRAIL-Expressing Mesenchymal Stem Cells Target Cancer Cells In Situ
    (Korean Breast Cancer Society, 2012) Reagan, Michaela Ruth; Seib, F. Philipp; McMillin, Douglas; Sage, Elizabeth K.; Mitsiades, Constantine; Janes, Sam M.; Ghobrial, Irene; Kaplan, David L.
    Purpose Tumor-specific delivery of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), an apoptosis-inducing peptide, at effective doses remains challenging. Herein we demonstrate the utility of a scaffold-based delivery system for sustained therapeutic cell release that capitalizes on the tumor-homing properties of mesenchymal stem cells (MSCs) and their ability to express genetically-introduced therapeutic genes. Methods: Implants were formed from porous, biocompatible silk scaffolds seeded with full length TRAIL-expressing MSCs (FLT-MSCs). under a doxycycline inducible promoter. In vitro studies with FLT-MSCs demonstrated TRAIL expression and antitumor effects on breast cancer cells. Next, FLT-MSCs were administered to mice using three administration routes (mammary fat pad co-injections, tail vein injections, and subcutaneous implantation on scaffolds). Results: In vitro cell-specific bioluminescent imaging measured tumor cell specific growth in the presence of stromal cells and demonstrated FLT-MSC inhibition of breast cancer growth. FLT-MSC implants successfully decreased bone and lung metastasis, whereas liver metastasis decreased only with tail vein and co-injection administration routes. Average tumor burden was decreased when doxycycline was used to induce TRAIL expression for co-injection and scaffold groups, as compared to controls with no induced TRAIL expression. Conclusion: This implant-based therapeutic delivery system is an effective and completely novel method of anticancer therapy and holds great potential for clinical applications.