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Accession Number ADA570263
Title Preclinical Testing of Combination Therapy for Malignant Tumors Arising from Neurofibromas.
Publication Date Jun 2012
Media Count 25p
Personal Author G. Riggins
Abstract This is the final report that shows the results obtained during the funding. The aim of this study was identify combinations of currently approved drugs that would be effective for treating MPNST. The resources attained along the first phase of this project were valuable for the subsequent drug screen performed in human MPNST cells and in vivo experiments. The inhibition of mammalian target of rapamycin (mTOR) by drugs (Rapamycin and RAD001) or RNA interference shows synergism with ionizing radiation decreasing human MPNST cell proliferation. Cell-based drug screen in combination with mTOR inhibitiors uncovers three potential candidates (toremifene, riluzole and bortezomib) with different mechanism of action. We further characterized the interaction between bortezomib, a proteasome inhibitor, and mTOR signaling inhibition in MPNST cells proliferation, cell cycle and apoptosis. Finally, dual targeting of proteasome and mTOR signaling associated with radiotherapy delay MPNST tumor growth in xenograft nude mice.
Keywords Apoptosis
Clinical medicine
Drug screen
Drug testing
In vivo analysis
Ionizing radiation
Mpnst(Malignant peripheral nerve sheath tumors)
Mtor signaling
Neurofibromatosis type 1
Nf1(Neurofibromatosis type 1)
Ribonucleic acids
Surgical transplantation
Test and evaluation

Source Agency Non Paid ADAS
NTIS Subject Category 57F - Cytology, Genetics, & Molecular Biology
57E - Clinical Medicine
57Q - Pharmacology & Pharmacological Chemistry
Corporate Author Johns Hopkins Univ., Baltimore, MD.
Document Type Technical report
Title Note Revised final rept. 1 Jun 2010-31 May 2012.
NTIS Issue Number 1314
Contract Number W81XWH-10-1-0387

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