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dc.contributor.authorLiu, Fangbing
dc.contributor.authorLunsford, Elaine P.
dc.contributor.authorTong, Jingli
dc.contributor.authorAshitate, Yoshitomo
dc.contributor.authorGibbs, Summer L.
dc.contributor.authorYu, Jane J
dc.contributor.authorChoi, Hak Soo
dc.contributor.authorHenske, Elizabeth Petri
dc.contributor.authorFrangioni, John Vincent
dc.date.accessioned2013-03-18T19:01:46Z
dc.date.issued2012
dc.identifier.citationLiu, Fangbing, Elaine P. Lunsford, Jingli Tong, Yoshitomo Ashitate, Summer L. Gibbs, Jane Yu, Hak Soo Choi, Elizabeth P. Henske, and John V. Frangioni. 2012. Real-time monitoring of tumorigenesis, dissemination, & drug response in a preclinical model of lymphangioleiomyomatosis/tuberous sclerosis complex. PLoS ONE 7(6): e38589.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10436300
dc.description.abstractBackground: TSC2-deficient cells can proliferate in the lungs, kidneys, and other organs causing devastating progressive multisystem disorders such as lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC). Preclinical models utilizing LAM patient-derived cells have been difficult to establish. We developed a novel animal model system to study the molecular mechanisms of TSC/LAM pathogenesis and tumorigenesis and provide a platform for drug testing. Methods and Findings: TSC2-deficient human cells, derived from the angiomyolipoma of a LAM patient, were engineered to co-express both sodium-iodide symporter (NIS) and green fluorescent protein (GFP). Cells were inoculated intraparenchymally, intravenously, or intratracheally into athymic NCr nu/nu mice and cells were tracked and quantified using single photon emission computed tomography (SPECT) and computed tomography (CT). Surprisingly, TSC2-deficient cells administered intratracheally resulted in rapid dissemination to lymph node basins throughout the body, and histopathological changes in the lung consistent with LAM. Estrogen was found to be permissive for tumor growth and dissemination. Rapamycin inhibited tumor growth, but tumors regrew after the drug treatment was withdrawn. Conclusions: We generated homogeneous NIS/GFP co-expressing TSC2-deficient, patient-derived cells that can proliferate and migrate in vivo after intratracheal instillation. Although the animal model we describe has some limitations, we demonstrate that systemic tumors formed from TSC2-deficient cells can be monitored and quantified noninvasively over time using SPECT/CT, thus providing a much needed model system for in vivo drug testing and mechanistic studies of TSC2-deficient cells and their related clinical syndromes.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0038589en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376142/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectBiotechnologyen_US
dc.subjectModel Organismsen_US
dc.subjectAnimal Modelsen_US
dc.subjectMouseen_US
dc.subjectChemistryen_US
dc.subjectRadiochemistryen_US
dc.subjectEngineeringen_US
dc.subjectBioengineeringen_US
dc.subjectMedicineen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectClinical Research Designen_US
dc.subjectAnimal Models of Diseaseen_US
dc.subjectPreclinical Modelsen_US
dc.subjectDiagnostic Medicineen_US
dc.subjectDrugs and Devicesen_US
dc.subjectOncologyen_US
dc.subjectBasic Cancer Researchen_US
dc.subjectMetastasisen_US
dc.subjectRadiologyen_US
dc.titleReal-Time Monitoring of Tumorigenesis, Dissemination, & Drug Response in a Preclinical Model of Lymphangioleiomyomatosis/Tuberous Sclerosis Complexen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorYu, Jane J
dc.date.available2013-03-18T19:01:46Z
dc.identifier.doi10.1371/journal.pone.0038589*
dash.contributor.affiliatedLiu, Fangbing
dash.contributor.affiliatedYu, Jane J
dash.contributor.affiliatedHenske, Elizabeth
dash.contributor.affiliatedFrangioni, John
dash.contributor.affiliatedAshitate, Yoshitomo
dash.contributor.affiliatedChoi, Hak Soo


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