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X-Ray Psoralen Activated Cancer Therapy (X-PACT).

dc.contributor.author Adamson, Justus D
dc.contributor.author Alcorta, DA
dc.contributor.author Beyer, WF
dc.contributor.author Dewhirst, Mark Wesley
dc.contributor.author Dodd, RD
dc.contributor.author Fathi, Z
dc.contributor.author Fecci, Peter Edward
dc.contributor.author Herndon, James Emmett II
dc.contributor.author Kirsch, David Guy
dc.contributor.author Liu, Cong-Xiao
dc.contributor.author Liu, Leihua
dc.contributor.author Lyerly, Herbert Kim
dc.contributor.author Meng, B
dc.contributor.author Oldham, Mark
dc.contributor.author Osada, Takuya
dc.contributor.author Spector, NL
dc.contributor.author Walder, H
dc.contributor.author Xia, W
dc.contributor.author Yang, XY
dc.contributor.author Yoon, Paul
dc.coverage.spatial United States
dc.date.accessioned 2016-12-01T14:18:39Z
dc.date.issued 2016
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/27583569
dc.identifier PONE-D-15-48311
dc.identifier.uri https://hdl.handle.net/10161/13034
dc.description.abstract This work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of solid cancer. X-PACT utilizes psoralen, a potent anti-cancer therapeutic with current application to proliferative disease and extracorporeal photopheresis (ECP) of cutaneous T Cell Lymphoma. An immunogenic role for light-activated psoralen has been reported, contributing to long-term clinical responses. Psoralen therapies have to-date been limited to superficial or extracorporeal scenarios due to the requirement for psoralen activation by UVA light, which has limited penetration in tissue. X-PACT solves this challenge by activating psoralen with UV light emitted from novel non-tethered phosphors (co-incubated with psoralen) that absorb x-rays and re-radiate (phosphoresce) at UV wavelengths. The efficacy of X-PACT was evaluated in both in-vitro and in-vivo settings. In-vitro studies utilized breast (4T1), glioma (CT2A) and sarcoma (KP-B) cell lines. Cells were exposed to X-PACT treatments where the concentrations of drug (psoralen and phosphor) and radiation parameters (energy, dose, and dose rate) were varied. Efficacy was evaluated primarily using flow cell cytometry in combination with complimentary assays, and the in-vivo mouse study. In an in-vitro study, we show that X-PACT induces significant tumor cell apoptosis and cytotoxicity, unlike psoralen or phosphor alone (p<0.0001). We also show that apoptosis increases as doses of phosphor, psoralen, or radiation increase. Finally, in an in-vivo pilot study of BALBc mice with syngeneic 4T1 tumors, we show that the rate of tumor growth is slower with X-PACT than with saline or AMT + X-ray (p<0.0001). Overall these studies demonstrate a potential therapeutic effect for X-PACT, and provide a foundation and rationale for future studies. In summary, X-PACT represents a novel treatment approach in which well-tolerated low doses of x-ray radiation are delivered to a specific tumor site to generate UVA light which in-turn unleashes both short- and potentially long-term antitumor activity of photo-active therapeutics like psoralen.
dc.language eng
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0162078
dc.title X-Ray Psoralen Activated Cancer Therapy (X-PACT).
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/27583569
pubs.begin-page e0162078
pubs.issue 9
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biostatistics & Bioinformatics
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Global Health Institute
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Medical Oncology
pubs.organisational-group Pathology
pubs.organisational-group Pharmacology & Cancer Biology
pubs.organisational-group Radiation Oncology
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Surgical Oncology Molecular Theraputics
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published online
pubs.volume 11
dc.identifier.eissn 1932-6203


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