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14 August 2019 Evaluation of photomedicine and anti-microRNA combination therapies in 3D cell culture models of pancreatic ductal adenocarcinoma (Conference Presentation)
Ljubica Petrovic, Tomas Materdey Jr., Eric Struth, Maud-Emmanuelle Gilles, Meirav Segal, Frank Slack, Jonathan Celli
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Proceedings Volume 11070, 17th International Photodynamic Association World Congress; 110705U (2019) https://doi.org/10.1117/12.2526199
Event: 17th International Photodynamic Association World Congress, 2019, Cambridge, Massachusetts, United States
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease marked by poor response to virtually all available treatments. Clinical trials of chemo, targeted therapies, and radiation, have resulted in minimal advances, and survival after diagnosis is generally less than a year. In the pursuit of new avenues for therapeutic development for this lethal disease, a number of studies have implicated the role of tumor-promoting microRNAs with altered expression PDAC tissues. Here, using in vitro 3D organoids we explore the strategy of combining photodynamic therapy (PDT) with a novel microRNA therapeutic platform to target miR21, an established onco-miR that targets multiple tumor suppressors. This approach is motivated by recent clinical studies establishing the technical feasibility of light delivery to the pancreas, combined by evidence that PDT may disrupt or loosen stroma and potentially increase delivery of anti-miR agents. To evaluate this hypothesis, we use in vitro co-culture models of PDAC cells and stromal fibroblasts that recapitulate the dense fibrotic stroma of PDAC tumors to evaluate response to treatment in verteporfin PDT and anti-miR combination and monotherapy treatment arms. Using stably-transfected miR-21 sponge expressing we also perform mechanistic studies to investigate the role of miR 21 in response to PDT and chemotherapy in 3D cultures with and without stromal partners.
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Ljubica Petrovic, Tomas Materdey Jr., Eric Struth, Maud-Emmanuelle Gilles, Meirav Segal, Frank Slack, and Jonathan Celli "Evaluation of photomedicine and anti-microRNA combination therapies in 3D cell culture models of pancreatic ductal adenocarcinoma (Conference Presentation)", Proc. SPIE 11070, 17th International Photodynamic Association World Congress, 110705U (14 August 2019); https://doi.org/10.1117/12.2526199
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KEYWORDS
3D modeling
Photodynamic therapy
Therapeutics
Photomedicine
3D acquisition
Tumors
In vitro testing
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