Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts

Martyna Krzykawska-Serda; Mahdi S Agha; Jason Chak-Shing Ho; Matthew J Ware; Justin J Law; Jared M Newton; Lam Nguyen; Steven A Curley; Stuart J Corr

doi:10.1016/j.tranon.2018.02.023

Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts

Transl Oncol. 2018 Jun;11(3):664-671. doi: 10.1016/j.tranon.2018.02.023. Epub 2018 Apr 3.

Authors

Martyna Krzykawska-Serda¹, Mahdi S Agha², Jason Chak-Shing Ho², Matthew J Ware², Justin J Law², Jared M Newton³, Lam Nguyen², Steven A Curley⁴, Stuart J Corr⁵

Affiliations

¹ Baylor College of Medicine, Dept. of Surgery, Houston, TX, USA; Jagiellonian University, Dept. Biophysics Faculty of Biochemistry, Biophysics and Biotechnology, Krakow, Poland.
² Baylor College of Medicine, Dept. of Surgery, Houston, TX, USA.
³ Baylor College of Medicine, Department of Otolaryngology-Head and Neck Surgery, Houston, TX, USA; Baylor College of Medicine, Interdepartmental Graduate Program in Translational Biology and Molecular Medicine, Houston, TX, USA.
⁴ Baylor College of Medicine, Dept. of Surgery, Houston, TX, USA; Rice University, Dept. of Mechanical Engineering and Materials Science, Houston, TX, USA.
⁵ Baylor College of Medicine, Dept. of Surgery, Houston, TX, USA; Rice University, Dept. of Chemistry and Smalley-Curl Institute, Houston, TX, USA; University of Houston, Dept. of Biomedical Engineering, Houston, TX, USA; Swansea University, Medical School, Swansea, Wales, UK. Electronic address: scorr@bcm.edu.

Abstract

Patients with pancreatic ductal adenocarcinomas (PDAC) have one of the poorest survival rates of all cancers. The main reason for this is related to the unique tumor stroma and poor vascularization of PDAC. As a consequence, chemotherapeutic drugs, such as nab-paclitaxel and gemcitabine, cannot efficiently penetrate into the tumor tissue. Non-invasive radiofrequency (RF) mild hyperthermia treatment was proposed as a synergistic therapy to enhance drug uptake into the tumor by increasing tumor vascular inflow and perfusion, thus, increasing the effect of chemotherapy. RF-induced hyperthermia is a safer and non-invasive technique of tumor heating compared to conventional contact heating procedures. In this study, we investigated the short- and long-term effects (~20 days and 65 days, respectively) of combination chemotherapy and RF hyperthermia in an orthotopic PDAC model in mice. The benefit of nab-paclitaxel and gemcitabine treatment was confirmed in mice; however, the effect of treatment was statistically insignificant in comparison to saline treated mice during long-term observation. The benefit of RF was minimal in the short-term and completely insignificant during long-term observation.

Abstract

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