HPB
Jennifer Castle, MD, PhD
Resident
University of Kentucky, United States
Jennifer Castle, MD, PhD
Resident
University of Kentucky, United States
Jennifer Castle, MD, PhD
Resident
University of Kentucky, United States
Evelyn Winter da Silva, PhD
Research Scientist
University of Kentucky, United States
Aman Chauhan, MD
Medical Oncologist
University of Miami, United States
Percy Ivy, MD
Associate Chief
NIH, United States
Susanne Arnold, MD
Medical Oncologist
University of Kentucky, United States
William Carson, III, MD
Surgical Oncologist
Ohio State University, United States
B. Mark Evers, MD
Surgical Oncologist
University of Kentucky, United States
Jessica Blackburn, PhD
Professor
University of Kentucky, United States
Piotr Rychahou, MD
Research Professor
University of Kentucky, United States
Jill Kolesar, PharmD
Collaborating Principal Investigator
The University of Kentucky College of Pharmacy, United States
(i) Tumor samples showed increased expression of cleaved-caspase 3 and Ki-67, and (ii) immunoblot analysis revealed greater expression of cleaved PARP indicating increased apoptosis with combination therapy. (iii) Zebrafish embryos treated with combination therapy (triapine+BAY+IR) had significantly greater (p< 0.001) morphological changes (i.e., shortened body length, curved spine, pericardial edema, and head/tail/yolk malformation) indicative of treatment effect. (iv) Similarly, embryos treated with combination therapy demonstrated greater apoptosis determined by acridine orange assay (Figure) and TUNEL analysis (triapine+BAY+IR 129 ± 40, BAY+IR 94 ± 49, triapine+IR 62 ± 19, IR 53 ± 26 positive cells; p< 0.001). (v) Combination therapy had statistically more DNA damage than the controls (triapine+BAY+IR 87 ± 45, BAY+IR 29 ± 19, triapine+IR 26 ± 31, IR 13 ± 5 positive cells; p< 0.001).
Conclusions:
The combination of triapine and BAY1895344 sensitized pNETs to radiation therapy in vivo and represents a novel treatment strategy for pNETs. By capitalizing on the synergy of this combination, clinical efficacy may be achieved at lower doses of radiation potentially leading to less adverse side effects for patients.