@article{9d1b575ce0794142b9614c136fee746d,
title = "Topical Esomeprazole Mitigates Radiation-Induced Dermal Inflammation and Fibrosis",
abstract = "Radiation therapy is a mainstream strategy in the treatment of several cancer types that are surgically unresectable. Unfortunately, cancer patients often suffer from unintended consequences of radiotherapy, including the development of skin inflammation (dermatitis), which may progress to fibrosis. These morbid complications often require interruption of radiotherapy and threaten the relapse of underlying cancer. Current treatment options for radiation dermatitis are suboptimal and compel the need to develop safer, more effective therapies. In this study, we assessed the biophysical properties of topically-formulated esomeprazole (here referred to as dermaprazole) and performed proof-of-concept studies to evaluate its efficacy in vitro and in vivo. We found that dermaprazole induced nuclear translocation of erythroid 2-related factor 2 (Nrf2) and significantly upregulated heme oxygenase 1 (HO1) gene and protein expression in a 3D human skin model. Our animal study demonstrated that dermaprazole improved macroscopic appearance of the irradiated skin and accelerated healing of the wounds. Histopathology data corroborated the photographic evidence and confirmed that both prophylactically and therapeutically administered dermaprazole conferred potent anti-inflammatory and antifibrotic effects. Gene expression data showed that dermaprazole downregulated several pro-oxidant, pro-inflammatory and profibrotic genes. In conclusion, topical formulation of the FDA-approved drug esomeprazole is highly effective in attenuating dermal inflammation and fibrosis.",
author = "Ngoc Pham and Ludwig, {Michelle S.} and Min Wang and Afshin Ebrahimpour and Bonnen, {Mark D.} and Diwan, {Abdul Hafeez} and Kim, {Soo Jung} and Jason Bryan and Newton, {Jared M.} and Sikora, {Andrew G.} and Donovan, {Donald T.} and Vlad Sandulache and Ghebre, {Yohannes T.}",
note = "Funding Information: We acknowledge the NMR and Drug Metabolism Core Facility at Baylor College of Medicine, which is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01 HD087157-01A1) and Cancer Prevention and Research Institute of Texas (RP160805) to Dr. Martin M. Matzuk. This study was supported in part by the National Institutes of Health (NIH grant no. P30 CA125123, which supports the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine). JMN acknowledges financial support from the NIDCR F31 NRSA (grant no. F31DE026682) of the NIH. AGS acknowledges support from the FDA (no. 1R01FD005109-01A1) and the Veterans Affairs Administration (no. I01 BX004183-01A1). YTG is supported by grants from the NHLBI (grant nos. K01HL118683; R01HL137703), American Heart Association (grant no. 17GRNT33460159) and by intramural funding from Baylor College of Medicine (project ID 2690000104). This content is solely the responsibility of the authors and does not necessarily represent the official views of the sponsors. YTG is an inventor on patents, owned by Stanford University and Baylor College of Medicine, that protect the use of agents, including proton pump inhibitors (PPIs), for therapeutic use of new indications. MSL and MDB are inventors on the patent owned by Baylor College of Medicine. Publisher Copyright: {\textcopyright} 2019 by Radiation Research Society. All rights of reproduction in any form reserved.",
year = "2019",
month = nov,
day = "1",
doi = "10.1667/RR15398.1",
language = "English (US)",
volume = "192",
pages = "473--482",
journal = "Radiation research",
issn = "0033-7587",
publisher = "Radiation Research Society",
number = "5",
}