Fluence Rate Differences in Photodynamic Therapy Efficacy and Activation of Epidermal Growth Factor Receptor after Treatment of the Tumor-Involved Murine Thoracic Cavity
by
Craig E. Grossman 1,†,‡,
Shirron L. Carter 1,†,
Julie Czupryna 2,§,
Le Wang 3,
Mary E. Putt 3 and
Theresa M. Busch 1,*
Craig E. Grossman 1,†,‡,
Shirron L. Carter 1,†,
Julie Czupryna 2,§,
Le Wang 3,
Mary E. Putt 3 and
Theresa M. Busch 1,*
1
Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
2
Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
3
Department of Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
Current address: Department of Radiation Oncology, Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA
§
Current address: PerkinElmer, 68 Elm Street, Hopkinton, MA 01748, USA
Academic Editor: Michael R. Hamblin
Int. J. Mol. Sci. 2016, 17(1), 101; https://doi.org/10.3390/ijms17010101
Received: 28 November 2015 / Revised: 28 December 2015 / Accepted: 7 January 2016 / Published: 14 January 2016
(This article belongs to the Special Issue Advances in Photodynamic Therapy)
Photodynamic therapy (PDT) of the thoracic cavity can be performed in conjunction with surgery to treat cancers of the lung and its pleura. However, illumination of the cavity results in tissue exposure to a broad range of fluence rates. In a murine model of intrathoracic PDT, we studied the efficacy of 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH; Photochlor®)-mediated PDT in reducing the burden of non-small cell lung cancer for treatments performed at different incident fluence rates (75 versus 150 mW/cm). To better understand a role for growth factor signaling in disease progression after intrathoracic PDT, the expression and activation of epidermal growth factor receptor (EGFR) was evaluated in areas of post-treatment proliferation. The low fluence rate of 75 mW/cm produced the largest reductions in tumor burden. Bioluminescent imaging and histological staining for cell proliferation (anti-Ki-67) identified areas of disease progression at both fluence rates after PDT. However, increased EGFR activation in proliferative areas was detected only after treatment at the higher fluence rate of 150 mW/cm. These data suggest that fluence rate may affect the activation of survival factors, such as EGFR, and weaker activation at lower fluence rate could contribute to a smaller tumor burden after PDT at 75 mW/cm.
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Keywords:
photodynamic therapy; fluence rate; lung; HPPH; epidermal growth factor receptor; optical imaging; proliferation; thoracic cavity; non-small cell lung carcinoma
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MDPI and ACS Style
Grossman, C.E.; Carter, S.L.; Czupryna, J.; Wang, L.; Putt, M.E.; Busch, T.M. Fluence Rate Differences in Photodynamic Therapy Efficacy and Activation of Epidermal Growth Factor Receptor after Treatment of the Tumor-Involved Murine Thoracic Cavity. Int. J. Mol. Sci. 2016, 17, 101.
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