Our primary research focus is the investigation of photodynamic therapy (PDT) for the treatment of solid malignancies. In PDT, diseased tissue is illuminated by specific wavelengths of visible light after the delivery of a photosensitizer to that tissue. The light-excited photosensitizer interacts with oxygen to produce reactive oxygen species that damage the tissue and its associated stroma, including the supporting vascular network.
Our research centers on the study of biophysical limitations of treatment response to PDT. This includes the study of heterogeneities in the distributions of oxygen, photosensitizing drug, and light. Our studies have found that PDT can create widespread, severe hypoxia during illumination, even in tumor cells immediately adjacent to perfused blood vessels. Furthermore, noninvasive monitoring has shown PDT effect on tumor oxygenation and blood flow during the illumination period to be predictive of an animal’s long-term response to therapy. Such findings are extremely relevant to clinical PDT applications, where significant heterogeneity in hypoxia and photosensitizer distributions among the tumors of PDT patients will contribute to variable therapeutic outcomes. Indeed, we have documented a relationship between biochemical (PSA) response to PDT in prostate cancer patients and levels of photosensitizer drug and light energy in their prostates. Ultimately, in order to improve the clinical therapeutic index and efficacy of PDT, we aim to alter the microenvironment of tumors undergoing treatment as guided by noninvasive monitoring of their response.
Gallagher-Colombo SM, Miller J, Cengel KA, Putt ME, Vinogradov SA, Busch TM.
: Erlotinib pretreatment improves photodynamic therapy of non-small cell lung carcinoma xenografts via multiple mechanisms.
Cancer Res. in press, Jun 8 2015.
Gallagher-Colombo SM, Quon H, Malloy KM, Ahn PH, Cengel KA, Simone CB 2nd, Chalian AA, O'Malley BW, Weinstein GS, Zhu TC, Putt ME, Finlay JC, Busch TM.
: Measuring the Physiologic Properties of Oral Lesions Receiving Fractionated Photodynamic Therapy.
Photochemistry and Photobiology in press, Jun 2 2015.
Cerniglia GJ, Dey S, Gallagher-Colombo SM, Daurio NA, Tuttle S, Busch TM, Lin A, Sun R, Esipova TV, Vinogradov SA, Denko N, Koumenis C, Maity A: The PI3K/Akt Pathway Regulates Oxygen Metabolism via Pyruvate Dehydrogenase (PDH)-E1α Phosphorylation.
Molecular Cancer Therapeutics in press, May 20 2015.
Ghosh G, Minnis M, Ghogare AA, Abramova I, Cengel KA, Busch TM, Greer A: Photoactive fluoropolymer surfaces that release sensitizer drug molecules. Journal of Physical Chemistry-B 119(10): 4155-64, Mar 2015.
Zhu TC, Kim MM, Liang X, Finlay JC, Busch TM: In–vivo singlet oxygen threshold doses for PDT. Photonics and Lasers in Medicine 4(1): 59-71, Feb 2015.
Hana SW, Mesquitab RC, Busch TM, Putt ME: A method for choosing the smoothing parameter in a semi-parametric model for detecting change-points in blood flow. Journal of Applied Statistics 41(1): 26-45, Apr 2014 Notes: Manuscript ID: 830085.
Pietrofesa R, Turowski J, Tyagi S, Dukes F, Arguiri E, Busch TM, Gallagher-Colombo SM, Solomides CC, Cengel KA, Christofidou-Solomidou M: Radiation mitigating properties of the lignan component in flaxseed. BMC Cancer 13(1): 179, Apr 2013.
Edmonds C, Hagan S, Gallagher-Colombo SM, Busch TM, Cengel KA: Photodynamic therapy activated signaling from epidermal growth factor receptor and STAT3: Targeting survival pathways to increase PDT efficacy in ovarian and lung cancer. Cancer Biology & Therapy 13(14): 1463-70, Dec 2012.
Gallagher-Colombo SM, Maas AL, Yuan M, Busch TM: Photodynamic therapy-induced angiogenic signaling: consequences and solutions to improve therapeutic response. Israel Journal of Chemistry 52(8-9): 681-90, Sep 2012.
Maas AL, Carter SL, Wileyto EP, Miller J, Yuan M, Yu G, Durham D, Busch TM: Tumor vascular microenvironment determines responsiveness to photodynamic therapy. Cancer Research 72(8): 2079-88, Apr 2012.
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Last updated: 06/29/2015
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