The purpose of the Bioanalysis Core is to provide centralized bioanalysis support. This Core will promote standardization and efficiency of analysis and provide essential information that can be shared and compared across all three Projects in the Program. This new, reorganized Core will provide support for all aspects of clinical and preclinical tissue and biofluid distribution of existing photodynamic sensitizers (PS) used in clinical and preclinical studies and any newly developed PS for photodynamic therapy (PDT). These data are essential for interpreting PDT activity in patients and animal models. PSs described in Project 2 have absorption in the red or NIR regions of the visible spectrum and are strongly fluorescent. As such, standardized detection methods have been developed to exploit the photophysical properties of these compounds. The Bioanalysis Core will evaluate the tumor tissue retention of select compounds in mice bearing established and patient- derived human tumors using fluorescence spectrophotometry (and, if possible, liquid scintillation counting to detect radioisotopically-labeled [14C] photosensitizers). Fluorescence spectrophotometry will be used to determine photosensitizer levels in human serum and solubilized biopsy and surgical specimens. Core A will measure SADA (serum alkaline DNase) as a circulating biomarker that has the potential to predict PDT response in head and neck patients. This will involve routine blood collection from patients followed by standard spectrophotometric analysis of SADA activity. The Core will also collect blood and isolate and store immune cells from our head and neck patients for analysis. Specifically, the individual Projects have identified a number of areas of support for both clinical and translational science studies.
The specific aims of the Core are: 1) to determine photosensitizer levels in tissues and biological fluids of patients, 2) to collect, isolate and store immune cells from patients for subsequent analysis, 3) to measure noninvasive, circulating biomarker (serum alkaline DNase) and 4) to measure the retention of photosensitizers in mice bearing xenografted head and neck tumors.

Public Health Relevance

Photodynamic therapy (PDT) is a minimally invasive cancer treatment that involves the interaction of photosensitizer in tissue with light and oxygen. Our experience and that of others suggest that PDT can be a highly effective therapeutic option for patients with head and neck cancer (HNSCC). Core A of this PPG provides centralized bioanalysis support services for preclinical studies of HPPH optimization and clinical treatment design, which will ultimately improve treatment outcomes for HNSCC patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA055791-24
Application #
9421474
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
24
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
824771034
City
Buffalo
State
NY
Country
United States
Zip Code
14263
Shafirstein, Gal; Bellnier, David A; Oakley, Emily et al. (2018) Irradiance controls photodynamic efficacy and tissue heating in experimental tumours: implication for interstitial PDT of locally advanced cancer. Br J Cancer 119:1191-1199
Tracy, Erin C; Bowman, Mary-Jo; Pandey, Ravendra K et al. (2018) Cell-specific Retention and Action of Pheophorbide-based Photosensitizers in Human Lung Cancer Cells. Photochem Photobiol :
Shafirstein, Gal; Bellnier, David; Oakley, Emily et al. (2017) Interstitial Photodynamic Therapy-A Focused Review. Cancers (Basel) 9:
Saenz, Courtney; Cheruku, Ravindra R; Ohulchanskyy, Tymish Y et al. (2017) Structural and Epimeric Isomers of HPPH [3-Devinyl 3-{1-(1-hexyloxy) ethyl}pyropheophorbide-a]: Effects on Uptake and Photodynamic Therapy of Cancer. ACS Chem Biol 12:933-946
Oakley, Emily; Bellnier, David A; Hutson, Alan et al. (2017) Surface markers for guiding cylindrical diffuser fiber insertion in interstitial photodynamic therapy of head and neck cancer. Lasers Surg Med 49:599-608
Egan, Shawn M; Karasik, Ellen; Ellis, Leigh et al. (2017) miR-30e* is overexpressed in prostate cancer and promotes NF-?B-mediated proliferation and tumor growth. Oncotarget 8:67626-67638
Harris, Kassem; Oakley, Emily; Bellnier, David et al. (2017) Endobronchial ultrasound-guidance for interstitial photodynamic therapy of locally advanced lung cancer-a new interventional concept. J Thorac Dis 9:2613-2618
Hall, Brandon M; Balan, Vitaly; Gleiberman, Anatoli S et al. (2017) p16(Ink4a) and senescence-associated ?-galactosidase can be induced in macrophages as part of a reversible response to physiological stimuli. Aging (Albany NY) 9:1867-1884
Mimikos, Christina; Shafirstein, Gal; Arshad, Hassan (2016) Current state and future of photodynamic therapy for the treatment of head and neck squamous cell carcinoma. World J Otorhinolaryngol Head Neck Surg 2:126-129
Patel, Nayan; Pera, Paula; Joshi, Penny et al. (2016) Highly Effective Dual-Function Near-Infrared (NIR) Photosensitizer for Fluorescence Imaging and Photodynamic Therapy (PDT) of Cancer. J Med Chem 59:9774-9787

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