The overall goals of the Program Project are to gain an increased understanding of the mechanisms of photodynamic therapy (PDT) and to optimize treatment parameters. This will be achieved through the following individual research projects: 1. New, congeneric series of photosensitizers will be prepared and characterized, in order to elucidate those parameters which are important for optimal activity and those which are irrelevant. Quantitative data will be obtained which allow use of multi-dimensional QSAR models, and the predictive value of these models will be examined. The relationship between effective sensitizers and their ability to bind to specific intracellular sites will be examined. 2. The kinetics and tissue distributions of certain cytokines which are induced in vivo by PDT via oxidative stress mechanisms will be explored. The hypotheses that these cytokines can, at least in part, account for the immunopotentiating as well as immunosuppressive effects of PDT will be examined. 3. The questions of whether intracellular binding sites of effective photosensitizers are primarily mitochondrial and if the peripheral benzopdiazepine receptor in this organelle is important in sensitizer binding will be explored. The hypothesis that mitochondrial and PBR- associated sensitizers are important in inducing photodamage and the physiological responses which lead to cell death will be explored. 4. Surrogate variables which will provide real-time and short-term information on the underlying mechanistic processes and probably outcomes in clinical PDT and permit tailoring of the therapy to individual patients and lesions will be developed. As a general paradigm, light dose and dose rate effects will be explored in ALA-PDT with different ALA application times in basal cell carcinomas and cutaneous lymphomas, with examination of the photochemical and biological processes contributing to differences in efficacy, efficiency and selectivity. The Program will be supported by three important technical Core components and an Administrative Core.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA055791-10
Application #
6497740
Study Section
Subcommittee G - Education (NCI)
Program Officer
Stone, Helen B
Project Start
1992-09-30
Project End
2003-04-30
Budget Start
2002-03-20
Budget End
2003-04-30
Support Year
10
Fiscal Year
2002
Total Cost
$1,661,302
Indirect Cost
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
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 :
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
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
Baran, Timothy M (2016) Recovery of optical properties using interstitial cylindrical diffusers as source and detector fibers. J Biomed Opt 21:77001
Patel, Nayan J; Chen, Yihui; Joshi, Penny et al. (2016) Effect of Metalation on Porphyrin-Based Bifunctional Agents in Tumor Imaging and Photodynamic Therapy. Bioconjug Chem 27:667-80

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