This is a five year proposal to continue studies on the mechanism(s) and efficacy (human) of photodynamic therapy (PDT) of cancer. This is a combined basic and applied approach involving basic scientists and clinicians. Studies are proposed at three levels: (1) subcellular/cellular, (2) tissue/animal, (3) human clinical. HpD (DHE/Photorin II) will be investigated and compared to new photosensitizers that will be synthesized by a collaborating chemist. The subcellular and cellular studies will involve studies on (a) subcellular binding, (b) kinetics of sensitizer uptake and excretion, (c) cellular phototoxicity, (d) detection and measurement of singlet oxygen. The tissue and animal model studies will involve (a) examination of three rodent animal models (EMT-6, RIF, and rat colon adenocarcinoma), (b) a vascular chicken comb model, (c) and angiogenic-induce ocular vascular model. The mechanism of PDT will be examined using techniques of histology, electron microscopy, spectroscopy, and cell culture. The human clinical studies will involve correlation of tumor fluorescence with therapeutic response in recurrent breast cancer, and the development of a topical application of photosensitizer for the treatment of early stage neoplasia in the gynecological tract.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032248-11
Application #
2088317
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1982-05-01
Project End
1994-12-31
Budget Start
1993-01-01
Budget End
1994-12-31
Support Year
11
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Surgery
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Degen, Andrea F; Gabrecht, Tanja; Mosimann, Laurent et al. (2004) Photodynamic endometrial ablation for the treatment of dysfunctional uterine bleeding: a preliminary report. Lasers Surg Med 34:1-4
Kimel, Sol; Svaasand, Lars O; Hammer-Wilson, Marie J et al. (2003) Influence of wavelength on response to laser photothermolysis of blood vessels: implications for port wine stain laser therapy. Lasers Surg Med 33:288-95
Keefe, Kristin A; Tadir, Yona; Tromberg, Bruce et al. (2002) Photodynamic therapy of high-grade cervical intraepithelial neoplasia with 5-aminolevulinic acid. Lasers Surg Med 31:289-93
Hammer-Wilson, Marie J; Cao, Danielle; Kimel, Sol et al. (2002) Photodynamic parameters in the chick chorioallantoic membrane (CAM) bioassay for photosensitizers administered intraperitoneally (IP) into the chick embryo. Photochem Photobiol Sci 1:721-8
Chan, John K; Monk, Bradley J; Cuccia, David et al. (2002) Laparoscopic photodynamic diagnosis of ovarian cancer using 5-aminolevulinic acid in a rat model. Gynecol Oncol 87:64-70
Kimel, Sol; Svaasand, Lars O; Cao, Danielle et al. (2002) Vascular response to laser photothermolysis as a function of pulse duration, vessel type, and diameter: implications for port wine stain laser therapy. Lasers Surg Med 30:160-9
Keefe, K A; Chahine, E B; DiSaia, P J et al. (2001) Fluorescence detection of cervical intraepithelial neoplasia for photodynamic therapy with the topical agents 5-aminolevulinic acid and benzoporphyrin-derivative monoacid ring. Am J Obstet Gynecol 184:1164-9
Pham, T H; Hornung, R; Berns, M W et al. (2001) Monitoring tumor response during photodynamic therapy using near-infrared photon-migration spectroscopy. Photochem Photobiol 73:669-77
Liang, H; Do, T; Kasravi, S et al. (2000) Chromosomes are target sites for photodynamic therapy as demonstrated by subcellular laser microirradiation. J Photochem Photobiol B 54:175-84
Tadir, Y; Hornung, R; Pham, T H et al. (1999) Intrauterine light probe for photodynamic ablation therapy. Obstet Gynecol 93:299-303

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