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| Content Provider | PubMed Central |
|---|---|
| Author | Miller, Janine D. Baron, Elma D. Scull, Heather Hsia, Andrew Berlin, Jeffrey C. Mccormick, Thomas Colussi, Valdir Kenney, Malcolm E. Cooper, Kevin D. Oleinick, Nancy L. |
| Abstract | Photodynamic therapy (PDT) is emerging as a promising non-invasive treatment for cancers. PDT involves either local or systemic administration of a photosensitizing drug, which preferentially localizes within the tumor, followed by illumination of the involved organ with light, usually from a laser source. Here, we provide a selective overview of our experience with PDT at Case Western Reserve University, specifically with the silicon phthalocyanine photosensitizer Pc 4. We first review our in-vitro studies evaluating the mechanism of cell killing by Pc 4-PDT. Then we briefly describe our clinical experience in a Phase I trial of Pc 4-PDT and our preliminary translational studies evaluating the mechanisms behind tumor responses. Preclinical work identified (a) cardiolipin and the anti-apoptotic proteins Bcl-2 and Bcl-xL as targets of Pc 4-PDT, (b) the intrinsic pathway of apoptosis, with the key participation of caspase-3, as a central response of many human cancer cells to Pc 4-PDT, (c) signaling pathways that could modify apoptosis, and (d) a formulation by which Pc 4 could be applied topically to human skin and penetrate at least through the basal layer of the epidermis. Clinical-translational studies enabled us to develop an immunohistochemical assay for caspase-3 activation, using biopsies from patients treated with topical Pc 4 in a Phase I PDT trial for cutaneous T-cell lymphoma. Results suggest that this assay may be used as an early biomarker of clinical response. |
| Related Links | http://dx.doi.org/10.1016/j.taap.2007.01.025 |
| Starting Page | 290 |
| File Format | |
| ISSN | 10960333 |
| e-ISSN | 10960333 |
| Journal | Toxicology and applied pharmacology |
| Issue Number | 3 |
| Volume Number | 224 |
| Language | English |
| Publisher Date | 2007-11-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Toxicology Pharmacology |
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