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Cell Death and Resistance Mechanisms Triggered by Photodynamic Therapy pp. 187-230 $100.00
Authors:  (Viviana A. Rivarola, Natalia B. Rumie Vittar, María Julia Lamberti, Laura Milla Sanabria, María Florencia Pansa, Ivana M. Fernández, Ingrid S. Cogno and Matías E. Rodríguez, Departmento de Biología Molecular, Facultad de Ciencias Exactas, Universidad Naciona de Río Cuarto, Río Cuarto, Argentina)
Photodynamic Therapy (PDT) was the first drug-device combination approved by the US Food and Drug Administration (FDA) almost 2 decades ago, but even so remains underutilized clinically. In principle, PDT is a simple adaptation of chemotherapy that consists of 3 essential components: photosensitizer (PS), light, and oxygen. None of these is individually noxious, but together they initiate a photochemical reaction that culminates in significant toxicity leading to cell death. Antitumor effects of PDT derive from 3 inter-related mechanisms: direct cytotoxic effects on tumor cells, damage to the tumor vasculature, and induction of a strong inflammatory reaction that can lead to the development of systemic immunity (Agostinis et al, 2004).
PDT is frequently regarded as a dual specificity treatment. The selectivity is achieved by an increased PS accumulation within the tumor as compared to normal tissues and by the fact that illumination is limited to a specified location. Several possible mechanisms of selective PS retention within tumors include greater proliferative rates of neoplastic cells, a lack of or poor lymphatic drainage, high expression of LDL receptors on tumor cells (many photosensitizers bind to LDL), low pH (which facilitates cellular uptake), increased vascular permeability, or tumor infiltration by macrophages that are efficient traps for hydrophobic photosensitizers (Moan and Berg, 1992; Moan and Peng, 2003). Therefore, selectivity is derived from both the ability of useful PSs to localize in neoplastic lesions and the precise delivery of light to the treated sites (Figure 1). A limitation of PDT is that it cannot be a curative procedure for large and disseminated tumors. Nonetheless, even for an advanced disease it can improve the quality of patients’ life and prolong survival. In addition, PDT can be performed repetitively without the accumulation of serious side effects, and it can be combined with most other treatment modalities. Its minimally invasive nature and scar free wound-healing have made it a good option for the treatment of skin cancers and other skin disorders (Szeimies et al, 1996b; Szeimies and Landthaler, 2002).
Finally, many PDT procedures can be performed in an outpatient or ambulatory setting, thereby not only alleviating costs, but also making the treatment patient-friendly. The only adverse effects of PDT relate to pain during some treatment protocols and a persistent skin photosensitization that has been circumvented by the newer agents (Agostinis et al, 2011).
This chapter will address the most important biological aspects of PDT, photophysics and photochemistry, different modes of cell death, resistance to therapy and impact of PDT on angiogenesis as the growing tumor´s favorite. 

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Cell Death and Resistance Mechanisms Triggered by Photodynamic Therapy pp. 187-230