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Responses to sublethal PDT

ANNE C.E. MOOR, BERNHARD ORTEL AND TAYYABA HASAN [Pg.36]

In summary, these studies into the working mechanisms of PDT at a cellular level have shown that (a) PDT with mitochondria-based photosensitizers can induce extremely rapid apoptosis, (b) it can bypass some of the normal control mechanisms, such as bcl-2 and (c) although PDT induced apoptosis is dependent on p53 status, overall cell killing is not, which is of importance since many human tumors have non-functional p53. The majority of these studies have been performed in vitro and further studies should indicate whether the same responses occur in vivo. In addition, the role of apoptosis in the overall tumor response is not clear and recent data, using cell lines deficient in apoptotic machinery, indicate that these cells are still sensitive to PDT, probably by using a necrotic pathway [134]. This sensitivity could possibly be used in the treatment of tumors which are chemoresistant, and indeed several studies have already shown the effective use of PDT in this area [84,85,88,156]. [Pg.36]


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