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Shedding light on PDT
Sunday 06.00 PT: As promised, here’s a brief report on the PDT sessions I attended yesterday. First up, Anna-Liisa Nieminen, associate professor of pharmaceutical and biomedical sciences at the Medical University of South Carolina (Charleston, SC), presented the latest results of a collaboration with Case Western Reserve University (Cleveland, OH). Nieminen and her colleagues are currently evaluating the relative performance of two types of cell organelles - lysosomes versus mitochondria - as binding sites for PDT photosensitizers.
“It is often found that mitochondrion-bound photosensitizers are more effective than lysosome-bound ones,” Nieminen told BiOS delegates. The phthalocyanine photosensitizer Pc 4, for example, binds preferentially to mitochondria and endoplasmic reticulum and upon photoactivation induces apoptosis with high efficiency.
However, the Case-South Carolina researchers have synthesized a series of Pc 4 analogues, including a molecule called Pc 181 that appears to be taken up into human cancer cells more efficiently than Pc 4. What’s intriguing about Pc 181 is that it binds preferentially to lysosomes (intracellular structures containing digestive enzymes) and is more efficient at overall cell killing than Pc 4.
Those unique properties, she added, may offer insights into the killing of cells via lysosomal photodamage and ultimately to “new photosensitizers providing much better cell kill power”.
Later, the session chair Charles Gomer, professor of cancer biology, paediatrics, at the Children’s Hospital Los Angeles, CA, presented a paper entitled “PDT effects on the tumour microenvironment: growing evidence for a combined-modality approach”. Gomer is interested in how PDT can induce significant changes within the tumour microenvironment, changes that can lead to an angiogenic and/or a survival response.
A case in point is a molecule called survivin, an apoptosis-inhibiting protein, which is increased and activated in tumour cells and tissues following PDT. “Does PDT-mediated expression of survivin modulate treatment responsiveness?” he asked.
Gomer presented data confirming as much and concluded that a multimodality treatment approach that switches off the expression of survivin will lead to increased PDT efficacy.
