Vascular shutdown as an effect of using photodynamic therapy to treat cancer
Pascucci, Elizabeth Mary.
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Photodynamic therapy (PDT) is a treatment that uses the combination of a photosensitizing drug and light to selectively kill cancer cells. PDT has many potential advantages such as minimal side effects, excellent cosmetic results, and no cellular resistance burdening traditional cancer treatments such as chemotherapy and radiation. Currently used in the clinic, a limitation is depth of light penetration; therefore, PDT can only be used to treat superficial disease. Our novel PDT agent utilizes two-photon laser technology, which increases the depth of light penetration, greatly increasing the potential uses. Our PDT is able to kill selective cells because the PDT drug has a targeting agent so the drug only goes to cancer cells that overexpress the Somatostatin receptor 2 (SSTr2) on their cell surface. Laser light irradiates the cancer cells causing cytotoxic singlet oxygen to be produced damaging the cells. It was observed, through in vivo imaging of the tumors before and after treatment, that vascular flow was diminished as a result of PDT. It is well established that angiogenesis must occur when a tumor reaches a certain size in order for the cells to remain viable and the tumor to continue to grow; therefore, vascular shutdown could be an important mechanism of how PDT works. A series of experiments on the tumor vasculature using in vivo imaging, immunohistochemistry and confocal microscopy has taken place since this observation to determine what may be happening. Results of these studies have shown that tumor vessels do express the SSTr2 and therefore effected by treatment. Experiments using a somatostatin analog, octreoate, detected by a fluor has shown that the endothelial cells do take the drug up. To ensure that it is blood vessels that were being studied, tumor tissue was stained for both SSTr2 and vonWillebrand Factor (vWF), a recognized endothelial cell marker. Staining patterns for both antibodies were similar. To strengthen the argument, SSTr2- negative tumor cells also showed a positive staining pattern of their vessels, demonstrating that even though the tumor cells are SSTr2- negative, the tumor vessels can be SSTr2-positive and thus responsive to PDT.