ELECTROCHEMOTHERAPY FOR TREATING SOFT TISSUE SARCOMAS

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The long term goal of this research is the development of drug delivery methods that can be used to increase the effectiveness of chemotherapeutic agents. The combination of electric pulses with a nonpermeant drug such as bleomycin, electrochemotherapy (ECT), has been shown to be an effective localized therapy for the treatment of various cancers. It is quite probable that the success of ECT is due to increased drug uptake which is directly related to the physiological effects of the electric field (increased membrane permeability). Therefore, since ECT has shown promise in the treatment of other tumor types, it should also be effective in the treatment of sarcomas as well. It is important to establish effective preoperative procedures that can minimize the extent of surgery and minimize adverse effects. ECT has the potential to fill this role. This will be determined by completing the following specific aims: i) to determine if ECT causes any toxicity to normal tissue; ii) to establish the range of electrical field strength and drug dosage that is effective in treating sarcomas in a rat model; iii) to determine the effectiveness of treating sarcomas with a combination of bleomycin and electroporation; [iv) to determine the specific distribution of the drug before and after application of the electric field]; v) to determine if ECT can be used to treat large sarcomas. The work will be performed using an athymic rat model. Tumors will be induced in the hind limbs of the rat with human A-204 sarcoma cells. The first set of experiments will be focused on determining the level of drug and electric field doses that can cause toxicity to normal tissue, particularly muscle, blood vessels and nerves. Once the upper limit of electric field strength and drug dose is established the work will be focused on determining if ECT can be used to effectively treat soft tissue sarcomas. This will include establishing a range of effective dosages and then treating average and very large tumors in the rat model. An important consideration in the treatment of soft tissue sarcoma is to be able to perform limb sparing procedures which maintain functionality. ECT combined with surgery could fill this role.