Mathematical model of tumor volume dynamics in mice treated with electrochemotherapy
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The effectiveness of electrochemotherapy, a local treatment using electric pulses to increase the uptake of chemotherapeutic drug, includes several antitumor mechanisms. In addition to the cytotoxic action of chemotherapeutic drug, treatment outcome also depends on antitumor immune response. In order to assess the contribution of different antitumor mechanisms to the observed treatment outcome, we designed a model of tumor volume dynamics, which is able to quantify early and late treatment effects. Model integrates characteristics of both main posttreatment processes, namely removal of lethally damaged cells from tumor volume and tumor–immune interaction. Fitting to individual responses gives the insight into the dynamics of tumor cell elimination. Two more or less clearly separable peaks can be observed from these dynamics. Model was used to quantify responses obtained after chemotherapy and electrochemotherapy with bleomycin and cisplatin in immunocompetent and immunodeficient mice. As expected, electrochemotherapy resulted in higher number of lethally damaged cells as well as in stronger immune response compared to chemotherapy alone. Additionally, bleomycin-treated tumors proved to be more immunogenic than cisplatin-treated tumors in the given range of doses.
KeywordsElectroporation Electrochemotherapy Mathematical model Tumor growth
This work was supported by the Slovenian Research Agency (ARRS) and conducted within the scope of Electroporation in Biology and Medicine (EBAM) European Associated Laboratory (LEA) and the COST Action TD1104 (in particular by a short-term scientific mission COST-STSM-TD1104-21001). Authors would like to thank Gregor Sersa from Institute of Oncology Ljubljana for providing us with the raw data.
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