Antitumor Effectiveness Of Electrochemotherapy Research Articles

Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases

Solid tumors of various etiologies can be treated efficiently by electrochemotherapy (ECT), a combined use of electroporation (EP) and chemotherapeutic drugs, such as bleomycin and cisplatin. EP alone and ECT in particular, induce a profound reduction in tumor blood flow, which contributes to the antitumor effect. After EP and ECT, the time course of blood flow changes and follows the same two-phase pattern. The first rapid and short-lived vasoconstriction phase is followed by the second much longer-lived phase resulting from disrupted cytoskeletal structures and a compromised barrier function of the microvascular endothelium. In the case of ECT, however, tumor vascular endothelial cells are also affected by the chemotherapeutic drug, which leads to irrecoverable damage to tumor vessels and to a further decrease in tumor blood flow within hours after application of ECT. Tumor cells surviving the direct effects of ECT are consequently exposed to lack of oxygen and nutrients and are pushed into the secondary cascade of induced cell death. Clinically, the antitumor effectiveness of ECT has been proven extensively in the treatment of melanoma metastases, with 70–80% complete responses. The antivascular effects of ECT were also exploited for palliative treatment of bleeding melanoma metastases, with immediate cessation of bleeding and very good antitumor effectiveness. The antivascular effect of ECT is of utmost importance for translation of ECT into the treatment of deep-seated tumors, especially in well vascularized organs, such as the liver, where it prevents bleeding of the treated area.

Radiosensitizing Effect of Electrochemotherapy in a Fractionated Radiation Regimen in Radiosensitive Murine Sarcoma and Radioresistant Adenocarcinoma Tumor Model

Electrochemotherapy can potentiate the radiosensitizing effect of bleomycin, as shown in our previous studies. To bring this treatment closer to use in clinical practice, we evaluated the interaction between electrochemotherapy with bleomycin and single-dose or fractionated radiation in two murine tumor models with different histology and radiosensitivity. Radiosensitive sarcoma SA-1 and radioresistant adenocarcinoma CaNT subcutaneous tumors grown in A/J and CBA mice, respectively, were used. The anti-tumor effect and skin damage around the treated tumors were evaluated after electrochemotherapy with bleomycin alone or combined with single-dose radiation or a fractionated radiation regimen. The anti-tumor effectiveness of electrochemotherapy was more pronounced in SA-1 than CaNT tumors. In both tumor models, the tumor response to radiation was not significantly influenced by bleomycin alone or by electroporation alone. However, electrochemotherapy before the first tumor irradiation potentiated the response to a single-dose or fractionated radiation regimen in both tumors. For the fractionated radiation regimen, normal skin around the treated tumors was damaged fourfold less than for the single-dose regimen. Electrochemotherapy prior to single-dose irradiation induced more damage to the skin around the treated tumors and greater loss of body weight compared to other irradiated groups, whereas electrochemotherapy combined with the fractionated radiation regimen did not. Electrochemotherapy with low doses of bleomycin can also be used safely for radiosensitization of different types of tumors in a fractionated radiation regimen, resulting in a good anti-tumor effect and no major potentiating effect on radiation-induced skin damage.

Electrochemotherapy with CDDP on LPB sarcoma: comparison of the anti-tumor effectiveness in immunocompotent and immunodeficient mice

Electrochemotherapy combines chemotherapy with electric pulses in order to potentiate anti-tumor effectiveness of chemotherapeutic drugs. Electrochemotherapy with drugs that normally do not accumulate in the tumor cells in sufficient quantities, such as bleomycin and, to some extent, cis-platin, has already been well elaborated. For complete tumor eradication, the immune system of the organism is essential. In this study, LPB sarcoma was treated in immunocompetent C57B1/6 and immunodeficient nude mice, with the aim to determine the differences in anti-tumor effectiveness of electrochemotherapy with cis-platin. Differences observed in anti-tumor effectiveness were evaluated by tumor growth delay and the percentage of tumor cures obtained. The tumor growth delay in immunocompetent mice was approximately twice longer than in immunodeficient mice. Furthermore, a high percentage of tumor cures was achieved in immunocompetent mice, but none in immunodeficient mice. The results of our study clearly demonstrate that the host immune system is essential for obtaining cures after electrochemotherapy with cis-platin.

Effects of Electrochemotherapy on CaSki Cells Derived from a Cervical Squamous Cell Carcinoma

Electrochemotherapy is a new approach to the treatment of tumors that takes advantage of the permeabilization of the cell membranes by electric pulses to facilitate the intracellular delivery of chemotherapeutic drugs into cells. Using the female genital squamous cell carcinoma cell line, CaSki, the antitumor effectiveness of electrochemotherapy was tested.In vitrostudies showed that the cytotoxicity of some anticancer drugs, especially bleomycin, can be greatly enhanced by exposing cells to noncytotoxic electric pulses. This enhancement was significantly greater when the electric treatment was given after exposure to the drug than when applied preexposure. Treatment of nude mice bearing subcutaneous transplanted tumors with noneffective intraperitoneal doses of bleomycin followed by local delivery of electric pulses similar to those performedin vitroresulted in tumor reduction and complete disappearance after 12 days this electrochemotherapy. Histological changes in tumor tissue such as necrosis and degeneration were extensive even 6 hr after the electrochemotherapy. Thus the antitumor effects of bleomycin in mice can be considerably potentiated by local electric pulses, suggesting that electrochemotherapy with bleomycin may have promise for treatment of vulvar or ectocervical squamous cell carcinomas with early invasion.

Electrochemotherapy: variable anti-tumor effect on different tumor models

Electrochemotherapy is a new approach in the treatment of tumors that takes advantage of the permeabilization of the cell membrane by electric pulses to facilitate the delivery of chemotherapeutic drugs into the cells. According to the procedures described previously, the anti-tumor effectiveness of electrochemotherapy with bleomycin (BLM) was tested on three different murine tumor models, with different biological characteristics, to determine the variability in anti-tumor response. An arrest of growth of fibrosarcoma SA-1, malignant melanoma B-16 and Ehrlich ascites tumor (EAT) was observed in all mice subjected to electrochemotherapy, whereas neither BLM nor electric pulses had an effect on tumor growth when compared with controls. Partial and complete responses were also observed. The best anti-tumor response was observed for the SA-1 tumor model, where tumor growth delay was 31 days and 62% of the animals were free of tumor 100 days after the treatment. Side-effects of electrochemotherapy were demonstrated by body weight loss of the treated animals as well as some animal mortality recorded up to 7 days after the treatment, especially in the animals where tumors were located close to the spine. Our results are in accordance with previous results, and prove that use of high voltage electric pulses is promising for potentiation of BLM anti-tumor effectiveness.