The Journal of Visualized Experiments (JoVE) is a peer reviewed, PubMed-indexed video journal. Our mission is to increase the productivity of scientific research.
Authors
The Journal of Visualized Experiments (JoVE) is a peer reviewed, PubMed-indexed video journal. Our mission is to increase the productivity of scientific research.
1Department of Experimental Oncology, Institute of Oncology Ljubljana, 2Faculty of Electrical Engineering, University of Ljubljana
Sersa, G., Miklavcic, D. Electrochemotherapy of Tumours. J. Vis. Exp. (22), e1038, doi:10.3791/1038 (2008).
The treatment procedure for electrochemotherapy consists of local or systemic drug injection followed by delivery of electric pulses applied to the tumour 1. Detailed information about the treatment is published in Standard Operating Procedures (SOP) 2.
Treatment indications:
Treatment procedure:
Other features of the treatment:
Due to lack of systemic toxicity - because very low doses of bleomycin or cisplatin are needed - patients can be treated on an out-patient basis, and can leave the hospital soon after the treatment.
Increase in cytotoxicity of bleomycin by exposure of cells to electroporative electric pulses was first described by Okino M and Mir LM 3,4. Thereafter electrochemotherapy was demonstrated to be effective also for cisplatin 5. Extensive preclinical data were collected on in vitro and in vivo tumour models in the following years. Treatment effectiveness was determined in relation to drug dosage, route of its administration, timing of drug injection and application of electric pulses, intensity of the electric field, coverage with sufficiently high electric field (E), and appropriate selection of electrodes and positioning with respect to the tumour 1,6,7,8. Furthermore, mechanisms underlying the effectiveness of electrochemotherapy were elaborated, demonstrating that, besides direct effect of electrochemotherapy to tumour cells, vascular disrupting effect and immune response are involved 1,6,9. All of these collected data enabled translation of electrochemotherapy into the clinics.
The first clinical trials demonstrated effectiveness of electrochemotherapy on head and neck and melanoma tumour nodules 10. Later on, its effectiveness was demonstrated on other tumour types, such as basal cell carcinoma of the skin, cutaneous metastases of melanoma, mammary tumours, hypernephroma and Kaposi's sarcoma. There are several reports evaluating collectively all clinical data published on electrochemotherapy with bleomycin and cisplatin 11-15. Overall, the response rate of the treated tumours was approximately 80% objective responses and approximately 70% complete responses 15,16. The effectiveness can be even higher by repetitive treatment 17.
All of these clinical data have enabled electrochemotherapy to be adopted in some European countries as standard treatment, with palliative intent, on various tumours. The future of this treatment is to introduce electrochemotherapy in treatment of internal tumours and metastases, and in combined treatment, either with gene therapy or radiation therapy. These attempts are already under way.
The authors gratefully acknowledge financial support from the state budget of the Slovenian Research Agency and the European Commission's ESOPE project (QLK-2002-02003), funded under the 5th Framework Programme. The authors acknowledge the contribution of prof. Marko Snoj, prof. Maja Cemazar, Matej Merkac and Rado Likon in preparation of this Video-article.
| Name | Type | Company | Catalog Number | Comments |
| Bleomycin (Blenamax) | Reagent | Teva Pharmachemie | chemotherapeutic drug used in electrochemotherapy | |
| Cliniporator | Other | IGEA | Generator of electric pulses |
1. Mir, L.M. Bases and rationale of the electrochemotherapy. EJC Suppl. 4, 38–44 (2006).
2. Mir, L.M., Gehl, J., Sersa, G., Collins, C.G., Garbay, J.R., Billard, V., Geertsen, P., Rudolf, Z., O’Sullivan, G.C., Marty, M. Standard operating procedures of the electrochemotherapy: instructions for the use of bleomycin or cisplatin administered either systemically or locally and electric pulses delivered by the CliniporatorTM by means of invasive or non-invasive electrodes. EJC Suppl. 4, 14–25 (2006).
3. Okino, M., Mohri, H. Effects of high-voltage electrical impulse and an anticancer drug on in vivo growing tumors. Jpn. J. Cancer Res. 78, 1319-1321 (1987).
4. Mir, L.M., Banoun, H., Paoletti, C. Introduction of definite amounts of nonpermeant molecules into living cells after electropermeabilization: direct access to the cytosol. Exp. Cell Res. 175, 15-25 (1988).
5. Sersa, G., Cemazar, M., Miklavcic, D. Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice. Cancer Res. 55, 3450–3455 (1995).
6. Sersa, G., Cemazar, M., Miklavcic, D., Rudolf, Z. Electrochemotherapy of tumours. Radiol. Oncol. 40, 163–174 (2006).
7. Miklavcic, D., Beravs, K., Semrov, D., Cemazar, M., Demsar, F., Sersa, G. The importance of electric field distribution for effective in vivo electroporation of tissues. Biophys. J. 74, 2152-2158 (1998).
8. Miklavcic, D., Corovic, S., Pucihar, G., Pavselj, N. Importance of tumour coverage by sufficiently high local electric field for effective electrochemotherapy. EJC Suppl. 4, 45–51 (2006).
9. Sersa, G., Jarm, T., Kotnik, T., Coer, A., Podkrajsek, M., Sentjurc, M., Miklavcic, D., Kadivec, M., Kranjc, S., Secerov, A., Cemazar, M. Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma. Brit. J. Cancer. 98, 388-398 (2008).
10. Mir, L.M., Belehradek, M., Domenge, C., Orlowski, S., Poddevin, B., Belehradek, J. Jr., Schwaab, G., Luboinski, B., Paoletti, C. Electrochemotherapy, a new antitumor treatment: first clinical trial. C. R. Acad. Sci. III 313, 613–618 (1991).
11. Mir, L.M., Glass, L.F., Sersa, G., Teissie, J., Domenge, C., Miklavcic, D., Jaroszeski, M.J., Orlowski, S., Reintgen, D.S., Rudolf, Z., Belehradek, M., Gilbert, R., Rols, M.P., Belehradek, J.Jr., Bachaud, J.M., DeConti, R., Stabuc, B., Cemazar, M., Coninx, P., Heller, R. Effective treatment of cutaneous and subcutaneous malignant tumours by electrochemotherapy. Brit. J. Cancer 77, 2336–2342 (1998).
12. Gothelf, A., Mir, L.M., Gehl, J. Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation. Cancer Treat. Rev. 29, 371-387 (2003).
13. Byrne, C.M., Thompson, J.F., Johnston, H., Hersey, P., Quinn, M.J., Hughes, M., McCarthy, W.H. Treatment of metastatic melanoma using electroporation therapy with bleomycin (electrochemotherapy). Melanoma Res. 15, 45–51 (2005).
14. Sersa, G. The state-of-the-art of electrochemotherapy before the ESOPE study: advantages and clinical uses. EJC Suppl. 4, 52–59 (2006).
15. Sersa, G., Miklavcic, D., Cemazar, M., Rudolf, Z., Pucihar, G., Snoj, M. Electrochemotherapy in treatment of tumours. EJSO 34, 232-240 (2008).
16. Marty, M., Sersa, G., Garbay, J.R., Gehl, J., Collins, C.G., Snoj, M., Billard, V., Geertsen, P.F., Larkin, J.O., Miklavcic, D., Pavlovic, I., Paulin-Kosir, S.M., Cemazar, M., Morsli, N., Soden, D.M., Rudolf, Z., Robert, C., O’Sullivan, G.C., Mir, L.M. Electrochemotherapy – an easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. EJC Suppl. 4, 3–13 (2006).
17. Quaglino, P., Mortera, C., Osella-Abate, S., Barberis, M., Illengo, M., Rissone, M., Savoia, P., Bernengo, M.G. Electrochemotherapy with intravenous bleomycin in the local treatment of skin melanoma metastases. Ann. Surg. Oncol. 15, 2215-2222 (2008).
I wonder if this is an experimental study (i.e. a study to test a scientific hypothesis) or a study on a clinical treatment. Reading the cited literature it comes out that the utilized technique was already studied from the experimental point of view and the possible mechanisms underlying the observed effects were discussed.
Aram Megighian, MD, PhD
Neurobiology and Neurophysiology Lab
Department of Human Anatomy and Physiology
University of Padova
Via Marzolo 3, 35131 Padova - ITALY
1
ReplyPosted by: Aram MegighianDecember 17, 2008, 4:24 AM