Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2007, vol. 16, nr 5, September-October, p. 601–607

Publication type: editorial article

Language: English

Electrochemotherapy in Cancer Treatment

Elektrochemioterapia w leczeniu nowotworów

Małgorzata Kotulska1,

1 Institute of Biomedical Engineering and Instrumentation, Wroclaw University of Technology, Poland

Abstract

An electric field of high intensity changes the organization of lipids in the cell membrane, creating transient hydrophilic pores through which ions can freely permeate. This phenomenon, called electroporation (EP), greatly facilitates molecular transport across the membrane and permits enhanced delivery of biologically active molecules, such as drugs and nucleic acids, into the cell. Currently, EP is commonly used for in vitro cell transfection as the cleanest method available. It can also be applied in genetic therapy or immunotherapy in vivo. The most recent application of EP, becoming increasingly popular in the EU, the USA, and Australia, is electrochemotherapy (ECT), in which electroporation significantly increases the intracellular concentration of a cytotoxic agent. ECT applied with a drug that can hardly permeate through the plasma membrane without EP, such as bleomycin, allows localized treatment of a tumor, thereby reducing the side effects of systemic chemotherapy. In some cases, ECT eliminates the necessity of surgery.

Streszczenie

Pod wpływem silnego pola elektrycznego cząsteczki lipidów w błonie komórkowej zmieniają swoją organizację, tworząc przejściowe hydrofilowe pory, które umożliwiają swobodny transport jonów poprzez membranę. Zjawisko takie, nazywane elektroporacją (EP), pozwala na pokonanie bariery błony komórkowej i ułatwione wprowadzanie do wnętrza komórek substancji biologicznie czynnych, takich jak leki lub kwasy nukleinowe. Obecnie EP jest standardowo wykorzystywana w hodowlach komórkowych in vitro, jako najczystsza dostępna metoda transfekcji genów. EP można też stosować w genoterapii oraz immunogenoterapii in vivo. Najnowszym zastosowaniem EP, które staje się coraz bardziej powszechne w krajach europejskich, a także w USA i Australii, jest elektrochemioterapia (ECT), w której elektroporacja istotnie podnosi wewnątrzkomórkowe stężenie substancji cytotoksycznej. Zastosowanie w ECT leku, który samoistnie jest bardzo słabo transportowany do wnętrza komórki, jak np. bleomycyny, umożliwia miejscowe leczenie nowotworu, ograniczając skutki uboczne chemioterapii ogólnoustrojowej. W niektórych przypadkach ECT eliminuje konieczność interwencji chirurgicznej.

Key words

electroporation, electrochemotherapy, drug internalization, cancer

Słowa kluczowe

elektroporacja, elektrochemioterapia, rak

References (40)

  1. Beebe SJ, Fox PM, Rec LJ, Lauren E, Willis K, Schoenbach H: Nanosecond, high intensity pulsed electric fields induce apoptosis in human cells. FASEB 2003, 17, 1493–1495.
  2. Byrne CM, Thompson JF: Role of electrochemotherapy in the treatment of metastatic melanoma and other metastatic and primary skin tumors. Expert Rev Anticancer Ther 2006, 6, 671–678.
  3. Cemazar M, Parkins CS, Holder AL, Kranjc S, Chaplin DJ, Sersa G: Cytotoxicity of bioreductive drug tirapazamine is increased by application of electric pulses in SA−1 tumours in mice. Anticancer Res 2001, 21, 1151–1156.
  4. Chang DC, Chassy BM, Saunders JA, Sowers AE (Eds.): Guide to Electroporation and Electrofusion. Academic Press, San Diego 1992.
  5. Dev SB, Rabussay DP, Widera G, Hofmann GA: Medical applications of electroporation. IEEE Transactions on Plasma Sci 2000, 28, 206–223.
  6. Gehl J, Sorensen TH, Nielsen K, Raskmark P, Nielsen SL, Skovsgaard T, Mir LM: In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution. Biochim Biophys Acta 1999, 1428, 233–240.
  7. Gehl J, Skovsgaard T, Mir LM: Enhancement of cytotoxicity by electropermeabilization: an improved method for screening drugs. Anticancer Drugs 1998, 9, 319–325.
  8. Gilbert RA, Jaroszeski MJ, Heller R: Novel electrode designs for electrochemotherapy. Biochim Biophys Acta 1997, 1334, 9–14.
  9. Gothelf A, Mir LM, Gehl J: Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation. Cancer Treat Rev 2003, 29, 371–387.
  10. Heller R, Gilbert R, Jaroszeski MJ: Clinical applications of electrochemothrapy. Adv Drug Deliv Rev 1999, 35, 119–129.
  11. Heller LC, Heller R: In vivo electroporation for gene therapy. Hum Gene Ther 2006, 17, 890–897.
  12. Jaroszeski MJ, Dang V, Pottinger C, Hickey J, Gilbert R, Heller R: Toxicity of anticancer agents mediated by electroporation in vitro. Anticancer Drugs 2000, 11, 201–208.
  13. Kalinowski S: Elektrochemia membran lipidowych. Wyd. Uniwersytetu Warmińsko−Mazurskiego 2004.
  14. Kalinowski S, Koronkiewicz S, Kotulska M, Kubica K: Simulation of electroporated cell by chronopotentiometry. Bioelectrochemistry 2007, 70, 83–90.
  15. Koronkiewicz S, Kalinowski S, Bryl K: Programmable chronopotentiometry as a tool for the study of electroporation and resealing of pores in bilayer lipid membranes. Biochim Biophys Acta 2002, 1561, 222–229.
  16. Kotulska M, Koronkiewicz S, Kalinowski S: Cholesterol induced changes in the characteristics of the time series from planar lipid bilayer membrane during electroporation. Acta Phys Pol B 2002, 33, 1115–1124.
  17. Kotulska M, Koronkiewicz S, Kalinowski S: Self−similar processes and flicker noise from a fluctuating nanopore in a lipid membrane. Phys Rev E 2004, 69, 031920–031930.
  18. Kotulska M: 1/f noise in nanopores and its potential application in biosensors. Elektronika 2004, 8–9, 130–134.
  19. Kotulska M, Kubica K: Structural and energetical effects of ionic strength in modeling lipid membranes. Acta Phys Pol B 2005, 36, 1641–1651.
  20. Kotulska M, Kubica K: Structural and energetic model of the mechanisms for reduced self−diffusion in a lipid bilayer with increasing ionic strength. Phys Rev E 2005, 72, 061903–061909.
  21. Kotulska M, Kubica K, Koronkiewicz S, Kalinowski S: Modeling the induction of lipid membrane electropermeabilization. Bioelectrochemistry 2007, 70, 64–70.
  22. Kotulska M: Natural fluctuations of an electropore show fractional Lévy stable motion. Biophys J 2007, 92, 2412–2421.
  23. Kranjc S, Cemazar M, Grosel A, Sentjurc M, Sersa G: Radiosensitising effect of electrochemotherapy with bleomycin in LPB sarcoma cells and tumors in mice. BMC Cancer 2005, 5, 115–124.
  24. Labanauskiene J, Gehl J, Didziapetriene J: Evaluation of cytotoxic effect of photodynamic therapy in combination with electroporation in vitro. Bioelectrochemistry 2007, 70, 78–82.
  25. Maxim PG, Carson JJ, Ning S, Knox SJ, Boyer AL, Hsu CP, Benaron DA, Walleczek J: Enhanced effectiveness of radiochemotherapy with tirapazamine by local application of electric pulses to tumors. Radiat Res 2004, 162, 185–193.
  26. Mir LM, Orlowski S, Poddevin B, Belehradek J Jr: Electrochemotherapy tumor treatment is improved by interleukin−2 stimulation of the host’s defenses. Eur Cytokine Netw 1992, 3, 331–334.
  27. Mir LM, Roth C, Orlowski S, Quintin−Colonna F, Fradelizi D, Belehradek J Jr, Kourilsky P: Systemic antitumor effects of electrochemotherapy combined with histoincompatible cells secreting interleukin−2. J Immunother Emphasis Tumor Immunol 1995, 17, 30–38.
  28. Mir LM, Orlowski S: Mechanisms of electrochemotherapy. Adv Drug Deliv Rev 1999, 35, 107–118.
  29. Mir LM, Ed.: Eur J Cancer – Supplements 2006, 4, 1–51.
  30. Neumann E, Kakorin S, Toensing K: Fundamentals of electroporative delivery of drugs and genes. Bioelectrochem Bioenerg 1999, 48, 3–16.
  31. Okino M, Mohri H: Effects of a high−voltage electrical impulse and an anticancer drug on in vivo growing tumors. Jpn J Cancer Res 1987, 78, 1319–1321.
  32. Orlowski S, Belehradek J Jr, Paoletti C, Mir LM: Transient electropermeabilization of cells in culture. Increase of the cytotoxicity of anticancer drugs. Biochem Pharmacol 1988, 37, 4727–4733.
  33. Orlowski S, An D, Belehradek J Jr, Mir LM: Antimetastatic effects of electrochemotherapy and of histoincompatible interleukin−2−secreting cells in the murine Lewis lung tumor. Anticancer Drugs 1998, 9, 551–556.
  34. Pucihar G, Mir LM, Miklavcic D: The effect of pulse repetition frequency on the uptake into electropermeabilized cells in vitro with possible applications in electrochemotherapy. Bioelectrochemistry 2002, 57, 167–172.
  35. Ramirez LH, Orlowski S, An D, Bindoula G, Dzodic R, Ardouin P, Bognel C, Belehradek J Jr, Munck JN, Mir LM: Electrochemotherapy on liver tumours in rabbits. Br J Cancer 1998, 77, 2104–2111.
  36. Schantz SP, Hsu TC, Ainslie N, Moser RP: Young adults with head and neck cancer express increased susceptibility to mutagen−induced chromosome damage. JAMA 1989, 262, 3313–3315.
  37. Sersa G, Cemazar M, Miklavcic D: Antitumor effectiveness of electrochemotherapy with cis−diamminedichloroplatinum(II) in mice. Cancer Res 1995, 55, 3450–3455.
  38. Snoj M, Rudolf Z, Cemazar M, Jancar B, Sersa G: Successful sphincter−saving treatment of anorectal malignant melanoma with electrochemotherapy, local excision and adjuvant brachytherapy. Anticancer Drugs 2005, 16, 345–348.
  39. Weaver JC, Chizmadzhev YA: Theory of electroporation: a review. Bioelectrochem Bioenerg 1996, 41, 135–160.
  40. Whelan MC, Larkin JO, Collins CG, Cashman J, Breathnach O, Soden DM, O’Sullivan GC: Effective treatment of an extensive recurrent breast cancer which was refractory to multimodal therapy by multiple applications of electrochemotherapy. Eur J Cancer Supplements 2006, 4, 32–34.