Bioelectrics pp 275-388 | Cite as

Medical Applications

  • Richard HellerEmail author
  • Justin Teissie
  • Marie-Pierre Rols
  • Julie Gehl
  • Gregor Sersa
  • Lluis M. Mir
  • Robert E. NealII
  • Suyashree Bhonsle
  • Rafael Davalos
  • Stephen Beebe
  • Barbara Hargrave
  • Richard Nuccitelli
  • Chunqi Jiang
  • Maja Cemazar
  • Youssef Tamzali
  • Natasa Tozon


Bioelectrics is a rapidly growing field at the intersection of the biological and physical sciences. Research has focused on understanding the basic interactions of pulse electric fields on biological systems, development of therapeutic and diagnostic approaches, and environmental applications. This chapter focuses on potential therapeutic and prophylactic applications of bioelectrics in human and veterinary medicine. Pulse electric fields can be ultrashort (picosecond to nanosecond) or longer (microsecond to millisecond), and dependent on the parameters of the applied pulse, the cellular effects on cells can be direct or indirect. Direct effect can include exciting cells or induction of apoptosis and/or necrosis. Indirect effects have been used to deliver molecules such as chemotherapeutics, nucleic acids, or protein into the cell interior. Therapeutic applications of bioelectrics have been developed for a large number of indications including many medical conditions including cancer, wound healing, ischemia, cardiovascular, and diabetes. The utilization of bioelectric-based medical techniques has recently surged, and the potential of such techniques has stemmed from a more wholistic understanding of the fundamental biophysical mechanisms driving underlying success.


Electrochemotherapy Gene electrotransfer Nanosecond pulse electric fields Plasma medicine Veterinary Clinical trials Wound healing Cancer therapy 


  1. 1.
    Coster, H.G.: A quantitative analysis of the voltage-current relationships of fixed charge membranes and the associated property of “punch-through”. Biophys. J. 5(5), 669–686 (1965)CrossRefGoogle Scholar
  2. 2.
    Sale, A.J.H., Hamilton, W.A.: Effects of high electric fields on microorganisms: I. Killing of bacteria and yeasts. Biochim. Biophys. Acta Gen. Subj. 148(3), 781–788 (1967)CrossRefGoogle Scholar
  3. 3.
    Sale, A.J.H., Hamilton, W.A.: Effects of high electric fields on micro-organisms: III. Lysis of erythrocytes and protoplasts. Biochim. Biophys. Acta Biomembr. 163(1), 37–43 (1968)CrossRefGoogle Scholar
  4. 4.
    Pohl, H.A., Crane, J.S.: Dielectrophoresis of cells. Biophys. J. 11(9), 711–727 (1971)CrossRefGoogle Scholar
  5. 5.
    Crowley, J.M.: Electrical breakdown of bimolecular lipid membranes as an electromechanical instability. Biophys. J. 13(7), 711–724 (1973)CrossRefGoogle Scholar
  6. 6.
    Zimmermann, U., Pilwat, G., Riemann, F.: Dielectric breakdown of cell membranes. Biophys. J. 14(11), 881–899 (1974)CrossRefGoogle Scholar
  7. 7.
    Hamilton, W.A., Sale, A.J.H.: Effects of high electric fields on microorganisms II. Mechanism of action of the lethal effect. Biochim. Biophys. Acta 148, 789–800 (1967)CrossRefGoogle Scholar
  8. 8.
    Neumann, E., Rosenheck, K.: Permeability changes induced by electric impulses in vesicular membranes. J. Membr. Biol. 10, 279–290 (1972)CrossRefGoogle Scholar
  9. 9.
    Kinosita Jr., K., Tsong, T.Y.: Hemolysis of human erythrocytes by transient electric field. Proc. Natl. Acad. Sci. U. S. A. 74, 1923–1927 (1977)CrossRefGoogle Scholar
  10. 10.
    Schoenbach, K.H., Beebe, S.J., Buescher, E.S.: Intracellular effect of ultrashort electrical pulses. Bioelectromagnetics 22(6), 440–448 (2001)CrossRefGoogle Scholar
  11. 11.
    Beebe, S.J., Fox, P.M., Rec, L.H., Buescher, E.S., Somers, K., Schoenbach, K.H.: Nanosecond pulsed electric field (nsPEF) effects on cells and tissues: apoptosis induction and tumor growth inhibition. IEEE. T. Plasma Sci. 30, 286–292 (2002)CrossRefGoogle Scholar
  12. 12.
    Nuccitelli, R., Wood, R., Kreis, M., Athos, B., Huynh, J., Lui, K., Nuccitelli, P., Epstein Jr., E.H.: First-in-human trial of nanoelectroablation therapy for basal cell carcinoma: proof of method. Exp. Dermatol. 23, 135–137 (2014)CrossRefGoogle Scholar
  13. 13.
    Chen, R., Chen, X., Beebe, S.J.: Nanosecond Pulsed Electric Field (nsPEF) ablation as an alternative or adjunct to surgery for treatment of cancer. Surg. Curr. Res. S12, 005 (2013)Google Scholar
  14. 14.
    Chen, R., Sain, N.M., Harlow, K.T., Chen, Y.J., Shires, P.K., Heller, R., Beebe, S.J.: A protective effect after clearance of orthotopic rat hepatocellular carcinoma by nanosecond pulsed electric fields. Eur. J. Cancer 50(15), 2705–2713 (2014)CrossRefGoogle Scholar
  15. 15.
    Chen, X., Zhuang, J., Kolb, J.F., Schoenbach, K.H., Beebe, S.J.: Long term survival of mice with hepatocellular carcinoma after pulse power ablation with nanosecond pulsed electric fields. Technol. Cancer Res. Treat. 11, 83–93 (2012)Google Scholar
  16. 16.
    Garon, E.B., Sawcer, D., Vernier, P.T., Tang, T., Sun, Y., Marcu, L., Gundersen, M.A., Koeffler, H.P.: In vitro and in vivo evaluation and a case report of intense nanosecond pulsed electric field as a local therapy for human malignancies. Int. J. Cancer 121, 675–682 (2007)CrossRefGoogle Scholar
  17. 17.
    Chalise, P.R., Perni, S., Shama, G., Novac, B.M., Smith, R., et al.: Lethality mechanisms in Escherichia coli induced by intense sub-microsecond electrical pulses. Appl. Phys. Lett. 89, 153902 (2006)CrossRefGoogle Scholar
  18. 18.
    Wang, S., Chen, J., Chen, M.T., Vernier, P.T., Gundersen, M.A., Valderrábano, M.: Cardiac myocyte excitation by ultrashort high-field pulses. Biophys. J. 96, 1640–1648 (2009)CrossRefGoogle Scholar
  19. 19.
    Hargrave, B., Li, F.: Platelet Rich Plasma (PRP) Reduces Reactive Oxygen Species (ROS) production and mitochondrial depolarization in H9c2 cells in culture, reduces infarct size and improves left ventricular mechanical function in the rabbit langendorff heart and in the rabbit heart in vivo. J. Extra Corp. Technol. 44(4), 198–204 (2012)Google Scholar
  20. 20.
    Hargrave, B.Y.: Autologous Platelet rich plasma (Platelet Gel): an appropriate intervention for salvaging cardiac myocytes under oxidative stress after myocardial infarction. Anat. Physiol. 4, 1 (2014)Google Scholar
  21. 21.
    Edelblute, C.M., Amy, L., Donate, A.L., Hargrave, B.Y., Heller, L.C.: Human Platelet Gel Supernatant Inactivates Opportunistic Wound Pathogens on Skin Platelets, Online: Informa UK Ltd, 1–41, London, England (2014)Google Scholar
  22. 22.
    Hargrave, B., Li, F.: Nanosecond pulse electric field activated-platelet rich plasma enhances the return of blood flow to large and ischemic wounds in a rabbit model. Physiol. Rep. 3(7), 1–9 (2015)CrossRefGoogle Scholar
  23. 23.
    Kolb, J.F., Xiao, S., Camp, J.T., Migliaccio, M., Bajracharya, C., Schoenbach, K.H.: Sub-nanosecond electrical pulses for medical therapies and imaging. Proceedings of the Fourth European Conference Antennas and Propagation, pp. 1–5 (2010)Google Scholar
  24. 24.
    Semenov, I., Xiao, S., Kang, D., Schoenbach, K.H., Pakhomov, A.G.: Cell stimulation and calcium mobilization by picosecond electric pulses. Bioelectrochemistry 105, 65–71 (2015)CrossRefGoogle Scholar
  25. 25.
    Joshi, R.P., Mishra, A., Song, J., Pakhomov, A., Schoenbach, K.H.: Simulation studies of ultrashort, high-intensity electric pulse induced action potential block in whole-animal nerves. IEEE. T. Plasma Sci. 55, 1391–1398 (2008)Google Scholar
  26. 26.
    Davalos, R.V., Mir, L., Rubinsky, B.: Tissue ablation with irreversible electroporation. Ann. Biomed. Eng. 33(2), 223–231 (2005)CrossRefGoogle Scholar
  27. 27.
    Al-Sakere, B., Andre, F., Bernat, C., Connault, E., Opolon, P., Davalos, R.V., Rubinsky, B., Mir, L.M.: Tumor ablation with irreversible electroporation. PLoS ONE 2(11), e1135 (2007)CrossRefGoogle Scholar
  28. 28.
    Garcia, P.A., Rossmeisl Jr., J.H., Neal 2nd, R.E., Ellis, T.L., Davalos, R.V.: A parametric study delineating irreversible electroporation from thermal damage based on a minimally invasive intracranial procedure. Biomed. Eng. Online 10(1), 34 (2011)CrossRefGoogle Scholar
  29. 29.
    Garcia, P.A., Rossmeisl Jr., J.H., Neal II, R.E., Ellis, T.L., Olson, J.D., Henao-Guerrero, N., Robertson, J., Davalos, R.V.: Intracranial nonthermal irreversible electroporation: in vivo analysis. J. Membr. Biol. 236(1), 127–136 (2010)CrossRefGoogle Scholar
  30. 30.
    Martin 2nd, R.C., McFarland, K., Ellis, S., Velanovich, V.: Irreversible electroporation therapy in the management of locally advanced pancreatic adenocarcinoma. J. Am. Coll. Surg. 215(3), 361–369 (2012)CrossRefGoogle Scholar
  31. 31.
    Pech, M., Janitzky, A., Wendler, J.J., Strang, C., Blaschke, S., Dudeck, O., Ricke, J., Liehr, U.B.: Irreversible electroporation of renal cell carcinoma: a first-in-man phase I clinical study. Cardiovasc. Intervent. Radiol. 34(1), 132–138 (2011)CrossRefGoogle Scholar
  32. 32.
    Thomson, K.R., Cheung, W., Ellis, S.J., Federman, D., Kavnoudias, H., Loader-Oliver, D., Roberts, S., Evans, P., Ball, C., Haydon, A.: Investigation of the safety of irreversible electroporation in humans. J. Vasc. Interv. Radiol.: JVIR 22(5), 611–621 (2011)CrossRefGoogle Scholar
  33. 33.
    Kingham, T.P., Karkar, A.M., D’Angelica, M.I., Allen, P.J., DeMatteo, R.P., Getrajdman, G.I., Sofocleous, C.T., Solomon, S.B., Jarnagin, W.R., Fong, Y.: Ablation of perivascular hepatic malignant tumors with irreversible electroporation. J. Am. Coll. Surg. 215(3), 379–387 (2012)CrossRefGoogle Scholar
  34. 34.
    Golberg, A., Yarmush, M.L.: Nonthermal irreversible electroporation: fundamentals, applications, and challenges. Biomed. Eng. IEEE. Trans. 60(3), 707–714 (2013)CrossRefGoogle Scholar
  35. 35.
    Cheung, W., Kavnoudias, H., Roberts, S., Szkandera, B., Kemp, W., Thomson, K.R.: Irreversible electroporation for unresectable hepatocellular carcinoma: initial experience and review of safety and outcomes. Technol. Cancer Res. Treat. 12, 233–241 (2013)Google Scholar
  36. 36.
    Garcia, P.A., Pancotto, T., Rossmeisl Jr., J.H., Henao-Guerrero, N., Gustafson, N.R., Daniel, G.B., Robertson, J.L., Ellis, T.L., Davalos, R.V.: Non-thermal irreversible electroporation (N-TIRE) and adjuvant fractionated radiotherapeutic multimodal therapy for intracranial malignant glioma in a canine patient. Technol. Cancer Res. Treat. 10(1), 73–83 (2011)Google Scholar
  37. 37.
    Laroussi, M.: Low temperature plasma-based sterilization: overview and state-of-the-art. Plasma Process. Polym. 2, 391–400 (2005)CrossRefGoogle Scholar
  38. 38.
    Lu, X., Ye, T., Cao, Y.G., Sun, Z.Y., Xiong, Q., Tang, Z.Y., Xiong, Z.L., Hu, J., Jiang, Z.H., Pan, Y.: The roles of the various plasma agents in the inactivation of bacteria. J. Appl. Phys. 104, 053309-1-5 (2008)Google Scholar
  39. 39.
    Graves, D.B.: The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology. J. Phys. D. Appl. Phys. 45, 263001-1-42 (2012)CrossRefGoogle Scholar
  40. 40.
    Kieft, I.E., Kurdi, M., Stoffels, E.: Reattachment and apoptosis after plasma-needle treatment of cultured cells. IEEE. T. Plasma Sci. 34, 1331–1336 (2006)CrossRefGoogle Scholar
  41. 41.
    Jiang, C., Vernier, P.T., Chen, M.T., Wu, Y.H., Wang, L.L., Gundersen, M.A.: Low Energy Nanosecond Pulsed Plasma Sterilization for Endodontic Applications, Proceedings of the 2008 I.E. International Power Modulators and High Voltage Conference, pp. 77–79 (2008)Google Scholar
  42. 42.
    Jiang, C.Q., Chen, M.T., Gorur, A., Schaudinn, C., Jaramillo, D.E., Costerton, J.W., Sedghizadeh, P.P., Vernier, P.T., Gundersen, M.A.: Nanosecond pulsed plasma dental probe. Plasma Process. Polym. 6, 479–483 (2009)CrossRefGoogle Scholar
  43. 43.
    Isbary, G., Morfill, G., Schmidt, H.U., Georgi, M., Ramrath, K., Heinlin, J., Karrer, S., Landthaler, M., Shimizu, T., Steffes, B., Bunk, W., Monetti, R., Zimmermann, J.L., Pompl, R., Stolz, W.: A first prospective randomized controlled trial to decrease bacterial load using cold atmospheric argon plasma on chronic wounds in patients. Br. J. Dermatol. 163, 78–82 (2010)Google Scholar
  44. 44.
    Fridman, G., Peddinghaus, M., Ayan, H., Fridman, A., Balasubramanian, M., Gutsol, A., Brooks, A., Friedman, G.: Blood coagulation and living tissue sterilization by floating-electrode dielectric barrier discharge in air. Plasma Chem. Plasma P. 26, 425–442 (2006)CrossRefGoogle Scholar
  45. 45.
    Sladek, R.E.J., Stoffels, E., Walraven, R., Tielbeek, P.J.A., Koolhoven, R.A.: Plasma treatment of dental cavities: a feasibility study. IEEE. T. Plasma Sci. 32, 1540–1543 (2004)CrossRefGoogle Scholar
  46. 46.
    Sladek, R.E.J., Filoche, S.K., Sissons, C.H., Stoffels, E.: Treatment of Streptococcus mutans biofilms with a nonthermal atmospheric plasma. Lett. Appl. Microbiol. 45, 318–323 (2007)CrossRefGoogle Scholar
  47. 47.
    Kieft, I.E., Darios, D., Roks, A.J.M., Stoffels, E.: Plasma treatment of mammalian vascular cells: a quantitative description. IEEE. T. Plasma Sci. 33, 771–775 (2005)CrossRefGoogle Scholar
  48. 48.
    Okino, M., Mohri, H.: Effects of a high-voltage electrical impulse and an anticancer drug on in vivo growing tumors. Jpn. J. Cancer Res. 78, 1319–1321 (1987)Google Scholar
  49. 49.
    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)CrossRefGoogle Scholar
  50. 50.
    Gothelf, A., Mir, L.M., Gehl, J.: Electrochemotherapy: results of cancer treatment using enhanced delivery of bleomycin by electroporation. Cancer Treat. Rev. 29(5), 371–387 (2003)CrossRefGoogle Scholar
  51. 51.
    Mir, L.M., Gehl, J., Sersa, G., Collins, C.G., Garbay, J.R., Billard, V., et al.: 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 Cliniporator (TM) by means of invasive or non-invasive electrodes. EJC Suppl. 4(11), 14–25 (2006)CrossRefGoogle Scholar
  52. 52.
    Gilbert, R., Jaroszeski, M.J., Heller, R.: Novel electrode designs for electrochemotherapy. Biochem. Biophys. Acta 1334, 9–14 (1997)CrossRefGoogle Scholar
  53. 53.
    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(5), 2152–2158 (1998)CrossRefGoogle Scholar
  54. 54.
    Mahmood, F., Gehl, J.: Optimizing clinical performance and geometrical robustness of a new electrode device for intracranial tumor electroporation. Bioelectrochemistry 81, 10–16 (2011)CrossRefGoogle Scholar
  55. 55.
    Staal, L.G., Gilbert, R.: In: Kee, S., Gehl, J., Lee, E. (eds.) Generators and Applicators: Equipment for Electroporation, pp. 45–65. Springer, New York (2011)Google Scholar
  56. 56.
    Miklavcic, D., Sersa, G., Brecelj, E., Gehl, J., Soden, D., Bianchi, G., et al.: Electrochemotherapy: technological advancements for efficient electroporation-based treatment of internal tumors. Med. Biol. Eng. Comput. 50(12), 1213–1225 (2012)CrossRefGoogle Scholar
  57. 57.
    Sersa, G., Krzic, M., Sentjurc, M., Ivanusa, T., Beravs, K., Kotnik, V., et al.: Reduced blood flow and oxygenation in SA-1 tumours after electrochemotherapy with cisplatin. Br. J. Cancer 87(9), 1047–1054 (2002)CrossRefGoogle Scholar
  58. 58.
    Gehl, J., Skovsgaard, T., Mir, L.M.: Vascular reactions to in vivo electroporation: characterization and consequences for drug and gene delivery. Biochim. Biophys. Acta 1569(1–3), 51–58 (2002)CrossRefGoogle Scholar
  59. 59.
    Mir, L.M., Belehradek, M., Domenge, C., Orlowski, S., Poddevin, B., Belehradek Jr., J., Schwaab, G., Luboinski, B., Paoletti, C.: Electrochemotherapy, a new antitumor treatment: first clinical trial. C. R. Acad. Sci. III 313, 613–618 (1991)Google Scholar
  60. 60.
    Marty, M., Sersa, G., Garbay, J.R., Gehl, J., Collins, C.G., Snoj, M., et al.: 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(11), 3–13 (2006)CrossRefGoogle Scholar
  61. 61.
    Matthiessen, L.W., Chalmers, R.L., Sainsbury, D.C., Veeramani, S., Kessell, G., Humphreys, A.C., et al.: Management of cutaneous metastases using electrochemotherapy. Acta Oncol. 50(5), 621–629 (2011)CrossRefGoogle Scholar
  62. 62.
    Matthiessen, L.W., Johannesen, H.H., Hendel, H.W., Moss, T., Kamby, C., Gehl, J.: Electrochemotherapy for large cutaneous recurrence of breast cancer: a phase II clinical trial. Acta Oncol. 51(6), 713–721 (2012)CrossRefGoogle Scholar
  63. 63.
    Heller, R., Jaroszeski, M.J., Reintgen, D.S., Puleo, C.A., DeConti, R.C., Gilbert, R.A., et al.: Treatment of cutaneous and subcutaneous tumors with electrochemotherapy using intralesional bleomycin. Cancer 83(1), 148–157 (1998)CrossRefGoogle Scholar
  64. 64.
    Spratt, D.E., Spratt, E.A.G., Wu, S.: Efficacy of skin-directed therapy for cutaneous metastases from advanced cancer: a meta-analysis. J. Clin. Oncol. 32, 3144–3155 (2014)CrossRefGoogle Scholar
  65. 65.
    National Institute for H, Care E.: Electrochemotherapy for metastases in the skin from tumours of non-skin origin and melanoma. (2013)
  66. 66.
    Cadossi, R., Ronchetti, M., Cadossi, M.: Locally enhanced chemotherapy by electroporation: clinical experiences and perspective of use of electrochemotherapy. Future Oncol. 10, 877–890 (2014)CrossRefGoogle Scholar
  67. 67.
    Edhemovic, I., Brecelj, E., Gasljevic, G., Marolt Music, M., Gorjup, V., Mali, B., et al.: Intraoperative electrochemotherapy of colorectal liver metastases. J. Surg. Oncol. 110(3), 320–327 (2014)CrossRefGoogle Scholar
  68. 68.
    Granata, V., Fusco, R., Piccirillo, M., Palaia, R., Petrillo, A., Izzo, F.: Electrochemotherapy in locally advanced pancreatic cancer: preliminary results. Int. J. Surg. 18, 230–236 (2015)CrossRefGoogle Scholar
  69. 69.
    Agerholm-Larsen, B., Iversen, H.K., Ibsen, P., Moller, J.M., Mahmood, F., Jensen, K.S., et al.: Preclinical validation of electrochemotherapy as an effective treatment for brain tumors. Cancer Res. 71, 3753–3762 (2011)CrossRefGoogle Scholar
  70. 70.
    Bourke, M.G., Salwa, S., Sadadcharam, M., Forde, P., O’Sullivan, G.C., Soden, D.: Development of an endoscopically delivered ablative treatment for gastrointestinal tumours. Ir. J. Med. Sci. 179, S361–S61 (2010)CrossRefGoogle Scholar
  71. 71.
    Fini, M., Salamanna, F., Parrilli, A., Martini, L., Cadossi, M., Maglio, M., et al.: Electrochemotherapy is effective in the treatment of rat bone metastases. Clin. Exp. Metastasis 30(8), 1033–1045 (2013)CrossRefGoogle Scholar
  72. 72.
    Cemazar, M., et al.: Electrochemotherapy in veterinary oncology. J. Vet. Intern. Med. 22(4), 826–831 (2008)CrossRefGoogle Scholar
  73. 73.
    Frandsen, S.K., Gissel, H., Hojman, P., Tramm, T., Eriksen, J., Gehl, J.: Direct therapeutic applications of calcium electroporation to effectively induce tumor necrosis. Cancer Res. 72(6), 1336–1341 (2012)CrossRefGoogle Scholar
  74. 74.
    Heller, R., Jaroszeski, M., Atkin, A., Moradpour, D., Gilbert, R., Wands, J., Nicolau, C.: In vivo gene electroinjection and expression in rat liver. FEBS Lett. 389(3), 225–228 (1996)CrossRefGoogle Scholar
  75. 75.
    Aihara, H., Miyazaki, J.: Gene transfer into muscle by electroporation in vivo. Nat. Biotechnol. 16(9), 867–870 (1998). doi: 10.1038/nbt0998-867 CrossRefGoogle Scholar
  76. 76.
    Titomirov, A.V., Sukharev, S., Kistanova, E.: In vivo electroporation and stable transformation of skin cells of newborn mice by plasmid DNA. Biochim. Biophys. Acta 1088(1), 131–134 (1991)CrossRefGoogle Scholar
  77. 77.
    Rols, M.P., Delteil, C., Golzio, M., Dumond, P., Cros, S., Teissie, J.: In vivo electrically mediated protein and gene transfer in murine melanoma. Nat. Biotechnol. 16(2), 168–171 (1998). doi: 10.1038/nbt0298-168 CrossRefGoogle Scholar
  78. 78.
    Niu, G., Heller, R., Catlett-Falcone, R., Coppola, D., Jaroszeski, M., Dalton, W., Jove, R., Yu, H.: Gene therapy with dominant-negative Stat3 suppresses growth of the murine melanoma B16 tumor in vivo. Cancer Res. 59(20), 5059–5063 (1999)Google Scholar
  79. 79.
    Young, J.L., Dean, D.A.: Electroporation-mediated gene delivery. Adv. Genet. 89, 49–88 (2015)Google Scholar
  80. 80.
    Heller, R., Heller, L.C.: Gene electrotransfer clinical trials. Adv. Genet. 89, 235–262 (2015)Google Scholar
  81. 81.
    Daud, A.I., DeConti, R.C., Andrews, S., Urbas, P., Riker, A.I., Sondak, V.K., Munster, P.N., Sullivan, D.M., Ugen, K.E., Messina, J.L., Heller, R.: Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J. Clin. Oncol. 26, 5896–5903 (2008)CrossRefGoogle Scholar
  82. 82.
    Yang, L.J., Yu, W.D., Du, J.B., Chao, S., Chen, M.X., Zhao, H.H., Guo, J.Z.: Overexpression or knock-down of runt-related transcription factor 1 affects BCR-ABL-induced proliferation and migration in vitro and leukemogenesis in vivo in mice. Chin. Med. J. (Engl.) 122(3), 331–337 (2009)Google Scholar
  83. 83.
    Magee, T.R., Artaza, J.N., Ferrini, M.G., Vernet, D., Zuniga, F.I., Cantini, L., Reisz-Porszasz, S., Rajfer, J., Gonzalez-Cadavid, N.F.: Myostatin short interfering hairpin RNA gene transfer increases skeletal muscle mass. J. Gene Med. 8(9), 1171–1181 (2006)CrossRefGoogle Scholar
  84. 84.
    Magee, T.R., Kovanecz, I., Davila, H.H., Ferrini, M.G., Cantini, L., Vernet, D., Zuniga, F.I., Rajfer, J., Gonzalez-Cadavid, N.F.: Antisense and short hairpin RNA (shRNA) constructs targeting PIN (Protein Inhibitor of NOS) ameliorate aging-related erectile dysfunction in the rat. J. Sex. Med. 4(3), 633–643 (2007)CrossRefGoogle Scholar
  85. 85.
    Takahashi, Y., Nishikawa, M., Takakura, Y.: Suppression of tumor growth by intratumoral injection of short hairpin RNA-expressing plasmid DNA targeting beta-catenin or hypoxia-inducible factor 1alpha. J. Control. Release 116(1), 90–95 (2006)CrossRefGoogle Scholar
  86. 86.
    Dolinsek, T., Markelc, B., Sersa, G., Coer, A., Stimac, M., Lavrencak, J., Brozic, A., Kranjc, S., Cemazar, M.: Multiple delivery of siRNA against endoglin into murine mammary adenocarcinoma prevents angiogenesis and delays tumor growth. PLoS ONE 8(3), e58723 (2013)CrossRefGoogle Scholar
  87. 87.
    Benteyn, D., Van Nuffel, A.M., Wilgenhof, S., Corthals, J., Heirman, C., Neyns, B., Thielemans, K., Bonehill, A.: Characterization of CD8+ T-cell responses in the peripheral blood and skin injection sites of melanoma patients treated with mRNA electroporated autologous dendritic cells (TriMixDC-MEL). Biomed. Res. Int. 2013, 976383 (2013)CrossRefGoogle Scholar
  88. 88.
    Van Nuffel, A.M., Benteyn, D., Wilgenhof, S., Corthals, J., Heirman, C., Neyns, B., Thielemans, K., Bonehill, A.: Intravenous and intradermal TriMix-dendritic cell therapy results in a broad T-cell response and durable tumor response in a chemorefractory stage IV-M1c melanoma patient. Cancer Immunol. Immunother. 61(7), 1033–1043 (2012)CrossRefGoogle Scholar
  89. 89.
    Van Nuffel, A.M., Benteyn, D., Wilgenhof, S., Pierret, L., Corthals, J., Heirman, C., van der Bruggen, P., Coulie, P.G., Neyns, B., Thielemans, K., Bonehill, A.: Dendritic cells loaded with mRNA encoding full-length tumor antigens prime CD4+ and CD8+ T cells in melanoma patients. Mol. Ther. 20(5), 1063–1074 (2012)CrossRefGoogle Scholar
  90. 90.
    Wilgenhof, S., Corthals, J., Van Nuffel, A.M., Benteyn, D., Heirman, C., Bonehill, A., Thielemans, K., Neyns, B.: Long-term clinical outcome of melanoma patients treated with messenger RNA-electroporated dendritic cell therapy following complete resection of metastases. Cancer Immunol. Immunother. 64(3), 381–388 (2015)CrossRefGoogle Scholar
  91. 91.
    Wilgenhof, S., Van Nuffel, A.M., Corthals, J., Heirman, C., Tuyaerts, S., Benteyn, D., De Coninck, A., Van Riet, I., Verfaillie, G., Vandeloo, J., Bonehill, A., Thielemans, K., Neyns, B.: Therapeutic vaccination with an autologous mRNA electroporated dendritic cell vaccine in patients with advanced melanoma. J. Immunother. 34(5), 448–456 (2011)CrossRefGoogle Scholar
  92. 92.
    Beatty, G.L., Haas, A.R., Maus, M.V., Torigian, D.A., Soulen, M.C., Plesa, G., Chew, A., Zhao, Y., Levine, B.L., Albelda, S.M., Kalos, M., June, C.H.: Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol. Res. 2(2), 112–120 (2014)CrossRefGoogle Scholar
  93. 93.
    Pavlin, D., Cemazar, M., Sersa, G., Tozon, N.: IL-12 based gene therapy in veterinary medicine. J. Transl. Med. 10, 234-1-10 (2012)CrossRefGoogle Scholar
  94. 94.
    Neumann, E., Sowers, A.E., Jordan, C.A.: Electroporation and Electrofusion in Cell Biology. Plenum press, York (1989)CrossRefGoogle Scholar
  95. 95.
    Weaver, J.C., Chizmadzhev, Y.A.: Theory of electroporation: a review. Bioelectrochem. Bioenerg. 41, 135–160 (1996)CrossRefGoogle Scholar
  96. 96.
    Teissié, J., Golzio, M., Rols, M.P.: Mechanisms of cell membrane electropermeabilization: a mini-review of our present (lack of?) knowledge. Biochim. Biophys. Acta 2005, 270–280 (1724)Google Scholar
  97. 97.
    Tekle, E., Astumian, R.D., Chock, P.B.: Selective and asymmetric molecular transport across electroporated cell membranes. Proc. Natl. Acad. Sci. U. S. A. 91, 11512–11516 (1994)CrossRefGoogle Scholar
  98. 98.
    siRNA, Paganin-Gioanni, A., et al.: Direct visualization at the single-cell level of siRNA electrotransfer into cancer cells. Proc. Natl. Acad. Sci. U. S. A. 108(26), 10443–10447 (2011)CrossRefGoogle Scholar
  99. 99.
    pDNA, Neumann, E., Shaefer-Ridder, M., Wang, Y., Hofschneider, P.H.: Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J. 1, 841–845 (1982)Google Scholar
  100. 100.
    Tekle, E., Astumian, R.D., Chock, P.B.: Electroporation by using bipolar oscillating electric field: an improved method for DNA transfection of NIH 3T3 cells. Proc. Natl. Acad. Sci. U. S. A. 88, 4230–4234 (1991)CrossRefGoogle Scholar
  101. 101.
    Golzio, M., Teissié, J., Rols, M.P.: Direct visualization at the single-cell level of electrically mediated gene delivery. Proc. Natl. Acad. Sci. U. S. A. 99, 1292–1297 (2002)CrossRefGoogle Scholar
  102. 102.
    Escoffre, J.M., Portet, T., Favard, C., Teissié, J., Dean, D.S., Rols, M.P.: Electromediated formation of DNA complexes with cell membranes and its consequences for gene delivery. Biochim. Biophys. Acta. 1808(6), 1538–1543 (2011)CrossRefGoogle Scholar
  103. 103.
    Rosazza, C., Buntz, A., Rieß, T., Wöll, D., Zumbusch, A., Rols, M.P.: Intracellular tracking of single-plasmid DNA particles after delivery by electroporation. Mol. Ther. 21(12), 2217–2226 (2013)CrossRefGoogle Scholar
  104. 104.
    Golzio, M., Mora, M.P., Raynaud, C., Delteil, C., Teissie, J., Rols, M.P.: Control by osmotic pressure of voltage-induced permeabilization and gene transfer in mammalian cells. Biophys. J. 74, 3015–3022 (1998)CrossRefGoogle Scholar
  105. 105.
    Faurie, C., Phez, E., Golzio, M., Vossen, C., Lesbordes, J.C., Delteil, C., Teissié, J., Rols, M.P.: Effect of electric field vectoriality on electrically mediated gene delivery in mammalian cells. Biochim. Biophys. Acta 1665(1–2), 92–100 (2004)CrossRefGoogle Scholar
  106. 106.
    Kanduser, M., Miklavcic, D., Pavlin, M.: Mechanisms involved in gene electrotransfer using high- and low-voltage pulse—an in vitro study. Bioelectrochemistry 74, 265–271 (2009)CrossRefGoogle Scholar
  107. 107.
    Cemazar, M., Sersa, G.: Electrotransfer of therapeutic molecules into tissues. Curr. Opin. Mol. Ther. 9(6), 554–562 (2007)Google Scholar
  108. 108.
    siRNA, Golzio, M., et al.: Inhibition of gene expression in mice muscle by in vivo electrically mediated siRNA delivery. Gene Ther. 12(3), 246–251 (2005)CrossRefGoogle Scholar
  109. 109.
    Golzio, M., et al.: In vivo gene silencing in solid tumors by targeted electrically mediated siRNA delivery. Gene Ther. 14(9), 752–759 (2007)CrossRefGoogle Scholar
  110. 110.
    pDNA, Cemazar, M., Golzio, M., Sersa, G., Rols, M.P., Teissié, J.: Electrically-assisted nucleic acids delivery to tissues in vivo: where do we stand? Curr. Pharm. Des. 12(29), 3817–3825 (2006)CrossRefGoogle Scholar
  111. 111.
    Hojman, P.: Basic principles and clinical advancements of muscle electrotransfer. Curr. Gene Ther. 10(2), 128–138 (2010)CrossRefGoogle Scholar
  112. 112.
    Bodles-Brakhop, A.M., Heller, R., Draghia-Akli, R.: Electroporation for the delivery of DNA-based vaccines and immunotherapeutics. Curr. Clin. Dev. Mol. Ther. 17(4), 585–592 (2009)Google Scholar
  113. 113.
    Satkauskas, S., Bureau, M.F., Puc, M., Mahfoudi, A., Scherman, D., Miklavcic, D., Mir, L.M.: Mechanisms of in vivo DNA electrotransfer: respective contributions of cell electropermeabilization and DNA electrophoresis. Mol. Ther. 5, 133–140 (2002)CrossRefGoogle Scholar
  114. 114.
    André, F.M., Gehl, J., Sersa, G., Préat, V., Hojman, P., Eriksen, J., Golzio, M., Cemazar, M., Pavselj, N., Rols, M.P., Miklavcic, D., Neumann, E., Teissié, J., Mir, L.M.: Efficiency of high- and low-voltage pulse combinations for gene electrotransfer in muscle, liver, tumor, and skin. Hum. Gene Ther. 19(11), 1261–1271 (2008)CrossRefGoogle Scholar
  115. 115.
    Cemazar, M., Golzio, M., Sersa, G., Escoffre, J.M., Coer, A., Vidic, S., Teissie, J.: Hyaluronidase and collagenase increase the transfection efficiency of gene electrotransfer in various murine tumors. Hum. Gene Ther. 23(1), 128–137 (2012)CrossRefGoogle Scholar
  116. 116.
    McMahon, J.M., Signori, E., Wells, K.E., Fazio, V.M., Wells, D.J.: Optimisation of electrotransfer of plasmid into skeletal muscle by pretreatment with hyaluronidase – increased expression with reduced muscle damage. Gene Ther. 8(16), 1264–1270 (2001)CrossRefGoogle Scholar
  117. 117.
    Levine, Z.A., Vernier, P.T.: Life cycle of an electropore: field-dependent and field-independent steps in pore creation and annihilation. J. Membr. Biol. 236(1), 27–36 (2010)CrossRefGoogle Scholar
  118. 118.
    Gabriel, B., Teissie, J.: Direct observation in the millisecond time range of fluorescent molecule asymmetrical interaction with the electropermeabilized cell membrane. Biophys. J. 73(5), 2630–2637 (1997)CrossRefGoogle Scholar
  119. 119.
    Canatella, P.J., Karr, J.F., Petros, J.A., Prausnitz, M.R.: Quantitative study of electroporation-mediated molecular uptake and cell viability. Biophys. J. 80, 755–764 (2001)CrossRefGoogle Scholar
  120. 120.
    Gehl, J., Skovsgaard, T., Mir, L.M.: Enhancement of cytotoxicity by electropermeabilization: an improved method for screening drugs. Anti-Cancer Drugs 9(4), 319–325 (1998)CrossRefGoogle Scholar
  121. 121.
    Jaroszeski, M.J., Dang, V., Pottinger, C., Hickey, J., Gilbert, R., Heller, R.: Toxicity of anticancer agents mediated by electroporation in vitro. Anti-Cancer Drugs 11, 201–208 (2000)CrossRefGoogle Scholar
  122. 122.
    Orlowski, S., Belehradek Jr., J., Paoletti, C., Mir, L.M.: Transient electropermeabilization of cells in culture. Increase of the cytotoxicity of anticancer drugs. Biochem. Pharmacol. 37(24), 4727–4733 (1988)CrossRefGoogle Scholar
  123. 123.
    Sersa, G., Cemazar, M., Miklavcic, D.: Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice. Cancer Res. 55(15), 3450–3455 (1995)Google Scholar
  124. 124.
    Umezawa, H., Maeda, K., Takeuchi, T., Okami, Y.: New antibiotics, bleomycin A and B. J. Antibiot. (Tokyo) 19(5), 200–209 (1966)Google Scholar
  125. 125.
    Tounekti, O., Kenani, A., Foray, N., Orlowski, S., Mir, L.M.: The ratio of single- to double-strand DNA breaks and their absolute values determine cell death pathway. Br. J. Cancer 84(9), 1272–1279 (2001)CrossRefGoogle Scholar
  126. 126.
    Vermorken, J.B., Mesia, R., Rivera, F., Remenar, E., Kawecki, A., Rottey, S., et al.: Platinum-based chemotherapy plus cetuximab in head and neck cancer. N. Engl. J. Med. 359, 1116–1127 (2008)CrossRefGoogle Scholar
  127. 127.
    Vasquez, J.L., Ibsen, P., Lindberg, H., Gehl, J.: In vitro and in vivo experiments on electrochemotherapy for bladder cancer. J. Urol. 193(3), 1009–1015 (2015)CrossRefGoogle Scholar
  128. 128.
    Frandsen, S.K., Gissel, H., Hojman, P., Eriksen, J., Gehl, J.: Calcium electroporation in three cell lines: a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions. Biochim. Biophys. Acta 2014, 1204–1208 (1840)Google Scholar
  129. 129.
    Glass, L.F., Pepine, M.L., Fenske, N.A., Jaroszeski, M., Reintgen, D.S., Heller, R.: Bleomycin-mediated electrochemotherapy of metastatic melanoma. Arch. Dermatol. 132(11), 1353–1357 (1996)CrossRefGoogle Scholar
  130. 130.
    Gehl, J., Sorensen, T.H., Nielsen, K., Raskmark, P., Nielsen, S.L., Skovsgaard, T., et al.: In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution. Biochim. Biophys. Acta 1428(2–3), 233–240 (1999)CrossRefGoogle Scholar
  131. 131.
    Gothelf, A., Mahmood, F., Dagnaes-Hansen, F., Gehl, J.: Efficacy of transgene expression in porcine skin as a function of electrode choice. Bioelectrochemistry 82, 95–102 (2011)CrossRefGoogle Scholar
  132. 132.
    Heller, R., Jaroszeski, M.J., Glass, L.F., Messina, J.L., Rapaport, D.P., DeConti, R.C., et al.: Phase I/II trial for the treatment of cutaneous and subcutaneous tumors using electrochemotherapy. Cancer 77(5), 964–971 (1996)CrossRefGoogle Scholar
  133. 133.
    Sersa, G., Stabuc, B., Cemazar, M., Miklavcic, D., Rudolf, Z.: Electrochemotherapy with cisplatin: clinical experience in malignant melanoma patients. Clin. Cancer Res. 6(3), 863–867 (2000)Google Scholar
  134. 134.
    Campana, L.G., Valpione, S., Mocellin, S., Sundararajan, R., Granziera, E., Sartore, L., et al.: Electrochemotherapy for disseminated superficial metastases from malignant melanoma. Br. J. Surg. 99, 821–830 (2012)CrossRefGoogle Scholar
  135. 135.
    Quaglino, P., Mortera, C., Osella-Abate, S., Barberis, M., Illengo, M., Rissone, M., et al.: Electrochemotherapy with intravenous bleomycin in the local treatment of skin melanoma metastases. Ann. Surg. Oncol. 15, 2215–2222 (2008)CrossRefGoogle Scholar
  136. 136.
    Sersa, G., Stabuc, B., Cemazar, M., Miklavcic, D., Rudolf, Z.: Electrochemotherapy with cisplatin: the systemic antitumour effectiveness of cisplatin can be potentiated locally by the application of electric pulses in the treatment of malignant melanoma skin metastases. Melanoma Res. 10(4), 381–385 (2000)CrossRefGoogle Scholar
  137. 137.
    Glass, L.F., Jaroszeski, M., Gilbert, R., Reintgen, D.S., Heller, R.: Intralesional bleomycin-mediated electrochemotherapy in 20 patients with basal cell carcinoma. J. Am. Acad. Dermatol. 37(0190-9622 SB - IM), 596–599 (1997)CrossRefGoogle Scholar
  138. 138.
    Curatolo, P., Rotunno, R., Miraglia, E., Mancini, M., Calvieri, S., Giustini, S.: Complete remission of Merkel cell carcinoma treated with electrochemotherapy and etoposide. G. Ital. Dermatol. Venereol. 148(3), 310–311 (2013)Google Scholar
  139. 139.
    Curatolo, P., Quaglino, P., Marenco, F., Mancini, M., Nardo, T., Mortera, C., et al.: Electrochemotherapy in the treatment of Kaposi sarcoma cutaneous lesions: a two-center prospective phase II trial. Ann. Surg. Oncol. 19(1), 192–198 (2012)CrossRefGoogle Scholar
  140. 140.
    Curatolo, P., Miraglia, E., Rotunno, R., Calvieri, S., Giustini, S.: Electrochemotherapy: a valid treatment for Gorlin-Goltz syndrome. Acta Dermatovenerol. Croat. 21(2), 132–133 (2013)Google Scholar
  141. 141.
    Belehradek, M., Domenge, C., Luboinski, B., Orlowski, S., Belehradek Jr., J., Mir, L.M.: Electrochemotherapy, a new antitumor treatment. First clinical phase I-II trial. Cancer 72(12), 3694–3700 (1993)CrossRefGoogle Scholar
  142. 142.
    Campana, L.G., Valpione, S., Falci, C., Mocellin, S., Basso, M., Corti, L., et al.: The activity and safety of electrochemotherapy in persistent chest wall recurrence from breast cancer after mastectomy: a phase-II study. Breast Cancer Res. Treat. 134, 1169–1178 (2012)CrossRefGoogle Scholar
  143. 143.
    Campana, L.G., Mali, B., Sersa, G., Valpione, S., Giorgi, C.A., Strojan, P., et al.: Electrochemotherapy in non-melanoma head and neck cancers: a retrospective analysis of the treated cases. Br. J. Oral Maxillofac. Surg. 52(10), 957–964 (2014)CrossRefGoogle Scholar
  144. 144.
    Campana, L.G., Galuppo, S., Valpione, S., Brunello, A., Ghiotto, C., Ongaro, A., et al.: Bleomycin electrochemotherapy in elderly metastatic breast cancer patients: clinical outcome and management considerations. J. Cancer Res. Clin. Oncol. 140(9), 1557–1565 (2014)CrossRefGoogle Scholar
  145. 145.
    Kubota, Y., Mir, L.M., Nakada, T., Sasagawa, I., Suzuki, H., Aoyama, N.: Successful treatment of metastatic skin lesions with electrochemotherapy. J. Urol. 160(4), 1426–26 (1998)CrossRefGoogle Scholar
  146. 146.
    Wasungu, L., Marty, A.L., Bureau, M.F., Kichler, A., Bessodes, M., Teissie, J., et al.: Pre-treatment of cells with pluronic L64 increases DNA transfection mediated by electrotransfer. J. Control. Release 149(2), 117–125 (2011)CrossRefGoogle Scholar
  147. 147.
    Sersa, G., Stabuc, B., Cemazar, M., Jancar, B., Miklavcic, D., Rudolf, Z.: Electrochemotherapy with cisplatin: potentiation of local cisplatin antitumour effectiveness by application of electric pulses in cancer patients. Eur. J. Cancer 34(8), 1213–1218 (1998)CrossRefGoogle Scholar
  148. 148.
    Glass, L.F., Fenske, N.A., Jaroszeski, M., Perrott, R., Harvey, D.T., Reintgen, D.S., et al.: Bleomycin-mediated electrochemotherapy of basal cell carcinoma. J. Am. Acad. Dermatol. 34(1), 82–86 (1996)CrossRefGoogle Scholar
  149. 149.
    Salwa, S.P., Bourke, M.G., Forde, P.F., O’Shaughnessy, M., O’Sullivan, S.T., Kelly, E.J., et al.: Electrochemotherapy for the treatment of ocular basal cell carcinoma; a novel adjunct in the disease management. J. Plast. Reconstr. Aesthet. Surg. 67(3), 403–406 (2014)CrossRefGoogle Scholar
  150. 150.
    Rodriguez-Cuevas, S., Barroso-Bravo, S., Almanza-Estrada, J., Cristobal-Martinez, L., Gonzalez-Rodriguez, E.: Electrochemotherapy in primary and metastatic skin tumors: phase II trial using intralesional bleomycin. Arch. Med. Res. 32(4), 273–276 (2001)CrossRefGoogle Scholar
  151. 151.
    Gargiulo, M., Papa, A., Capasso, P., Moio, M., Cubicciotti, E., Parascandolo, S.: Electrochemotherapy for non-melanoma head and neck cancers: clinical outcomes in 25 patients. Ann. Surg. 255(6), 1158–1164 (2012)CrossRefGoogle Scholar
  152. 152.
    Richetta, A.G., Curatolo, P., D’Epiro, S., Mancini, M., Mattozzi, C., Giancristoforo, S., et al.: Efficacy of electrochemotherapy in ulcerated basal cell carcinoma. Clin. Ter. 162(5), 443–445 (2011)Google Scholar
  153. 153.
    Fantini, F., Gualdi, G., Cimitan, A., Giannetti, A.: Metastatic basal cell carcinoma with squamous differentiation. Arch. Dermatol. 144(9), 1186–1188 (2008)CrossRefGoogle Scholar
  154. 154.
    Quaglino, P., Matthiessen, L.W., Curatolo, P., Muir, T., Bertino, G., Kunte, C., et al.: Predicting patients at risk for pain associated with electrochemotherapy. Acta Oncol. 54(3), 298–306 (2015)CrossRefGoogle Scholar
  155. 155.
    Ramirez, L.H., Orlowski, S., An, D., Bindoula, G., Dzodic, R., Ardouin, P., et al.: Electrochemotherapy on liver tumours in rabbits. Br. J. Cancer 77(12), 2104–2111 (1998)CrossRefGoogle Scholar
  156. 156.
    Edhemovic, I., Gadzijev, E.M., Brecelj, E., Miklavcic, D., Kos, B., Zupanic, A., et al.: Electrochemotherapy: a new technological approach in treatment of metastases in the liver. Technol. Cancer Res. Treat. 10(5), 475–485 (2011)Google Scholar
  157. 157.
    Panje, W.R., Sadeghi, N.: Endoscopic and electroporation therapy of paranasal sinus tumors. Am. J. Rhinol. 14(3), 187–191 (2000)CrossRefGoogle Scholar
  158. 158.
    Panje, W.R., Hier, M.P., Garman, G.R., Harrell, E., Goldman, A., Bloch, I.: Electroporation therapy of head and neck cancer. Ann. Otol. Rhinol. Laryngol. 107(9), 779–785 (1998)CrossRefGoogle Scholar
  159. 159.
    Goldfarb, P., Biel, M., Hanna, E., Houck, J., Klotch, C., Nathan, C., et al.: A Phase II Study Using Electroporation (EPT) and Intratumoral Bleomycin in Patients with Recurrent Head and Neck Cancer: A Safe and Active Treatment Approach. ASCO Proceedings (1999)Google Scholar
  160. 160.
    Allegretti, J.P., Panje, W.R.: Electroporation therapy for head and neck cancer including carotid artery involvement. Laryngoscope 111(1), 52–56 (2001)CrossRefGoogle Scholar
  161. 161.
    Linnert, M., Agerholm-Larsen, B., Mahmood, F., Iversen, H.K., Gehl, J.: Electrochemotherapy for primary and secondary brain tumors. In: Hayat MA, editor. Tumors of the Central Nervous System, pp. 195–206 (2011)Google Scholar
  162. 162.
    (NICE) NIfHaCE: Electrochemotherapy for primary basal cell carcinoma and primary squamous cell carcinoma. (2014)
  163. 163.
    Valpione, S., Campana, L.G., Pigozzo, J., Chiarion-Sileni, V.: Consolidation electrochemotherapy with bleomycin in metastatic melanoma during treatment with dabrafenib. Radiol. Oncol. 49(1), 71–74 (2015)CrossRefGoogle Scholar
  164. 164.
    Mir, L.M., Orlowski, S., Poddevin, B., Belehradek Jr., J.: Electrochemotherapy tumor treatment is improved by interleukin-2 stimulation of the host’s defenses. Eur. Cytokine Netw. 3(3), 331–334 (1992)Google Scholar
  165. 165.
    Calvet, C.Y., Famin, D., Andre, F.M., Mir, L.M.: Electrochemotherapy with bleomycin induces hallmarks of immunogenic cell death in murine colon cancer cells. Oncoimmunology 3, e28131 (2014)CrossRefGoogle Scholar
  166. 166.
    Andersen, M.H., Gehl, J., Reker, S., Pedersen, L.O., Becker, J.C., Geertsen, P., et al.: Dynamic changes of specific T cell responses to melanoma correlate with IL-2 administration. Semin. Cancer Biol. 13(1044-579X), 449–459 (2003)CrossRefGoogle Scholar
  167. 167.
    Maxim, P.G., Carson, J.J., Ning, S., Knox, S.J., Boyer, A.L., Hsu, C.P., et al.: Enhanced effectiveness of radiochemotherapy with tirapazamine by local application of electric pulses to tumors. Radiat. Res. 162, 185–193 (2004)CrossRefGoogle Scholar
  168. 168.
    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 5, 115 (2005)CrossRefGoogle Scholar
  169. 169.
    Gehl, J., Andersen, M.H., Straten, P.T., Geertsen, P.: Tumor autovaccination by electrochemotherapy followed by low-dose Il-2 in advanced malignant melanoma: efficient with low toxicity. J Clin Oncol; 20 (Proceedings, Am Soc Clin Oncol) (2001)Google Scholar
  170. 170.
    Sersa, G., Teissie, J., Cemazar, M., Signori, E., Kamensek, U., Marshall, G.D., et al.: Electrochemotherapy of tumors as in situ vaccination boosted by immunogene electrotransfer. Cancer Immunol. Immunother. 64, 1315–1327 (2015)CrossRefGoogle Scholar
  171. 171.
    Edd, J.F., Horowitz, L., Davalos, R.V., Mir, L.M., Rubinsky, B.: In vivo results of a new focal tissue ablation technique: irreversible electroporation. IEEE. Trans. Biomed. Eng. 53(7), 1409–1415 (2006)CrossRefGoogle Scholar
  172. 172.
    Phillips, M.A., Narayan, R., Padath, T., Rubinsky, B.: Irreversible electroporation on the small intestine. Br. J. Cancer 106(3), 490–495 (2012)CrossRefGoogle Scholar
  173. 173.
    Neal II, R.E., Rossmeisl Jr., J.H., Garcia, P.A., Lanz, O.I., Henao-Guerrero, N., Davalos, R.V.: Successful treatment of a large soft tissue sarcoma with irreversible electroporation. J. Clin. Oncol. 29(13), e372–e377 (2011)CrossRefGoogle Scholar
  174. 174.
    Wagstaff, P.G.K., de Bruin, D.M., van den Bos, W., Ingels, A., van Gemert, M.J.C., Zondervan, P.J., Verdaasdonk, R.M., van Lienden, K.P., van Leeuwen, T.G., de la Rosette, J.J.: Irreversible electroporation of the porcine kidney: temperature development and distribution. Urol. Oncol. Semin. Orig. Invest. 33(4), 168e1–168.e7 (2015)CrossRefGoogle Scholar
  175. 175.
    Qin, Z., Jiang, J., Long, G., Lindgren, B., Bischof, J.C.: Irreversible electroporation: an in vivo study with dorsal skin fold chamber. Ann. Biomed. Eng. 41(3), 619–629 (2013)CrossRefGoogle Scholar
  176. 176.
    Becker, S.M., Kuznetsov, A.V.: Thermal damage reduction associated with in vivo skin electroporation: a numerical investigation justifying aggressive pre-cooling. Int. J. Heat Mass Transf. 50(1), 105–116 (2007)zbMATHCrossRefGoogle Scholar
  177. 177.
    Arena, C.B., Mahajan, R.L., Rylander, M.N., Davalos, R.V.: An experimental and numerical investigation of phase change electrodes for therapeutic irreversible electroporation. J. Biomech. Eng. 135(11), 111009 (2013)CrossRefGoogle Scholar
  178. 178.
    Appelbaum, L., Ben-David, E., Faroja, M., Nissenbaum, Y., Sosna, J., Goldberg, S.N.: Irreversible electroporation ablation: creation of large-volume ablation zones in in vivo porcine liver with four-electrode arrays. Radiology 270(2), 416–424 (2014)CrossRefGoogle Scholar
  179. 179.
    Jiang, C., Shao, Q., Bischof, J.: Pulse timing during irreversible electroporation achieves enhanced destruction in a hindlimb model of cancer. Ann. Biomed. Eng. 43(4), 887–895 (2015)CrossRefGoogle Scholar
  180. 180.
    Maor, E., Ivorra, A., Leor, J., Rubinsky, B.: The effect of irreversible electroporation on blood vessels. Technol. Cancer Res. Treat. 6(4), 307–312 (2007)CrossRefGoogle Scholar
  181. 181.
    Lee, E.W., Chen, C., Prieto, V.E., Dry, S.M., Loh, C.T., Kee, S.T.: Advanced hepatic ablation technique for creating complete cell death: irreversible electroporation 1. Radiology 255(2), 426–433 (2010)CrossRefGoogle Scholar
  182. 182.
    Rossmeisl Jr., J.H., Garcia, P.A., Roberston, J.L., Ellis, T.L., Davalos, R.V.: Pathology of non-thermal irreversible electroporation (N-TIRE)-induced ablation of the canine brain. J. Vet. Sci. 14(4), 433–440 (2013)CrossRefGoogle Scholar
  183. 183.
    Appelbaum, L., Ben-David, E., Sosna, J., Nissenbaum, Y., Goldberg, S.N.: US findings after irreversible electroporation ablation: radiologic-pathologic correlation. Radiology 262(1), 117–125 (2012)CrossRefGoogle Scholar
  184. 184.
    Ortiz, M.V., Davalos, R.V.: Cell electroporation mechanisms and preclinical foundation for focal therapy. In: Polascik, J., (ed.) Imaging and Focal Therapy of Early Prostate Cancer. Springer, pp. 309–329 (2013)Google Scholar
  185. 185.
    Onik, G., Mikus, P., Rubinsky, B.: Irreversible electroporation: implications for prostate ablation. Technol. Cancer Res. Treat. 6(4), 295–300 (2007)CrossRefGoogle Scholar
  186. 186.
    Li, W., Fan, Q., Ji, Z., Qiu, X., Li, Z.: The effects of irreversible electroporation (IRE) on nerves. PLoS ONE 6(4), e18831 (2011)CrossRefGoogle Scholar
  187. 187.
    Schoellnast, H., Monette, S., Ezell, P.C., Maybody, M., Erinjeri, J.P., Stubblefield, M.D., Single, G., Solomon, S.B.: The delayed effects of irreversible electroporation ablation on nerves. Eur. Radiol. 23(2), 375–380 (2013)CrossRefGoogle Scholar
  188. 188.
    Bower, M., Sherwood, L., Li, Y., Martin, R.: Irreversible electroporation of the pancreas: definitive local therapy without systemic effects. J. Surg. Oncol. 104(1), 22–28 (2011)CrossRefGoogle Scholar
  189. 189.
    Charpentier, K.P., Wolf, F., Noble, L., Winn, B., Resnick, M., Dupuy, D.E.: Irreversible electroporation of the liver and liver hilum in swine. HPB 13(3), 168–173 (2011)CrossRefGoogle Scholar
  190. 190.
    Deodhar, A., Monette, S., Single Jr., G.W., Hamilton Jr., W.C., Thornton, R., Maybody, M., Coleman, J.A., Solomon, S.B.: Renal tissue ablation with irreversible electroporation: preliminary results in a porcine model. Urology 77(3), 754–760 (2011)CrossRefGoogle Scholar
  191. 191.
    Wendler, J.J., Pech, M., Porsch, M., Janitzky, A., Fischbach, F., Buhtz, P., Vogler, K., Huhne, S., Borucki, K., Strang, C., Mahnkopf, D., Ricke, J., Liehr, U.B.: Urinary tract effects after multifocal nonthermal irreversible electroporation of the kidney: acute and chronic monitoring by magnetic resonance imaging, intravenous urography and urinary cytology. Cardiovasc. Intervent. Radiol. 35(4), 921–926 (2012)CrossRefGoogle Scholar
  192. 192.
    Willett, C.G., Czito, B.G., Bendell, J.C., Ryan, D.P.: Locally advanced pancreatic cancer. J. Clin. Oncol. 23(20), 4538–4544 (2005)CrossRefGoogle Scholar
  193. 193.
    Von Hoff, D.D., Evans, D.B., Hruban, R.H.: Pancreatic Cancer. Jones & Bartlett Learning, Burlington (2005)Google Scholar
  194. 194.
    Charpentier, K.P., Wolf, F., Noble, L., Winn, B., Resnick, M., Dupuy, D.E.: Irreversible electroporation of the pancreas in swine: a pilot study. HPB 12(5), 348–351 (2010)CrossRefGoogle Scholar
  195. 195.
    Pantuck, A.J., Zisman, A., Belldegrun, A.S.: The changing natural history of renal cell carcinoma. J. Urol. 166(5), 1611–1623 (2001)CrossRefGoogle Scholar
  196. 196.
    José, A., Sobrevals, L., Ivorra, A., Fillat, C.: Irreversible electroporation shows efficacy against pancreatic carcinoma without systemic toxicity in mouse models. Cancer Lett. 317(1), 16–23 (2012)CrossRefGoogle Scholar
  197. 197.
    Martin, R.C.G., Kwon, D., Chalikonda, S., Sellars, M., Kortz, E., Scoggins, C.R., Watkins K.T., McMasters, K.: Treatment of 200 Locally Advanced (Stage III) Pancreatic Adenocarcinoma Patients with Irreversible Electroporation: Safety and Efficacy. American Surgical Association 136th Annual Meeting (2015).Google Scholar
  198. 198.
    Martin 2nd, R.C., McFarland, K., Ellis, S., Velanovich, V.: Irreversible electroporation in locally advanced pancreatic cancer: potential improved overall survival. Ann. Surg. Oncol. 20(Suppl 3), S443–S449 (2013)CrossRefGoogle Scholar
  199. 199.
    Narayanan, G., Hosein, P.J., Arora, G., Barbery, K.J., Froud, T., Livingstone, A.S., Franceschi, D., Rocha Lima, C.M., Yrizarry, J.: Percutaneous irreversible electroporation for downstaging and control of unresectable pancreatic adenocarcinoma. J. Vasc. Interv. Radiol. 23(12), 1613–1621 (2012)CrossRefGoogle Scholar
  200. 200.
    Phillips, M., Maor, E., Rubinsky, B.: Principles of tissue engineering with nonthermal irreversible electroporation. J. Heat Transf. 133(1), 011004 (2011)CrossRefGoogle Scholar
  201. 201.
    Tracy, C.R., Kabbani, W., Cadeddu, J.A.: Irreversible electroporation (IRE): a novel method for renal tissue ablation. BJU Int. 107(12), 1982–1987 (2011)CrossRefGoogle Scholar
  202. 202.
    Wendler, J.J., Porsch, M., Hühne, S., Baumunk, D., Buhtz, P., Fischbach, F., Pech, M., Mahnkopf, D., Kropf, S., Roessner, A., Ricke, J., Schostak, M., Liehr, U.B.: Short- and mid-term effects of irreversible electroporation on normal renal tissue: an animal model. Cardiovasc. Intervent. Radiol. 36(2), 512–520 (2013)CrossRefGoogle Scholar
  203. 203.
    Lee, E.W., Loh, C.T., Kee, S.T.: Imaging guided percutaneous irreversible electroporation: ultrasound and immunohistological correlation. Technol. Cancer Res. Treat. 6(4), 287–293 (2007)CrossRefGoogle Scholar
  204. 204.
    Schmidt, C.R., Shires, P., Mootoo, M.: Real‐time ultrasound imaging of irreversible electroporation in a porcine liver model adequately characterizes the zone of cellular necrosis. HPB 14(2), 98–102 (2012)CrossRefGoogle Scholar
  205. 205.
    Liu, Y., Xiong, Z., Zhou, W., Hua, Y., Li, C., Yao, C.: Percutaneous ultrasound-guided irreversible electroporation: a goat liver study. Oncol. Lett. 4(3), 450–454 (2012)Google Scholar
  206. 206.
    Ben-David, E., Appelbaum, L., Sosna, J., Nissenbaum, I., Goldberg, S.N.: Characterization of irreversible electroporation ablation in in vivo porcine liver. Am. J. Roentgenol. 198(1), W62–W68 (2012)CrossRefGoogle Scholar
  207. 207.
    Rubinsky, B., Onik, G., Mikus, P.: Irreversible electroporation: a new ablation modality – clinical implications. Technol. Cancer Res. Treat. 6(1), 37–48 (2007)CrossRefGoogle Scholar
  208. 208.
    Guo, Y., Zhang, Y., Klein, R., Nijm, G.M., Sahakian, A.V., Omary, R.A., Yang, G.Y., Larson, A.C.: Irreversible electroporation therapy in the liver: longitudinal efficacy studies in a rat model of hepatocellular carcinoma. Cancer Res. 70(4), 1555–1563 (2010)CrossRefGoogle Scholar
  209. 209.
    Lee, E.W., Wong, D., Tafti, B.A., Prieto, V., Totonchy, M., Hilton, J., Dry, S., Cho, S., Loh, C.T., Kee, S.T.: Irreversible electroporation in eradication of rabbit VX2 liver tumor. J. Vasc. Interv. Radiol. 23(6), 833–840 (2012)CrossRefGoogle Scholar
  210. 210.
    Ginzburg, S., Uzzo, R., Kutikov, A.: The role of minimally invasive surgery in multifocal renal cell carcinoma. Curr. Urol. Rep. 13(3), 202–210 (2012)CrossRefGoogle Scholar
  211. 211.
    Venkatesan, A.M., Wood, B.J., Gervais, D.A.: Percutaneous ablation in the kidney. Radiology 261(2), 375–391 (2011)CrossRefGoogle Scholar
  212. 212.
    Fini, M., Tschon, M., Alberghini, M., Bianchi, G., Mercuri, M., Campanacci, L., Cavani, F., Ronchetti, M., de Terlizzi, F., Cadossi, R.: Cell electroporation in bone tissue. In: Kee, S.T., Gehl, J., Lee, E.W. (eds.) Clinical Aspects of Electroporation, pp. 115–127. Springer, New York (2011)Google Scholar
  213. 213.
    Tam, A.L., Abdelsalam, M.E., Gagea, M., Ensor, J.E., Moussa, M., Ahmed, M., Goldberg, S.N., Dixon, K., McWatters, A., Miller, J.J., Srimathveeravalli, G., Solomon, S.B., Avritscher, R., Wallace, M.J., Gupta, S.: Irreversible electroporation of the lumbar vertebrae in a porcine model: is there clinical-pathologic evidence of neural toxicity? Radiology 272(3), 709–719 (2014)CrossRefGoogle Scholar
  214. 214.
    Garcia, P.A., Rossmeisl, Jr J.H., Ellis, T.L., Davalos, R.V.: Nonthermal irreversible electroporation as a focal ablation treatment for brain cancer. In: Hayat, M.A. (ed.) Tumors of the Central Nervous System, vol. 12, pp. 171–182. Springer, Dordrecht (2014)Google Scholar
  215. 215.
    Ellis, T.L., Garcia, P.A., Rossmeisl Jr., J.H., Henao-Guerrero, N., Robertson, J., Davalos, R.V.: Nonthermal irreversible electroporation for intracranial surgical applications: laboratory investigation. J. Neurosurg. 114(3), 681–688 (2011)CrossRefGoogle Scholar
  216. 216.
    Rossmeisl Jr., J.H., Garcia, P., Pancotto, T.E., Robertson, J.L., Henao-Geurrero, N., Neal 2nd, R.E., Ellis, T.L., Davalos, R.V.: Safety and feasibility of the NanoKnife system for irreversible electroporation ablative treatment of canine spontaneous intracranial gliomas. J. Neurosurg. 123(4), 1008–1018 (2015)CrossRefGoogle Scholar
  217. 217.
    Ari Hakimi, A., Feder, M., Ghavamian, R.: Minimally invasive approaches to prostate cancer: a review of the current literature. Urol. J. 4(3), 130–137 (2009)Google Scholar
  218. 218.
    Nguyen, C.T., Jones, J.S.: Focal therapy in the management of localized prostate cancer. BJU Int. 107(9), 1362–1368 (2011)CrossRefGoogle Scholar
  219. 219.
    Neal II, R.E., Cheung, W., Kavnoudias, H., Thomson, K.R.: Spectrum of imaging and characteristics for liver tumors treated with irreversible electroporation. J. Biomed. Sci. Eng. 5(12A), 813–818 (2012)CrossRefGoogle Scholar
  220. 220.
    Scheffer, S.R., Nave, H., Korangy, F., Schlote, K., Pabst, R., Jaffee, E.M., Manns, M.P., Greten, T.F.: Apoptotic, but not necrotic, tumor cell vaccines induce a potent immune response in vivo. Int. J. Cancer 103(2), 205–211 (2003)CrossRefGoogle Scholar
  221. 221.
    Neal II, R.E., Kavnoudias, H., Cheung, W., Golebiowski, B., McLean, C.A., Thomson, K.R.: Hepatic epithelioid hemangioendothelioma treated with irreversible electroporation and antibiotics. J. Clin. Oncol. 31(27), e422–e426 (2013)CrossRefGoogle Scholar
  222. 222.
    Sabel, M.S.: Cryo-immunology: a review of the literature and proposed mechanisms for stimulatory versus suppressive immune responses. Cryobiology 58(1), 1–11 (2009)MathSciNetCrossRefGoogle Scholar
  223. 223.
    Neal II, R.E., Rossmeisl Jr., J.H., Robertson, J.L., Arena, C.B., Davis, E.M., Singh, R.N., Stallings, J., Davalos, R.V.: Improved local and systemic anti-tumor efficacy for irreversible electroporation in immunocompetent versus immunodeficient mice. PLoS ONE 8(5), e64559 (2013)CrossRefGoogle Scholar
  224. 224.
    Jiang, C., Qin, Z., Bischof, J.: Membrane-targeting approaches for enhanced cancer cell destruction with irreversible electroporation. Ann. Biomed. Eng. 42(1), 193–204 (2014)CrossRefGoogle Scholar
  225. 225.
    Vannucci, L., Lai, M., Chiuppesi, F., Ceccherini-Nelli, L., Pistello, M.: Viral vectors: a look back and ahead on gene transfer technology. New Microbiol. 36(1), 1–22 (2013)Google Scholar
  226. 226.
    Wirth, T., Parker, N., Yla-Herttuala, S.: History of gene therapy. Gene 525(2), 162–169 (2013)CrossRefGoogle Scholar
  227. 227.
    Kaufmann, K.B., Buning, H., Galy, A., Schambach, A., Grez, M.: Gene therapy on the move. EMBO. Mol. Med. 5(11), 1642–1661 (2013)CrossRefGoogle Scholar
  228. 228.
    Ramamoorth, M., Narvekar, A.: Non viral vectors in gene therapy – an overview. J. Clin. Diagn. Res. 9(1), GE01–GE06 (2015)Google Scholar
  229. 229.
    Yin, H., Kanasty, R.L., Eltoukhy, A.A., Vegas, A.J., Dorkin, J.R., Anderson, D.G.: Non-viral vectors for gene-based therapy. Nat. Rev. Genet. 15(8), 541–555 (2014)CrossRefGoogle Scholar
  230. 230.
    Alsaggar, M., Liu, D.: Physical methods for gene transfer. Adv. Genet. 89, 1–24 (2015)Google Scholar
  231. 231.
    Li, S.D., Huang, L.: Gene therapy progress and prospects: non-viral gene therapy by systemic delivery. Gene Ther. 13(18), 1313–1319 (2006)CrossRefGoogle Scholar
  232. 232.
    Song, S., Shen, Z., Chen, L., Brayman, A.A., Miao, C.H.: Explorations of high-intensity therapeutic ultrasound and microbubble-mediated gene delivery in mouse liver. Gene Ther. 18(10), 1006–1014 (2011)CrossRefGoogle Scholar
  233. 233.
    Noble, M.L., Kuhr, C.S., Graves, S.S., Loeb, K.R., Sun, S.S., Keilman, G.W., Morrison, K.P., Paun, M., Storb, R.F., Miao, C.H.: Ultrasound-targeted microbubble destruction-mediated gene delivery into canine livers. Mol. Ther. 21(9), 1687–1694 (2013)CrossRefGoogle Scholar
  234. 234.
    Bonamassa, B., Hai, L., Liu, D.: Hydrodynamic gene delivery and its applications in pharmaceutical research. Pharm. Res. 28(4), 694–701 (2011)CrossRefGoogle Scholar
  235. 235.
    Suda, T., Liu, D.: Hydrodynamic gene delivery: its principles and applications. Mol. Ther. 15(12), 2063–2069 (2007)CrossRefGoogle Scholar
  236. 236.
    Heller, L.C., Heller, R.: In vivo electroporation for gene therapy. Hum. Gene Ther. 17(9), 890–897 (2006)CrossRefGoogle Scholar
  237. 237.
    Gothelf, A., Gehl, J.: Gene electrotransfer to skin; review of existing literature and clinical perspectives. Curr. Gene Ther. 10(4), 287–299 (2010)CrossRefGoogle Scholar
  238. 238.
    Shirley, S.A., Lundberg, C.G., Li, F., Burcus, N., Heller, R.: Controlled gene delivery can enhance therapeutic outcome for cancer immune therapy for melanoma. Curr. Gene Ther. 15(1), 32–43 (2015)CrossRefGoogle Scholar
  239. 239.
    Heller, L.C., Heller, R.: Electroporation gene therapy preclinical and clinical trials for melanoma. Curr. Gene Ther. 10(4), 312–317 (2010)MathSciNetCrossRefGoogle Scholar
  240. 240.
    Marshall Jr., W.G., Boone, B.A., Burgos, J.D., Gografe, S.I., Baldwin, M.K., Danielson, M.L., Larson, M.J., Caretto, D.R., Cruz, Y., Ferraro, B., Heller, L.C., Ugen, K.E., Jaroszeski, M.J., Heller, R.: Electroporation-mediated delivery of a naked DNA plasmid expressing VEGF to the porcine heart enhances protein expression. Gene Ther. 17(3), 419–423 (2010)CrossRefGoogle Scholar
  241. 241.
    Hargrave, B., Downey, H., Strange Jr., R., Murray, L., Cinnamond, C., Lundberg, C., Israel, A., Chen, Y.J., Marshall Jr., W., Heller, R.: Electroporation-mediated gene transfer directly to the swine heart. Gene Ther. 20(2), 151–157 (2013)CrossRefGoogle Scholar
  242. 242.
    Dean, D.A.: Nonviral gene transfer to skeletal, smooth, and cardiac muscle in living animals. Am. J. Physiol. Cell Physiol. 289(2), C233–C245 (2005)CrossRefGoogle Scholar
  243. 243.
    Dean, D.A.: Electroporation of the vasculature and the lung. DNA Cell Biol. 22(12), 797–806 (2003)CrossRefGoogle Scholar
  244. 244.
    Dean, D.A., Machado-Aranda, D., Blair-Parks, K., Yeldandi, A.V., Young, J.L.: Electroporation as a method for high-level nonviral gene transfer to the lung. Gene Ther. 10(18), 1608–1615 (2003)CrossRefGoogle Scholar
  245. 245.
    Zhou, R., Norton, J.E., Zhang, N., Dean, D.A.: Electroporation-mediated transfer of plasmids to the lung results in reduced TLR9 signaling and inflammation. Gene Ther. 14(9), 775–780 (2007)CrossRefGoogle Scholar
  246. 246.
    Ding, X.F., Ma, D.L., Zhang, Q., Peng, W., Fan, M., Suo, W.Z.: Progress of in vivo electroporation in the rodent brain. Curr. Gene Ther. 14(3), 211–217 (2014)CrossRefGoogle Scholar
  247. 247.
    Murakami, T., Sunada, Y.: Plasmid DNA gene therapy by electroporation: principles and recent advances. Curr. Gene Ther 11(6), 447–456 (2011)CrossRefGoogle Scholar
  248. 248.
    Isaka, Y.: Gene therapy targeting kidney diseases: routes and vehicles. Clin. Exp. Nephrol. 10(4), 229–235 (2006)CrossRefGoogle Scholar
  249. 249.
    Scherman, D., Bigey, P., Bureau, M.F.: Applications of plasmid electrotransfer. Technol. Cancer Res. Treat. 1(5), 351–354 (2002)CrossRefGoogle Scholar
  250. 250.
    Andre, F.M., Gehl, J., Sersa, G., Preat, V., Hojman, P., Eriksen, J., Golzio, M., Cemazar, M., Pavselj, N., Rols, M.P., Miklavcic, D., Neumann, E., Teissie, J., Mir, L.M.: Efficiency of high- and low-voltage pulse combinations for gene electrotransfer in muscle, liver, tumor, and skin. Hum. Gene Ther. 19(11), 1261–1271 (2008)CrossRefGoogle Scholar
  251. 251.
    Corovic, S., Lackovic, I., Sustaric, P., Sustar, T., Rodic, T., Miklavcic, D.: Modeling of electric field distribution in tissues during electroporation. Biomed. Eng. Online 12, 16 (2013)CrossRefGoogle Scholar
  252. 252.
    Mesojednik, S., Pavlin, D., Sersa, G., Coer, A., Kranjc, S., Grosel, A., Tevz, G., Cemazar, M.: The effect of the histological properties of tumors on transfection efficiency of electrically assisted gene delivery to solid tumors in mice. Gene Ther. 14(17), 1261–1269 (2007)CrossRefGoogle Scholar
  253. 253.
    Trollet, C., Bloquel, C., Scherman, D., Bigey, P.: Electrotransfer into skeletal muscle for protein expression. Curr. Gene Ther. 6(5), 561–578 (2006)CrossRefGoogle Scholar
  254. 254.
    Trollet, C., Scherman, D., Bigey, P.: Delivery of DNA into muscle for treating systemic diseases: advantages and challenges. Methods Mol. Biol. 423, 199–214 (2008)CrossRefGoogle Scholar
  255. 255.
    Gothelf, A., Gehl, J.: What you always needed to know about electroporation based DNA vaccines. Hum. Vaccin Immunother. 8(11), 1694–1702 (2012)CrossRefGoogle Scholar
  256. 256.
    Hirao, L.A., Wu, L., Khan, A.S., Satishchandran, A., Draghia-Akli, R., Weiner, D.B.: Intradermal/subcutaneous immunization by electroporation improves plasmid vaccine delivery and potency in pigs and rhesus macaques. Vaccine 26(3), 440–448 (2008)CrossRefGoogle Scholar
  257. 257.
    Donate, A., Heller, R.: Assessment of delivery parameters with the multi-electrode array for development of a DNA vaccine against Bacillus anthracis. Bioelectrochemistry 94C, 1–6 (2013)CrossRefGoogle Scholar
  258. 258.
    Donate, A., Coppola, D., Cruz, Y., Heller, R.: Evaluation of a novel non-penetrating electrode for use in DNA vaccination. PLoS ONE 6(4), e19181 (2011)CrossRefGoogle Scholar
  259. 259.
    Hojman, P., Gissel, H., Andre, F.M., Cournil-Henrionnet, C., Eriksen, J., Gehl, J., Mir, L.M.: Physiological effects of high- and low-voltage pulse combinations for gene electrotransfer in muscle. Hum. Gene Ther. 19(11), 1249–1260 (2008)CrossRefGoogle Scholar
  260. 260.
    Guo, S., Jackson, D.L., Burcus, N.I., Chen, Y.J., Xiao, S., Heller, R.: Gene electrotransfer enhanced by nanosecond pulsed electric fields. Mol. Ther. Methods Clin. Dev. 1, 14043 (2014)CrossRefGoogle Scholar
  261. 261.
    Bigey, P., Bureau, M.F., Scherman, D.: In vivo plasmid DNA electrotransfer. Curr. Opin. Biotechnol. 13(5), 443–447 (2002)CrossRefGoogle Scholar
  262. 262.
    Gehl, J.: Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research. Acta Physiol. Scand. 177(4), 437–447 (2003)CrossRefGoogle Scholar
  263. 263.
    Hojman, P., Zibert, J.R., Gissel, H., Eriksen, J., Gehl, J.: Gene expression profiles in skeletal muscle after gene electrotransfer. BMC Mol. Biol. 8, 56 (2007)CrossRefGoogle Scholar
  264. 264.
    Heller, L., Jaroszeski, M.J., Coppola, D., Pottinger, C., Gilbert, R., Heller, R.: Electrically mediated plasmid DNA delivery to hepatocellular carcinomas in vivo. Gene Ther. 7(10), 826–829 (2000)CrossRefGoogle Scholar
  265. 265.
    Andre, F.M., Mir, L.M.: Nucleic acids electrotransfer in vivo: mechanisms and practical aspects. Curr. Gene Ther. 10(4), 267–280 (2010)CrossRefGoogle Scholar
  266. 266.
    Guo, S., Israel, A.L., Basu, G., Donate, A., Heller, R.: Topical gene electrotransfer to the epidermis of hairless guinea pig by non-invasive multielectrode array. PLoS ONE 8(8), e73423 (2013)CrossRefGoogle Scholar
  267. 267.
    Heller, R., Cruz, Y., Heller, L.C., Gilbert, R.A., Jaroszeski, M.J.: Electrically mediated delivery of plasmid DNA to the skin, using a multielectrode array. Hum. Gene Ther. 21(3), 357–362 (2010)CrossRefGoogle Scholar
  268. 268.
    Heller, L.C., Jaroszeski, M.J., Coppola, D., McCray, A.N., Hickey, J., Heller, R.: Optimization of cutaneous electrically mediated plasmid DNA delivery using novel electrode. Gene Ther. 14(3), 275–280 (2007)CrossRefGoogle Scholar
  269. 269.
    Potter, H.: Electroporation in biology: methods, applications, and instrumentation. Anal. Biochem. 174(2), 361–373 (1988)CrossRefGoogle Scholar
  270. 270.
    Potter, H., Weir, L., Leder, P.: Enhancer-dependent expression of human kappa immunoglobulin genes introduced into mouse pre-B lymphocytes by electroporation. Proc. Natl. Acad. Sci. U. S. A. 81(22), 7161–7165 (1984)CrossRefGoogle Scholar
  271. 271.
    Faurie, C., Rebersek, M., Golzio, M., Kanduser, M., Escoffre, J.M., Pavlin, M., Teissie, J., Miklavcic, D., Rols, M.P.: Electro-mediated gene transfer and expression are controlled by the life-time of DNA/membrane complex formation. J Gene Med 12(1), 117–125 (2010)CrossRefGoogle Scholar
  272. 272.
    Kotnik, T., Mir, L.M., Flisar, K., Puc, M., Miklavcic, D.: Cell membrane electropermeabilization by symmetrical bipolar rectangular pulses. Part I. Increased efficiency of permeabilization. Bioelectrochemistry 54(1), 83–90 (2010)CrossRefGoogle Scholar
  273. 273.
    Rols, M.P., Teissie, J.: Electropermeabilization of mammalian cells to macromolecules: control by pulse duration. Biophys. J. 75(3), 1415–1423 (1998)CrossRefGoogle Scholar
  274. 274.
    Wolf, H., Rols, M.P., Boldt, E., Neumann, E., Teissie, J.: Control by pulse parameters of electric field-mediated gene transfer in mammalian cells. Biophys. J. 66(2 Pt 1), 524–531 (1994)CrossRefGoogle Scholar
  275. 275.
    Cemazar, M., Golzio, M., Sersa, G., Hojman, P., Kranjc, S., Mesojednik, S., Rols, M.P., Teissie, J.: Control by pulse parameters of DNA electrotransfer into solid tumors in mice. Gene Ther. 16(5), 635–644 (2009)CrossRefGoogle Scholar
  276. 276.
    Kotnik, T., Pucihar, G., Miklavcic, D.: Induced transmembrane voltage and its correlation with electroporation-mediated molecular transport. J. Membr. Biol. 236(1), 3–13 (2010)CrossRefGoogle Scholar
  277. 277.
    Sel, D., Mazeres, S., Teissie, J., Miklavcic, D.: Finite-element modeling of needle electrodes in tissue from the perspective of frequent model computation. IEEE Trans. Biomed. Eng. 50(11), 1221–1232 (2003)CrossRefGoogle Scholar
  278. 278.
    Singh, N., Kalluri, H., Herwadkar, A., Badkar, A., Banga, A.K.: Transcending the skin barrier to deliver peptides and proteins using active technologies. Crit. Rev. Ther. Drug Carrier Syst. 29(4), 265–298 (2012)CrossRefGoogle Scholar
  279. 279.
    Prausnitz, M.R., Mikszta, J.A., Cormier, M., Andrianov, A.K.: Microneedle-based vaccines. Curr. Top. Microbiol. Immunol. 333, 369–393 (2009)Google Scholar
  280. 280.
    Daugimont, L., Baron, N., Vandermeulen, G., Pavselj, N., Miklavcic, D., Jullien, M.C., Cabodevila, G., Mir, L.M., Preat, V.: Hollow microneedle arrays for intradermal drug delivery and DNA electroporation. J. Membr. Biol. 236(1), 117–125 (2010)CrossRefGoogle Scholar
  281. 281.
    Gehl, J., Mir, L.M.: Determination of optimal parameters for in vivo gene transfer by electroporation, using a rapid in vivo test for cell permeabilization. Biochem. Biophys. Res. Commun. 261(2), 377–380 (1999)CrossRefGoogle Scholar
  282. 282.
    Ferraro, B., Heller, L.C., Cruz, Y.L., Guo, S., Donate, A., Heller, R.: Evaluation of delivery conditions for cutaneous plasmid electrotransfer using a multielectrode array. Gene Ther. 18(5), 496–500 (2011)CrossRefGoogle Scholar
  283. 283.
    Martin, J.B., Young, J.L., Benoit, J.N., Dean, D.A.: Gene transfer to intact mesenteric arteries by electroporation. J. Vasc. Res. 37(5), 372–380 (2000)CrossRefGoogle Scholar
  284. 284.
    Soden, D., Larkin, J., Collins, C., Piggott, J., Morrissey, A., Norman, A., Dunne, C., O’Sullivan, G.C.: The development of novel flexible electrode arrays for the electrochemotherapy of solid tumour tissue. (Potential for endoscopic treatment of inaccessible cancers). Conf. Proc. IEEE. Eng. Med. Biol. Soc. 5, 3547–3550 (2004)Google Scholar
  285. 285.
    Soden, D.M., Larkin, J.O., Collins, C.G., Tangney, M., Aarons, S., Piggott, J., Morrissey, A., Dunne, C., O’Sullivan, G.C.: Successful application of targeted electrochemotherapy using novel flexible electrodes and low dose bleomycin to solid tumours. Cancer Lett. 232(2), 300–310 (2006)CrossRefGoogle Scholar
  286. 286.
    Tolmachov, O.: Designing plasmid vectors. Methods Mol. Biol. 542, 117–129 (2009)CrossRefGoogle Scholar
  287. 287.
    Gill, D.R., Pringle, I.A., Hyde, S.C.: Progress and prospects: the design and production of plasmid vectors. Gene Ther. 16(2), 165–171 (2009)CrossRefGoogle Scholar
  288. 288.
    Vandermeulen, G., Richiardi, H., Escriou, V., Ni, J., Fournier, P., Schirrmacher, V., Scherman, D., Preat, V.: Skin-specific promoters for genetic immunisation by DNA electroporation. Vaccine 27(32), 4272–4277 (2009)CrossRefGoogle Scholar
  289. 289.
    Hojman, P., Eriksen, J., Gehl, J.: Tet-On induction with doxycycline after gene transfer in mice: sweetening of drinking water is not a good idea. Anim. Biotechnol. 18(3), 183–188 (2007)CrossRefGoogle Scholar
  290. 290.
    Hojman, P., Gissel, H., Gehl, J.: Sensitive and precise regulation of haemoglobin after gene transfer of erythropoietin to muscle tissue using electroporation. Gene Ther. 14(12), 950–959 (2007)CrossRefGoogle Scholar
  291. 291.
    Dean, D.A.: Cell-specific targeting strategies for electroporation-mediated gene delivery in cells and animals. J. Membr. Biol. 246(10), 737–744 (2013)CrossRefGoogle Scholar
  292. 292.
    Vaughan, E.E., DeGiulio, J.V., Dean, D.A.: Intracellular trafficking of plasmids for gene therapy: mechanisms of cytoplasmic movement and nuclear import. Curr. Gene Ther. 6(6), 671–681 (2006)CrossRefGoogle Scholar
  293. 293.
    Marie, C., Vandermeulen, G., Quiviger, M., Richard, M., Preat, V., Scherman, D.: pFARs, plasmids free of antibiotic resistance markers, display high-level transgene expression in muscle, skin and tumour cells. J. Gene Med. 12(4), 323–332 (2010)CrossRefGoogle Scholar
  294. 294.
    Mignon, C., Sodoyer, R., Werle, B.: Antibiotic-free selection in biotherapeutics: now and forever. Pathogens 4(2), 157–181 (2015)CrossRefGoogle Scholar
  295. 295.
    Mairhofer, J., Cserjan-Puschmann, M., Striedner, G., Nobauer, K., Razzazi-Fazeli, E., Grabherr, R.: Marker-free plasmids for gene therapeutic applications – lack of antibiotic resistance gene substantially improves the manufacturing process. J. Biotechnol. 146(3), 130–137 (2010)CrossRefGoogle Scholar
  296. 296.
    Mairhofer, J., Pfaffenzeller, I., Merz, D., Grabherr, R.: A novel antibiotic free plasmid selection system: advances in safe and efficient DNA therapy. Biotechnol. J. 3(1), 83–89 (2008)CrossRefGoogle Scholar
  297. 297.
    Mayrhofer, P., Blaesen, M., Schleef, M., Jechlinger, W.: Minicircle-DNA production by site specific recombination and protein-DNA interaction chromatography. J. Gene Med. 10(11), 1253–1269 (2008). doi: 10.1002/jgm.1243 CrossRefGoogle Scholar
  298. 298.
    Bigger, B.W., Tolmachov, O., Collombet, J.M., Fragkos, M., Palaszewski, I., Coutelle, C.: An araC-controlled bacterial cre expression system to produce DNA minicircle vectors for nuclear and mitochondrial gene therapy. J. Biol. Chem. 276(25), 23018–23027 (2001)CrossRefGoogle Scholar
  299. 299.
    Broll, S., Oumard, A., Hahn, K., Schambach, A., Bode, J.: Minicircle performance depending on S/MAR-nuclear matrix interactions. J. Mol. Biol. 395(5), 950–965 (2010)CrossRefGoogle Scholar
  300. 300.
    Chen, Z.Y., He, C.Y., Ehrhardt, A., Kay, M.A.: Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo. Mol. Ther. 8(3), 495–500 (2003)CrossRefGoogle Scholar
  301. 301.
    Izsvak, Z., Ivics, Z.: Sleeping beauty transposition: biology and applications for molecular therapy. Mol. Ther. 9(2), 147–156 (2004)CrossRefGoogle Scholar
  302. 302.
    Izsvak, Z., Ivics, Z., Plasterk, R.H.: Sleeping Beauty, a wide host-range transposon vector for genetic transformation in vertebrates. J. Mol. Biol. 302(1), 93–102 (2000)CrossRefGoogle Scholar
  303. 303.
    Swierczek, M., Izsvak, Z., Ivics, Z.: The Sleeping Beauty transposon system for clinical applications. Expert. Opin. Biol. Ther. 12(2), 139–153 (2012)CrossRefGoogle Scholar
  304. 304.
    Aronovich, E.L., McIvor, R.S., Hackett, P.B.: The Sleeping Beauty transposon system: a non-viral vector for gene therapy. Hum. Mol. Genet. 20(R1), R14–R20 (2011)CrossRefGoogle Scholar
  305. 305.
    Hackett Jr., P.B., Aronovich, E.L., Hunter, D., Urness, M., Bell, J.B., Kass, S.J., Cooper, L.J., McIvor, S.: Efficacy and safety of Sleeping Beauty transposon-mediated gene transfer in preclinical animal studies. Curr. Gene Ther. 11(5), 341–349 (2011)CrossRefGoogle Scholar
  306. 306.
    Olivares, E.C., Hollis, R.P., Chalberg, T.W., Meuse, L., Kay, M.A., Calos, M.P.: Site-specific genomic integration produces therapeutic Factor IX levels in mice. Nat. Biotechnol. 20(11), 1124–1128 (2002)CrossRefGoogle Scholar
  307. 307.
    Lucas, M.L., Heller, R.: Immunomodulation by electrically enhanced delivery of plasmid DNA encoding IL-12 to murine skeletal muscle. Mol. Ther. 3(1), 47–53 (2001)CrossRefGoogle Scholar
  308. 308.
    Mir, L.M., Bureau, M.F., Rangara, R., Schwartz, B., Scherman, D.: Long-term, high level in vivo gene expression after electric pulse-mediated gene transfer into skeletal muscle. C. R. Acad. Sci. III 321(11), 893–899 (1998)CrossRefGoogle Scholar
  309. 309.
    Bloquel, C., Fabre, E., Bureau, M.F., Scherman, D.: Plasmid DNA electrotransfer for intracellular and secreted proteins expression: new methodological developments and applications. J. Gene Med. 6(Suppl 1), S11–S23 (2004)CrossRefGoogle Scholar
  310. 310.
    McMahon, J.M., Wells, D.J.: Electroporation for gene transfer to skeletal muscles: current status. BioDrugs 18(3), 155–165 (2004)CrossRefGoogle Scholar
  311. 311.
    Khavari, P.A., Krueger, G.G.: Cutaneous gene therapy. Dermatol. Clin. 15(1), 27–35 (1997)CrossRefGoogle Scholar
  312. 312.
    Khavari, P.A., Rollman, O., Vahlquist, A.: Cutaneous gene transfer for skin and systemic diseases. J. Intern. Med. 252(1), 1–10 (2002)CrossRefGoogle Scholar
  313. 313.
    Ariza, M.E., Williams, M.V., Wong, H.K.: Targeting IL-17 in psoriasis: from cutaneous immunobiology to clinical application. Clin. Immunol. 146(2), 131–139 (2013)CrossRefGoogle Scholar
  314. 314.
    Vicentini, F.T., Borgheti-Cardoso, L.N., Depieri, L.V., de Macedo, M.D., Abelha, T.F., Petrilli, R., Bentley, M.V.: Delivery systems and local administration routes for therapeutic siRNA. Pharm. Res. 30(4), 915–931 (2013)CrossRefGoogle Scholar
  315. 315.
    Geusens, B., Strobbe, T., Bracke, S., Dynoodt, P., Sanders, N., Van Gele, M., Lambert, J.: Lipid-mediated gene delivery to the skin. Eur. J. Pharm. Sci. 43(4), 199–211 (2011)CrossRefGoogle Scholar
  316. 316.
    Kim, Y.C., Jarrahian, C., Zehrung, D., Mitragotri, S., Prausnitz, M.R.: Delivery systems for intradermal vaccination. Curr. Top. Microbiol. Immunol. 351, 77–112 (2012)Google Scholar
  317. 317.
    Medi, B.M., Singh, J.: Skin targeted DNA vaccine delivery using electroporation in rabbits II. Safety. Int. J. Pharm. 308(1–2), 61–68 (2006)CrossRefGoogle Scholar
  318. 318.
    Hooper, J.W., Golden, J.W., Ferro, A.M., King, A.D.: Smallpox DNA vaccine delivered by novel skin electroporation device protects mice against intranasal poxvirus challenge. Vaccine 25(10), 1814–1823 (2007)CrossRefGoogle Scholar
  319. 319.
    Roos, A.K., Moreno, S., Leder, C., Pavlenko, M., King, A., Pisa, P.: Enhancement of cellular immune response to a prostate cancer DNA vaccine by intradermal electroporation. Mol. Ther. 13(2), 320–327 (2006)CrossRefGoogle Scholar
  320. 320.
    Ferguson, M., Byrnes, C., Sun, L., Marti, G., Bonde, P., Duncan, M., Harmon, J.W.: Wound healing enhancement: electroporation to address a classic problem of military medicine. World J. Surg. 29(Suppl 1), S55–S59 (2005)CrossRefGoogle Scholar
  321. 321.
    Marti, G., Ferguson, M., Wang, J., Byrnes, C., Dieb, R., Qaiser, R., Bonde, P., Duncan, M.D., Harmon, J.W.: Electroporative transfection with KGF-1 DNA improves wound healing in a diabetic mouse model. Gene Ther. 11(24), 1780–1785 (2004)CrossRefGoogle Scholar
  322. 322.
    Steinstraesser, L., Lam, M.C., Jacobsen, F., Porporato, P.E., Chereddy, K.K., Becerikli, M., Stricker, I., Hancock, R.E., Lehnhardt, M., Sonveaux, P., Preat, V., Vandermeulen, G.: Skin electroporation of a plasmid encoding hCAP-18/LL-37 host defense peptide promotes wound healing. Mol. Ther. 22(4), 734–742 (2014)CrossRefGoogle Scholar
  323. 323.
    Gothelf, A., Hojman, P., Gehl, J.: Therapeutic levels of erythropoietin (EPO) achieved after gene electrotransfer to skin in mice. Gene Ther. 17(9), 1077–1084 (2010)CrossRefGoogle Scholar
  324. 324.
    Ferraro, B., Cruz, Y.L., Baldwin, M., Coppola, D., Heller, R.: Increased perfusion and angiogenesis in a hindlimb ischemia model with plasmid FGF-2 delivered by noninvasive electroporation. Gene Ther. 17(6), 763–769 (2010). doi: 10.1038/gt.2010.43 CrossRefGoogle Scholar
  325. 325.
    Ferraro, B., Cruz, Y.L., Coppola, D., Heller, R.: Intradermal delivery of plasmid VEGF(165) by electroporation promotes wound healing. Mol. Ther. 17(4), 651–657 (2009)CrossRefGoogle Scholar
  326. 326.
    Suzuki, T., Shin, B.C., Fujikura, K., Matsuzaki, T., Takata, K.: Direct gene transfer into rat liver cells by in vivo electroporation. FEBS Lett. 425(3), 436–440 (1998)CrossRefGoogle Scholar
  327. 327.
    Jaichandran, S., Yap, S.T., Khoo, A.B., Ho, L.P., Tien, S.L., Kon, O.L.: In vivo liver electroporation: optimization and demonstration of therapeutic efficacy. Hum. Gene Ther. 17(3), 362–375 (2006)CrossRefGoogle Scholar
  328. 328.
    Sakai, M., Nishikawa, M., Thanaketpaisarn, O., Yamashita, F., Hashida, M.: Hepatocyte-targeted gene transfer by combination of vascularly delivered plasmid DNA and in vivo electroporation. Gene Ther. 12(7), 607–616 (2005)CrossRefGoogle Scholar
  329. 329.
    Chi, C.H., Liu, I.L., Lo, W.Y., Liaw, B.S., Wang, Y.S., Chi, K.H.: Hepatocyte growth factor gene therapy prevents radiation-induced liver damage. World J. Gastroenterol.: WJG 11(10), 1496–1502 (2005)CrossRefGoogle Scholar
  330. 330.
    Pringle, I.A., McLachlan, G., Collie, D.D., Sumner-Jones, S.G., Lawton, A.E., Tennant, P., Baker, A., Gordon, C., Blundell, R., Varathalingam, A., Davies, L.A., Schmid, R.A., Cheng, S.H., Porteous, D.J., Gill, D.R., Hyde, S.C.: Electroporation enhances reporter gene expression following delivery of naked plasmid DNA to the lung. J. Gene Med. 9(5), 369–380 (2007)CrossRefGoogle Scholar
  331. 331.
    Gazdhar, A., Bilici, M., Pierog, J., Ayuni, E.L., Gugger, M., Wetterwald, A., Cecchini, M., Schmid, R.A.: In vivo electroporation and ubiquitin promoter – a protocol for sustained gene expression in the lung. J. Gene Med. 8(7), 910–918 (2006)CrossRefGoogle Scholar
  332. 332.
    Machado-Aranda, D., Adir, Y., Young, J.L., Briva, A., Budinger, G.R., Yeldandi, A.V., Sznajder, J.I., Dean, D.A.: Gene transfer of the Na+, K+-ATPase beta1 subunit using electroporation increases lung liquid clearance. Am. J. Respir. Crit. Care Med. 171(3), 204–211 (2005)CrossRefGoogle Scholar
  333. 333.
    Mutlu, G.M., Machado-Aranda, D., Norton, J.E., Bellmeyer, A., Urich, D., Zhou, R., Dean, D.A.: Electroporation-mediated gene transfer of the Na+, K+ -ATPase rescues endotoxin-induced lung injury. Am. J. Respir. Crit. Care Med. 176(6), 582–590 (2007)CrossRefGoogle Scholar
  334. 334.
    Gazdhar, A., Fachinger, P., van Leer, C., Pierog, J., Gugger, M., Friis, R., Schmid, R.A., Geiser, T.: Gene transfer of hepatocyte growth factor by electroporation reduces bleomycin-induced lung fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol. 292(2), L529–L536 (2007)CrossRefGoogle Scholar
  335. 335.
    Davies, J.C., Alton, E.W.: Airway gene therapy. Adv. Genet. 54, 291–314 (2005)Google Scholar
  336. 336.
    Harrison, R.L., Byrne, B.J., Tung, L.: Electroporation-mediated gene transfer in cardiac tissue. FEBS Lett. 435(1), 1–5 (1998)CrossRefGoogle Scholar
  337. 337.
    Wang, Y., Bai, Y., Price, C., Boros, P., Qin, L., Bielinska, A.U., Kukowska-Latallo, J.F., Baker Jr., J.R., Bromberg, J.S.: Combination of electroporation and DNA/dendrimer complexes enhances gene transfer into murine cardiac transplants. Am. J. Transplant. 1(4), 334–338 (2001)CrossRefGoogle Scholar
  338. 338.
    Nikolski, V.P., Efimov, I.R.: Electroporation of the heart. Eur.: Eur. Pacing Arrhythmias Card Electrophysiol: J. Work. Groups Card. Pacing Arrhythmias Card. Cell. Electrophysiol. Eur. Soc. Cardiol. 7(Suppl 2), 146–154 (2005)Google Scholar
  339. 339.
    Hargrave, B., Strange Jr., R., Navare, S., Stratton, M., Burcus, N., Murray, L., Lundberg, C., Bulysheva, A., Li, F., Heller, R.: Gene electro transfer of plasmid encoding vascular endothelial growth factor for enhanced expression and perfusion in the ischemic swine heart. PLoS ONE 9(12), e115235 (2014)CrossRefGoogle Scholar
  340. 340.
    Seidler, R.W., Allgauer, S., Ailinger, S., Sterner, A., Dev, N., Rabussay, D., Doods, H., Lenter, M.C.: In vivo human MCP-1 transfection in porcine arteries by intravascular electroporation. Pharm. Res. 22(10), 1685–1691 (2005)CrossRefGoogle Scholar
  341. 341.
    Matsumoto, T., Komori, K., Shoji, T., Kuma, S., Kume, M., Yamaoka, T., Mori, E., Furuyama, T., Yonemitsu, Y., Sugimachi, K.: Successful and optimized in vivo gene transfer to rabbit carotid artery mediated by electronic pulse. Gene Ther. 8(15), 1174–1179 (2001)CrossRefGoogle Scholar
  342. 342.
    Miyahara, T., Koyama, H., Miyata, T., Shigematsu, H., Inoue, J.-I., Takato, T., Nagawa, H.: Inflammatory responses involving tumor necrosis factor receptor-associated factor 6 contribute to in-stent lesion formation in a stent implantation model of rabbit carotid artery. J. Vasc. Surg. 43(3), 592–600 (2006)CrossRefGoogle Scholar
  343. 343.
    Touchard, E., Berdugo, M., Bigey, P., El Sanharawi, M., Savoldelli, M., Naud, M.C., Jeanny, J.C., Behar-Cohen, F.: Suprachoroidal electrotransfer: a nonviral gene delivery method to transfect the choroid and the retina without detaching the retina. Mol. Ther. 20(8), 1559–1570 (2012). doi: 10.1038/mt.2011.304 CrossRefGoogle Scholar
  344. 344.
    Touchard, E., Bloquel, C., Bigey, P., Kowalczuk, L., Jonet, L., Thillaye-Goldenberg, B., Naud, M.C., Scherman, D., de Kozak, Y., Benezra, D., Behar-Cohen, F.: Effects of ciliary muscle plasmid electrotransfer of TNF-alpha soluble receptor variants in experimental uveitis. Gene Ther. 16(7), 862–873 (2009)CrossRefGoogle Scholar
  345. 345.
    Touchard, E., Kowalczuk, L., Bloquel, C., Naud, M.C., Bigey, P., Behar-Cohen, F.: The ciliary smooth muscle electrotransfer: basic principles and potential for sustained intraocular production of therapeutic proteins. J. Gene Med. 12(11), 904–919 (2010)CrossRefGoogle Scholar
  346. 346.
    Bejjani, R.A., Andrieu, C., Bloquel, C., Berdugo, M., BenEzra, D., Behar-Cohen, F.: Electrically assisted ocular gene therapy. Surv. Ophthalmol. 52(2), 196–208 (2007)CrossRefGoogle Scholar
  347. 347.
    Bloquel, C., Bejjani, R., Bigey, P., Bedioui, F., Doat, M., BenEzra, D., Scherman, D., Behar-Cohen, F.: Plasmid electrotransfer of eye ciliary muscle: principles and therapeutic efficacy using hTNF-alpha soluble receptor in uveitis. FASEB J. 20(2), 389–391 (2006)Google Scholar
  348. 348.
    Kutzler, M.A., Weiner, D.B.: DNA vaccines: ready for prime time? Nat. Rev. Genet. 9(10), 776–788 (2008)CrossRefGoogle Scholar
  349. 349.
    Sardesai, N.Y., Weiner, D.B.: Electroporation delivery of DNA vaccines: prospects for success. Curr. Opin. Immunol. 23(3), 421–429 (2011)CrossRefGoogle Scholar
  350. 350.
    Heller, L., Merkler, K., Westover, J., Cruz, Y., Coppola, D., Benson, K., Daud, A., Heller, R.: Evaluation of toxicity following electrically mediated interleukin-12 gene delivery in a B16 mouse melanoma model. Clin. Cancer Res. 12(10), 3177–3183 (2006)CrossRefGoogle Scholar
  351. 351.
    Cemazar, M., Sersa, G., Wilson, J., Tozer, G.M., Hart, S.L., Grosel, A., Dachs, G.U.: Effective gene transfer to solid tumors using different nonviral gene delivery techniques: electroporation, liposomes, and integrin-targeted vector. Cancer Gene Ther. 9(4), 399–406 (2002)CrossRefGoogle Scholar
  352. 352.
    Canatella, P.J., Prausnitz, M.R.: Prediction and optimization of gene transfection and drug delivery by electroporation. Gene Ther. 8(19), 1464–1469 (2001)CrossRefGoogle Scholar
  353. 353.
    Spanggaard, I., Snoj, M., Cavalcanti, A., Bouquet, C., Sersa, G., Robert, C., Cemazar, M., Dam, E., Vasseur, B., Attali, P., Mir, L.M., Gehl, J.: Gene electrotransfer of plasmid antiangiogenic metargidin peptide (AMEP) in disseminated melanoma: safety and efficacy results of a phase I first-in-man study. Hum. Gene Ther. Clin. Dev. 24(3), 99–107 (2013)CrossRefGoogle Scholar
  354. 354.
    Yuan, J., Ku, G.Y., Adamow, M., Mu, Z., Tandon, S., Hannaman, D., Chapman, P., Schwartz, G., Carvajal, R., Panageas, K.S., Houghton, A.N., Wolchok, J.D.: Immunologic responses to xenogeneic tyrosinase DNA vaccine administered by electroporation in patients with malignant melanoma. J. Immunother. Cancer 1, 20 (2013)CrossRefGoogle Scholar
  355. 355.
    Chudley, L., McCann, K., Mander, A., Tjelle, T., Campos-Perez, J., Godeseth, R., Creak, A., Dobbyn, J., Johnson, B., Bass, P., Heath, C., Kerr, P., Mathiesen, I., Dearnaley, D., Stevenson, F., Ottensmeier, C.: DNA fusion-gene vaccination in patients with prostate cancer induces high-frequency CD8(+) T-cell responses and increases PSA doubling time. Cancer Immunol. Immunother. 61(11), 2161–2170 (2012)CrossRefGoogle Scholar
  356. 356.
    Low, L., Mander, A., McCann, K.J., Dearnaley, D., Tjelle, T.E., Mathiesen, I., Stevenson, F.K., Ottensmeier, C.H.: DNA vaccination with electroporation induces increased antibody responses in patients with prostate cancer. Hum. Gene Ther. 20(11), 1269–1278 (2009)CrossRefGoogle Scholar
  357. 357.
    Eriksson, F., Totterman, T., Maltais, A.K., Pisa, P., Yachnin, J.: DNA vaccine coding for the rhesus prostate specific antigen delivered by intradermal electroporation in patients with relapsed prostate cancer. Vaccine 31(37), 3843–3848 (2013)CrossRefGoogle Scholar
  358. 358.
    Bagarazzi, M.L., Yan, J., Morrow, M.P., Shen, X., Parker, R.L., Lee, J.C., Giffear, M., Pankhong, P., Khan, A.S., Broderick, K.E., Knott, C., Lin, F., Boyer, J.D., Draghia-Akli, R., White, C.J., Kim, J.J., Weiner, D.B., Sardesai, N.Y.: Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci. Transl. Med. 4(155), 155ra138 (2012)CrossRefGoogle Scholar
  359. 359.
    Kopycinski, J., Cheeseman, H., Ashraf, A., Gill, D., Hayes, P., Hannaman, D., Gilmour, J., Cox, J.H., Vasan, S.: A DNA-based candidate HIV vaccine delivered via in vivo electroporation induces CD4 responses toward the alpha4beta7-binding V2 loop of HIV gp120 in healthy volunteers. Clin. Vaccine Immunol. 19(9), 1557–1559 (2012)CrossRefGoogle Scholar
  360. 360.
    Vasan, S., Hurley, A., Schlesinger, S.J., Hannaman, D., Gardiner, D.F., Dugin, D.P., Boente-Carrera, M., Vittorino, R., Caskey, M., Andersen, J., Huang, Y., Cox, J.H., Tarragona-Fiol, T., Gill, D.K., Cheeseman, H., Clark, L., Dally, L., Smith, C., Schmidt, C., Park, H.H., Kopycinski, J.T., Gilmour, J., Fast, P., Bernard, R., Ho, D.D.: In vivo electroporation enhances the immunogenicity of an HIV-1 DNA vaccine candidate in healthy volunteers. PLoS ONE 6(5), e19252 (2011)CrossRefGoogle Scholar
  361. 361.
    Dolter, K.E., Evans, C.F., Ellefsen, B., Song, J., Boente-Carrera, M., Vittorino, R., Rosenberg, T.J., Hannaman, D., Vasan, S.: Immunogenicity, safety, biodistribution and persistence of ADVAX, a prophylactic DNA vaccine for HIV-1, delivered by in vivo electroporation. Vaccine 29(4), 795–803 (2011)CrossRefGoogle Scholar
  362. 362.
    Kalams, S.A., Parker, S.D., Elizaga, M., Metch, B., Edupuganti, S., Hural, J., De Rosa, S., Carter, D.K., Rybczyk, K., Frank, I., Fuchs, J., Koblin, B., Kim, D.H., Joseph, P., Keefer, M.C., Baden, L.R., Eldridge, J., Boyer, J., Sherwat, A., Cardinali, M., Allen, M., Pensiero, M., Butler, C., Khan, A.S., Yan, J., Sardesai, N.Y., Kublin, J.G., Weiner, D.B.: Safety and comparative immunogenicity of an HIV-1 DNA vaccine in combination with plasmid interleukin 12 and impact of intramuscular electroporation for delivery. J. Infect. Dis. 208(5), 818–829 (2013)CrossRefGoogle Scholar
  363. 363.
    Yang, F.Q., Yu, Y.Y., Wang, G.Q., Chen, J., Li, J.H., Li, Y.Q., Rao, G.R., Mo, G.Y., Luo, X.R., Chen, G.M.: A pilot randomized controlled trial of dual-plasmid HBV DNA vaccine mediated by in vivo electroporation in chronic hepatitis B patients under lamivudine chemotherapy. J. Viral Hepat. 19(8), 581–593 (2012)CrossRefGoogle Scholar
  364. 364.
    Weiland, O., Ahlen, G., Diepolder, H., Jung, M.C., Levander, S., Fons, M., Mathiesen, I., Sardesai, N.Y., Vahlne, A., Frelin, L., Sallberg, M.: Therapeutic DNA vaccination using in vivo electroporation followed by standard of care therapy in patients with genotype 1 chronic hepatitis C. Mol. Ther. 21(9), 1796–1805 (2013)CrossRefGoogle Scholar
  365. 365.
    Aurisicchio, L., Mancini, R., Ciliberto, G.: Cancer vaccination by electro-gene-transfer. Expert Rev. Vaccines 12(10), 1127–1137 (2013). doi: 10.1586/14760584.2013.836903 CrossRefGoogle Scholar
  366. 366.
    Fioretti, D., Iurescia, S., Fazio, V.M., Rinaldi, M.: In vivo DNA electrotransfer for immunotherapy of cancer and neurodegenerative diseases. Curr. Drug Metab. 14(3), 279–290 (2013)CrossRefGoogle Scholar
  367. 367.
    Neumann, E., Schaefer-Ridder, M., Wang, Y., Hofschneider, P.H.: Gene transfer into mouse lyoma cells by electroporation in high electric fields. EMBO J. 1(7), 841–845 (1982)Google Scholar
  368. 368.
    Beebe, S.J.: Bioelectrics in basic science and medicine: impact of electric fields on cellular structures and functions. J. Nanomed. Nanotechnol. 4, 163 (2013)CrossRefGoogle Scholar
  369. 369.
    Nuccitelli, R., Pliquett, U., Chen, X., Ford, W., James Swanson, R., Beebe, S.J., Kolb, J.F., Schoenbach, K.H.: Nanosecond pulsed electric fields cause melanomas to self-destruct. Biochem. Biophys. Res. Commun. 343, 351–360 (2006)CrossRefGoogle Scholar
  370. 370.
    Chen, X., Kolb, J.F., Swanson, R.J., Schoenbach, K.H., Beebe, S.J.: Apoptosis initiation and angiogenesis inhibition: melanoma targets for nanosecond pulsed electric fields. Pigment Cell Melanoma Res. 23, 554–563 (2010)CrossRefGoogle Scholar
  371. 371.
    Zhang, J., Blackmore, P.F., Hargrave, B.Y., Xiao, S., Beebe, S.J., Schoenbach, K.H.: Nanosecond pulse electric field (nanopulse): a novel non-ligand agonist for platelet activation. Arch. Biochem. Biophys. 471, 240–248 (2008)CrossRefGoogle Scholar
  372. 372.
    Schoenbach, K.H., Katsuki, S., Stark, R.H., Buescher, E.S., Beebe, S.J.: Bioelectrics-new applications for pulsed power technology. IEEE. Trans. Plasma Sci. 30, 293–300 (2002)CrossRefGoogle Scholar
  373. 373.
    Malik, M.A., Xiao, S., Schoenbach, K.H.: Scaling of surface-plasma reactors with a significantly increased energy density for NO conversion. J. Hazard. Mater. 209, 293–298 (2012)CrossRefGoogle Scholar
  374. 374.
    Malik, M.A.: Water purification by plasmas: which reactors are most energy efficient? Plasma Chem. Plasma Process. 30, 21–31 (2010)CrossRefGoogle Scholar
  375. 375.
    Kong, M.G., Kroesen, G., Morfill, G., Nosenko, T., Shimizu, T., et al.: Plasma medicine: an introductory review. New J. Phys. 11, 115012 (2009)CrossRefGoogle Scholar
  376. 376.
    Beebe, S.J., Fox, P.M., Rec, L.J., Willis, E.L., Schoenbach, K.H.: Nanosecond, high-intensity pulsed electric fields induce apoptosis in human cells. FASEB J. 17, 1493–1495 (2003)Google Scholar
  377. 377.
    Nuccitelli, R., Chen, X., Pakhomov, A.G., Baldwin, W.H., Sheikh, S., et al.: A new pulsed electric field therapy for melanoma disrupts the tumor’s blood supply and causes complete remission without recurrence. Int. J. Cancer 125, 438–445 (2009)CrossRefGoogle Scholar
  378. 378.
    Rogakou, E.P., Pilch, D.R., Orr, A.H., Ivanova, V.S., Bonner, W.M.: DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem. 273, 5858–5868 (1998)CrossRefGoogle Scholar
  379. 379.
    Esser, A.T., Smith, K.C., Gowrishankar, T.R., Weaver, J.C.: Towards solid tumor treatment by nanosecond pulsed electric fields. Technol. Cancer Res. Treat. 8(4), 289–306 (2009)CrossRefGoogle Scholar
  380. 380.
    Nuccitelli, R., Tran, K., Athos, B., Kreis, M., Nuccitelli, P., Chang, K.S., Epstein Jr., E.H., Tang, J.Y.: Nanoelectroablation therapy for murine basal cell carcinoma. Biochem. Biophys. Res. Commun. 424, 446–450 (2012)CrossRefGoogle Scholar
  381. 381.
    Yin, D., Yang, W.G., Weissberg, J., Goff, C.B., Chen, W., Kuwayama, Y., Leiter, A., Xing, H., Meixel, A., Gaut, D., Kirkbir, F., Sawcer, D., Vernier, P.T., Said, J.W., Gundersen, M.A., Koeffler, H.P.: Cutaneous papilloma and squamous cell carcinoma therapy utilizing nanosecond pulsed electric fields (nsPEF). PLoS ONE 7(8), e43891 (2012)CrossRefGoogle Scholar
  382. 382.
    Yin, S., Chen, X., Hu, C., Zhang, X., Hu, Z., Yu, J., Feng, X., Jiang, K., Ye, S., Shen, K., Xie, H., Zhou, L., James Swanson, R., Zheng, S.: Nanosecond pulsed electric field (nsPEF) treatment for hepatocellular carcinoma: a novel locoregional ablation decreasing lung metastasis. Cancer Lett. 346, 85–291 (2014)CrossRefGoogle Scholar
  383. 383.
    Nuccitelli, R., Huynh, J., Lui, K., Wood, R., Kreis, M., Athos, B., Nuccitelli, P.: Nanoelectroablation of human pancreatic carcinoma in a murine xenograft model without recurrence. Int. J. Cancer 132, 1933–1939 (2013)CrossRefGoogle Scholar
  384. 384.
    Vaughn, L., Beckel, N.: Severe burn injury, burn shock, and smoke inhalation injury in small animals. Part 1: burn classification and pathophysiology. J. Vet. Emerg. Crit. Care (San Antonio) 22(2), 179–186 (2012)CrossRefGoogle Scholar
  385. 385.
    Martin, P.: Wound healing – aiming for perfect skin regeneration. Science 276, 75–81 (1997)CrossRefGoogle Scholar
  386. 386.
    Martin, P., Leibovich, S.J.: Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol. 15, 599–607 (2005)CrossRefGoogle Scholar
  387. 387.
    Gurtner, G.C., Werner, S., Barrandon, Y., Longaker, M.T.: Wound repair and regeneration. Nature 453, 314–321 (2008)CrossRefGoogle Scholar
  388. 388.
    Yeaman, M.R.: Platelets: at the nexus of antimicrobial defense. Nat. Rev. Microbiol. 12, 426–437 (2014)CrossRefGoogle Scholar
  389. 389.
    Raivio, P., Lassila, R., Petaja, J.: Thrombin in myocardial ischemia-reperfusion during cardiac surgery. Ann. Thorac. Surg. 88, 318–325 (2009)CrossRefGoogle Scholar
  390. 390.
    Raivio, P., Kuitunen, A., Suojaranta-Ylinen, R., Lassila, R., Petaja, J.: Thrombin generation during reperfusion after coronary artery bypass surgery associates with postoperative myocardial damage. J. Throm. Homeostat. 4, 1523–1529 (2006)CrossRefGoogle Scholar
  391. 391.
    Edmunds, L.H., Colman, R.W.: Thrombin during cardiopulmonary bypass. Ann. Thorac. Surg. 82, 2315–2322 (2006)CrossRefGoogle Scholar
  392. 392.
    Lopez, J.J., Salido, G.M., Gómez-Arteta, E., et al.: Thrombin induces apoptotic events through the generation of reactive oxygen species in human platelets. J. Thromb. Haemost. 5(6), 1283–1291 (2007)CrossRefGoogle Scholar
  393. 393.
    Han, B., Woodell-May, J., Ponticiello, M., et al.: The effect of thrombin activation of platelet-rich plasma on demineralized bone matrix osteoinductivity. J. Bone. Joint Surg. 91, 1459–1470 (2009)CrossRefGoogle Scholar
  394. 394.
    Thon, J.N., Italiano, J.E.: Platelets: production, morphology and ultrastructure. Handb. Exp. Pharmacol. 210, 3–22 (2012)CrossRefGoogle Scholar
  395. 395.
    Cimmino, G., Golino, P.: Platelet biology and receptor pathways. J. Cardiovasc. Transl. Res. 6, 299–309 (2013)CrossRefGoogle Scholar
  396. 396.
    Golebiewska, E.M., Poole, A.W.: Platelet secretion: from haemostasis to wound healing and beyond. Blood Rev. 29(3), 153–162 (2015)CrossRefGoogle Scholar
  397. 397.
    Nurden, A.T., Nurden, P., Sanchez, M., Andia, I., Anitua, E.: Platelets and wound healing. Front. Biosci. 13, 3532–3548 (2008)Google Scholar
  398. 398.
    Kevin, L.G., Enis Novalija, F., David, F., Stowe, D.F.: Reactive oxygen species as mediators of cardiac injury and protection: the relevance to anesthesia practice. Anesth. Analg. 101, 1275–1287 (2005)CrossRefGoogle Scholar
  399. 399.
    Elahi, M.M., Kong, Y.X., Matata, B.M.: Oxidative stress as a mediator of cardiovascular disease. Oxid. Med. Cell Longev. 2(5), 259–269 (2009)CrossRefGoogle Scholar
  400. 400.
    Vernier, P.T., Sun, Y., Gundersen, M.A.: Nanoelectropulse-driven membrane perturbation and small molecule permeabilization. BMC Cell Biol. 7, 37 (2006)CrossRefGoogle Scholar
  401. 401.
    Wong, T.K., Neumann, E.: Electric field mediated gene transfer. Biochem. Biophys. Res. Commun. 107, 584–587 (1982)CrossRefGoogle Scholar
  402. 402.
    Chen, X., Swanson, R.J., Kolb, J.F., Nuccitelli, R., Schoenbach, K.H.: Histopathology of normal skin and melanomas after nanosecond pulsed electric field treatment. Melanoma Res. 19, 361–371 (2009)CrossRefGoogle Scholar
  403. 403.
    Vernier, P.T., Sun, Y., Marcu, L., Salemi, S., Craft, C.M., Gundersen, M.A.: Calcium bursts induced by nanosecond electric pulses. Biochem. Biophys. Res. Commun. 310, 286–295 (2003)CrossRefGoogle Scholar
  404. 404.
    White, J.A., Blackmore, P.F., Schoenbach, K.H., Beebe, S.J.: Stimulation of capacitative calcium entry in HL-60 cells by nanosecond pulsed electric fields. J. Biol. Chem. 279, 22964–22972 (2004)CrossRefGoogle Scholar
  405. 405.
    Pakhomova, O.N., Khorokhorina, V.A., Bowman, A.M., Rodaite-Riseviciene, R., Saulis, G., Xiao, S., Pakhomov, A.G.: Oxidative effects of nanosecond pulsed electric field exposure in cells and cell-free media. Arch. Biochem. Biophys. 527, 55–64 (2012)CrossRefGoogle Scholar
  406. 406.
    Nuccitelli, R., Lui, K., Kreis, M., Athos, B., Nuccitelli, P.: Nanosecond pulsed electric field stimulation of reactive oxygen species in human pancreatic cancer cells is Ca2+-dependent. Biochem. Biophys. Res. Commun. 435, 580–585 (2013)CrossRefGoogle Scholar
  407. 407.
    Beebe, S.J., Sain, N.M., Ren, W.: Induction of cell death mechanisms and apoptosis by nanosecond pulsed electric fields (nsPEFs). Cells 2, 136–162 (2013)CrossRefGoogle Scholar
  408. 408.
    Nuccitelli, R., Tran, K., Sheikh, S., Athos, B., Kreis, M., Nuccitelli, P.: Optimized nanosecond pulsed electric field therapy can cause murine malignant melanomas to self-destruct with a single treatment. Int. J. Cancer 127, 1727–1736 (2010)CrossRefGoogle Scholar
  409. 409.
    Nuccitelli, R., Tran, K., Lui, K., Huynh, J., Athos, B., Kreis, M., Nuccitelli, P., De Fabo, E.C.: Non-thermal nanoelectroablation of UV-induced murine melanomas stimulates an immune response. Pigment Cell Melanoma Res. 25, 618–629 (2012)CrossRefGoogle Scholar
  410. 410.
    Chen, X., Yin, S., Hu, C., Chen, X., Jiang, K., Ye, S., Feng, X., Fan, S., Xie, H., Zhou, L., Zheng, S.: Comparative study of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma indicate macrophage infiltration contribute to tumor ablation in vivo. PLoS ONE 9, e86421 (2014)CrossRefGoogle Scholar
  411. 411.
    Nuccitelli, R., Berridge, J.C., Mallon, Z., Kreis, M., Athos, B., Nuccitelli, P.: Nanoelectroablation of rat orthotopic hepatocellular carcinoma triggers a CD8-dependent adaptive immune response. PLoS ONE 10(7), e0134364 (2015)CrossRefGoogle Scholar
  412. 412.
    Ibey, B.L., Roth, C.C., Pakhomov, A.G., Bernhard, J.A., Wilmink, G.J., Pakhomova, O.N.: Dose-dependent thresholds of 10-ns electric pulse induced plasma membrane disruption and cytotoxicity in multiple cell lines. PLoS ONE 6, e15642 (2011)CrossRefGoogle Scholar
  413. 413.
    Yang, W., Wu, Y.H., Yin, D., Koeffler, H.P., Sawcer, D.E., Vernier, P.T., Gundersen, M.A.: Differential sensitivities of malignant and normal skin cells to nanosecond pulsed electric fields. Technol. Cancer Res. Treat. 10, 281–286 (2011)Google Scholar
  414. 414.
    Graves, D.B.: The emerging role of reactive oxygen and nitrogen species in redox biology and some implications for plasma applications to medicine and biology. J. Phys. D. Appl. Phys. 45, 263001 (2012)CrossRefGoogle Scholar
  415. 415.
    Babaeva, N.Y., Ning, N., Graves, D.B., Kushner, M.J.: Ion activation energy delivered to wounds by atmospheric pressure dielectric-barrier discharges: sputtering of lipid-like surfaces. J. Phys. D. Appl. Phys. 45, 115203 (2012)CrossRefGoogle Scholar
  416. 416.
    Moreau, M., Orange, N., Feuilloley, M.G.J.: Non-thermal plasma technologies: new tools for bio-decontamination. Biotechnol. Adv. 26, 610–617 (2008)CrossRefGoogle Scholar
  417. 417.
    Weltmann, K.D., Kindel, E., von Woedtke, T., Hahnel, M., Stieber, M., Brandenburg, R.: Atmospheric-pressure plasma sources: prospective tools for plasma medicine. Pure Appl. Chem. 82, 1223–1237 (2010)CrossRefGoogle Scholar
  418. 418.
    Weltmann, K.D., Polak, M., Masur, K., von Woedtke, T., Winter, J., Reuter, S.: Plasma processes and plasma sources in medicine. Contrib. Plasm. Phys. 52, 644–654 (2012)CrossRefGoogle Scholar
  419. 419.
    Lloyd, G., Friedman, G., Jafri, S., Schultz, G., Fridman, A., Harding, K.: Gas plasma: medical uses and developments in wound care. Plasma Process. Polym. 7, 194–211 (2010)CrossRefGoogle Scholar
  420. 420.
    Lu, X., Naidis, G.V., Laroussi, M., Ostrikov, K.: Guided ionization waves: theory and experiments. Phys. Rep. 540, 123–166 (2014)CrossRefGoogle Scholar
  421. 421.
    Jiang, C. Emerging applications of plasmas in medicine: fashion vs. efficacy. In: Chu, P.K., Lu, X. (eds.) Low Temperature Plasma Technology: Methods and Applications. Taylor & Francis Group, CRC Press (2013)Google Scholar
  422. 422.
    Lazarus, G.S., Cooper, D.M., Knighton, D.R., Margolis, D.J., Pecoraro, R.E., Rodeheaver, G., Robson, M.C.: Definitions and guidelines for assessment of wounds and evaluation of healing. Arch. Dermatol. 130, 489–493 (1994)CrossRefGoogle Scholar
  423. 423.
    Robson, M.C.: Wound infection. A failure of wound healing caused by an imbalance of bacteria. Surg. Clin. North Am. 77, 637–650 (1997)CrossRefGoogle Scholar
  424. 424.
    Tarnuzzer, R.W., Schultz, G.S.: Biochemical analysis of acute and chronic wound environments. Wound Repair Regen. 4, 321–325 (1996)CrossRefGoogle Scholar
  425. 425.
    Park, B.J., Lee, D.H., Park, J.C., Lee, I.S., Lee, K.Y., Hyun, S.O., Chun, M.S., Chung, K.H.: Sterilization using a microwave-induced argon plasma system at atmospheric pressure. Phys. Plasmas 10, 4539–4544 (2003)CrossRefGoogle Scholar
  426. 426.
    Montie, T.C., Kelly-Wintenberg, K., Roth, J.R.: An overview of research using the one atmosphere uniform glow discharge plasma (OAUGDP) for sterilization of surfaces and materials. IEEE. T. Plasma Sci. 28, 41–50 (2000)CrossRefGoogle Scholar
  427. 427.
    Lee, M.H., Park, B.J., Jin, S.C., Kim, D., Han, I., Kim, J., Hyun, S.O., Chung, K.H., Park, J.C.: Removal and sterilization of biofilms and planktonic bacteria by microwave-induced argon plasma at atmospheric pressure. New J. Phys. 11, 115022 (2009)CrossRefGoogle Scholar
  428. 428.
    Morrison, JCF: Electrosurgical method and apparatus for initiating an electrical discharge in an inert gas flow. In: U.S. Patent (ed.) U.S. Patent, U.S.A. (1977)Google Scholar
  429. 429.
    Farin, G., Grund, K.E.: Technology of argon plasma coagulation with particular regard to endoscopic applications. Endosc. Surg. Allied Technol. 2, 71–77 (1994)Google Scholar
  430. 430.
    Grund, K.E., Storek, D., Farin, G.: Endoscopic argon plasma coagulation (APC) first clinical experiences in flexible endoscopy. Endosc. Surg. Allied Technol. 2, 42–46 (1994)Google Scholar
  431. 431.
    Vargo, J.J.: Clinical applications of the argon plasma coagulator. Gastrointest. Endosc. 59, 81–88 (2004)CrossRefGoogle Scholar
  432. 432.
    Raiser, J., Zenker, M.: Argon plasma coagulation for open surgical and endoscopic applications: state of the art. J. Phys. D. Appl. Phys. 39, 3520–3523 (2006)CrossRefGoogle Scholar
  433. 433.
    Stoffels, E., Kieft, I.E., Sladek, R.E.J.: Superficial treatment of mammalian cells using plasma needle. J. Phys. D. Appl. Phys. 36, 2908–2913 (2003)CrossRefGoogle Scholar
  434. 434.
    Kieft, I.E., Broers, J.L.V., Caubet-Hilloutou, V., Slaaf, D.W., Ramaekers, F.C.S., Stoffels, E.: Electric discharge plasmas influence attachment of cultured CHO k1 cells. Bioelectromagnetics 25, 362–368 (2004)CrossRefGoogle Scholar
  435. 435.
    Lee, D.H., Lee, J.O., Jeon, W., Choi, I.G., Kim, J.S., Jeong, J.H., Kang, T.C., Seo, C.H.: Suppression of scar formation in a murine burn wound model by the application of non-thermal plasma. Appl. Phys. Lett. 99, 203701-1-3 (2011)Google Scholar
  436. 436.
    Stoffels, E., Roks, A.J.M., Deelmm, L.E.: Delayed effects of cold atmospheric plasma on vascular cells. Plasma Process. Polym. 5, 599–605 (2008)CrossRefGoogle Scholar
  437. 437.
    Kalghatgi, S.U., Fridman, G., Cooper, M., Nagaraj, G., Peddinghaus, M., Balasubramanian, M., Vasilets, V.N., Gutsol, A.F., Fridman, A., Friedman, G.: Mechanism of blood coagulation by nonthermal atmospheric pressure dielectric barrier discharge plasma. IEEE. T. Plasma Sci. 35, 1559–1566 (2007)CrossRefGoogle Scholar
  438. 438.
    Costerton, J.W., Stewart, P.S., Greenberg, E.P.: Bacterial biofilms: a common cause of persistent infections. Science 284, 1318–1322 (1999)CrossRefGoogle Scholar
  439. 439.
    Estrela, C., Sydney, G.B., Figueiredo, J.A., Estrela, C.R.: Antibacterial efficacy of intracanal medicaments on bacterial biofilm: a critical review. J. Appl. Oral Sci. 17, 1–7 (2009)CrossRefGoogle Scholar
  440. 440.
    Moore, W.E., Moore, L.V.: The bacteria of periodontal diseases. Periodontol. 5, 66–77 (1994)CrossRefGoogle Scholar
  441. 441.
    Paster, B.J., Boches, S.K., Galvin, J.L., Ericson, R.E., Lau, C.N., Levanos, V.A., Sahasrabudhe, A., Dewhirst, F.E.: Bacterial diversity in human subgingival plaque. J. Bacteriol. 183, 3770–3783 (2001)CrossRefGoogle Scholar
  442. 442.
    Marsh, P.D.: Microbiologic aspects of dental plaque and dental caries. Dent. Clin. N. Am. 43, 599–614, v–vi (1999)Google Scholar
  443. 443.
    Yip, H.K., Samaranayake, L.P.: Caries removal techniques and instrumentation: a review. Clin. Oral Invest. 2, 148–154 (1998)CrossRefGoogle Scholar
  444. 444.
    Banerjee, A., Watson, T.F., Kidd, E.A.: Dentine caries excavation: a review of current clinical techniques. Br. Dent. J. 188, 476–482 (2000)Google Scholar
  445. 445.
    Buchanan, L.S.: Cleaning and shaping the root canal system: negotiating canals to the termini. Dent. Today 13(76), 78–81 (1994)Google Scholar
  446. 446.
    Schilder, H.: Cleaning and shaping the root canal. Dent. Clin. N. Am. 18, 269–296 (1974)Google Scholar
  447. 447.
    Chavez de Paz, L.E.: Redefining the persistent infection in root canals: possible role of biofilm communities. J. Endod. 33, 652–662 (2007)CrossRefGoogle Scholar
  448. 448.
    Chavez De Paz, L.E., Dahlen, G., Molander, A., Moller, A., Bergenholtz, G.: Bacteria recovered from teeth with apical periodontitis after antimicrobial endodontic treatment. Int. Endod. J. 36, 500–508 (2003)CrossRefGoogle Scholar
  449. 449.
    Nair, P.N., Henry, S., Cano, V., Vera, J.: Microbial status of apical root canal system of human mandibular first molars with primary apical periodontitis after “one-visit” endodontic treatment. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 99, 231–252 (2005)CrossRefGoogle Scholar
  450. 450.
    Nair, P.N., Sjogren, U., Krey, G., Kahnberg, K.E., Sundqvist, G.: Intraradicular bacteria and fungi in root-filled, asymptomatic human teeth with therapy-resistant periapical lesions: a long-term light and electron microscopic follow-up study. J. Endod. 16, 580–588 (1990)CrossRefGoogle Scholar
  451. 451.
    Sjogren, U., Figdor, D., Persson, S., Sundqvist, G.: Influence of infection at the time of root filling on the outcome of endodontic treatment of teeth with apical periodontitis. Int. Endod. J. 30, 297–306 (1997)CrossRefGoogle Scholar
  452. 452.
    Moritz, A., Schoop, U., Goharkhay, K., Jakolitsch, S., Kluger, W., Wernisch, J., Sperr, W.: The bactericidal effect of Nd:YAG, Ho:YAG, and Er:YAG laser irradiation in the root canal: an in vitro comparison. J. Clin. Laser Med. Surg. 17, 161–164 (1999)Google Scholar
  453. 453.
    Bergmans, L., Moisiadis, P., Huybrechts, B., Van Meerbeek, B., Quirynen, M., Lambrechts, P.: Effect of photo-activated disinfection on endodontic pathogens ex vivo. Int. Endod. J. 41, 227–239 (2008)CrossRefGoogle Scholar
  454. 454.
    Soukos, N.S., Chen, P.S., Morris, J.T., Ruggiero, K., Abernethy, A.D., Som, S., Foschi, F., Doucette, S., Bammann, L.L., Fontana, C.R., Doukas, A.G., Stashenko, P.P.: Photodynamic therapy for endodontic disinfection. J. Endod. 32, 979–984 (2006)CrossRefGoogle Scholar
  455. 455.
    Bergmans, L., Moisiadis, P., Teughels, W., Van Meerbeek, B., Quirynen, M., Lambrechts, P.: Bactericidal effect of Nd:YAG laser irradiation on some endodontic pathogens ex vivo. Int. Endod. J. 39, 547–557 (2006)CrossRefGoogle Scholar
  456. 456.
    Noiri, Y., Katsumoto, T., Azakami, H., Ebisu, S.: Effects of Er:YAG laser irradiation on biofilm-forming bacteria associated with endodontic pathogens in vitro. J. Endod. 34, 826–829 (2008)CrossRefGoogle Scholar
  457. 457.
    Dederich, D.N., Bushick, R.D.: Lasers in dentistry: separating science from hype. J. Am. Dent. Assoc. 135, 204–212; quiz 229 (2004)CrossRefGoogle Scholar
  458. 458.
    Ahmady, K., Marsh, P.D., Newman, H.N., Bulman, J.S.: Distribution of Streptococcus mutans and Streptococcus sobrinus at subsites in human approximal dental plaque. Caries Res. 27, 135–139 (1993)CrossRefGoogle Scholar
  459. 459.
    Babaahmady, K.G., Challacombe, S.J., Marsh, P.D., Newman, H.N.: Ecological study of Streptococcus mutans, Streptococcus sobrinus and Lactobacillus spp. at sub-sites from approximal dental plaque from children. Caries Res. 32, 51–58 (1998)CrossRefGoogle Scholar
  460. 460.
    Badet, C., Thebaud, N.B.: Ecology of lactobacilli in the oral cavity: a review of literature. Open Microbiol. J. 2, 38–48 (2008)Google Scholar
  461. 461.
    Sedgley, C.M., Lennan, S.L., Clewell, D.B.: Prevalence, phenotype and genotype of oral enterococci. Oral Microbiol. Immunol. 19, 95–101 (2004)CrossRefGoogle Scholar
  462. 462.
    Waltimo, T.M., Sen, B.H., Meurman, J.H., Orstavik, D., Haapasalo, M.P.: Yeasts in apical periodontitis. Crit. Rev. Oral Biol. Med. 14, 128–137 (2003)CrossRefGoogle Scholar
  463. 463.
    Lee, H.W., Nam, S.H., Mohamed, A.A.H., Kim, G.C., Lee, J.K.: Atmospheric pressure plasma jet composed of three electrodes: application to tooth bleaching. Plasma Process. Polym. 7, 274–280 (2010)CrossRefGoogle Scholar
  464. 464.
    Goree, J., Liu, B., Drake, D., Stoffels, E.: Killing of S-mutans bacteria using a plasma needle at atmospheric pressure. IEEE. T. Plasma Sci. 34, 1317–1324 (2006)CrossRefGoogle Scholar
  465. 465.
    Gonzalvo, Y.A., Whitmore, T.D., Rees, J.A., Seymour, D.L., Stoffels, E.: Atmospheric pressure plasma analysis by modulated molecular beam mass spectrometry. J. Vac. Sci. Technol. A 24, 550–553 (2006)CrossRefGoogle Scholar
  466. 466.
    Duan, Y.X., Huang, C., Yu, Q.S.: Cold plasma brush generated at atmospheric pressure. Rev. Sci. Instrum. 78, 015104-1-5 (2007)CrossRefGoogle Scholar
  467. 467.
    Yang, B., Chen, J.R., Yu, Q.S., Li, H., Lin, M.S., Mustapha, A., Hong, L.A., Wang, Y.: Oral bacterial deactivation using a low-temperature atmospheric argon plasma brush. J. Dent. 39, 48–56 (2011)CrossRefGoogle Scholar
  468. 468.
    Koban, I., Matthes, R., Hubner, N.O., Welk, A., Meisel, P., Holtfreter, B., Sietmann, R., Kindel, E., Weltmann, K.D., Kramer, A., Kocher, T.: Treatment of Candida albicans biofilms with low-temperature plasma induced by dielectric barrier discharge and atmospheric pressure plasma jet. New J. Phys. 12, 073039-1-12 (2010)CrossRefGoogle Scholar
  469. 469.
    Rupf, S., Lehmann, A., Hannig, M., Schafer, B., Schubert, A., Feldmann, U., Schindler, A.: Killing of adherent oral microbes by a non-thermal atmospheric plasma jet. J. Med. Microbiol. 59, 206–212 (2010)CrossRefGoogle Scholar
  470. 470.
    Yamazaki, H., Ohshima, T., Tsubota, Y., Yamaguchi, H., Jayawardena, J.A., Nishimura, Y.: Microbicidal activities of low frequency atmospheric pressure plasma jets on oral pathogens. Dent. Mater. J. 30, 384–391 (2011)CrossRefGoogle Scholar
  471. 471.
    Jiang, C., Schaudinn, C., Jaramillo, D.E., Gundersen, M.A., Costerton, J.W.: A sub-microsecond pulsed plasma jet for endodontic biofilm disinfection. In: Machala, Z., Hensel, K., Akishev, Y. (eds.) Plasma for Bio-Decontamination, Medicine and Food Security. Springer, Heidelberg (2012)Google Scholar
  472. 472.
    Jiang, C.Q., Chen, M.T., Schaudinn, C., Gorur, A., Vernier, P.T., Costerton, J.W., Jaramillo, D.E., Sedghizadeh, P.P., Gundersen, M.A.: Pulsed atmospheric-pressure cold plasma for endodontic disinfection. IEEE. T. Plasma Sci. 37, 1190–1195 (2009)CrossRefGoogle Scholar
  473. 473.
    Jiang, C., Schaudinn, C.: A curving bactericidal plasma needle. IEEE. T. Plasma Sci. 39, 2966–2967 (2011)CrossRefGoogle Scholar
  474. 474.
    Jiang, C., Schaudinn, C., Jaramillo, D.E., Webster, P., Costerton, J.W.: In vitro antimicrobial effect of a cold plasma jet against enterococcus faecalis biofilms. ISRN Dent. 2012, 295736 (2012)Google Scholar
  475. 475.
    Schaudinn, C., Jaramillo, D., Freire, M.O., Sedghizadeh, P.P., Nguyen, A., Webster, P., Costerton, J.W., Jiang, C.: Evaluation of a nonthermal plasma needle to eliminate ex vivo biofilms in root canals of extracted human teeth. Int. Endod. J. 46, 930–937 (2013)CrossRefGoogle Scholar
  476. 476.
    Lu, X.P., Cao, Y.G., Yang, P., Xiong, Q., Xiong, Z.L., Xian, Y.B., Pan, Y.: An RC plasma device for sterilization of root canal of teeth. IEEE. T. Plasma Sci. 37, 668–673 (2009)CrossRefGoogle Scholar
  477. 477.
    Du, T., Ma, J., Yang, P., Xiong, Z., Lu, X., Cao, Y.: Evaluation of antibacterial effects by atmospheric pressure nonequilibrium plasmas against Enterococcus faecalis biofilms in vitro. J. Endod. 38, 545–549 (2012)CrossRefGoogle Scholar
  478. 478.
    Du, T., Shi, Q., Shen, Y., Cao, Y., Ma, J., Lu, X., Xiong, Z., Haapasalo, M.: Effect of modified nonequilibrium plasma with chlorhexidine digluconate against endodontic biofilms in vitro. J. Endod. 39, 1438–1443 (2013)CrossRefGoogle Scholar
  479. 479.
    Casal, M., Haskins, M.: Large animal models and gene therapy. Eur. J. Hum. Genet. 14(3), 266–272 (2006)CrossRefGoogle Scholar
  480. 480.
    Khanna, C., Lindblad-Toh, K., Vail, D., London, C., Bergman, P., Barber, L., Breen, M., Kitchell, B., McNeil, E., Modiano, J.F., Niemi, S., Comstock, K.E., Ostrander, E., Westmoreland, S., Withrow, S.: The dog as a cancer model. Nat. Biotechnol. 24(9), 1065–1066 (2006)CrossRefGoogle Scholar
  481. 481.
    Ranieri, G., Panteleo, M., Piccinno, M., Roncetti, M., Mutinati, M., Patruno, R., Rizzo, A., Sciorsci, R.L.: Tyrosine kinase inhibitors (TKIs) in human and pet tumours with special reference to breast cancer: a comparative review. Crit. Rev. Oncol. Hematol. 88(2), 293–308 (2013)CrossRefGoogle Scholar
  482. 482.
    Marconato, L.: Chemioterapici utilizzati in medicina veterinaria. In: Marconato, L., e Del Piero, F. (eds.) Oncologia medica dei piccoli animali, 1st edn, pp. 108–144. Poletto editore, Millano (2005)Google Scholar
  483. 483.
    Plumb, D.C.: Veterinary Drug Handbook, 7th edn, p. 1208. PharmaVet, Stocholm (2011)Google Scholar
  484. 484.
    Mir, L.M., Devauchelle, P., Quintin-Colonna, F., Delisle, F., Doliger, S., Fradelizi, D., Belehradek Jr., J., Orlowski, S.: First clinical trial of cat soft-tissue sarcomas treatment by electrochemotherapy. Br. J. Cancer 76(12), 1617–1622 (1997)CrossRefGoogle Scholar
  485. 485.
    Tozon, N., Sersa, G., Cemazar, M.: Electrochemotherapy: potentiation of local antitumour effectiveness of cisplatin in dogs and cats. Anticancer Res. 21(4A), 2483–2488 (2001)Google Scholar
  486. 486.
    Rols, M.P., Tamzali, Y., Teissié, J.: Electrochemotherapy of horses. A preliminary clinical report. Bioelectrochemistry 55(1–2), 101–105 (2002)CrossRefGoogle Scholar
  487. 487.
    Spugnini, E.P., Porrello, A.: Potentiation of chemotherapy in companion animals with spontaneous large neoplasms by application of biphasic electric pulses. J. Exp. Clin. Cancer Res. 22(4), 571–580 (2003)Google Scholar
  488. 488.
    Spugnini, E.P., Filliponni, M., Romani, L., Dotinsky, I., Mudrov, N., Baroni, A., Ruocco, E., Laieta, M.T., Montesarchio, V., Cassandro, R., Citro, G., Baldi, A.: Local control and distant metastasis after electrochemotherapy of a canine anal melanoma. In Vivo 21(5), 897–899 (2007)Google Scholar
  489. 489.
    Kodre, V., Cemazar, M., Pecar, J., Sersa, G., Cor, A., Tozon, N.: Electrochemotherapy compared to surgery for treatment of canine mast cell tumours. In Vivo 23(1), 55–62 (2009)Google Scholar
  490. 490.
    Spugnini, E.P., Citro, G., Baldi, A.: Electrochemotherapy in veterinary oncology part I: solid tumors. In: Spugnini, E.P., Baldi, A. (eds.) Electroporation in Laboratory and Clinical Investigations, pp. 245–255. Nova Science Publishers, New York (2011). cap. 12Google Scholar
  491. 491.
    Spugnini, E.P., Baldi, A., Citro, G.: Electrochemotherapy in veterinary oncology part II: round cell tumors. In: Spugnini, E.P., Baldi, A. (eds.) Electroporation in Laboratory and Clinical Investigations, pp. 257–264. Nova Science Publishers, New York (2011). cap. 13Google Scholar
  492. 492.
    Spugnini, E.P., Vincenzi, B., Citro, G., Dotsinsky, I., Mudrov, T., Baldi, A.: Evaluation of Cisplatin as an electrochemotherapy agent for the treatment of incompletely excised mast cell tumors in dogs. J. Vet. Intern. Med. 25(2), 407–411 (2011)CrossRefGoogle Scholar
  493. 493.
    Tamzali, Y., Borde, L., Rols, M.P., Golzio, M., Lyazrhi, F., Teissie, J.: Successful treatment of equine sarcoids with cisplatin electrochemotherapy: a retrospective study of 48 cases. Equine Vet. J. 44(2), 214–220 (2012)CrossRefGoogle Scholar
  494. 494.
    Tozon, N., Pavlin, D., Sersa, G., Dolinsek, T., Cemazar, M.: Electrochemotherapy with intravenous bleomycin injection: an observational study in superficial squamous cell carcinoma in cats. J. Feline Med. Surg. 16(4), 291–299 (2014)CrossRefGoogle Scholar
  495. 495.
    Reed, S.D., Fulmer, A., Buckholtz, J., Zhang, B., Cutera, J., Shiomitsu, K., Li, S.: Bleomycin/interleukin-12 electrochemogene therapy for treating naturally occurring spontaneous neoplasms in dogs. Cancer Gene Ther. 17(7), 457–464 (2010)CrossRefGoogle Scholar
  496. 496.
    Pavlin, D., Cemazar, M., Cor, A., Sersa, G., Poqacnik, A., Tozon, N.: Electrogene therapy with interleukin-12 in canine mast cell tumors. Radiol. Oncol. 45(1), 31–39 (2010)Google Scholar
  497. 497.
    Liu, F., Huang, L.A.: Syringe electrode device for simultaneous injection of DNA and electrotransfer. Mol. Ther. 5(3), 323–328 (2002)CrossRefGoogle Scholar
  498. 498.
    Spugnini, E.P., Citro, G., Porrello, A.: Rational design of new electrodes for electrochemotherapy. J. Exp. Clin. Cancer Res. 24(2), 245–254 (2005)Google Scholar
  499. 499.
    Tjelle, T.E., Salte, R., Mathiesen, I., Kjeken, R.: A novel electroporation device for gene delivery in large animals and humans. Vaccine 24(21), 4667–4670 (2006)CrossRefGoogle Scholar
  500. 500.
    Mazeres, S., Sel, D., Golzio, M., Pucihar, G., Tamzali, Y., Miklavcic, D., Teissie, J.: Non invasive contact electrodes for in vivo localized cutaneous electropulsation and associated drug and nucleic acid delivery. J. Control Release 134(2), 125–131 (2009), Mar 4 2009. ISSN 1873-4995 (Electronic) 0168-3659 (Linking). Disponível em:
  501. 501.
    Tozon, N., Kodre, V., Sersa, G., Cemazar, M.: Effective treatment of perianal tumors in dogs with electrochemotherapy. Anticancer Res. 25(2A), 839–845 (2005)Google Scholar
  502. 502.
    Theon, A.P., Pascoe, J.R., Carlson, G.P., Krag, D.N.: Intratumoral chemotherapy with cisplatin in oily emulsion in horses. J. Am. Vet. Med. Assoc. 202(2), 261–267 (1993)Google Scholar
  503. 503.
    Sersa, G., Cemazar, M., Miklavcic, D., Chaplin, D.J.: Tumor blood flow modifying effect of electrochemotherapy with bleomycin. Anticancer Res. 19(5B), 4017–4022 (1999)Google Scholar

Copyright information

© Springer Japan 2017

Authors and Affiliations

  • Richard Heller
    • 1
    Email author
  • Justin Teissie
    • 2
  • Marie-Pierre Rols
    • 2
  • Julie Gehl
    • 3
  • Gregor Sersa
    • 4
  • Lluis M. Mir
    • 5
  • Robert E. NealII
    • 6
  • Suyashree Bhonsle
    • 6
  • Rafael Davalos
    • 6
  • Stephen Beebe
    • 1
  • Barbara Hargrave
    • 1
  • Richard Nuccitelli
    • 7
  • Chunqi Jiang
    • 1
  • Maja Cemazar
    • 8
    • 9
  • Youssef Tamzali
    • 10
  • Natasa Tozon
    • 11
  1. 1.Frank Reidy Research Center for BioelectricsOld Dominion UniversityNorfolkUSA
  2. 2.Institute of Pharmacology and Structural BiologyCNRS and University of ToulouseToulouseFrance
  3. 3.Center for Experimental Drug and Gene ElectrotransferCopenhagen University HospitalHerlevDenmark
  4. 4.Department of Experimental OncologyInstitute of Oncology LjubljanaLjubljanaSlovenia
  5. 5.Laboratory of Vectorology and Anticancer TherapeuticsCNRS and University of Paris-SudVillejuifFrance
  6. 6.Bioelectromechanical Systems LaboratoryVirginia TechBlacksburgUSA
  7. 7.Pulse Biosciences, Inc.BurlingameUSA
  8. 8.Department of Experimental OncologyInstitute of Oncology LjubljanaLjubljanaSlovenia
  9. 9.Faculty of Health SciencesUniversity of PrimorskaIzolaSlovenia
  10. 10.École Nationale Vétérinaire de ToulouseToulouseFrance
  11. 11.Veterinary FacultyUniversity of LjubljanaLjubljanaSlovenia

Personalised recommendations