Skip to main content
SpringerLink
Log in

In situ Ablation of Solid Tumors by Electric Forces and Its Effect on the Tumor Microenvironment and Anti-tumor Immunity

  • Chapter
  • First Online:
Book cover Tumor Ablation

Part of the book series: The Tumor Microenvironment ((TTME,volume 5))

Abstract

Several electric-based cancer treatments were developed for in situ ablation of solid tumors. The electrical parameters used for treatment range from several volts per cm delivered for a long time period, to high electric fields (300–3000 V/cm) and very high electric fields (up to 300 kV/cm, 3–300 ns pulse duration).

The treatment can be delivered as a continuous treatment or pulses. These treatments are either based on electrostimulation alone or in conjunction with chemotherapeutic drugs.

In this chapter, we summarized data on the effect of various types of electric ablation of cancer in various metastatic tumors in mice and in clinical trials. We discuss the role of electric ablation in changes that occur in the tumor microenvironment, infiltration of immune cells into the tumor, and induction of antitumor immunity. Special focus is given to the role of these responses in the elimination of residual metastatic cells, and the possible enforcement of such antitumor reactions by various immunostimulators.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Vannucci L (2011) Cancer immunology and colorectal cancer recurrence. Front Biosci (Schol Ed) 3:1421–1431

    Article  Google Scholar 

  2. Ma Y, Conforti R, Aymeric L, Locher C, Kepp O, Kroemer G, Zitvogel L (2011) How to improve the immunogenicity of chemotherapy and radiotherapy. Cancer Metastasis Rev 30:71–82

    Article  PubMed  CAS  Google Scholar 

  3. Mellman I, Coukos G, Dranoff G (2011) Cancer immunotherapy comes of age. Nature 480:480–489

    Article  PubMed  CAS  Google Scholar 

  4. Klein O, Schmidt C, Knights A, Davis ID, Chen W, Cebon J (2011) Melanoma vaccines: developments over the past 10 years. Expert Rev Vaccines 10:853–873

    Article  PubMed  CAS  Google Scholar 

  5. Lesterhuis WJ, Haanen JB, Punt CJ (2011) Cancer immunotherapy—revisited. Nat Rev Drug Discov 10:591–600

    Article  PubMed  CAS  Google Scholar 

  6. Adema GJ (2009) Dendritic cells from bench to bedside and back. Immunol Lett 122:128–130

    Article  PubMed  CAS  Google Scholar 

  7. Apetoh L, Tesniere A, Ghiringhelli F, Kroemer G, Zitvogel L (2008) Molecular interactions between dying tumor cells and the innate immune system determine the efficacy of conventional anticancer therapies. Cancer Res 68:4026–4030

    Article  PubMed  CAS  Google Scholar 

  8. Myc LA, Gamian A, Myc A (2011) Cancer vaccines. Any future? Arch Immunol Ther Exp (Warsz) 59:249–259

    Article  Google Scholar 

  9. Ahmed M, Brace CL, Lee FT Jr, Goldberg SN (2011) Principles of and advances in percutaneous ablation. Radiology 258:351–369

    Article  PubMed  Google Scholar 

  10. Kepp O, Galluzzi L, Martins I, Schlemmer F, Adjemian S, Michaud M, Sukkurwala AQ, Menger L, Zitvogel L, Kroemer G (2011) Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy. Cancer Metastasis Rev 30:61–69

    Article  PubMed  CAS  Google Scholar 

  11. Prestwich RJ, Errington F, Hatfield P, Merrick AE, Ilett EJ, Selby PJ, Melcher AA (2008) The immune system—is it relevant to cancer development, progression, and treatment? Clin Oncol (R Coll Radiol) 20:101–112

    Article  CAS  Google Scholar 

  12. Van Der Most RG, Currie A, Robinson BW, Lake RA (2006) Cranking the immunologic engine with chemotherapy: using context to drive tumor antigen cross-presentation towards useful antitumor immunity. Cancer Res 66:601–604

    Article  PubMed  CAS  Google Scholar 

  13. Nordenstrom BE (1978) Preliminary trials of electrophoretic ionization in the treatment of malignant tumors. IRCS J Med Sci 6:537

    Google Scholar 

  14. Nordenstrom B (1984) Biologically closed electric circuits: activation of vascular interstitial closed electric circuits for treatment of inoperable cancers. Bioelectricity 3:137–153

    Google Scholar 

  15. Berendson J, Simonsson D (1994) Electrochemical aspects of treatment of tissue with direct current. Eur J Surg Suppl 574:111–115

    PubMed  Google Scholar 

  16. Robertson GSM, Wemyss-Holden SA, Dennison AR, de la M Hall P, Baxter PS, Maddern GJ (1998) Experimental study of electrolysis-induced hepatic necrosis. Br J Surg 85:1212–1216

    Article  PubMed  CAS  Google Scholar 

  17. Habal MB, Schauble MK (1973) Clinical device note: an implantable DC power unit for control of experimental tumor growth in hamsters. Med Instrum 7:305–306

    PubMed  CAS  Google Scholar 

  18. Humphrey CE, Seal EH (1959) Biophysical approach toward tumor regression in mice. Science 130:388–390

    Article  PubMed  CAS  Google Scholar 

  19. Schauble MK, Habal MB, Gullick HD (1977) Inhibition of experimental tumor growth in hamsters by small direct currents. Arch Pathol Lab Med 101:294–297

    PubMed  CAS  Google Scholar 

  20. Morris DM, Marino AA, Gonzalez, E (1992) Electrochemical modification of tumor growth in mice. J Surg Res 53:306–309

    Article  PubMed  CAS  Google Scholar 

  21. Heiberg E, Nalesnik WJ, Janney C (1991) Effects of varying potential and electrolytic dosage in direct current treatment of tumors. Acta Radiol 32:174–177

    Article  PubMed  CAS  Google Scholar 

  22. Samuelsson L, Jonsson L, Lamm IL, Lindén CJ, Ewers SB (1991) Electrolysis with different electrode materials and combined with irradiation for treatment of experimental rat tumors. Acta Radiol 32:178–181

    Article  PubMed  CAS  Google Scholar 

  23. Chou CK, McDougall JA, Ahn C, Vora N (1997) Electrochemical treatment of mouse and rat fibrosarcomas with direct current. Bioelectromagnetics 18:18–24

    Google Scholar 

  24. Turler A, Schaefer H, Schaefer N, Wagner M, Maintz D, Qiao JC, Hoelscher AH (2000) Experimental low-level direct current therapy in liver metastases: influence of polarity and current dose. Bioelectromagnetics 21:395–401

    Article  PubMed  CAS  Google Scholar 

  25. Wemyss-Holden SA, Robertson GSM, de la M Hall P, Dennison AR, Maddern GJ (2000a) Electrolytic treatment of colorectal liver tumor deposits in a rat model: a technique with potential for patients with unresectable liver tumors. Dig Dis 18:50–57

    Article  CAS  Google Scholar 

  26. Dennison AR, Maddern GJ (2000) A new treatment for unresectable liver tumors: long-term studies of electrolytic lesions in the pig liver. Clin Sci 98:561–567

    Article  PubMed  Google Scholar 

  27. Wemyss-Holden SA, de la M Hall P, Robertson GS, Dennison AR, Vanderzon PS, Maddern GJ (2000b) The safety of electrolytically induced hepatic necrosis in a pig model. Aust N Z J Surg 70:607–612

    Article  CAS  Google Scholar 

  28. Wemyss-Holden SA, Dennison AR, Finch JG, de la M Hall P, Maddern GJ (2002) Electrolytic ablation as an adjunct to liver resection: experimental studies of predictability and safety. Br J Surg 89:579–585

    Article  PubMed  CAS  Google Scholar 

  29. Telló M, Oliveira L, Parise O, Buzaid AC, Oliveira RT, Zanella R, Cardona A (2007) Electrochemical therapy to treat cancer (in vivo treatment). Conf Proc IEEE Eng Med Biol Soc 2007:3524–3527

    PubMed  Google Scholar 

  30. von Euler H, Strahle K, Yongqing G (2004) Cell proliferation and apoptosis in rat mammary cancer after electrochemical treatment (EChT). Bioelectrochemistry 62:57–65

    Article  PubMed  CAS  Google Scholar 

  31. Gravante G, Ong SL, Metcalfe MS, Bhardwaj N, Maddern GJ, Lloyd DM, Dennison AR (2011) Experimental application of electrolysis in the treatment of liver and pancreatic tumors: principles, preclinical and clinical observations and future perspectives. Surg Oncol 20:106–120

    Article  PubMed  CAS  Google Scholar 

  32. Nordenstrom BE (1989) Electrochemical treatment of cancer. I: Variable response to anodic and cathodic fields. Am J Clin Oncol 12:530–536

    Article  PubMed  CAS  Google Scholar 

  33. Nordenström BE, Eksborg S, Beving H (1990) Electrochemical treatment of cancer. II: Effect of electrophoretic influence on adriamycin. Am J Clin Oncol 13:75–88

    Article  PubMed  Google Scholar 

  34. Lao YH, Ge TG, Zheng XL, Zhang JZ, Hua YW, Mao SM, Feng X (1994) Electrochemical therapy for intermediate and advanced liver cancer: a report of 50 cases. Eur J Surg (Suppl 564):51–53

    Google Scholar 

  35. Xin Y (1994a) Organization and spread of electrochemical therapy in China. Eur J Surg (Suppl 574):25–29

    Google Scholar 

  36. Xin YL, Xue FZ, Ge BS, Zhao FR, Shi B, Zhang W (1997) Electrochemical treatment of lung cancer. Bioelectromagnetics 18:8–13

    Article  PubMed  CAS  Google Scholar 

  37. Xin YL (1994b) Advances in the treatment of malignant tumors by electrochemical therapy (EChT). Eur J Surg (Suppl 574):31–35

    Google Scholar 

  38. Berry D, Dennison AR, Ward R, Maddern GJ (2000) Electrolytic ablation of colorectal metastases: 1-year histological patient follow-up. Dig Surg 17:518–519

    Article  PubMed  CAS  Google Scholar 

  39. Fosh BG, Finch JG, Lea M, Black C, Wong S, Wemyss-Holden S, Maddern GJ (2002) The use of electrolysis as an adjunct to liver resection. Br J Surg 89:1–6

    Article  Google Scholar 

  40. Nilsson E, von Euler H, Berendson J, Thorne A, Wersall P, Naslund I, Lagerstedt AS, Narfstrom K, Olsson JM (2000) Electrochemical treatment of tumors. Bioelectrochemistry 51:1–11

    Article  PubMed  CAS  Google Scholar 

  41. Wemyss-Holden SA, Dennison AR, Berry DP, Maddern GJ (2004) Local ablation for unresectable liver tumors: is thermal best? J Hepatobiliary Pancreat Surg 11:97–106

    Article  PubMed  Google Scholar 

  42. Keisari Y, Korenstein R (2011) Antitumoral effects of pulsed low electric field enhanced chemotherapy: lessons from experimental malignant tumors. In: Spugnini EP, Baldi A (eds) Electroporation in laboratory and clinical investigations. Nova Science Publishers Inc, New York

    Google Scholar 

  43. Antov Y, Barbul A, Korenstein R (2004) Electroendocytosis: stimulation of adsorptive and fluid-phase uptake by pulsed low electric fields. Exp Cell Res 297:348–362

    Article  PubMed  CAS  Google Scholar 

  44. Antov Y, Barbul A, Mantsur H, Korenstein R (2005) Electroendocytosis: exposure of cells to pulsed low electric fields enhances adsorption and uptake of macromolecules. Biophys J 88:2206–2223

    Article  PubMed  CAS  Google Scholar 

  45. Barbul A, Antov Y, Rosenberg Y, Korenstein R (2009) Enhanced delivery of macromolecules into cells by electroendocytosis. In: Belting M (ed) Macromolecular drug delivery—methods in molecular medicine, vol 480. Humana Press, New York, pp 141–150

    Chapter  Google Scholar 

  46. Rosenberg Y, Korenstein R (1997) Incorporation of macromolecules into cells and vesicles by low electric fields: induction of endocytotic-like processes. Bioelectrochem Bioenerg 42:275–281

    Article  Google Scholar 

  47. Entin I, Plotnikov A, Korenstein R, Keisari Y (2003) Tumor growth retardation, cure, and induction of antitumor immunity in B16 melanoma bearing mice by low electric field enhanced chemotherapy. Clin Cancer Res 9:3190–3197

    PubMed  CAS  Google Scholar 

  48. Plotnikov A, Fishman D, Tichler T, Korenstein R, Keisari Y (2004) Low electric field enhanced chemotherapy can cure mice with CT-26 colon carcinoma and induce anti tumor immunity. Clin Exp Immunol 138:410–416

    Article  PubMed  CAS  Google Scholar 

  49. Plotnikov A, Tichler T, Korenstein R, Keisari Y (2005) Involvement of the immune response in the cure of metastatic murine CT-26 colon carcinoma by low electric field enhanced chemotherapy. Int J Cancer 117:816–824

    Article  PubMed  CAS  Google Scholar 

  50. Plotnikov A, Niego B, Ophir R, Korenstein R, Keisari Y (2006) Effective treatment of mouse metastatic prostate cancer by low electric field enhanced chemotherapy. The Prostate 66:1620–1630

    Article  PubMed  CAS  Google Scholar 

  51. Kirson ED, Gurvich Z, Schneiderman R, Dekel E, Itzhaki A, Wasserman Y, Schatzberger R, Palti Y (2004) Disruption of cancer cell replication by alternating electric fields. Cancer Res 64:3288–3295

    Article  PubMed  CAS  Google Scholar 

  52. Kirson ED, Dbaly V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneiderman R, Wasserman Y, Salzberg M, Ryffel B, Goldsher D, Dekel E, Palti Y (2007) Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci USA 104:10152–10157

    Article  PubMed  CAS  Google Scholar 

  53. Salzberg M, Kirson E, Palti Y, Rochlitz C (2008) A pilot study with very low-intensity, intermediate-frequency electric fields in patients with locally advanced and/or metastatic solid tumors. Onkologie 31:362–365

    Article  PubMed  Google Scholar 

  54. Kirson ED, Giladi M, Gurvich Z, Itzhaki A, Mordechovich D, Schneiderman RS, Wasserman Y, Ryffel B, Goldsher D, Palti Y (2009) Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs. Clin Exp Metastasis 26:633–640

    Article  Google Scholar 

  55. Chidichimo G, Beneduci A, Nicoletta M, Critelli M, De Rose R, Tkatchenko Y, Abonante S, Tripepi S, Perrotta E (2002) Selective inhibition of tumoral cell growth by low power millimeter waves. Anticancer Res 22:1681–1688

    PubMed  Google Scholar 

  56. Teppone M, Avakyan R (2010) Extremely high-frequency therapy in oncology. The J Alternative Complementary Medicine 16:1211–1216

    Article  Google Scholar 

  57. Mir LM, Tounekti O, Orlowski S (1996) Bleomycin: revival of an old drug. Gen Pharmacol 27:745–748

    Article  PubMed  CAS  Google Scholar 

  58. Orlowski S, Belehradek JJ, Paoletti C, Mir LM (1988) Transient electropermeabilization of cells in culture. Increase of the cytotoxicity of anticancer drugs. Biochem Pharmacol 37:4727–4733

    Article  PubMed  CAS  Google Scholar 

  59. Sersa G, Miklavcic D, Cemazar M, Rudolf Z, Pucihar G, Snoja M (2008) Electrochemotherapy in treatment of tumors. Eur J Surg Oncol 34:232–240

    Article  PubMed  CAS  Google Scholar 

  60. Yabushita H, Yoshikawa K, Hirata M, Furuya H, Hojyoh T, Fukatsu H, Noguchi M, Nakanishi M (1997) Effects of electrochemotherapy on CaSki cells derived from a cervical squamous cell carcinoma. Gynecol Oncol 65:297–303

    Article  PubMed  CAS  Google Scholar 

  61. Belehradek JJ, Orlowski S, Poddevin B, Paoletti C, Mir LM (1991) Electrochemotherapy of spontaneous mammary tumors in mice. Eur J Cancer 27:73–76

    Article  PubMed  Google Scholar 

  62. Chazal M, Benchimol D, Baque P, Pierrefite V, Milano G, Bourgeon A (1998) Treatment of hepatic metastases of colorectal cancer by electrochemotherapy: an experimental study in the rat. Surgery 124:536–540

    Article  PubMed  CAS  Google Scholar 

  63. Heller R, Jaroszeski M, Perrott R, Messina J, Gilbert R (1997) Effective treatment of B16 melanoma by direct delivery of bleomycin using electrochemotherapy. Melanoma Res 7:10–18

    Article  PubMed  CAS  Google Scholar 

  64. Jaroszeski MJ, Gilbert RA, Heller R (1997) In vivo antitumor effects of electrochemotherapy in a hepatoma model. Biochim Biophys Acta 1334:15–18

    Article  PubMed  CAS  Google Scholar 

  65. Kubota Y, Nakada T, Yanai H, Kakizaki H, Sasagawa I, Watanabe M (1996) Electropermeabilization in bladder cancer chemotherapy. Cancer Chemother Pharmacol 39:67–70

    Article  PubMed  CAS  Google Scholar 

  66. Mir LM, Orlowski J, Belehradek J Jr, Paoletti C (1991) Electrochemotherapy: potentiation of antitumor effect of bleomycin by local electric pulses. Eur J Cancer 27:68–72

    Article  PubMed  CAS  Google Scholar 

  67. Ramirez LH, Orlowski S, An D, Bindoula G, Dzodic R, Ardouin P, Bognel C, Belehradek JJ, Munck JN, Mir LM (1998) Electrochemotherapy on liver tumors in rabbits. Br J Cancer 77:2104–2111

    Article  PubMed  CAS  Google Scholar 

  68. Salford LG, Persson BR, Brun A, Ceberg CP, Kongstad PC, Mir LM (1993) A new brain tumor therapy combining bleomycin with in vivo electropermeabilization. Biochem Biophys Res Commun 194:938–943

    Article  PubMed  CAS  Google Scholar 

  69. Sersa G, Cemazar M, Miklavcic D, Mir LM (1994) Electrochemotherapy: variable antitumor effect on different tumor models. Bioelectrochem Bioenerg 35:23–27

    Article  CAS  Google Scholar 

  70. Sersa G, Cemazar M, Miklavcic D (1995) Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice. Cancer Res 55:3450–3455

    PubMed  CAS  Google Scholar 

  71. Mir LM, Devauchelle P, Quintin-Colonna F, Delisle F, Doliger S, Fradelizi D, Belehradek J Jr, Orlowski S (1997) First clinical trial of cat soft-tissue sarcomas treatment by electrochemotherapy. Br J Cancer 76:1617–1622

    Article  PubMed  CAS  Google Scholar 

  72. Tozon N, Sersa G, Cemazar M (2001) Electrochemotherapy: potentiation of local antitumour effectiveness of cisplatin in dogs and cats. Anticancer Res 21:2483–2486

    PubMed  CAS  Google Scholar 

  73. Rols MP, Tamzali Y, Teissie J (2002) Electrochemotherapy of horses: a preliminary clinical report. Bioelectrochem 55:101–105

    Article  CAS  Google Scholar 

  74. Spugnini EF, Porrello A (2003) Potentiation of chemotherapy in companion animals with spontaneous large neoplasms by application of biphasic electric pulses. J Exp Clin Cancer Res 22:571–580

    PubMed  CAS  Google Scholar 

  75. Cemazar M, Tamzali Y, Sersa G, Tozon N, Mir LM, Miklavcic D, Lowe R, Teissie J (2008) Electrochemotherapy in veterinary oncology. J Vet Intern Med 22:826–831

    Article  PubMed  CAS  Google Scholar 

  76. Nanda GS, Sun FX, Hofmann GA, Hoffman RM, Dev SB (1998a) Electroporation therapy of human larynx tumors HEp-2 implanted in nude mice. Anticancer Res 18(2A):999–1004

    CAS  Google Scholar 

  77. Nanda GS, Sun FX, Hofmann GA, Hoffman RM, Dev SB (1998b) Electroporation enhances therapeutic efficacy of anticancer drugs: treatment of human pancreatic tumor in animal model. Anticancer Res 18(3A):1361–1366

    CAS  Google Scholar 

  78. Mir LM (2006) Bases and rationale of the electrochemotherapy. Eur J Cancer Suppl 4:38–44

    Article  Google Scholar 

  79. Belehradek M, Domenge C, Luboinski B, Orlowsky S, Belehradek J, Mir LM (1993) Electrochemotherapy, a new antitumor treatment, first clinical phase I-II trial. Cancer 72:3694–3700

    Article  PubMed  CAS  Google Scholar 

  80. Bloom DC, Goldfarb PM (2005) The role of intratumour therapy with electroporation and bleomycin in the management of advanced squamous cell carcinoma of the head and neck. Eur J Surg Oncol 31:1029–1035

    Article  PubMed  CAS  Google Scholar 

  81. Domenge C, Orlowski S, Luboinski B, De Baere T, Scwaab G, Belehradek J, Mir LM (1996) Antitumor electrochemotherapy: new advances in the clinical protocol. Cancer 77:956–963

    Article  PubMed  CAS  Google Scholar 

  82. Heller R, Jaroszeski MJ, Reintgen DS, Puleo CA, DeConti RC, Gilbert RA, Glass LF (1998) Treatment of cutaneous and subcutaneous tumors with electrochemotherapy using intralesional bleomycin. Cancer 83:148–157

    Article  PubMed  CAS  Google Scholar 

  83. Hofmann GA, Dev SB, Dimmer S, Nanda GS (1999) Electroporation therapy: a new approach for the treatment of head and neck cancer. IEEE Trans Biomed Eng 46:752–759

    Article  PubMed  CAS  Google Scholar 

  84. Dev SB, Hofmann GA (1994) Electrochemotherapy—a novel method of cancer treatment. Cancer Treat Rev 20:105–115

    Article  PubMed  CAS  Google Scholar 

  85. Giardino R, Fini M, Bonazzi V, Cadossi R, Nicolini A, Carpi A (2006) Electrochemotherapy a novel approach to the treatment of metastatic nodules on the skin and subcutaneous tissues. Biomed Pharmacother 60:458–462

    Article  PubMed  CAS  Google Scholar 

  86. Kis E, Oláh J, Ócsai H, Baltas E, Gyulai R, Kemény L, Horvath AR (2011) Electrochemotherapy of cutaneous metastases of melanoma—a case series study and systematic review of the evidence. Dermatol Surg 37:816–824

    Article  PubMed  CAS  Google Scholar 

  87. Mir LM, Glass LF, Sersa G, Teissie J, Domenge C, Miclavcic D, Jaroszeski MJ, Orlowski S, Reintgen DS, Rudolf Z, Belehradek J, Bachaud JM, DeConti R, Stabuc B, Cemazar M, Coninx P, Heller R (1998) Effective treatment of cutaneous and subcutaneous tumors by electrochemotherapy. Brit J Cancer 77:2336–2342

    Article  PubMed  CAS  Google Scholar 

  88. Sersa G (2006) The state-of-the-art of electrochemotherapy before the ESOPE study: advantages and clinical uses. Eur J Cancer Suppl 4:52–59

    Article  Google Scholar 

  89. Byrne CM, Thompson JF, Johnston H, Hersey P, Quinn MJ, Michael Hughes T, McCarthy WH (2005) Treatment of metastatic melanoma using electroporation therapy with bleomycin (electrochemotherapy). Melanoma Res 15:45–51

    Article  PubMed  CAS  Google Scholar 

  90. Sersa G, Stabuc B, Cemazar M, Miklavcic D, Rudolf Z (2000) Electrochemotherapy with cisplatin: clinical experience in malignant melanoma patients. Clin Cancer Res 6:863–867

    PubMed  CAS  Google Scholar 

  91. Möller MG, Salwa S, Soden DM, O’Sullivan GC (2009) Electrochemotherapy as an adjunct or alternative to other treatments for unresectable or in-transit melanoma. Expert Rev Anticancer Ther 9:1611–1630

    Article  PubMed  Google Scholar 

  92. Beebe SJ, Blackmore PF, White J, Joshi RP, Schoenbach KH (2004) Nanosecond pulsed electric fields modulate cell function through intracellular signal transduction mechanisms. Physiological Measurement 25:1077–1093

    Article  PubMed  Google Scholar 

  93. Schoenbach KH, Hargrave B, Joshi RP, Kolb JF, Nuccitelli R et al (2007) Bioelectric effects of intense nanosecond pulses. IEEE Transactions on dielectrics and electrical insulation 14:1088–1109

    Article  CAS  Google Scholar 

  94. Nuccitelli R, Pliquett U, Chen XH, Ford W, Swanson RJ, Beebe SJ, Kolb JF, Schoenbach KH (2006) Pulsed electric fields cause melanomas to self-destruct. Biochem Biophys Res Communication, 343:351–360

    Article  CAS  Google Scholar 

  95. Nuccitelli R, Chen X, Pakhomov AG, Baldwin WH, Sheikh S et al (2009) 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

    Article  PubMed  CAS  Google Scholar 

  96. Sersa G, Miklavcic D, Batista U, Novaković S, Bobanović F, Vodovnik L (1992) Antitumor effect of electrotherapy alone or in combination with interleukin-2 in mice with sarcoma and melanoma tumors. Anticancer Drugs 3:253–260

    Article  PubMed  CAS  Google Scholar 

  97. Miklavcic D, An D, Belehradek J Jr, Mir LM (1997) Host’s immune response in electrotherapy of murine tumors by direct current. Eur Cytokine Netw 8:275–279

    PubMed  CAS  Google Scholar 

  98. Cabrales LB, Ciria HC, Bruzón RP, Quevedo MS, Aldana RH, De Oca LM, Salas MF, Peña OG (2001) Electrochemical treatment of mouse Ehrlich tumor with direct electric current. Bioelectromagnetics 22:316–322

    Article  PubMed  CAS  Google Scholar 

  99. Miyazaki S, Gunji Y, Matsubara H, Shimada H, Uesato M, Suzuki T, Kouzu T, Ochiai T (2003) Possible involvement of antitumor immunity in the eradication of colon 26 induced by low-voltage electrochemotherapy with bleomycin. Surg Today 33:39–44

    Article  PubMed  CAS  Google Scholar 

  100. Fishman D (2002) Low electric field enhanced cancer chemotherapy (LEFCT-EC) as a treatment modality of murine colon cancer and squamous cell carcinoma. Dissertation, Tel Aviv University, Israel

    Google Scholar 

  101. Ohad S (2005) Involvement of the immune response in the cure of squamous cell carcinoma (SQ2) and colon cancer (CT-26) tumors, treated with Low Electric Field Cancer Therapy in the presence of chemotherapy. Dissertation, Tel Aviv University, Israel

    Google Scholar 

  102. Winn HJ (1961) Immune mechanisms in homotransplantation. II. Quantitative assay of the immunological activity of lymphoid cells stimulated by tumor homografts. J Immunol 86:228–239

    PubMed  CAS  Google Scholar 

  103. Ophir R, Moalem G, Pecht M, Shashoua M, Rashid G, Ben-Efraim S, Trainin N, Burstein Y, Keisari Y (1999) THF-gamma 2-mediated reduction of pulmonary metastases and augmentation of immunocompetence in C57BL/6 mice bearing B16-melanoma. J Immunother 22:103–113

    Article  PubMed  CAS  Google Scholar 

  104. Foster B, Gingrich J, Kwon E, Madias C, Greenberg N (1997) Characterization of prostatic epithelial cell lines derived from transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Cancer Res 57:3325–3330

    PubMed  CAS  Google Scholar 

  105. Greenberg N, DeMayo F, Finegolg M, Medina D, Tilley W, Aspinall J, Cunha G, Donjacour A, Matusik R, Rosen J (1995) Prostate cancer in a transgenic mouse. Proc Natl Acad Sci USA 92:3439–3443

    Article  PubMed  CAS  Google Scholar 

  106. Kanariou M, Huby R, Ladyman H, Colic M, Sivolapenko G, Lampert I, Ritter M (1989) Immunosuppression with cyclosporin A alters the thymic microenvironment. Clin Exp Immunol 78:263–270

    PubMed  CAS  Google Scholar 

  107. Brattain MG, Strobel-Stevens J, Fine D, Webb M, Sarrif AM (1980) Establishment of mouse colonic carcinoma cell lines with different metastatic properties. Cancer Res 40:2142–2146

    PubMed  CAS  Google Scholar 

  108. Cheever MA (2008) Twelve immunotherapy drugs that could cure cancers. Immunol Rev 222:357–368

    Article  PubMed  CAS  Google Scholar 

  109. Logani MK, Szabo I, Makar V, Bhanushali A, Alekseev S, Ziskin MC (2006) Effect of millimeter wave irradiation on tumor metastasis. Bioelectromagnetics 27:258–264

    Article  PubMed  Google Scholar 

  110. Gunji Y, Uesato M, Miyazaki S, Shimada H, Matsubara H, Nabeya Y, Kouda K, Makino H, Kouzu T, Ochiai T (2005) Generation of antitumor immunity against large colon tumors by repeated runs of electrochemotherapy. Hepatogastroenterology 52:770–774

    PubMed  Google Scholar 

  111. Sersa G, Kotnik V, Cemazar M, Miklavcic D, Kotnik A (1996) Electrochemotherapy with bleomycin in SA-1 tumor-bearing mice—natural resistance and immune responsiveness. Anticancer Drugs 7:785–791

    Article  PubMed  CAS  Google Scholar 

  112. Engstrom PE, Ivarsson K, Tanberg KG, Stenram U, Salford LG, Persson BR (2001) Electrically mediated drug delivery for treatment of an adenocarcinoma transplant into rat liver. Anticancer Res 21:1817–1822

    PubMed  CAS  Google Scholar 

  113. Kuriyama S, Mitoro A, Tsujinoue H, Toyokawa Y, Nakatani T, Yoshiji H, Okuda H, Nagao S, Fukui H (2000) Electrochemotherapy can eradicate established colorectal carcinoma and leaves a systemic protective memory in mice. Int J Oncol 16:979–985

    PubMed  CAS  Google Scholar 

  114. Mir LM, Orlowski S, Poddevin B, Belehradek JJ (1992) Electrochemotherapy tumor treatment is improved by IL-2 stimulation of the host defences. Eur Cytokine Netw 3:331–338

    PubMed  CAS  Google Scholar 

  115. Mir LM, Roth C, Orlowski S, Quintin-Colonna F, Fradelizi D, Belehradek J Jr, Kourilsky P (1995) Systemic antitumor effects of electrochemotherapy combined with histoincompatible cells secreting interleukin-2. J Immunother Emphasis Tumor Immunol 17:30–38

    Article  PubMed  CAS  Google Scholar 

  116. Orlowski S, An D, Belehradek J Jr, Mir LM (1998) Antimetastatic effects of electrochemotherapy and of histoincompatible interleukin-2-secreting cells in the murine Lewis lung tumor. Anticancer Drugs 9:551–556

    Article  PubMed  CAS  Google Scholar 

  117. Heller L, Pottinger C, Jaroszeski MJ, Gilbert R, Heller R (2000) In vivo electroporation of plasmids encoding GM-CSF or interleukin-2 into existing B16 melanomas combined with electrochemotherapy induces long-term antitumour immunity. Melanoma Res 10:577–583

    Article  PubMed  CAS  Google Scholar 

  118. Sersa G, Cemazar M, Menart V, Gaberc PV, Miklavcic D (1997) Antitumor effectiveness of electrochemotherapy with bleomycin is increased by TNF-alpha on SA-1 tumors in mice. Cancer Lett 116:85–92

    Article  PubMed  CAS  Google Scholar 

  119. Torrero MN, Henk WG, Li S (2006) Regression of high-grade malignancy in mice by bleomycin and interleukin-12 electrochemogenetherapy. Clin Cancer Res 12:257–263

    Article  PubMed  CAS  Google Scholar 

  120. Roux S, Bernat C, Al-Sakere B, Ghiringhelli F, Opolon P, Carpentier AF, Zitvogel L, Mir LM, Robert C (2008) Tumor destruction using electrochemotherapy followed by CpG oligodeoxynucleotide injection induces distant tumor responses. Cancer Immunol Immunother 57:1291–1300

    Article  PubMed  CAS  Google Scholar 

  121. Gehl J, Geertsen PF (2000) Efficient palliation of hemorrhaging malignant melanoma skin metastases by electrochemotherapy. Melanoma Res 10:585–589

    Article  PubMed  CAS  Google Scholar 

  122. Daud AI, DeConti RC, Andrews S, Urbas P, Riker AI, Sondak VK, Munster PN, Sullivan DM, Ugen KE, Messina JL, Heller R (2008) Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J Clin Oncol 26:5896–5903

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Roberts-Guthman Chair in Immunopharmacology, Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel-Aviv University, 69978, Tel Aviv, Israel

    Yona Keisari

  2. Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

    Rafi Korenstein

Authors
  1. Yona Keisari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rafi Korenstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yona Keisari .

Editor information

Editors and Affiliations

  1. and Immunology, Tel Aviv University, Department of Clinical Microbiology, Tel Aviv, 69978, Israel

    Yona Keisari

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Keisari, Y., Korenstein, R. (2013). In situ Ablation of Solid Tumors by Electric Forces and Its Effect on the Tumor Microenvironment and Anti-tumor Immunity. In: Keisari, Y. (eds) Tumor Ablation. The Tumor Microenvironment, vol 5. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4694-7_8

Download citation

Publish with us

Policies and ethics

Search

Navigation