In situ ablation of solid tumors by electric forces and its effect on the tumor microenvironment and anti-tumor immunity

Tumor Ablation: Effects on Systemic and Local Anti-Tumor Immunity and on Other Tumor-Microenvironment Interactions

Volumn , Issue , 2013, Pages 133-153

  Keisari, Yona ^a   Korenstein, Rafi ^a  

^a TEL AVIV UNIVERSITY   (Israel)

Author keywords

Antimetastatic; Antitumor immunity; Direct current; Electric ablation; Electric currents; Electric fields; Electrochemical; Electrochemotherapy; Electrodes; Electrolytic ablation; Electromagnetic radiation; Electropermeabilization; Electroporation; Electrotherapy; Experimental tumors; High electric fields; High frequency; Human tumors; Immunostimulation; Low electric fields; Low frequency; Low intensity; Metastatic tumors; Millimetric wave; Pulsed electric currents

Indexed keywords

EID: 84891890277     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-94-007-4694-7_8     Document Type: Chapter

References (122)

1. Vannucci L (2011) Cancer immunology and colorectal cancer recurrence. Front Biosci (Schol Ed) 3:1421-1431
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
3. Mellman I, Coukos G, Dranoff G (2011) Cancer immunotherapy comes of age. Nature 480:480-489
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
5. Lesterhuis WJ, Haanen JB, Punt CJ (2011) Cancer immunotherapy—revisited. Nat Rev Drug Discov 10:591-600
6. Adema GJ (2009) Dendritic cells from bench to bedside and back. Immunol Lett 122:128-130
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
8. Myc LA, Gamian A, Myc A (2011) Cancer vaccines. Any future? Arch Immunol Ther Exp (Warsz) 59:249-259
9. Ahmed M, Brace CL, Lee FT Jr, Goldberg SN (2011) Principles of and advances in percutaneous ablation. Radiology 258:351-369
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
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
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
13. Nordenstrom BE (1978) Preliminary trials of electrophoretic ionization in the treatment of malignant tumors. IRCS J Med Sci 6:537
14. Nordenstrom B (1984) Biologically closed electric circuits: activation of vascular interstitial closed electric circuits for treatment of inoperable cancers. Bioelectricity 3:137-153
15. Berendson J, Simonsson D (1994) Electrochemical aspects of treatment of tissue with direct current. Eur J Surg Suppl 574:111-115
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
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
18. Humphrey CE, Seal EH (1959) Biophysical approach toward tumor regression in mice. Science 130:388-390
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
20. Morris DM, Marino AA, Gonzalez, E (1992) Electrochemical modification of tumor growth in mice. J Surg Res 53:306-309
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
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
23. Chou CK, McDougall JA, Ahn C, Vora N (1997) Electrochemical treatment of mouse and rat fibrosarcomas with direct current. Bioelectromagnetics 18:18-24
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
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
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
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
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
29. Tello 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
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
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
32. Nordenstrom BE (1989) Electrochemical treatment of cancer. I: Variable response to anodic and cathodic fields. Am J Clin Oncol 12:530-536
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
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
35. Xin Y (1994a) Organizationand spread of electrochemical therapyin China. EurJ Surg(Suppl 574):25-29
36. Xin YL, Xue FZ, Ge BS, Zhao FR, Shi B, Zhang W (1997) Electrochemical treatment of lung cancer. Bioelectromagnetics 18:8-13
37. Xin YL (1994b) Advances in the treatment of malignant tumors by electrochemical therapy (EChT). Eur J Surg (Suppl 574):31-35
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
56. Teppone M, Avakyan R (2010) Extremely high-frequency therapy in oncology. The J Alternative Complementary Medicine 16:1211-1216
57. Mir LM, Tounekti O, Orlowski S (1996) Bleomycin: revival of an old drug. Gen Pharmacol 27:745-748
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
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
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
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
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
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
64. Jaroszeski MJ, Gilbert RA, Heller R (1997) In vivo antitumor effects of electrochemotherapy in a hepatoma model. Biochim Biophys Acta 1334:15-18
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
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
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
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
69. Sersa G, Cemazar M, Miklavcic D, Mir LM (1994) Electrochemotherapy: variable antitumor effect on different tumor models. Bioelectrochem Bioenerg 35:23-27
70. Sersa G, Cemazar M, Miklavcic D (1995) Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice. Cancer Res 55:3450-3455
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
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
73. Rols MP, Tamzali Y, Teissie J (2002) Electrochemotherapy of horses: a preliminary clinical report. Bioelectrochem 55:101-105
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
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
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
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
78. Mir LM (2006) Bases and rationale of the electrochemotherapy. Eur J Cancer Suppl 4:38-44
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
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
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
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
83. Hofmann GA, Dev SB, Dimmer S, Nanda GS (1999) Electroporation therapy: anew approach for the treatment of head and neck cancer. IEEE Trans Biomed Eng 46:752-759
84. Dev SB, Hofmann GA (1994) Electrochemotherapy—a novel method of cancer treatment. Cancer Treat Rev 20:105-115
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
86. Kis E, Olah J, Ocsai H, Baltas E, Gyulai R, Kemeny 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
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
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
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
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
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
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
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
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
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
96. Sersa G, Miklavcic D, Batista U, Novakovic S, Bobanovic 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
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
98. Cabrales LB, Ciria HC, Bruzon RP, Quevedo MS, Aldana RH, De Oca LM, Salas MF, Pea OG (2001) Electrochemical treatment of mouse Ehrlich tumor with direct electric current. Bioelectromagnetics 22:316-322
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
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
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
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
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/6mice bearing B16-melanoma. J Immunother 22:103-113
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
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
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
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
108. Cheever MA (2008) Twelve immunotherapy drugs that could cure cancers. Immunol Rev 222:357-368
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
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
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
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
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
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
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
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
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
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
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
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
121. Gehl J, Geertsen PF (2000) Efficient palliation of hemorrhaging malignant melanoma skin metastases by electrochemotherapy. Melanoma Res 10:585-589
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