All Title Author
Keywords Abstract

Cells  2013 

Induction of Cell Death Mechanisms and Apoptosis by Nanosecond Pulsed Electric Fields (nsPEFs)

DOI: 10.3390/cells2010136

Keywords: apoptosis, caspase-dependent, caspase-independent, Jurkat clones, APAF-1, FADD, N1-S1 hepatocellular carcinoma cells, Ca2+ mobilization, mitochondria membrane potential, mitochondria permeability transition pore, cytochrome c, electroporation, nanopores ?3-10

Full-Text   Cite this paper   Add to My Lib

Abstract:

Pulse power technology using nanosecond pulsed electric fields (nsPEFs) offers a new stimulus to modulate cell functions or induce cell death for cancer cell ablation . New data and a literature review demonstrate fundamental and basic cellular mechanisms when nsPEFs interact with cellular targets. NsPEFs supra-electroporate cells creating large numbers of nanopores in all cell membranes. While nsPEFs have multiple cellular targets, these studies show that nsPEF-induced dissipation of ΔΨm closely parallels deterioration in cell viability. Increases in intracellular Ca 2+ alone were not sufficient for cell death; however, cell death depended of the presence of Ca 2+. When both events occur, cell death ensues. Further, direct evidence supports the hypothesis that pulse rise-fall times or high frequency components of nsPEFs are important for decreasing ΔΨm and cell viability. Evidence indicates in Jurkat cells that cytochrome c release from mitochondria is caspase-independent indicating an absence of extrinsic apoptosis and that cell death can be caspase-dependent and –independent. The Ca 2+ dependence of nsPEF-induced dissipation of ΔΨm suggests that nanoporation of inner mitochondria membranes is less likely and effects on a Ca 2+-dependent protein(s) or the membrane in which it is embedded are more likely a target for nsPEF-induced cell death. The mitochondria permeability transition pore (mPTP) complex is a likely candidate. Data demonstrate that nsPEFs can bypass cancer mutations that evade apoptosis through mechanisms at either the DISC or the apoptosome.

References

[1]  Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell 2000, 100, 57–70, doi:10.1016/S0092-8674(00)81683-9.
[2]  Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674, doi:10.1016/j.cell.2011.02.013.
[3]  Loges, S.; Schmidt, T.; Carmeliet, P. Mechanisms of Resistance to Anti-Angiogenic Therapy and Development of Third-Generation Anti-Angiogenic Drug Candidates. Genes Cancer 2010, 1, 12–25, doi:10.1177/1947601909356574.
[4]  Mir, L.M.; Orlowski, S.; Belehradek, J.; Paoletti, C. Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. Eur. J. Cancer 1991, 27, 68–72, doi:10.1016/0277-5379(91)90064-K.
[5]  Sersa, G.; Cemazar, M.; Miklavcic, D. Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice. Cancer Res. 1995, 55, 3450–3455.
[6]  Goto, T.; Nishi, T.; Tmura, T.; Dev, S.B.; Takeshima, H.; Kochi, M.; Yoshizato, K.; Kuratsu, K.; Sakata, T.; Hofmann, G.A.; Ushio, Y. Highly efficient electro-gene therapy of solid tumor by using an expression plasmid for t herpes simplex virus thymidine kinase gene. Proc. Natl. Acad. Sci. USA 2000, 97, 354–359, doi:10.1073/pnas.97.1.354.
[7]  Li, S.; Zhang, X.; Xia, X. Regression of Tumor Growth and Induction of Long-Term Antitumor Memory by Interleukin 12 Electro-Gene Therapy. J. Natl. Cancer Inst. 2002, 94, 762–768, doi:10.1093/jnci/94.10.762.
[8]  Davalos, R.V.; Mir, I.L.; Rubinsky, B. Tissue ablation with irreversible electroporation. Ann. Biomed. Eng. 2005, 33, 223–231, doi:10.1007/s10439-005-8981-8.
[9]  Beebe, S.J.; Fox, P.M.; Rec, L.J.; Somers, K.; Stark, R.H.; Schoenbach, K.H. Nanosecond pulsed electric field (nsPEF) effects on cells and tissues: apoptosis induction and tumor growth inhibition. IEEE Trans. Plasma Sci. 2002, 30, 286–292, doi:10.1109/TPS.2002.1003872.
[10]  Nuccitelli, R.; Pliquett, U.; Chen, X.; Ford, W.; Swanson, J.R.; Beebe, S.J.; Kolb, J.F.; Schoenbach, K.H. Nanosecond pulsed electric fields cause melanomas to self-destruct. Biochem. Biophys. Res. Commun. 2006, 343, 351–360, doi:10.1016/j.bbrc.2006.02.181.
[11]  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 2007, 121, 675–682, doi:10.1002/ijc.22723.
[12]  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. 2010, 23, 554–563, doi:10.1111/j.1755-148X.2010.00704.x.
[13]  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. 2012, 11, 83–93.
[14]  Tiong, L.; Maddern, G.J. Systematic review and meta-analysis of survival and disease recurrence after radiofrequency ablation for hepatocellular carcinoma. Br. J. Surg. 2011, 98, 1210–1224, doi:10.1002/bjs.7669.
[15]  Sersa, G.; Cemazar, M.; Snoj, M. Electrochemotherapy of solid tumors—Preclinical and clinical experience. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2011, 2011, 728–731.
[16]  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. 2008, 26, 5896–5903.
[17]  Heller, R.; Shirley, S.; Guo, S.; Donate, A.; Heller, L. Electroporation based gene therapy—From the bench to the bedside. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2011, 2011, 736–738.
[18]  Neal, R.E., 2nd; Rossmeis, J.H., Jr.; 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. 2011, 29, 372–377, doi:10.1200/JCO.2010.33.0902.
[19]  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. 2012, 215, 379–387.
[20]  Stewart, D.A.; Gowrishankar, T.R.; Weaver, J.C. Transport lattice approach to describing electroporation: use of local asymptotic model. IEEE Transact. Plasma Sci. 2004, 32, 1696–1708.
[21]  Gowrishankar, T.R.; Esser, A.T.; Vasilkoski, Z.; Smith, K.C.; Weaver, J.C. Microdosimetry for conventional and supra-electroporation in cells with organelles. Biochem. Biophys. Res. Commun. 2006, 341, 1266–1276.
[22]  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. 2003, 17, 1493–1495.
[23]  Vernier, P.T.; Aimin, L.; Marcu, L.; Craft, C.M.; Gundersen, M.A. Ultrashort pulsed electric fields induce membrane phospholipid translocation and caspase activation: Differential sensitivities of Jurkat T lymphoblasts and rat glioma C6 cells. IEEE Trans. Dielectr. Electr. Insul. 2003, 10, 795–809.
[24]  Beebe, S.J.; Blackmore, P.F.; White, J.; Joshi, R.P.; Schoenbach, K.H. Nanosecond pulsed electric fields modulate cell function through intracellular signal transduction mechanisms. Physiol. Meas. 2004, 25, 1077–1093.
[25]  Hall, E.H.; Schoenbach, K.H.; Beebe, S.J. Nanosecond pulsed electric fields induce apoptosis in p53-wildtype and p53-null HCT116 colon carcinoma cells. Apoptosis 2007, 12, 1721–1731, doi:10.1007/s10495-007-0083-7.
[26]  Ford, W.E.; Ren, W.; Blackmore, P.F.; Schoenbach, K.H.; Beebe, S.J. Nanosecond pulsed electric fields stimulate apoptosis without release of pro-apoptotic factors from mitochondria in B16f10 melanoma. Arch. Biochem. Biophys 2010, 497, 82–89.
[27]  Ren, W.; Beebe, S.J. An apoptosis targeted stimulus with nanosecond pulsed electric fields (nsPEFs) in E4 squamous cell carcinoma. Apoptosis 2011, 16, 382–393, doi:10.1007/s10495-010-0572-y.
[28]  Ren, W.; Sain, N.M.; Beebe, S.J. Nanosecond pulsed electric fields (nsPEFs) activate intrinsic caspase-dependent and caspase-independent cell death in Jurkat cells. Biochem Biophys. Res. Commun. 2012, 421, 808–812.
[29]  Schoenbach, K.H.; Beebe, S.J.; Buescher, E.S. Intracellular effect of ultrashort electrical pulses. Bioelectromagnetics 2001, 22, 440–448, doi:10.1002/bem.71.
[30]  Stacey, M.; Stickley, J.; Fox, P.; Statler, V.; Schoenbach, K.H.; Beebe, S.J.; Buescher, S. Differential effects in cells exposed to ultra-short, high intensity electric fields: Cell survival, DNA damage, and cell cycle analysis. Mutat. Res. 2003, 542, 65–75, doi:10.1016/j.mrgentox.2003.08.006.
[31]  Stacey, M.; Fox, P.; Buescher, S.; Kolb, J. Nanosecond pulsed electric field induced cytoskeleton, nuclear membrane and telomere damage adversely impact cell survival. Bioelectrochemistry 2011, 82, 131–134, doi:10.1016/j.bioelechem.2011.06.002.
[32]  Beebe, S.J.; White, J.; Blackmore, P.F.; Deng, Y.; Somers, K.; Schoenbach, K.H. Diverse effects of nanosecond pulsed electric fields on cells and tissues. DNA Cell Biol. 2003, 22, 785–796, doi:10.1089/104454903322624993.
[33]  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. 2003, 310, 286–295, doi:10.1016/j.bbrc.2003.08.140.
[34]  White, J.A.; Blackmore, P.F.; Schoenbach, K.H.; Beebe, S.J. Stimulation of capacitative Ca2+ entry in HL-60 cells by nanosecond pulsed electric fields. J. Biol. Chem. 2004, 279, 22964–22972.
[35]  Buescher, E.S.; Smith, R.R.; Schoenbach, K.H. Submicrosecond intense pulsed electric field effects on intracellular free Ca2+: mechanisms and effects. IEEE Trans. Plasma Sci. 2004, 32, 1563–1572, doi:10.1109/TPS.2004.832643.
[36]  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. 2008, 471, 240–248.
[37]  Vernier, P.T. Mitochondrial membrane permeabilization with nanosecond electric pulses. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2011, 2011, 743–745.
[38]  Batista Napotnik, T.; Wu, Y.H.; Gundersen, M.A.; Miklav?i?, D.; Vernier, P.T. Nanosecond electric pulses cause mitochondrial membrane permeabilization in Jurkat cells. Bioelectromagnetics 2012, 33, 257–264.
[39]  Shawgo, M.E.; Shelton, S.N.; Robertson, J.D. Caspase-mediated Bak activation and cytochrome c release during intrinsic apoptotic cell death in Jurkat cells. J. Biol. Chem. 2008, 283, 35532–35538.
[40]  Shelton, S.N.; Shawgo, M.E.; Robertson, J.D. Cleavage of Bid by executioner caspases mediates feed forward amplification of mitochondrial outer membrane permeabilization during genotoxic stress-induced apoptosis in Jurkat cells. J. Biol. Chem. 2009, 284, 11247–11255.
[41]  Shelton, S.N.; Dillard, C.D.; Robertson, J.D. Activation of caspase-9, but not caspase-2 or caspase-8, is essential for heat-induced apoptosis in Jurkat cells. J. Biol. Chem. 2010, 285, 40525–40533.
[42]  Deng, J.; Schoenbach, K.H.; Buescher, E.S.; Hair, P.; Fox, P.M.; Beebe, S.J. The effects of intense submicrosecond electrical pulses on cells. Biophys. J. 2003, 84, 2709–2714, doi:10.1016/S0006-3495(03)75076-0.
[43]  Tekle, E.; Oubrahim, H.; Dzekunov, S.M.; Kolb, J.F.; Schoenbach, K.H.; Chock, P.B. Selective field effects on intracellular vacuoles and vesicle membranes with nanosecond electric pulses. Biophys. J. 2005, 89, 274–284.
[44]  Pakhomov, A.G.; Bowman, A.M.; Ibey, B.L.; Andre, F.M.; Pakhomova, O.N.; Schoenbach, K.H. Lipid nanopores can form a stable, ion channel-like conduction pathway in cell membrane. Biochem Biophys. Res. Commun. 2009, 385, 181–186, doi:10.1016/j.bbrc.2009.05.035.
[45]  Bowman, A.M.; Nesin, O.M.; Pakhomova, O.N.; Pakhomov, A.G. Analysis of plasma membrane integrity by fluorescent detection of Tl(+) uptake. J. Membr. Biol. 2010, 236, 15–26, doi:10.1007/s00232-010-9269-y.
[46]  Creighton, T.E. Proteins: Structures and Molecular Properties; WH Freeman: New York, NY, USA, 1993.
[47]  Tieleman, D.P. The molecular basis of electroporation. BMC Biochem. 2004, 5, 10, doi:10.1186/1471-2091-5-10.
[48]  Tarek, M. Membrane electroporation: a molecular dynamics simulation. Biophys. J. 2005, 88, 4045–4053.
[49]  Vernier, P.T.; Ziegler, M.J.; Sun, Y.; Chang, W.V.; Gundersen, M.A.; Tieleman, D.P. Nanopore formation and phosphatidylserine externalization in a phospholipid bilayer at high transmembrane potential. J. Am. Chem. Soc. 2006, 128, 6288–6289.
[50]  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. 2010, 236, 27–36, doi:10.1007/s00232-010-9277-y.
[51]  Sugar, I.P.; Neumann, E. Stochastic model for electric field-induced membrane pores. Electroporation Biophys. Chem. 1984, 19, 211–225, doi:10.1016/0301-4622(84)87003-9.
[52]  Weaver, J.C. Electroporation of biological membranes from multicellular to nano scales. IEEE Trans. Dielect. Electr. Insul. 2003, 10, 754–768, doi:10.1109/TDEI.2003.1237325.
[53]  Delemotte, L.; Tarek, M. Molecular dynamics simulations of lipid membrane electroporation. J. Membr. Biol. 2012, 245, 531–543, doi:10.1007/s00232-012-9434-6.
[54]  Beebe, S.J.; Chen, Y.-J.; Sain, N.M.; Schoenbach, K.H.; Xiao, S. Transient features in nanosecond pulsed electric fields differentially modulate mitochondria and viability. PloS One 2012, 7, e51349.
[55]  Jacobson, J.; Duchen, M.R. Mitochondrial oxidative stress and cell death in astrocytes—Requirement for stored Ca2+ and sustained opening of the permeability transition pore. J. Cell Sci. 2002, 115, 1175–1188.
[56]  Brookes, P.S.; Yoon, Y.; Robotham, J.L.; Anders, M.W.; Sheu, S.S. Calcium, ATP, and ROS: A mitochondrial love-hate triangle. Am. J. Physiol. Cell Physiol. 2004, 287, C817–C833, doi:10.1152/ajpcell.00139.2004.
[57]  Pakhomova, O.N.; Khorokhorina, V.A.; Bowman, A.M.; Rodait?-Ri?evi?ien?, 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. 2012, 527, 55–64.
[58]  Leung, A.W.; Halestrap, A. Recent progress in elucidating the molecular mechanism of the mitochondrial permeability transition pore. Biochim. Biophys. Acta. 2008, 1777, 946–952, doi:10.1016/j.bbabio.2008.03.009.
[59]  Halestrap, A.P.; Pasdois, P. The role of the mitochondrial permeability transition pore in heart disease. Biochim. Biophys. Acta. 2009, 1787, 1402–1415, doi:10.1016/j.bbabio.2008.12.017.
[60]  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. 2009, 96, 1640–1648.
[61]  Morotomi-Yano, K.; Akiyama, H.; Yano, K.I. Nanosecond pulsed electric fields activate AMP-activated protein kinase: Implications for Ca2+-mediated activation of cellular signaling. Biochem. Biophys. Res. Commun. 2012, 428, 371–375, doi:10.1016/j.bbrc.2012.10.061.
[62]  Duchen, M.R. Mitochondria and Ca2+: From cell signaling to cell death. J. Physiol. 2002, 529, 57–68, doi:10.1111/j.1469-7793.2000.00057.x.
[63]  Zhivotovsky, B.; Orrenius, S. Calcium and cell death mechanisms: a perspective from the cell death community. Cell Calcium 2011, 50, 211–221, doi:10.1016/j.ceca.2011.03.003.
[64]  Ichas, F.; Mazat, J.P. From Ca2+ signaling to cell death: Two conformations for the mitochondrial permeability transition pore. Switching from low- to high-conductance state. Biochim. Biophys. Acta. 1998, 1366, 33–50, doi:10.1016/S0005-2728(98)00119-4.
[65]  Schoenbach, K.H.; Joshi, R.P.; Stark, R.H.; Dobbs, F.C.; Beebe, S.J. Bacterial decontamination of liquids with pulsed electric fields. IEEE Trans. Dielectr. Electr. Insul. 2000, 7, 637–645, doi:10.1109/94.879359.
[66]  Lawrence, C.P.; Chow, S.C. FADD deficiency sensitizes Jurkat T cells to TNF-alpha-dependent necrosis during activation-induced cell death. FEBS Lett. 2005, 579, 6465–6472, doi:10.1016/j.febslet.2005.10.041.
[67]  Vonarbourg, C.; Stolzenberg, M.C.; H?lzelova, E.; Fischer, A.; Deist, F.L.; Rieux-Laucat, F. Differential sensitivity of Jurkat and primary T cells to caspase-independent cell death triggered upon Fas stimulation. Eur. J. Immunol. 2002, 32, 2376–2384, doi:10.1002/1521-4141(200208)32:8<2376::AID-IMMU2376>3.0.CO;2-V.
[68]  Kroemer, G.; Martin, S.J. Caspase-independent cell death. Nat. Med. 2005, 11, 725–730, doi:10.1038/nm1263.
[69]  Proskuryakov, S.Y.; Gabai, V.L. Mechanisms of tumor cell necrosis. Curr. Pharm. Des. 2010, 16, 56–68, doi:10.2174/138161210789941793.
[70]  Nuccitelli, R.; Chen, X.; Pakhomov, A.G.; Baldwin, W.H.; Sheikh, S.; Pomicter, J.L.; Ren, W.; Osgood, C.; Swanson, R.J.; Kolb, J.F.; Beebe, S.J.; Schoenbach, K.H. A new pulsed electric field therapy for melanoma disrupts the tumor's blood supply and causes complete remission without recurrence. Int. J. Cancer 2009, 125, 438–445, doi:10.1002/ijc.24345.
[71]  Villunger, A.; Michalak, E.M.; Coultas, L.; Müllauer, F.; B?ck, G.; Ausserlechner, M.J.; Adams, J.M.; Strasser, A. p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science 2003, 302, 1036–1038, doi:10.1126/science.1090072.
[72]  Chen, M.; He, H.; Zhan, S.; Krajewski, S.; Reed, J.; Gottlieb, R.A. Bid is cleaved by calpain to an active fragment in vitro and during myocardial ischemia/reperfusion. J. Biol. Chem. 2001, 276, 30724–30728.
[73]  Mandic, A.; Viktorsson, K.; Strandberg, L.; Heiden, T.; Hansson, J.; Linder, S.; Shoshan, M.C. Calpain-mediated Bid cleavage and calpain-independent Bak modulation: two separate pathways in cisplatin-induced apoptosis. Mol. Cell. Biol. 2002, 22, 3003–3013.
[74]  Dejean, L.M.; Martinez-Caballero, S.; Kinnally, K.W. Is MAC the knife that cuts cytochrome c from mitochondria during apoptosis? Cell Death Differ. 2006, 13, 1387–1395, doi:10.1038/sj.cdd.4401949.
[75]  Shoshan-Barmatz, V.; De Pinto, V.; Zweckstetter, M.; Raviv, Z.; Keinan, N.; Arbel, N. VDAC, a multi-functional mitochondrial protein regulating cell life and death. Mol. Aspects Med. 2010, 31, 227–285, doi:10.1016/j.mam.2010.03.002.
[76]  Tornero, D.; Posadas, I.; Ce?a, V. Bcl-x(L) blocks a mitochondrial inner membrane channel and prevents Ca2+ overload-mediated cell death. PLoS One 2011, 6, e20423, doi:10.1371/journal.pone.0020423.
[77]  Peixoto, P.M.; Lue, J.K.; Ryu, S.Y.; Wroble, B.N.; Sible, J.C.; Kinnally, K.W. Mitochondrial Apoptosis-Induced Channel MAC) Function Triggers a Bax/Bak-Dependent Bystander Effect. Am. J. Pathol. 2011, 178, 48–54, doi:10.1016/j.ajpath.2010.11.014.
[78]  Hair, P.S.; Schoenbach, K.H.; Buescher, E.S. Sub-microsecond, intense pulsed electric field applications to cells show specificity of effects. Bioelectrochemistry 2003, 61, 65–72, doi:10.1016/S1567-5394(03)00076-8.
[79]  Ibey, B.L.; Pakhomov, A.G.; Gregory, B.W.; Khorokhorina, V.A.; Roth, C.C.; Rassokhin, M.A.; Bernhard, J.A.; Wilmink, G.J.; Pakhomova, O.N. Selective cytotoxicity of intense nanosecond-duration electric pulses in mammalian cells. Biochim. Biophys. Acta. 2010, 1800, 1210–1219, doi:10.1016/j.bbagen.2010.07.008.
[80]  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. 2011, 10, 281–286.
[81]  Nuccitelli, R.; Tran, K.; Athos, B.; Kreis, M.; Nuccitelli, P.; Chang, K.S.; Epstein, E.H., Jr.; Tang, J.Y. Nanoelectroablation therapy for murine basal cell carcinoma. Biochem Biophys. Res. Commun. 2012, 424, 446–450, doi:10.1016/j.bbrc.2012.06.129.
[82]  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.; Burinsky, B. Cutaneous papilloma and squamous cell carcinoma therapy utilizing nanosecond pulsed electric fields (nsPEF). PLoS One 2012, 7, e43891.
[83]  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 2012, 132, 1933–1939.

Full-Text

comments powered by Disqus