Nanoelectroablation therapy for murine basal cell carcinoma.

When skin tumors are exposed to non-thermal, low energy, nanosecond pulsed electric fields (nsPEF), apoptosis is initiated both in vitro and in vivo. This nanoelectroablation therapy has already been proven effective in treating subdermal murine allograft tumors. We wanted to determine if this therapy would be equally effective in the treatment of autochthonous BCC tumors in Ptch1(+/-)K14-Cre-ER p53 fl/fl mice. These tumors are similar to human BCCs in histology [2,20] and in response to drug therapy [19]. We have treated 27 BCCs across 8 mice with either 300 pulses of 300 ns duration or 2700 pulses of 100 ns duration, all at 30 kV/cm and 5-7 pulses per second. Every nsPEF-treated BCC began to shrink within a day after treatment and their initial mean volume of 36 ± 5 (SEM) mm(3) shrunk by 76 ± 3% over the ensuing two weeks. After four weeks, they were 99.8% ablated if the size of the treatment electrode matched the tumor size. If the tumor was larger than the 4mm wide electrode, multiple treatments were needed for complete ablation. Treated tumors were harvested for histological analysis at various times after treatment and exhibited apoptosis markers. Specifically, pyknosis of nuclei was evident as soon as 2 days after nsPEF treatment, and DNA fragmentation as detected via TUNEL staining was also evident post treatment. Nanoelectroablation is effective in triggering apoptosis and remission of radiation-induced BCCs with a single 6 min-long treatment of 2700 pulses.

[1]  U. Pliquett,et al.  Nanosecond pulsed electric fields cause melanomas to self-destruct , 2006, Conference Record of the 2006 Twenty-Seventh International Power Modulator Symposium.

[2]  Brett M. Coldiron,et al.  Incidence estimate of nonmelanoma skin cancer in the United States, 2006. , 2010, Archives of dermatology.

[3]  Ravindra P. Joshi,et al.  Ultrashort electrical pulses open a new gateway into biological cells , 2004, Proceedings of the IEEE.

[4]  Juergen F Kolb,et al.  Histopathology of normal skin and melanomas after nanosecond pulsed electric field treatment , 2009, Melanoma research.

[5]  Richard Nuccitelli,et al.  Non‐thermal Nanoelectroablation of UV‐induced Murine Melanomas Stimulates an Immune Response , 2012, Pigment cell & melanoma research.

[6]  F. Andre,et al.  Gadolinium blocks membrane permeabilization induced by nanosecond electric pulses and reduces cell death. , 2010, Bioelectrochemistry.

[7]  Julie Gehl,et al.  Electroporation for drug and gene delivery in the clinic: doctors go electric. , 2008, Methods in molecular biology.

[8]  Zap [extreme voltage for fighting diseases] , 2006 .

[9]  M. Scott,et al.  Altered neural cell fates and medulloblastoma in mouse patched mutants. , 1997, Science.

[10]  Richard Heller,et al.  In vivo electroporation for gene therapy. , 2006, Human gene therapy.

[11]  J. Simon,et al.  Surgical Excision of Basal Cell Carcinoma with Complete Margin Control: Outcome at 5-Year Follow-Up , 2010, Dermatology.

[12]  K. Schoenbach,et al.  Nanosecond pulsed electric fields stimulate apoptosis without release of pro-apoptotic factors from mitochondria in B16f10 melanoma. , 2010, Archives of biochemistry and biophysics.

[13]  E. Epstein,et al.  Basal cell carcinomas arise from hair follicle stem cells in Ptch1(+/-) mice. , 2011, Cancer cell.

[14]  Richard Nuccitelli,et al.  Optimized nanosecond pulsed electric field therapy can cause murine malignant melanomas to self‐destruct with a single treatment , 2010, International journal of cancer.

[15]  Bennett L Ibey,et al.  Lipid nanopores can form a stable, ion channel-like conduction pathway in cell membrane. , 2009, Biochemical and biophysical research communications.

[16]  Shu Xiao,et al.  Bioelectric Effects of Intense Nanosecond Pulses , 2007, IEEE Transactions on Dielectrics and Electrical Insulation.

[17]  Juergen F. Kolb,et al.  A new pulsed electric field therapy for melanoma disrupts the tumor's blood supply and causes complete remission without recurrence , 2009, International journal of cancer.

[18]  L. Mir,et al.  Electrochemotherapy: a new treatment of solid tumors. , 2003, Journal of experimental & clinical cancer research : CR.

[19]  M. Scott,et al.  Ultraviolet and ionizing radiation enhance the growth of BCCs and trichoblastomas in patched heterozygous knockout mice , 1999, Nature Medicine.

[20]  C. McCulloch,et al.  Basal Cell Carcinoma Chemoprevention with Nonsteroidal Anti-inflammatory Drugs in Genetically Predisposed PTCH1+/− Humans and Mice , 2010, Cancer Prevention Research.