A new pulsed electric field therapy for melanoma disrupts the tumor's blood supply and causes complete remission without recurrence

被引:170
作者
Nuccitelli, Richard [1 ,2 ]
Chen, Xinhua [1 ]
Pakhomov, Andrei G. [1 ]
Baldwin, Wallace H. [1 ]
Sheikh, Saleh [1 ,2 ]
Pomicter, Jennifer L. [1 ]
Ren, Wei [1 ]
Osgood, Christopher [1 ]
Swanson, R. James [1 ]
Kolb, Juergen F. [1 ]
Beebe, Stephen J. [1 ]
Schoenbach, Karl H. [1 ]
机构
[1] Old Dominion Univ, Frank Reidy Res Ctr Bioelect, Norfolk, VA 23510 USA
[2] BioElectroMed Corp, Burlingame, CA USA
关键词
nanosecond; pulsed electric fields; apoptosis; necrosis; angiogenesis; MEMBRANE PERMEABILIZATION; DNA-DAMAGE; NANOSECOND; CELLS; CALCIUM; APOPTOSIS; NSPEF;
D O I
10.1002/ijc.24345
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We have discovered a new, ultrafast therapy for treating skin cancer that is extremely effective with a total electric field exposure time of only 180 mu sec. The application of 300 high-voltage (40 kV/cm), ultrashort (300 nsec) electrical pulses to murine melanomas in vivo triggers both necrosis and apoptosis, resulting in complete tumor remission within an average of 47 days in the 17 animals treated. None of these melanomas recurred during a 4-month period after the initial melanoma had disappeared. These pulses generate small, long-lasting, rectifying nanopores in the plasma membrane of exposed cells, resulting in increased membrane permeability to small molecules and ions, as well as an increase in intracellular Ca2+, DNA fragmentation, disruption of the tumor's blood supply and the initiation of apoptosis. Apoptosis was indicated by a 3-fold increase in Bad labeling and a 72% decrease in Bcl-2 labeling. In addition, microvessel density within the treated tumors fell by 93%. This new therapy utilizing nanosecond pulsed electric fields has the advantages of highly localized targeting of tumor cells and a total exposure time of only 180 psec. These pulses penetrate into the interior of every tumor cell and initiate DNA fragmentation and apoptosis while at the same time reducing blood flow to the tumor. This new physical tumor therapy is drug free, highly localized, uses low energy, has no significant side effects and results in very little scarring. (C) 2009 UICC
引用
收藏
页码:438 / 445
页数:8
相关论文
共 24 条
[1]   Tumor Ablation with Irreversible Electroporation [J].
Al-Sakere, Bassim ;
Andre, Franck ;
Bernat, Claire ;
Connault, Elisabeth ;
Opolon, Paule ;
Davalos, Rafael V. ;
Rubinsky, Boris ;
Mir, Lluis M. .
PLOS ONE, 2007, 2 (11)
[2]   Nanosecond, high-intensity pulsed electric fields induce apoptosis in human cells [J].
Beebe, SJ ;
Fox, PM ;
Rec, LJ ;
Willis, LK ;
Schoenbach, KH .
FASEB JOURNAL, 2003, 17 (09) :1493-+
[3]   Nanosecond pulsed electric field (nsPEF) effects on cells and tissues: Apoptosis induction and tumor growth inhibition [J].
Beebe, SJ ;
Fox, PM ;
Rec, LJ ;
Somers, K ;
Stark, RH ;
Schoenbach, KH .
IEEE TRANSACTIONS ON PLASMA SCIENCE, 2002, 30 (01) :286-292
[4]   The comet assay for DNA damage and repair - Principles, applications, and limitations [J].
Collins, AR .
MOLECULAR BIOTECHNOLOGY, 2004, 26 (03) :249-261
[5]   Calcium in cell injury and death [J].
Dong, Zheng ;
Saikumar, Pothana ;
Weinberg, Joel M. ;
Venkatachalam, Manjeri A. .
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE, 2006, 1 (01) :405-434
[6]  
Folpe AL, 2007, ARCH PATHOL LAB MED, V131, P1517
[7]   Plasma membrane voltage changes during nanosecond pulsed electric field exposure [J].
Frey, W ;
White, JA ;
Price, RO ;
Blackmore, PF ;
Joshi, RP ;
Nuccitelli, R ;
Beebe, SJ ;
Schoenbach, KH ;
Kolb, JF .
BIOPHYSICAL JOURNAL, 2006, 90 (10) :3608-3615
[8]   In vitro and in vivo evaluation and a case report of intense nanosecond pulsed electric field as a local therapy for human malignancies [J].
Garon, Edward B. ;
Sawcer, David ;
Vernier, P. Thomas ;
Tang, Tao ;
Sun, Yinghua ;
Marcu, Laura ;
Gundersen, Martin A. ;
Koeffler, H. Phillip .
INTERNATIONAL JOURNAL OF CANCER, 2007, 121 (03) :675-682
[9]   Nanosecond pulsed electric field generators for the study of subcellular effects [J].
Kolb, JF ;
Kono, S ;
Schoenbach, KH .
BIOELECTROMAGNETICS, 2006, 27 (03) :172-187
[10]   A case of perineal malignant melanoma successfully treated with electrochemotherapy [J].
Kubota, Y ;
Tomita, Y ;
Tsukigi, M ;
Kurachi, H ;
Motoyama, T ;
Mir, LM .
MELANOMA RESEARCH, 2005, 15 (02) :133-134