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| Electrochemotheraphy – A New Way for Enhancing Cancer Treatment |
| Uwe Pliquett |
| Fachbereich Analysenmesstechnik, Institut für Bioprozess- und Analysenmesstechnik, Heilbad Heiligenstadt, Germany |
| *Corresponding author: |
Dr. Uwe Pliquett
Institut für Bioprozess- und
Analysenmesstechnik
Heilbad Heiligenstadt, Germany
E-mail: uwe.pliquett@iba-heiligenstadt.de |
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| Received April 21, 2012; Accepted April 23, 2012; Published April 25, 2012 |
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| Citation: Pliquett U (2012) Electrochemotheraphy – A New Way for Enhancing
Cancer Treatment. Chemotherapy 1:e106. doi:10.4172/2167-7700.1000e106 |
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| Copyright: © 2012 Pliquett U. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited. |
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| Chemotheraphy is a tool for killing fast proliferating cells, like
most tumor cell lines, by means of therapeutic agents. Since the cell
membrane is an efficient barrier for most chemical substances, many
anti-cancer agents need to be applied in a high dose in order to reach a
lethal level inside the cell. This in turn has implications for non-tumor
cells yielding most of the known side effect of chemotherapy. There are
perspectives for targeting drugs to the tumor in order to enhance the
selectivity of the treatment, i.e. by means of magnetic field, liposomes
or aptamers with high binding affinity to special cell lines. |
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| Another way is the enhancement of the activity of anticancer agent
at the site of a tumor using physical methods. First attempts to enhance
chemotherapy by utilizing electric field range back to the end of the
eighties of last century. First experiments by Okino and Mohri showed
a drastic concentration increase of anticancer drugs in solid tumors.
First clinical trials on head and neck tumors have been performed
at 1990 by the group of Lluis Mir in France. Since this time a great
development took place, involving many research groups, mostly
in Europe and USA, resulting in efficient treatment procedures and
commercialized equipment (e.g. Cliniporator, IGEA, Italy) for this
purpose. |
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| The most prominent anticancer agent used in Electrochemotherapy
is Bleomycin, an almost obsolete drug which denatures DNA. However,
for efficient action this drug should cross the cell membrane which is
almost impossible for hydrophilic substances like Bleomycin. It was
found, that a brief but intense electric field can enhance the transport
of hydrophilic substance across the cell membrane by an effect called
electroporation. |
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| If a cell is attributed to an outer electric field, the highly resistive
membrane will accumulate charges like a capacitor. This increases
the trans-membrane voltage (usually termed membrane potential)
from about -65 mV under resting condition up to about one volt.
Charged plasma membranes are stable up to about 200 mV. Above
this voltage water is forced into the membrane structure at preexisting
defects (pre-pore) randomly probable due to molecular motion of the
lipids. Increasing voltage increases the probability of creating a water
structure which spans the entire lipid membrane, thereby creating a
hydrophilic pathway with a dimension of about 1 nm. This is quite
sufficient for the transport of hydrophilic substance like Bleomycin.
Once the field ceases, self-organization forces a shrinking and finally
resealing of these pores, thereby trapping the molecules transported
into the cell during the presence of the electric field. Since the achievable
concentration of water soluble anticancer agents inside the cell is by
orders of magnitude higher than by passive diffusion through the low
permeable cell membrane, any cell experiencing electroporation even
in a low concentration of this drug will respond. This means, even if
all cells of the body experience a low concentration, for instance of
Bleomycin, only the cell attributed to intense electric field will respond.
It is interesting to mention that the electric treatment with a field
strength and duration as it is usually used in electrochemotherphy
is not sufficient for killing cells since electroporation under mild
conditions alone will be tolerated by most cells. |
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| The procedure for electrochemotheraphy involves commonly the
drug injection at the site of the tumor. After some minutes, the tumor
will be contacted by electrodes and the electric protocol with sufficient
field strength for reaching electroporation condition within the tumor
will be applied. First clinical trials were conducted at head and neck
tumors because of the simple assessment. Surface electrodes have been
the predominant electrode configuration in the early days. However,
more sophisticated electrode systems for treating almost all tumors, e.g.
caliper electrodes with adjustable electrode distance, needle electrodes
for deep volume treatment or catheter electrodesappeared soon after. |
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| Leading groups like L. Mir (France), J. Gehl (Denmark), G. Sersa,
D. Miklavcic (Slovenia) or R. Heller (USA) demonstrated the efficiency
of electrochemotherapy in clinical trials at humans but at animals
as well. This approach is especially useful when tumors cannot be
removed surgically like in case of bone metastasis. |
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| Today, two anticancer agents, Bleomycin and Cis-Platin are
mostly used for electrochemotherapy. Future work will focus on the
development of new drugs, electrodes and diagnostic tools for more
efficient guiding the electric field application and better feedback for
the physician, especially if the site of the tumor is hidden and visual
inspection possibilities are poor. Electrical characterization of the
treated area for instance, gives information about the electrically
induced changes on tissue level, even if they are invisible. |
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| Since most of the development in Electrochemotherapy is of
technical nature, many publications appeared in technical, often hard
to access journals with only little attention by oncologists. A better
attention from physicians was found for clinical trials published mostly
in medical or biomedical journals or at dedicated conferences. For the
success of new technologies a fast spread of the knowledge about it
without the barrier of limited access to publications is essential. |
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