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Kinetics <strong>of</strong> tumour growth and <strong>of</strong> vascular perfusion flow in<br />
electrochemotherapy<br />
Eberhard Neumann<br />
Physical and Biophysical Chemistry, Faculty <strong>of</strong> Chemistry, University <strong>of</strong> Bielefeld, D-33501 Bielefeld,<br />
POB 100131, Germany<br />
It is shown that experimental tumour growth and tumour perfusion flows in electroporationbased<br />
clinical treatments like electrochemotherapy (ECT) can be quantitatively analyzed<br />
in terms <strong>of</strong> nonlinear flow relationships, using the concept <strong>of</strong> time-dependent flow<br />
coefficients (reflecting time-dependences <strong>of</strong> flow cross sections, for instance <strong>of</strong> vascular<br />
blood flow).<br />
This novel, simple and powerful, approach <strong>of</strong> minimum complexity yields, for instance,<br />
characteristic perfusion flow coefficients, stationary recovery levels indicating efficiency <strong>of</strong><br />
perfusion blocks by ECT, and characteristic time constants for the recovery <strong>of</strong> electrically<br />
treated tumour cells and blood vessels under different pulse conditions (from staining the<br />
tumours as a function <strong>of</strong> time (t/h) during the recovery phase after drug application and<br />
electric pulses).<br />
The characteristic parameters <strong>of</strong> the integrated tumour growth equations are in terms <strong>of</strong><br />
up to 20 days and more.<br />
The new method for the quantitative analysis <strong>of</strong> the results <strong>of</strong> electroporation data<br />
obtained with pulse trains rationalizes, for instance, that a pulse train <strong>of</strong> 8 pulses and a<br />
repetition frequency 1 Hz (8 s total train time) is electroporatively more efficient than the<br />
shorter pulse train <strong>of</strong> 5 kHz (1.6 ms total train time).<br />
The reason for the efficiency <strong>of</strong> longer time intervals between the individual pulses <strong>of</strong><br />
a train is the well documented longevity <strong>of</strong> electroporation-induced structural changes,<br />
leading to long-lived permeability increase <strong>of</strong> membranes for drugs, and finally also to<br />
constrictively blocking tumour blood vessels.<br />
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