Author/Editor     Serša, G; Kržič, M; Šentjurc, M; Ivanuša, T; Beravs, K; Kotnik, V; Coer, A; Swartz, HM; Čemažar, M
Title     Reduced blood flow and oxygenation in SA-I tumours after electrochemotherapy with cisplatin
Type     članek
Source     Br J Cancer
Vol. and No.     Letnik 87, št. 9
Publication year     2002
Volume     str. 1047-54
Language     eng
Abstract     Electrochemotherapy is an antitumour treatment that utilises locally delivered electric pulses to increase cytotoxicity of chemotherapeutic drugs. Besides increased drug delivery, application of electric pulses affects tumour blood flow. The aim of this study was to determine tumour blood flow modifying effects of electrochemotherapy with cisplatin, its effects on tumour oxygenation and to determine their relation to antitumour effectiveness. Electrochemotherapy of SA-I subcutaneous tumours was performed by application of electric pulses to the tumours, following administration of cisplatin. Tumour blood flow modifying effects of electrochemotherapy were determined by measurement of tumour perfusion using the Patent blue staining technique, determination of tumour blood volume, and microvascular permeability using contrast enhanced magnetic resonance imaging, and tumour oxygenation using electron paramagnetic resonance oximetry. Antitumour effectiveness was determined by tumour growth delay and the extent of tumour necrosis and apoptosis. Tumour treatment by electrochemotherapy induced 9.4 days tumour growth delay. Tumour blood flow was reduced instantaneously and persisted for several days. This reduction in tumour blood flow was reflected in reduced tumour oxygenation. The maximal redudion in partial oxygen pressure (pO2) levels was observed at 2 h after the treatment, with steady recovery to the pretreatment level within 48 h. The reduced tumour blood flow and oxygenation con-elated well with the extent of tumour necrosis and tumour cells apoptosis induced by electrochemotherapy with cisplatin. Therefore, the data indicate that antitumour effectiveness of electrochemotherapy is not only due to increased cytotoxicity of cisplatin due to electroporation of tumour cells, but also due to anti-vascular effect of electrochemotherapy, which resulted in reduced tumour blood flow and oxygenation.
Descriptors     SARCOMA, EXPERIMENTAL
FIBROSARCOMA
ELECTROPORATION
DRUG DELIVERY SYSTEMS
CISPLATIN
MICE, INBRED A
NECROSIS
ANTINEOPLASTIC AGENTS
APOPTOSIS
BLOOD FLOW VELOCITY
OXYGEN
INJECTIONS, INTRAVENOUS