Contrast Enhanced MRI Assessment of Tumor Blood Volume After Application of Electric Pulses

Serša, Gregor; Beravs, Katarina; Čemažar, Maja; Miklavčič, Damijan; Demšar, Franci

doi:10.3109/15368379809022574

Cited by 28 publications

(18 citation statements)

References 23 publications

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“…According to the studies using rubidium extraction or PBV-staining techniques, a reduction of 70% was observed in blood flow of Sa-1 tumors in A/J mice 30 min after EP [72,81]. A similar effect was observed in one of the first studies on the effects of EP on tumor blood flow using CE MRI with contrast agent albumin-(Gd-DTPA) 30 , in which it was demonstrated that, 30 min after EP, blood flow was severely impeded in comparison with nontreated tumors on the contralateral side in the same animals [70]. In all studies, the blood flow in tumors 1 h after EP was on average less than 50% of the pretreatment value or when compared with the control tumors [66,67,72,82].…”

Section: Blood Flow-modifying Effects Of Epsupporting

confidence: 56%

“…This side-effect was observed on tissue exposed to electric pulses in the early studies involving EP and ECT [70][71][72][73][74], but its significance for antitumor effectiveness of ECT was at that time not fully recognized owing to the fact that in contrast to ECT, the antitumor effect of EP alone without the chemothera peutic drug was not significant even though the time course and extent of blood flow changes observed immediately after the two treatments (i.e., ECT or application of EP alone) appeared very similar. The differences between the effects of EP and ECT on blood flow become evident only several hours after the treatment, which suggests that EP and ECT share a common blood flow-modifying mechanism (as a result of electric pulses alone) with an important additional vascular-disrupting mechanism present only in the case of ECT.…”

Section: Mechanisms Of Antitumor Effectiveness Of Ectmentioning

confidence: 99%

“…It was demonstrated by a number of authors using several different methods in solid tumor models as well as in normal tissue that the application of electric pulses commonly used in ECT protocols induces rapid and profound reduction in local blood flow of exposed tissue [66,67,70,71,73,81]. The dynamic changes, as rapid as those following the application of EP, can be measured by the laser Doppler flowmetry method (LDF).…”

Section: Blood Flow-modifying Effects Of Epmentioning

confidence: 99%

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Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases

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Section: Blood Flow-modifying Effects Of Epsupporting

confidence: 56%

Section: Mechanisms Of Antitumor Effectiveness Of Ectmentioning

confidence: 99%

Section: Blood Flow-modifying Effects Of Epmentioning

confidence: 99%

See 1 more Smart Citation

Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases

Jarm

Čemažar

Miklavčič

et al. 2010

Expert Review of Anticancer Therapy

191

132

View full text Add to dashboard Cite

“…In addition to electroporation of tumour cells, electric pulses were found to modify blood flow in normal tissues and in tumours (Ramirez et al, 1998;Sersa et al, 1998Sersa et al, , 1999bEngstrom et al, 2001;Gehl et al, 2002). This phenomenon was well documented by different techniques demonstrating reduced blood flow and oxygenation in the tumours (Sersa et al, 1999b.…”

mentioning

confidence: 98%

Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

et al. 2008

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Electrochemotherapy has a direct cytotoxic effect on tumour cells, and presumably, a vascular disrupting effect. In this study, on the basis of the prediction of the mathematical model, histological evaluation and physiological measurements of the tumours were carried out to confirm that electroporation and electrochemotherapy of tumours have a vascular disrupting action. In the study, SA-1 solid subcutaneous sarcoma tumours in A/J mice were treated by bleomycin (BLM) given intravenously (1 mg kg À1 ), application of electric pulses (8 pulses, 1040 V, 100 ms, 1 Hz) or a combination of both -electrochemotherapy. The vascular effect was determined by laser Doppler flowmetry, power Doppler ultrasonographic imaging and Patent blue staining. The extent of tumour hypoxia was determined immunohistochemically by hypoxia marker pimonidazole and partial pressure of oxygen (pO 2 ) in tumours by electron paramagnetic resonance oximetry. Electrochemotherapy with BLM induced good antitumour effect with 22 days, tumour growth delay and 38% tumour cures. The application of electric pulses to the tumours induced instant but transient tumour blood flow reduction (for 70%) that was recovered in 24 h. During this tumour blood flow reduction, we determined an increase in hypoxic tumour area for up to 30%, which was also reflected in reduced tumour oxygenation (for 70%). According to the described mathematical model, endothelial cells lining in tumour blood vessels are exposed to a B40% higher electric field than the surrounding tumour cells, and therefore easily electroporated, allowing access of high BLM concentration to the cytosol. Consequently, electrochemotherapy has, besides the immediate vascular disrupting action, also a delayed one (after 24 h), as a consequence of endothelial cell swelling and apoptosis demonstrated by extensive tumour necrosis, tumour hypoxia, prolonged reduction of tumour blood flow and significant tumour growth delay, and tumour cures. Our results demonstrate that in addition to the well-established direct cytotoxic effect on tumour cells, electrochemotherapy also has an indirect vascular disrupting action resulting altogether in extensive tumour cell necrosis leading to complete regression of tumours.

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“…As observed in our previous study, besides electroporation, electric pulses can modify tumour blood flow (Sersa et al, 1998b). Application of electric pulses such as those used in this study reduce tumour blood flow by 60-70% and result in a tumour growth delay of 0.2 days.…”

Section: Discussionmentioning

confidence: 78%

Increased platinum accumulation in SA-1 tumour cells after in vivo electrochemotherapy with cisplatin

et al. 1999

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Summary Electrochemotherapy is an anti-tumour treatment that utilizes locally delivered electric pulses to increase cytotoxicity of chemotherapeutic drugs. The aim of our study was to determine whether anti-tumour effectiveness of electrochemotherapy with cisplatin is a consequence of increased plasma membrane permeability caused by electroporation that enables cisplatin binding to DNA. For this purpose, anti-tumour effectiveness of electrochemotherapy was evaluated on SA-1 tumours treated with electric pulses 3 min after intravenous injection of cisplatin (4 mg kg -1 ). Anti-tumour effectiveness was correlated with platinum accumulation in tumours and the amount of platinum bound to DNA, as determined by atomic absorption spectrometry. In tumours treated with electrochemotherapy, cell kill was increased by a factor of 20 compared with treatment with cisplatin only, as determined from tumour growth curves. The amount of platinum bound to DNA and platinum content in the tumours treated by electrochemotherapy was approximately two times higher than in cisplatin-treated tumours. Based on our results, we conclude that in vivo application of electric pulses potentiates anti-tumour effectiveness of cisplatin by electroporation that consequently results in cisplatin increased delivery into the cells. In addition, besides electroporation, immune system and tumour blood flow changes could be involved in the observed anti-tumour effectiveness of electrochemotherapy.

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Contrast Enhanced MRI Assessment of Tumor Blood Volume After Application of Electric Pulses

Cited by 28 publications

References 23 publications

Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases

Antivascular effects of electrochemotherapy: implications in treatment of bleeding metastases

Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

Increased platinum accumulation in SA-1 tumour cells after in vivo electrochemotherapy with cisplatin

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