Electrochemotherapy—a novel method of cancer treatment

Dev, Sukhendu B.; Hofmann, G.

doi:10.1016/0305-7372(94)90013-2

Cited by 84 publications

(34 citation statements)

References 13 publications

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“…[22][23][24] Its application to cisplatin has proven to be very effective. 23,24) Preclinical studies of ECT with BLM were performed on a variety of transplantable and spontaneous tumors in immunocompetent and immunodeficient mice.…”

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“…[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] This treatment was termed electrochemotherapy (ECT) and was also extended to other chemotherapeutic drugs. [22][23][24] Its application to cisplatin has proven to be very effective. 23,24) Preclinical studies of ECT with BLM were performed on a variety of transplantable and spontaneous tumors in immunocompetent and immunodeficient mice.…”

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“…In these preclinical studies a certain degree of variation in responsiveness to ECT was observed among the tumor types treated, as well as in the first clinical trials on basal cell carcinoma, malignant melanoma, head and neck squamous cell carcinoma and breast adenocarcinoma. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] The aim of our study was to compare the responsiveness of SA-1 and EAT tumors to BLM and ECT in vitro and in vivo, in order to confirm the existence of a difference in responsiveness to ECT and to cast light on the possible reasons for it.…”

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Intrinsic Sensitivity of Tumor Cells to Bleomycin as an Indicator of Tumor Response to Electrochemotherapy

Čemažar

Miklavčič

Serša

1998

Japanese Journal of Cancer Research

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Electrochemotherapy (ECT) involves the use of locally applied electric pulses to increase delivery of chemotherapeutic drugs into cells in tissues. ECT with bleomycin (BLM) is a very effective local treatment, but different tumors have different response rates to ECT. The aim of our study was to compare the responsiveness of SA-1 and EAT tumors to BLM and ECT in vitro and in vivo, in order to find possible reasons for the observed difference in response rate. The difference in sensitivity to ECT in vitro between the SA-1 and EAT cells was 10-fold and was the same as the difference in sensitivity to chronic BLM exposure, as measured by tetrazolium-based colorimetric (MTT) assay. This difference in sensitivity between SA-1 and EAT to ECT was also reflected in tumor cure rate. A six-times lower dose of BLM was needed to obtain local tumor control in SA-1 than in EAT tumors. Therefore, we suggest that the difference in sensitivity to BLM and ECT predominantly reflects the difference in intrinsic sensitivity of the cells to BLM.Key words: Electrochemotherapy -Bleomycin -Electroporation -Experimental tumor -Mice Bleomycin (BLM) is a water-soluble glycopeptidic antibiotic with limited antitumor effectiveness, and is currently used only in combined chemotherapeutic schedules in the treatment of cancer.1) The major reason for its limited antitumor effectiveness is the hampered transport of BLM through the plasma membrane. However, once inside the cell, BLM is highly cytotoxic, inducing single and double strand DNA breaks.2) Different approaches have been tested to increase the antitumor effectiveness of BLM, [3][4][5] mainly with the aim of facilitating entry of the drug into the cells. Electropermeabilization (electroporation), i.e., a technique for introduction of molecules into cells by exposure of the cells to intense electrical pulses, proved to be very effective. Under specific conditions, electropermeabilization is a reversible process which does not impair cell viability. 6)Use of electropermeabilization to increase BLM uptake into the cells and consequently to increase the antitumor effectiveness was demonstrated in vitro, in vivo and also in clinical trials.7-21) This treatment was termed electrochemotherapy (ECT) and was also extended to other chemotherapeutic drugs. [22][23][24] Its application to cisplatin has proven to be very effective. 23,24) Preclinical studies of ECT with BLM were performed on a variety of transplantable and spontaneous tumors in immunocompetent and immunodeficient mice. [9][10][11][12][13][14][15][16][17][18] In all of these studies ECT proved to be an effective antitumor treatment, inducing a prolonged tumor growth delay compared to BLM treatment only. In addition, ECT results in tumor cures. In these preclinical studies a certain degree of variation in responsiveness to ECT was observed among the tumor types treated, as well as in the first clinical trials on basal cell carcinoma, malignant melanoma, head and neck squamous cell carcinoma and breast adenocarcinoma. 7-24)The aim of our...

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Intrinsic Sensitivity of Tumor Cells to Bleomycin as an Indicator of Tumor Response to Electrochemotherapy

Čemažar

Miklavčič

Serša

1998

Japanese Journal of Cancer Research

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“…16,42,45 Reversible electroporation can also be used to increase permeability to allow delivery of cytotoxic agents for targeted cell death in a process referred to as electrochemotherapy. 12,23,24 When the electric field strength is above a critical value, irreversible electroporation occurs and results in cell death due to loss of homeostasis. 17 Under most conditions, the irreversible increase in membrane permeability has been reported in conjunction with tissue thermal damage caused by electrical Joule heating.…”

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Nonthermal irreversible electroporation for intracranial surgical applications

Ellis

García

Rossmeisl

et al. 2011

JNS

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Object. Nonthermal irreversible electroporation (NTIRE) is a novel, minimally invasive technique to treat cancer, which is unique because of its nonthermal mechanism of tumor ablation. This paper evaluates the safety of an NTIRE procedure to lesion normal canine brain tissue.Methods. The NTIRE procedure involved placing electrodes into a targeted area of brain in 3 dogs and delivering a series of short and intense electric pulses. The voltages of the pulses applied were varied between dogs. Another dog was used as a sham control. One additional dog was treated at an extreme voltage to determine the upper safety limits of the procedure. Ultrasonography was used at the time of the procedure to determine if the lesions could be visualized intraoperatively. The volumes of ablated tissue were then estimated on postprocedure MR imaging. Histological brain sections were then analyzed to evaluate the lesions produced.Results. The animals tolerated the procedure with no apparent complications except for the animal that was treated at the upper voltage limit. The lesion volume appeared to decrease with decreasing voltage of applied pulses. Histological examination revealed cell death within the treated volume with a submillimeter transition zone between necrotic and normal brain.Conclusions. The authors' results reveal that NTIRE at selected voltages can be safely administered in normal canine brain and that the volume of ablated tissue correlates with the voltage of the applied pulses. This preliminary study is the first step toward using NTIRE as a brain cancer treatment.

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“…18 Electroporation also has been used to deliver genes to living animals. [19][20][21] However, electroporation yields only a transient gene expression and not as efficient as viral vectors. 18 In this investigation, we have optimized gene transfer of Gdf11 to pulp cells to initiate odontoblast differentiation in vitro and reparative dentin formation in vivo by electroporation for the endodontic treatment of pulp tissue regeneration and dentin repair.…”

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