Electrochemotherapy with bleomycin in SA-1 tumor-bearing mice—natural resistance and immune responsiveness

Serša, Gregor; Kotnik, Vladimir; Čemažar, Maja; Miklavčič, Damijan; A, Kotnik

doi:10.1097/00001813-199609000-00011

Cited by 33 publications

(39 citation statements)

References 18 publications

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“…Our experience reveal that the morphologic pattern of necrotic cell mass is the coagulative necrosis 24 hours after direct current application [Cabrales et al, 2001;Ciria et al, 2004;Jarque et al, 2007]. Also, we observe in preclinical and clinical studies vascular congestion, peritumoral neutrophil infiltration, an acute inflammatory response, and a moderate peritumoral monocyte (and macrophages) infiltration, in agreement with other authors [Chou et al, 1997;Li et al, 1997;Serša et al, 1996;Vijh, 2004;Xin et al, 2004]. We are the opinion that apoptosis, necrosis and the electrochemical reactions into tumor (mainly around electrodes) may be explained from reactive oxygen species.…”

Section: Preclinical and Clinical Studiessupporting

confidence: 91%

“…These fields will avoid the insertion of electrodes in the tumor and therefore the little trauma that this provoke in the patients treated with electrotherapy. Weak magnetic fields activate the system of antitumor immunity (i.e., production of Tumor Necrosis Factor, activation of macrophages, among other) and produce reactive oxygen species, as is also observed on electrotherapy [Cabrales et al, 2001;Serša et al, 1994;Serša et al, 1996;Watemberg et al, 2008]. Different authors have experimentally evaluated the influence of direct current intensity [Ciria et al, 2004;Cabrales et al, 2010;Chou et al, 1997, Ren et al, 2001Xing et al, 2004] and electromagnetic field [Novikov et al, 2009] on tumor growth kinetic; however, the weight of the different parameters of an electrodes array in it has not been widely discussed.…”

Section: Electrode In Form Of Wire Of Length Finitementioning

confidence: 99%

“…The needles are connected to an electrical device that produces a direct current, which is generated by an Electrotherapy antitumor effectiveness can be enhanced when it is combined with intratumor injection of a chemostatic drug (i.e., bleomycin, cisplatin) [Jarque et al, 2007;Xin et al, 2004], saline solution [Jarque et al, 2007;Lin et al, 2000] and/or immunotherapy [Serša et al, 1990;Serša et al, 1992;Serša et al, 1994;Serša et al, 1996]. It has been demonstrated that intratumor bleomycin (cisplatin) treatment is more effective than intravenous treatment at the same dose and direct current potentiates the antitumor effectiveness of bleomycin several-fold [Xin et al, 2004].…”

Section: Preclinical and Clinical Studiesmentioning

confidence: 99%

“…They conclude, then, that the electrochemical effects of this therapy happen around the electrodes. Other antitumor mechanisms have been reported in the literature, such as: (1) immune system stimulation after treatment (the attraction of white blood cells to the tumor site) [Cabrales et al, 2001;Ciria et al, 2004;Jarque et al, 2007;Serša et al, 1996]; (2) lost of tissue water for electro-osmosis [Li et al, 1997;Vijh, 2004Vijh, , 2006; (3) change in the membrane potential of tumor cells, nutrient uptake by tumor cells and reduce deoxyribose nuclei acid production by tumor cells [Chou et al, 1997;Haltiwanger, 2008]; (4) both electrochemical reactions (fundamentally those in which reactive oxygen species are involved) and immune system stimulation induced by cytotoxic action of the direct current, could constitute the most important antitumor mechanisms [Cabrales et al, 2001]; (5) direct current treatment increases the expression of dihydronicotinamide adenine dinucleotide phosphate dehydrogenase (NADPH) oxidase subunits-derived reactive oxygen species which subsequently induces apoptosis of oral mucosa cancer cells [Wartenberg et al, 2008]. These authors also report that an increase of the reactive oxygen species brings about an increase of the expression of heat shock protein (Hsp 70) and Cu/Zn superoxide dismutase (antioxidative enzymes) and a decrease of intracellular concentration of reduced glutathione, whereas the expression of catalase remains unchanged.…”

Section: Preclinical and Clinical Studiesmentioning

confidence: 99%

See 3 more Smart Citations

Electrotherapy on Cancer: Experiment and Mathematical Modeling

Pupo¹,

Jiménez²,

Cabrales³

2011

Current Cancer Treatment - Novel Beyond Conventional Approaches

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Section: Preclinical and Clinical Studiessupporting

confidence: 91%

Section: Electrode In Form Of Wire Of Length Finitementioning

confidence: 99%

Section: Preclinical and Clinical Studiesmentioning

confidence: 99%

Section: Preclinical and Clinical Studiesmentioning

confidence: 99%

See 2 more Smart Citations

Electrotherapy on Cancer: Experiment and Mathematical Modeling

Pupo¹,

Jiménez²,

Cabrales³

2011

Current Cancer Treatment - Novel Beyond Conventional Approaches

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“…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.…”

mentioning

confidence: 99%

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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Electrochemical treatment of mouse Ehrlich tumor with direct electric current

Cabrales

Ciria

Bruzón

et al. 2001

Bioelectromagnetics

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Electrochemical treatment of cancer utilizes direct electric current (DEC) to produce direct alterations and chemical changes in tumors. However, the DEC treatment is not established and mechanisms are not well understood. In vivo studies were conducted to evaluate the effectiveness of DEC on animal tumor models. Ehrlich tumors were implanted subcutaneously in sixty male BALB/c mice. When the tumor volumes reached 850 mm(3), four platinum electrodes were inserted into the tumors. DEC of 4 mA was applied for 21 min to the treated group; the total charge was 5 C. The healthy and sick control groups were subjected to the same conditions but without DEC. Hematological and chemical parameters as well as histopathological and peritumoral findings were studied. After the electrochemical therapy it was observed that both tumor volume decrease and necrosis percentage increase were significant in the treated group. Moreover, 24 h after treatment an acute inflammatory response, as well as sodium ion decrease, and potassium ion and spleen weight increase were observed in this group. It was concluded that both electrochemical reactions (fundamentally those in which reactive oxygen species are involved), and immune system stimulation induced by cytotoxic action of the DEC could constitute the most important antitumor mechanisms.

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Electrochemotherapy with bleomycin in SA-1 tumor-bearing mice—natural resistance and immune responsiveness

Cited by 33 publications

References 18 publications

Electrotherapy on Cancer: Experiment and Mathematical Modeling

Electrotherapy on Cancer: Experiment and Mathematical Modeling

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

Electrochemical treatment of mouse Ehrlich tumor with direct electric current

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