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      Antitumor effectiveness of different amounts of electrical charge in Ehrlich and fibrosarcoma Sa-37 tumors

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          Abstract

          Background

          In vivo studies were conducted to quantify the effectiveness of low-level direct electric current for different amounts of electrical charge and the survival rate in fibrosarcoma Sa-37 and Ehrlich tumors, also the effect of direct electric in Ehrlich tumor was evaluate through the measurements of tumor volume and the peritumoral and tumoral findings.

          Methods

          BALB/c male mice, 7–8 week old and 20–22 g weight were used. Ehrlich and fibrosarcoma Sa-37 cell lines, growing in BALB/c mice. Solid and subcutaneous Ehrlich and fibrosarcoma Sa-37 tumors, located dorsolaterally in animals, were initiated by the inoculation of 5 × 10 6 and 1 × 10 5 viable tumor cells, respectively. For each type of tumor four groups (one control group and three treated groups) consisting of 10 mice randomly divided were formed. When the tumors reached approximately 0.5 cm 3, four platinum electrodes were inserted into their bases. The electric charge delivered to the tumors was varied in the range of 5.5 to 110 C/cm 3 for a constant time of 45 minutes. An additional experiment was performed in BALB/c male mice bearing Ehrlich tumor to examine from a histolological point of view the effects of direct electric current. A control group and a treated group with 77 C/cm 3 (27.0 C in 0.35 cm 3) and 10 mA for 45 min were formed. In this experiment when the tumor volumes reached 0.35 cm 3, two anodes and two cathodes were inserted into the base perpendicular to the tumor long axis.

          Results

          Significant tumor growth delay and survival rate were achieved after electrotherapy and both were dependent on direct electric current intensity, being more marked in fibrosarcoma Sa-37 tumor. Complete regressions for fibrosarcoma Sa-37 and Ehrlich tumors were observed for electrical charges of 80 and 92 C/cm 3, respectively.

          Histopathological and peritumoral findings in Ehrlich tumor revealed in the treated group marked tumor necrosis, vascular congestion, peritumoral neutrophil infiltration, an acute inflammatory response, and a moderate peritumoral monocyte infiltration. The morphologic pattern of necrotic cell mass after direct electric current treatment is the coagulative necrosis. These findings were not observed in any of the untreated tumors.

          Conclusion

          The data presented indicate that electrotherapy with low-level DEC is feasible and effective in the treatment of the Ehrlich and fibrosarcoma Sa-37 tumors. Our results demonstrate that the sensitivity of these tumors to direct electric current and survival rates of the mice depended on both the amount of electrical charge and the type of tumor. Also the complete regression of each type of tumor is obtained for a threshold amount of electrical charge.

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          Most cited references18

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          The effects of low-level direct current therapy on a preclinical mammary carcinoma: tumour regression and systemic biochemical sequelae.

          Low-level direct electric current has been shown to be capable of destroying tumour tissue. Using an early-passage subcutaneous murine mammary carcinoma, the relationships between the volume of tumour destruction, charge and polarity have been examined. The results revealed a direct correlation between charge passed and absolute volume regression when the intratumoral electrode was made either an anode or a cathode. Tumour destruction for a given charge was significantly greater following anodic than cathodic treatment. A direct correlation was also observed between the percentage volume of prompt treatment-induced regression and the in situ end point of tumour growth delay. During the course of these experiments, a highly reproducible toxic effect was discovered, which has not been previously reported for this modality. An anodic charge greater than 10.6 coulombs or a cathodic charge greater than 21.6 coulombs resulted in 100% mortality at 24-72 h, while lower charges had no influence on mortality. Quantitative assays of a number of blood parameters showed that mortality was associated with serum electrolyte imbalances and appeared to be the result of the metabolic load of tumour breakdown products. These effects are similar to the tumour lysis or surgical crush syndromes and should not constitute a significant problem in clinical practice, where the tumour mass to total body mass ratio will normally be much smaller.
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            Electrolytic ablation as an adjunct to liver resection: experimental studies of predictability and safety.

            Combined liver resection and local ablation may offer the only chance of cure to patients with liver metastases who are presently deemed unresectable because of a single awkwardly placed metastasis. By definition, such a metastasis is often close to a major vein. An ablative technique is needed that is both predictable and safe in such a circumstance. Electrolytic liver lesions were created in 21 pigs using platinum electrodes, connected to a direct current generator. Both electrolytic 'dose' and electrode separation were varied to produce different sized lesions. The 'dose' was correlated with the volume of necrosis and any vascular damage was determined histologically. There was a significant (P < 0.001) correlation between the electrolytic 'dose' and the volume of liver necrosis. For a given 'dose' the volume of necrosis was less when the electrodes were together, rather than separated. Liver enzymes were only transiently deranged. There were no significant vascular injuries. Predictable and reproducible necrosis is produced by electrolysis in the pig liver. The treatment appears to cause little or no damage to immediately adjacent liver or major vascular structures and, when combined with resection, may offer the chance of a cure to many patients who are currently unresectable.
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              Electrochemical treatment of mouse Ehrlich tumor with direct electric current.

              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. Copyright 2001 Wiley-Liss, Inc.
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                Author and article information

                Journal
                BMC Cancer
                BMC Cancer
                BioMed Central (London )
                1471-2407
                2004
                26 November 2004
                : 4
                : 87
                Affiliations
                [1 ]Sección de Bioelectricidad. Departamento de Bioingeniería y Equipos, Centro Nacional de Electromagnetismo Aplicado, Universidad de Oriente, Santiago de Cuba 90400, Cuba
                [2 ]Hospital Oncológico Docente Provincial Conrado Benítez, Santiago de Cuba 90100, Cuba
                [3 ]Departamento de Inmunología, Hospital Provincial Clínico Quirúrgico Docente Saturnino Lora, Santiago de Cuba 90500, Cuba
                [4 ]Hospital Infantil Norte Docente "Juan Martínez de la Cruz Maceira". Santiago de Cuba, Cuba
                [5 ]Dirección Municipal de Salud Pública. Santiago de Cuba, Cuba
                [6 ]Departamento de Investigación en Física, Universidad de Sonora, Apdo. Postal A-088, 83190 Hermosillo, Sonora, México
                Article
                1471-2407-4-87
                10.1186/1471-2407-4-87
                539271
                15566572
                874e1771-83b3-476d-934a-c83c898d1f46
                Copyright © 2004 Ciria et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 July 2004
                : 26 November 2004
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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