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Experimental Studies On Pulsed Electric Fields Inhibit Tumor Growth And Induce Myocardial Injury Of Melanoma-bearing Mice

Posted on:2017-05-07Degree:MasterType:Thesis
Country:ChinaCandidate:F Y PanFull Text:PDF
GTID:2284330503991357Subject:Internal Medicine
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Pulsed electric fields(PEF) is a novel modality for cancer treatment combining multi-subject, and has unique bioelectrical effect which at present has been widely used in the field of tumor therapy. Among them, high-intensity pulsed electric field(KV/cm field strength, the order of magnitude of μs~ns pulse width) is highly concerned by the researchers. It can cause irreversible electroporation effect to induce apoptosis of tumor cells selectively, and can achieve targeted ablation therapy of tumor. However, the body has the phenomenon of voltage tolerance, security issues of susceptible tissues have become a bottleneck of clinical application of high-intensity pulsed electric field(HPEF). Compare with HPEF, low-voltage electric current pulse(LVECP) could be a rewarding alternative. Our group test confirmed myocardium suffered differently degree influences under different parameters. Therefore, this research is to study the follow two aspects:1.Antitumor effect of pulsed electric fields on melanoma-bearing mice; 2.Effect of pulsed electric fields on myocardial injury of melanoma-bearing mice. PART I ANTITUMOR EFFECT OF PULSED ELECTRIC FIELDS ON MELANOMA-BEARING MICEObjective: To investigate the tumor inhiting effect of pulsed electric fields(PEFs) on melanoma-bearing mice.Methods: The melanoma models of the BALB/c mice were established successfully by subcutaneously injecting B16 melanoma cells. These mice were randomly divided into four groups including control group(n=10) and treated groups(n=30). The treated groups received pulsed electric stimulation at pulse width of 1, 3, 5 ms, with field strength of 100 V/cm and frequency of 10 Hz for 10 minutes daily in 15 consecutive days. Tumor volume was measured with vernier caliper. Morphological changes of tumors were observed by HE staining. The expression of proliferating cell nuclear antigen(PCNA) m RNA was tested by real-time quantitative PCR, and the expression of PCNA protein was detected by immunofluorescence histochemistry.Results: Compared with the control group(506.2±341.7mm3), tumor volumes in all treated groups(238.4±307.2mm3、81.9±63.4 mm3、63.9±83.9 mm3, respectively) were reduced(P<0.05) 15 days after PEFs treatment; more melanin granules, and degeneration and necrosis in tumor cells were found in the treated groups, the expressions of PCNA m RNA and protein were down-regulated both in 3 ms group and 5 ms group(P<0.05,P<0.01).Conclusion: PEFs can inhibit tumor growth in melanoma-bearing mice, which is associated with inhibiting the tumor cell proliferation. Part II Effect of pulsed electric fields on myocardial injuryof melanoma-bearing miceObjective: To observe the influence of pulsed electric fields on cardial electrical activity and myocardial cells.Methods: 40 melanoma-bearing mice were randomly divided into control group and treated groups which were exposed to electric pulse width of 1, 3, 5 ms, with field strength of 100 V/cm and frequency of 10 Hz for 10 minutes daily in 15 consecutive days. ECG of mice was recorded. The ultrastructural changes of the cardiac tissues were observed by transmission electron microscopy(TEM). The serum levels of cardial troponin T(c Tn T) and creatine kinase isoenzyme MB(CK-MB) were detected by ELISA.Results: Compared with the control group, ECG in treated groups was no significant change. Myocardial injury was found in 3 ms group and 5 ms group, and the expressions of c Tn T and CK-MB were significantly higher than those in the control group(P<0.01).Conclusion: Pulsed electric fields induce myocardial injury. Increase of pulse width will aggravate myocardial injury.
Keywords/Search Tags:pulsed electric fields, melanoma, antitumor effect, mice, myocardial injury
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