1.The anti-tumor efficacy of nanosecond pulsed electric fields on the mouse with melanoma xenograft in vivo.
Qiao PENG ; Shoulong DONG ; Fei GUO ; Chenguo YAO ; Junying TANG
Journal of Biomedical Engineering 2013;30(6):1302-1308
This study was conducted to investigate the anti-tumor efficacy of nanosecond pulsed electric fields (nsPEFs) on the mouse with A375-GFP melanoma xenograft in vivo. In vivo fluorescence image analysis system was used in this study to evaluate the effects of nsPEFs on human melanoma A375 cell xenograft. On the Day 90 af ter pulse delivery, the skin that had contained A375 cell xenograft was surgically excised and pathologically evalua ted. The changes of scar were recorded by digital camera. The experiment revealed that significant changes in fluorescence value trend and amplitude were found in the treated group from those in the control group. The fluorescence of tumor in the treated group decreased mostly 48 h after the treatment and completely disappeared 10 d after the treatment, while that in control group was increased gradually. Surgical excision of the area confirmed a complete pathologic response. Within a few days after the nsPEFs treatment, a hard scab formed at the treatment region. The scab fell off by the end of the second week. As time went on, the scar gradually became faded and all xenograft tumors were disappeared without recurrence. From the experiment, we learn that nsPEFs can bring good therapeutic effect. It may provide a new approach for the clinical treatment of superficial tumors.
Animals
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Electric Stimulation Therapy
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methods
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Heterografts
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Humans
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Melanoma
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therapy
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Mice
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Neoplasm Recurrence, Local
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Skin
;
pathology
2.The research progress of using electroporation therapy in treatment of tumor.
Chenguo YAO ; Caixin SUN ; Lan XIONG ; Yan MI ; Lina HU
Journal of Biomedical Engineering 2002;19(2):337-339
In these years, the electrical technology is widely applied in the study of biomedical engineering. Using electroporation therapy (EPT) to treat tumor is associated with biomedical engineering, electrical new technology, computer technology and microelectronic technology, which is a new marginal subject. Many experts have studied the mechanism and clinical treatment of the cell membrane electroporation phenomenon under electrical fields. These researches have shown that the membrane electroporation can stimulate the transport and intake of various drugs, which improves the tumoricidal effect of these drugs. The researchers have also been exploring the phenomenon that irreversible electrical breakdown (IREB) of cell membrane under high electrical fields and steep pulses leads to the death of tumor.
Cell Membrane
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ultrastructure
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Electrochemotherapy
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Humans
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Neoplasms
;
drug therapy
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Research
;
trends
3.Experimental study on effects of energy controllable steep pulses on cytoskeleton of human ovarian cancer cells SKOV3.
Anping LIN ; Lina HU ; Yao TANG ; Caixin SUN ; Yan MI ; Chenguo YAO
Journal of Biomedical Engineering 2009;26(2):268-272
The aim of our study was to determine the effects of energy controllable steep pulse (ECSP) on the cytoskeleton of human ovarian cancer cells SKOV3. SKOV3 cells were divided into five groups under ECSP treatment with different parameters (frequency, pulse duration, peak value of voltage). The positive control group included SKOV3 cells treated with volchicine; the negative control group included SKOV3 cells subjected to sham-lightning stroke. Rhodamine-phalloidine was used to label microfilament directly. After using immunofluorescence to label microbules, we observed them by means of Confocal Laser Scanning Microscope. Making specimen and using electronmicroscope, we observed the ultramicrostructure of cystoskeleton. The results showed that ECSP-treated-SKOV3 cells lost their normal cystoskeleton network structure. There were obvious microfilament disaggregation, diffused skeleton protein, and disappearance of cystoskeleton network structure. Also noticeable were microbule disaggregation, reduction of pseudopod, obvious microfilament disaggregation, permutation disorder and structure disappearance. Moreover, this effect bears a direct relation with dosage.
Cell Line, Tumor
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Cytoskeleton
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ultrastructure
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Electric Conductivity
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Electromagnetic Fields
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Electroporation
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Female
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Humans
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Ovarian Neoplasms
;
pathology
;
Pulse
4.Research progress of nanosecond pulsed electric field applied to intracellular electromanipulation.
Chenguo YAO ; Dengbin MO ; Caixin SUN ; Xin CHEN ; Zheng'ai XIONG
Journal of Biomedical Engineering 2008;25(5):1206-1209
In recent years, many experts have done some researches on experiment and mechanism of intracellular electromanipulation (IEM) under nanosecond pulsed electric field (nsPEF). The experiment results have shown that nsPEF could not induce electroporation of cell membrane, but could induce intracellular effects such as apoptosis, calcium release, enhancement of gene expression, and fragmentation of DNA and chromosome. In order to account for the phenomenon, researchers believe that when the pulse width of the pulsed electric field is larger than the charging time of plasma membrane, the pulsed electric field mainly targets on the outer membrane of cell; and that the effect of the pulsed electric field on nucleus and nuclear membrane increases with the decrease of the pulse width. It is also believed that the effect of electroporation changes from the outer membrane to intracellular electromanipulation when the pulse width decreases to a value being smaller than the charging time of plasma membrane.
Apoptosis
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Calcium
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metabolism
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Cell Membrane
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metabolism
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Cell Nucleus
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metabolism
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Cell Physiological Phenomena
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Electromagnetic Fields
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Electroporation
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Gene Expression
5.Analysis of frequency-domain and window effect for cellular inner and outer membranes subjected to pulsatile electric field.
Chenguo YAO ; Xin CHEN ; Chengxiang LI ; Yan MI ; Caixin SUN
Journal of Biomedical Engineering 2011;28(1):12-17
Based on multi-layer dielectric model of spherical biological cell, a simulating method of frequency characteristics of inner and outer membranes is presented in this paper. Frequency-domain analysis showed that inner and outer membranes subjected to pulsed electric field exhibit band-pass and low-pass filter characteristics, respectively. A calculating method of the transmembrane potential of inner and outer membranes induced by time-varying electric field was introduced, and the window effect between electric field and transmembrane potential was also analyzed. When the duration is reduced from microsecond to sub-microsecond, and to nanosecond, the target induced was from the outer membrane to inner membrane gradually. At the same time, the field intensity should be increased to induce corresponding bioelectric effects. Window effect provides theoretical guidance to choosing reasonable parameters for application of pulsatile electric field in tumor treatment.
Cell Membrane
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physiology
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radiation effects
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Computer Simulation
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Electromagnetic Fields
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Humans
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Membrane Potentials
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physiology
;
radiation effects
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Models, Biological
6.Focusing properties of picosecond electric pulses in non-invasive cancer treatment.
Zaiquan LONG ; Chenguo YAO ; Chengxiang LI ; Yan MI ; Caixin SUN
Journal of Biomedical Engineering 2010;27(5):1128-1132
In the light of optical theory, we advanc an ultra-wideband impulse radiating antenna (IRA) which is composed of an ellipsoidal reflector and a cone radiator. The high-intensity ultra-short electric pulses radiated by IRA can be transferred into the deep target in tissue non-invasively and be focused effectively. With the focused picosecond electric pulses, the organelles (mitochondria) transmembrane potential shall change to collapse under which the tumor cells will be targetly induced to apoptosis, so the method of non-invasive treatment of tumors would be achieved. Based on the time-domain electromagnetic field theory, the propagation characteristics of picosecond electric pulses were analyzed with and without the context of biological tissue, respectively. The results show that the impulse characteristics of input pulse were maintained and the picosecond electric pulses can keep high resolution in target areas. Meanwhile, because of the dispersive nature of medium, the pulse amplitude of the pulses will attenuate and the pulse width will be broadened.
Apoptosis
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radiation effects
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Electric Stimulation Therapy
;
methods
;
Electrodes
;
Electromagnetic Phenomena
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Electroporation
;
methods
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Humans
;
Neoplasms
;
pathology
;
therapy
7.Effects of steep pulsed electric fields on cancer cell proliferation and cell cycle.
Chenguo YAO ; Caixin SUN ; Yan MI ; Lan XIONG ; Lina HU ; Ya HU
Journal of Biomedical Engineering 2004;21(4):546-548
To assess study the cytocidal and inhibitory effects of steep pulsed electric fields (SPEFs) on ovarian cancer cell line SKOV3, the cancer cell suspension was treated by SPEFs with different parameters (frequency, pulse duration, peak value of voltage). Viability rate and growth curves of two test groups (high dosage and low dosage of SPEFs) and one control group were also measured. The DNA contents and cell cycle were analyzed by flow cytometry (FCM). Different dosing levels of SPEFs exerted obviously different effects on cancer cell viability. With the enhancement of each pulse parameter, the viability rate was promoted and the inhibitory effect on the proliferation of treated cells was more evident. The cells exposed to SPEFs grew slower than the control. The ratio of S+G2/M phase cells was decreased, which restrained the DNA synthesis and division, but the ratio of G0/G1 phase cells was increased in the treated groups. It was also indicated that the SPEFs blocked the cell transition from G0/G1 phase to S+G2/M phase. There was a significant difference in cell cycle between treated group and control group (P<0.01). Lethal effects of SPEFs were represented by inhibiting the cancer cell proliferation at the cell level and by influencing the cell cycle at the DNA level.
Adenocarcinoma
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pathology
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Cell Cycle
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radiation effects
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Cell Line, Tumor
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Cell Proliferation
;
radiation effects
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DNA
;
analysis
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Electromagnetic Fields
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Electroporation
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Female
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Flow Cytometry
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Humans
;
Ovarian Neoplasms
;
pathology
;
Pulse
8.The study of apoptosis and mechanism of cells exposed to steep pulse.
Huan LIU ; Liling TANG ; Caixin SUN ; Yan MI ; Chenguo YAO ; Chengxiang LI ; Yuanliang WANG
Journal of Biomedical Engineering 2008;25(3):637-641
This experiment was designed to study the apoptosis and related mechanism of adherent liver tumor cells (SMMC-7721) and adherent normal liver cells (HL-7702) when they were exposed to the steep pulse generated by the steep pulse apparatus for tumor treatment. The results showed that the steep pulse of 200 V could induce tumor cells apoptosis. The tumor cells presented with their apoptosis when they were exposed to the steep pulse from 200 V to 250 V. Laser scanning confocal microscopy was used to make a real time study of calcium burst when the adherent tumor cells were exposed to the steep pulse. The results showed:On the condition of no extracellular Ca2+, the concentration of Ca2+ in tumor cells exposed to the steep pulse of 150 V did not change; the concentration of Ca2+ in tumor cells exposed to the steep pulse of 200 V decreased; the concentration of Ca2+ in tumor cells exposed to the steep pulse of 250 V decreased more evidently. On the condition of existing extracellular Ca2+, the concentration of Ca2+ in tumor cells exposed to the steep pulse of 150 V did not change; the concentration of Ca2+ in tumor cells exposed to the steep pulse of 200 V decreased little; the concentration of Ca2+ in tumor cells exposed to the steep pulse of 250 V reduced little, too. Maybe the change of calcium burst in the tumor cells is the mechanism of apoptosis when cells are exposed to the steep pulse.
Apoptosis
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radiation effects
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Calcium
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metabolism
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Electricity
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Electromagnetic Fields
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Hepatocytes
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cytology
;
pathology
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Humans
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Liver Neoplasms
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metabolism
;
pathology
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Microscopy, Confocal
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Tumor Cells, Cultured
9.Effect of steep pulsed electric fields on survival of tumour-bearing mice.
Chenguo YAO ; Caixin SUN ; Lan XIONG ; Yan MI ; Ruijin LIAO ; Lina HU ; Ya HU
Journal of Biomedical Engineering 2004;21(3):433-435
To investigate the lethal effect of steep pulsed electric fields (SPEFs) on cancer cells and the life-prolonging effect of SPEFs on the survival of tumour-bearing mice, this study was carried out with the use of SPEFs to treat 40 BALB/C mice inoculated by cervical cancer. The lethal effect on cancer cells and the life-prolonging effect on tumour-bearing mice were examined and compared between the experiment group and control group. The survival periods of the experiment group and control group were 52.05 days and 33.03 days, respectively. There was a significant difference in survival curve between the two groups. The results confirmed the inhibitiory effect and lethal effect of SPEFs on cancer cells. SPEFs can prolong the survival period of tumour-bearing mice.
Animals
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Electrodes
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Electromagnetic Fields
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Electroporation
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Female
;
Mice
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Mice, Inbred BALB C
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Neoplasm Transplantation
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Pulse
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Survival Rate
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Uterine Cervical Neoplasms
;
pathology
;
therapy
10.Steep pulse changes the expression of tissue factor in ovarian tumor.
Cong LI ; Li'na HU ; Pingling WANG ; XiaoJing DONG ; Yunshan ZHU ; Chenguo YAO ; Yan MI
Journal of Biomedical Engineering 2008;25(2):402-406
As a micro-wound and target-aimed technology without special limitation, Electric Pulses have been widely researched in tumor treatment and the effects have been demonstrated by a series of experiments, yet the mechanism has not been explained clearly. In this experiment, energy controllable steep pulse (ECSP) was used to treat nude mice bearing human ovarian tumor, and the result was compared with that of the control group. The expression of an important coagulant factor-tissue factor (TF) was analyzed, as TF was also a tumor indicator of invasion and metastasis, the result may indicate the relationship among ECSP, thrombosis and tumor invasion. In this study, to shed light on the mechanism of tumor treatment in electrical fields, nude mice bearing ovarian tumors were randomly divided into the treated group and the untreated group. We treated the former group and took out the tumor instantly. The thrombosis and necrosis of ovarian tumor were observed under microscope. The expression of TF was analyzed by SP immunohistochemistry and RT-PCR. Lower level of TF expression was noticed in the tumor tissue treated by ECSP, and more apparent thrombosis was also seen in this group. The results make it clear that ECSP can accelerate thrombosis and consume coagulant factors such as TF, and that low expression of TF in tumor tissue can cut out the signal paths of tumor invasion. So it is suggested that ECSP may restrain tumor invasion and metastasis by modulating thrombosis.
Animals
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Electric Stimulation Therapy
;
methods
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Electromagnetic Fields
;
Electroporation
;
methods
;
Female
;
Humans
;
Mice
;
Mice, Nude
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Neoplasm Transplantation
;
Ovarian Neoplasms
;
metabolism
;
therapy
;
RNA, Messenger
;
biosynthesis
;
genetics
;
Random Allocation
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Thromboplastin
;
biosynthesis
;
genetics