1.Comparison of optimal parameters of electromagnetic impulse of electrochemotherapy for treatment of S-180 sarcomas
Baoyi WANG ; Hong ZHANG ; Zishu WANG ; Baoqiang XU
Chinese Journal of Tissue Engineering Research 2006;10(21):180-182
BACKGROUND: Electrochemotherapy(ECT) is a new and an efficient approach for the treatment of tumor. The technique is very easy to control and operate and is of little harm to normal tissue. Especially, it is very efficient in curing the superficial tumors. In the treatment process of ECT, the selection and constitute of electromagnetic impulse are the key factors.OBJECTIVE: To use the ECT as a therapeutic method for S-180 sarcomas in Kunming mice and obtain the optimal parameters of electromagnetic impulse in curing.SETTING: Department of Wireless Physics, College of Electronics-Information, Sichuan University DESIGN: Random grouping design and controlled experiment study MATERIALS: This experiment was conducted at the Laboratory of Cells, College of Life Sciences, Sichuan University from January 2003 to May 2004. Totally 106 Kunming mice were randomly divided into 12 groups: voltage 500 V, pulse number 5 and capacitance 6,10 and 14 μF, respectively in 3 groups, with 9 mice in each group;voltage 700 V, pulse number 5 and capacitance 6,10 and 14 μF, respectively in 3 groups, with 9 mice in each group; voltage 900 V, pulse number 5 and capacitance 6,10 and 14 μF, respectively in 3 groups,with 9 mice in each group; voltage 700 V, capacitance 10 μF, pulse number 7 and and 9 respectively in 2 groups , with 8 mice in each group , and control group with 9 mice in it.METHODS: The treatment includes injection of Bleomycin 0.04 mg per one (intraperitoneal injecting into tumors through multiple points), followed by application of electromagnetic impulse using the needles. The treatment was taken every three days andthree times in total. Mice were euthanized 18 days later. Tumor volume was measured before irradiation and 10 and 18 days after irradiation. Tumor volume (mm3)=3.141 59×length×width×height/6. Inhibitory rate(%)=(average tumor volume of the control group-average tumor volume after irradiation)/average tumor volume of control group×100%. The relative growth velocity=tumor volume after irradiation/Tumor volume before irradiation.MAIN OUTCOME MEASURES: Tumor volume; inhibitory rate; relative growth velocity RESULTS: Totally 106 animals were enrolled in the experiment and all of them entered the stage of result analysis. ①When the capacitance was 6 μF, the impulse numbers are 5, the voltage altered [for example the 10th day, when voltage was 500, 700, 900 V, the tumor volume was (66.99±91.17),(62.58±71.83),(78.43±73.91) mm3 , respectively]. The effect was the best when the voltage was 700 V, and was the worst when 900 V).②When the voltage and capacitance were fixed and the pulse numbers altered, for example voltage 700 V and capacitance 10 μF, taking the 10th day as the example , the pulse number was 5, 7 and 9, the tumor volume was (80.66±38.17),(41.33±36.40),(39.86±23.03) mm3, respectively. The inhibitory effect was better with the increase of pulse number, and the best when the pulse number was 9.CONCLUSION: According to experimental results, following parameters of electromagnetic impulse, can be concluded: ①The inhibitory effect is the best when the number of impulse is 5, voltage 700 V, capacitance 6 μF. ②The inhibitory effect increases with the increase of pulse number when the voltage is 700 V and capacitance is 10 μF, and is the best when the pulse number is 9.
2.Progress in electrochemotherapy.
Kong YANG ; Bisong YUE ; Zishu WANG
Journal of Biomedical Engineering 2004;21(6):1043-1046
Electrochemotherapy (ECT) is a novel cancer treatment in which electric pulses (EPs) inducing cell membrane pored (electroporation) are used as a means of delivering antitumor drugs to the cytoplasm of cancer cells. The minimal thresholds of electric field strength of in vitro tumor cell line and tumor tissue are 450-650 V/cm and 400-600 V/cm, respectively. The typical electrical requirement is 600-1300 V/cm, pulse width of 100 micros, 8 pulses, 1 Hz. More than 10 kinds of antitumor drugs have been applied to ECT, in which the most efficacious drug is Bleomycin, and then Cisplatin. Some exciting inhibitory effects on cells in vitro and on solid tumors in clinical trials have been noticed. The factors influencing ECT effects include the electric parameters, diameter of electrode, distribution of electric field lines, size of tumor, model of drugs injection and kinds of drugs. Some questions of ECT are still open, such as the dosages and kinds of drugs for clinical trials, model of drug injection, influence on normal tissues, therapeutic mechanism.
Antibiotics, Antineoplastic
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administration & dosage
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Antineoplastic Agents
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administration & dosage
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Bleomycin
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administration & dosage
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Cisplatin
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administration & dosage
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Electric Stimulation Therapy
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methods
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Electrochemistry
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Electroporation
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methods
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Humans
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Neoplasms
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therapy
3.Inhibitory Effect of siRNA Expression Vector Inhibiting IGF2 Gene on the Proliferation of Hepatoma Cell Line Huh-7
Wei HU ; Shenglan WU ; Kuangjing WANG ; Liangpeng ZHANG ; Zishu PAN ; Shaohui TANG
China Pharmacy 2015;(22):3059-3062
OBJECTIVE:To investigate the inhibitory effect of siRNA expression vector inhibiting human insulin-like growth factor 2(IGF2)gene on the proliferation of hepatoma cell line Huh-7. METHODS:siRNA expression vector pGL3-hAFP-hTERT-siRNA3(“siRNA3”)which inhibited IGF2 gene by dual promoter regulation of recombinant human alpha-foetoprotein(hAFP)and human telomerase reverse transcriptase(hTERT)was transfected into the Huh-7 cell and normal hepatocyte L-02,and then a nega-tive control group(vector pGL3-hAFP-hTERT)and a blank control group were set up. IGF2 mRNA expression was detected by re-al-time fluorescent quantitative polymerase chain reaction 48 h after transfection into the cells in all groups;the activity of the cells by the microplate reader 0,24,48 and 72 h thereafter;and the cell cycle and apoptosis by the flow cytometer 48 h thereafter,and the changes in the protein levels of IGF2,PCNA,Cyclin E2,Cyclin D2,Cdc2 and Bcl-2 in the cell were detected by Western blot. RESULTS:Compared with the negative control group and blank control group,IGF2 mRNA expression in the Huh-7 cell transfected with siRNA3 was obviously weaker;at 48 and 72 h after transfection,the activity of Huh-7 cell signigicantly reduced, Huh-7 cells at G1 phase obviously increased and those at S phase markedly decreased;the occurrence of early,late and total apopto-sis in Huh-7 cells apparently increased,and the protein expression of IGF2,PCNA,Cyclin E2,Cyclin D2,Cdc2 and Bcl-2 in cells significantly weakened,with statistically significance(P<0.01 or P<0.05). No obvious change in the above-mentioned index-es could be found in L-02 cells transfected with siRNA3 expression vector (P>0.05). CONCLUSIONS:siRNA which inhibited IGF2 gene by dual promoter regulation of recombinant hAFP and hTERT can specially inhibit IGF2 gene expression and the prolifer-ation of Huh-7 cells,which may be involved with down-regulated protein expression of cell proliferation-associated gene PCNA, cell cycle control-associated genes Cyclin E2,Cyclin D2 and Cdc2 and apoptosis regulation-associated gene Bcl-2 as a result of down-regulated IGF2 mRNA expression and protein expres-sion.
4.Inhibitory effect of electrochemotherapy on S180 tumor growth and angiogenesis and the possible mechanism.
Fangdong ZOU ; Hong LI ; Zishu WANG ; Bisong YUE ; Qin GENG ; Baoyi WANG
Journal of Biomedical Engineering 2004;21(6):888-892
This study evaluated the effects of electric pulses combined with antitumor drugs on S180 tumor cells. It was found that the growth of S180 sarcoma was inhibited with a maximum inhibition ratio of 95.5% after the use of electric pulses in combination with the injection of bleomycin (BLM), and the blood vessels of tumor were obviously fewer than those of the untreated tumor in vivo. The mitochondria of S180 tumor cells were swollen after the use of electric pulses in combination with adriamycin. The results showed that electrochemotherapy has evident inhibitory effect on the growth of S180 sarcoma and the mechanism may involve the suppression of tumor angiogenesis and changes in the ultrastructures of tumor cells.
Animals
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Antimetabolites, Antineoplastic
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administration & dosage
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Bleomycin
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administration & dosage
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Combined Modality Therapy
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Electric Stimulation Therapy
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methods
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Electrochemistry
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Mice
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Neovascularization, Pathologic
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prevention & control
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Sarcoma 180
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blood supply
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therapy
5.Electrochemotherapy and its mechanism for sarcoma of KM mice.
Kong YANG ; Miao HE ; Zishu WANG ; Fangdong ZOU ; Bisong YUE
Journal of Biomedical Engineering 2005;22(5):914-917
In this paper are analyzed the effect of electrochemotherapy and its mechanism. The favorable parameter of electric pulses (EP) was studied in vitro using the S-180 cells exposed to various EP. After the tumor model was copied, the tumor-bearing mice were randomly divided into four groups: control, chemotherapy, electrotherapy, and electrochemotherapy. The tumor inhibitory ratio, the cure ratio and the level of oxygen free radicals (OFR) were determined. The inhibitory ratio and cure ratio of electrochemotherapy group were significantly higher than those in the chemotherapy, electrotherapy and control groups (P < 0.05). The injury of OFR was decreased while the immunological competence was increased. The mechanism of electrochemotherapy may be related with the enhancement of cell membranepermeability, the depression of drug resistance, the improvement of immunological competence, and so on.
Animals
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Antineoplastic Agents
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administration & dosage
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Bleomycin
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administration & dosage
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Drug Delivery Systems
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methods
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Electric Stimulation Therapy
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methods
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Electrochemistry
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Electroporation
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methods
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Mice
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Random Allocation
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Sarcoma 180
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therapy
6.An experiment to study the treatment of sarcomas by electroporation.
Hong ZHANG ; Baoyi WANG ; Haichuan CHEN ; Zishu WANG ; Kong YANG ; Jingru SUN
Journal of Biomedical Engineering 2004;21(1):69-71
In this paper is reported a new approach for the treatment of sarcoma--electroporation therapy. Electroporation can accelerate pharmacal molecules into cytoplasm by transient electromagnetic pulses. We have utilized the phenomenon of electroporation treating the S-180 sarcomas in the hind legs of the Kunming mice by intratumoral injection of anti-tumor agent at low dose. From the experiment, we learned that this approach can bring about remarkable effect. The technical procedure is easy to do and easy to control. Especially, it is useful in curing the flat tumor and has little untoward side effect. It deserves to be recommended as a new approach to treating the tumor in clinics.
Animals
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Antineoplastic Agents
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therapeutic use
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Apoptosis
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drug effects
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Cell Line, Tumor
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Cyclophosphamide
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therapeutic use
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Electrochemotherapy
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methods
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Mice
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Neoplasm Transplantation
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Sarcoma 180
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drug therapy
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pathology
7.Study of high-intensity electric pulse inhibited sarcoma for improving antitumor drug effect.
Hong LI ; Zishu WANG ; Bisong YUE ; Fangdong ZOU ; Kong YANG ; Jingru SUN ; Baoyi WANG ; Hong ZHANG ; Haichuan CHEN ; Guo YANG
Journal of Biomedical Engineering 2003;20(4):612-614
This article reports the experiment studies on treating the S-180 sarcomas of KM mice with high-intensity electric pulse and antitumor drug (cyclophosphamide). The results showed that the experimental group of electric field combined with drug has the best effect on tumor, compared with the control group. In addition, electric field can inhibit the formation of vas Capillaries and decrease the supply of nutrition for tumor cell. In conclusion, electric field has inhibited the growth of tumor.
Animals
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Antineoplastic Agents
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therapeutic use
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Combined Modality Therapy
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Cyclophosphamide
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administration & dosage
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Electric Stimulation Therapy
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methods
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Injections, Intralesional
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Mice
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Sarcoma 180
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pathology
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therapy
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Treatment Outcome
8.Enhancing the cytotoxicity of antitumor drugs through electromagnetic pulses.
Guo YANG ; Baoyi WANG ; Hong ZHANG ; Haichuan CHEN ; Zishu WANG ; Kong YANG ; Jingru SUN
Journal of Biomedical Engineering 2003;20(3):497-499
We chose Hela cells as research object and studied the cytotoxicity generated by cyclophosphamide, an antitumor drug, after cell electroporation by the use of electromagnetic pulses. Comparison between the electroporation group and the contrast group revealed the greatly enhanced cytotoxicity of the electroporation group, indicating that under some conditions electromagnetic pulses can enhance the cytotoxicity of antitumor drugs. The results of this study provide reliable evidences and a feasible approach for clinical treatment of tumor.
Antineoplastic Agents
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pharmacology
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Apoptosis
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Cell Survival
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drug effects
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Cyclophosphamide
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pharmacology
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Drug Screening Assays, Antitumor
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Electromagnetic Phenomena
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Electroporation
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methods
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HeLa Cells
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Humans
9.Exploration on the application of standardization into the construction of modern hospital management system
Haihong YUAN ; Zishu WANG ; Yafang LI ; Ziyuan WANG
Chinese Journal of Hospital Administration 2022;38(12):877-881
Beijing Union Medical College Hospital applied the standardized management theory, focused on establishing a scientific and standardized system management mechanism, and carried out the exploration of modern hospital management standardization system construction through systematic practice. With the application of the principles of simplification, unification, coordination, optimization and competition of standardization into the construction of modern hospital management system, the basic method for the construction of standardization system was proposed based on standard system management theory. It included the standardization of system architecture, system construction process and system management mechanism. Its purpose was to effectively address the problems of the lack of systematicness, practicality and sustainability in the construction of hospital system. Importantly, the value and vitality of a system depended on its sustainable development. According to the standard system management principle of system effect, structural optimization, orderly development and circular control, the optimization of hospital system could be promoted, which is worth further practice and exploration.
10.Effects of apatinib in the treatment of advanced hepatocellular carcinoma associated with hepatitis B
Wei ZHANG ; Fang SU ; Zishu WANG
Journal of International Oncology 2019;46(1):27-31
Objective To observe the effects of apatinib in the treatment of advanced hepatocellular carcinoma associated with hepatitis B. Methods The clinical data of 72 patients with advanced hepatocellular carcinoma associated with hepatitis B admitted to the First Affiliated Hospital of Bengbu Medical College from January 2015 to May 2017 were retrospectively analyzed. Among them,37 patients were treated with apatinib once a day,as apatinib group;35 patients were treated with FOLFOX4(oxaliplatin + calcium folinate + 5-fluorouracil)palliative chemotherapy,as FOLFOX4 group. The objective response rate(ORR),disease con-trol rate(DCR),serum alpha fetal protein(AFP),improvement of clinical symptoms,Karnofsky functional status(KPS)score improvement rate,median progression-free survival(PFS),median overall survival(OS), and the incidence of adverse reactions from both groups were contrastively analyzed. Results The ORR of apa-tinib group(27. 03% ,10 / 37)was higher than that of FOLFOX4 group(17. 14% ,6 / 35),and DCR (64. 86% ,24 / 37)was also higher than that of FOLFOX4 group(48. 57% ,17 / 35). However,there were no significant difference in ORR and DCR between the two groups(χ2 = 1. 017,P = 0. 313;χ2 = 1. 948,P =0. 163). After 16 weeks of treatment,serum AFP of apatinib group[(280 ± 20)ng/ ml]was significantly lower than that in FOLFOX4 group[(450 ± 20)ng/ ml,t = 36. 049,P < 0. 001]. Improvement rate of KPS score(86. 49% ,32 / 37)was significantly more than that of FOLFOX4 group(57. 14% ,20 / 35;χ2 = 7. 720, P = 0. 006). Improvement rate of clinical symptoms(72. 97% ,27 / 37)was significantly more than that of FOLFOX4 group(42. 86% ,15 / 35;χ2 = 6. 712,P = 0. 010). The mean PFS of apatinib group was 6. 2 months,which was significantly longer than that of FOLFOX4 group(2. 8 months,χ2 = 4. 815,P = 0. 028). The mean OS of apatinib group was 10. 9 months,which was significantly longer than that of FOLFOX4 group (6. 6 months,χ2 = 26. 429,P < 0. 001). In apatinib group,the main adverse reactions were hypertension, proteinuria and hand-foot syndrome;and in FOLFOX4 group,the main adverse reactions were leukopenia,neu-rotoxicity and liver function damage. Moreover,the adverse reactions in both groups were mostly 1 or 2 grade, which could be relieved or improved through symptomatic treatment. Conclusion Apatinib is safe and effective in the treatment of advanced hepatocellular carcinoma associated with hepatitis B. It can significantly prolong the life of patients and improve the quality of life and the clinical symptoms of patients.