陡脉冲抗肿瘤效应的实验研究和机理分析
|
摘要
癌症是威胁人类生命的主要疾病，人们对肿瘤疗法的研究不仅限于对肿瘤组织的杀伤和抑制作用，在抗肿瘤血管效应、淋巴管效应、免疫效应和诱导凋亡效应等方面也开展着深入的研究。
陡脉冲疗法是本课题组开创的一种新的癌症物理治疗方法，在大量的离体、细胞和动物实验中已证实对肿瘤组织的有效杀伤和抑制作用。本文完成了上述四大效应的实验研究，观察到：(1)陡脉冲可破坏肿瘤营养血管和毛细淋巴管，使其栓塞、凝固性坏死，并下调血管内皮细胞生长因子VEGF-A和促淋巴管再生因子VEGF-C的水平，具有抗血管和淋巴管再生的作用，从而减少了残留、存活的肿瘤细胞经淋巴管途径转移到其他部位的可能性，防止肿瘤增生和转移。(2)陡脉冲能明显增强大鼠脾淋巴细胞的增殖反应和NK细胞的活性。具有活化巨噬细胞，增强其细胞毒功能并促进其分泌白细胞介素IL-4、IFN-γ和肿瘤坏死因子TNF-α的作用。导致脾淋巴细胞产生细胞因子的活性增强，诱导荷瘤宿主体内的免疫应答，有助于提高机体的免疫功能。(3)陡脉冲能抑制细胞增殖，改变细胞周期，下调Bcl-2／Bax表达的比值，造成细胞器内促凋亡因子的释放，诱导细胞凋亡。
同时，本文深入分析陡脉冲对肿瘤细胞的杀伤和诱导凋亡的机制。(1) 借助ANASYS电磁场分析软件，用有限元方法仿真计算陡脉冲在均匀介质中的电场强度分布，并与大白兔肝脏实验相结合，确定能有效杀伤肿瘤组织的电极尺寸和间距、阵列布置方式、脉冲峰值等因素，寻找兔肝组织不可逆性电击穿的电场强度阈值，最终有效控制陡脉冲的杀伤范围，实现最佳疗效。(2) 建立单细胞模型，推导陡脉冲电场作用下单细胞极点处的跨膜电位，明确跨膜电位按指数衰减的变化规律；分析了脉冲宽度与跨膜电位的关系，以及电穿孔过程中细胞膜电导率和细胞结构变化对跨膜电位的影响，分析陡脉冲导致细胞不可逆性电击穿的机制。(3) 通过傅立叶频谱分析，推证陡脉冲波形的选择依据。证实陡脉冲强化超高频效应，有可能诱导细胞凋亡，从而防止细胞膜破损后细胞器游离，引起肿瘤转移或复发；而且脉宽越窄，超高频杀伤效应越强，为脉冲特征参数的选择提供依据。
Cancer is the main disease which has been threatening human life, dozens of malignant tumor therapies come forth with their own dominance and deficiency. Today, the research is not limit to their cytocidal and inhibitory effect on tumor cell, but the anti-tumor effect on vessel, lymphatic, immunity system and apoptosis abduction.Steep pulse therapy (SPT) is a new physical therapy initiated by us. In forepassed experiments in cell line, BALB/c mice and tumor in vitro, we confirmed adequately its cytocidal and inhibitory effect on tumor cell. In this paper, experimental studies were developed from these four anti-tumor effects, they become conscious as follows: (1) Under the steep pulse field, tiny blood and lymphatic vessels were jammed or destroyed, the expression of VEGF-A and VEGF-C was descent, those mean that SPT can detain rudimental tumor cell transferring to other part by the way of blood and lymphatic vessel, and prevent tumor from proliferation and transfer. (2 )SPT can the proliferation of spleen lymphatic cell, arouse the activity of NK cell and huge-spit cell, enlarge latter secretion of IL-4 IFN and TNF-and then strengthen immunity function of organism (3) SPT can prohibit cellular proliferation, change cellular cycle, and induce cellular apoptosis by descending the expression ratio of Bcl-2/Bax to release the apoptosis factors,.Moreover, this paper analyses SPT's mechanism in killing tumor cell and inducing cellular apoptosis. (1) With ANASYS electromagnetic field analysis software and finite element method (FEM), electric field intensity (EFI) distribution in symmetrical medium is calculated. Combined with rabbit liver experiment, we find the relationship between electrode size distance between different electrode and electrode array arrangement and killing efficiency, select the EFI threshold leading liver cell to irreversible breakdown. (2) Single cell model is built to calculate the transmembrane potentials(TMP) in polar points. TMP curve follows exponential attenuation rule, the more narrow pulse width is, the faster attenuation pace is. During the electroporation, membrane conductivity raises, cellular radius prolongs, membrane thickness is thinner, because of these change, ascend time of TMP is shortened and attenuation pace slows down. (3) Compared with square pulse, SPT owns the more superior ultra high frequency (VHF) killing effect on organelle after frequency spectrum analysis, which means that SPT can induce cellular apoptosis, prevent organelle drifting away from destroyed membrane, stop the tumor transferring or recurring. The more narrow pulse width is, the higher killing effect of VHF part is. With these results, we can control freely the killing effect of SPT in proper scope with the best curative effect.
陡脉冲疗法是本课题组开创的一种新的癌症物理治疗方法，在大量的离体、细胞和动物实验中已证实对肿瘤组织的有效杀伤和抑制作用。本文完成了上述四大效应的实验研究，观察到：(1)陡脉冲可破坏肿瘤营养血管和毛细淋巴管，使其栓塞、凝固性坏死，并下调血管内皮细胞生长因子VEGF-A和促淋巴管再生因子VEGF-C的水平，具有抗血管和淋巴管再生的作用，从而减少了残留、存活的肿瘤细胞经淋巴管途径转移到其他部位的可能性，防止肿瘤增生和转移。(2)陡脉冲能明显增强大鼠脾淋巴细胞的增殖反应和NK细胞的活性。具有活化巨噬细胞，增强其细胞毒功能并促进其分泌白细胞介素IL-4、IFN-γ和肿瘤坏死因子TNF-α的作用。导致脾淋巴细胞产生细胞因子的活性增强，诱导荷瘤宿主体内的免疫应答，有助于提高机体的免疫功能。(3)陡脉冲能抑制细胞增殖，改变细胞周期，下调Bcl-2／Bax表达的比值，造成细胞器内促凋亡因子的释放，诱导细胞凋亡。
同时，本文深入分析陡脉冲对肿瘤细胞的杀伤和诱导凋亡的机制。(1) 借助ANASYS电磁场分析软件，用有限元方法仿真计算陡脉冲在均匀介质中的电场强度分布，并与大白兔肝脏实验相结合，确定能有效杀伤肿瘤组织的电极尺寸和间距、阵列布置方式、脉冲峰值等因素，寻找兔肝组织不可逆性电击穿的电场强度阈值，最终有效控制陡脉冲的杀伤范围，实现最佳疗效。(2) 建立单细胞模型，推导陡脉冲电场作用下单细胞极点处的跨膜电位，明确跨膜电位按指数衰减的变化规律；分析了脉冲宽度与跨膜电位的关系，以及电穿孔过程中细胞膜电导率和细胞结构变化对跨膜电位的影响，分析陡脉冲导致细胞不可逆性电击穿的机制。(3) 通过傅立叶频谱分析，推证陡脉冲波形的选择依据。证实陡脉冲强化超高频效应，有可能诱导细胞凋亡，从而防止细胞膜破损后细胞器游离，引起肿瘤转移或复发；而且脉宽越窄，超高频杀伤效应越强，为脉冲特征参数的选择提供依据。
Cancer is the main disease which has been threatening human life, dozens of malignant tumor therapies come forth with their own dominance and deficiency. Today, the research is not limit to their cytocidal and inhibitory effect on tumor cell, but the anti-tumor effect on vessel, lymphatic, immunity system and apoptosis abduction.Steep pulse therapy (SPT) is a new physical therapy initiated by us. In forepassed experiments in cell line, BALB/c mice and tumor in vitro, we confirmed adequately its cytocidal and inhibitory effect on tumor cell. In this paper, experimental studies were developed from these four anti-tumor effects, they become conscious as follows: (1) Under the steep pulse field, tiny blood and lymphatic vessels were jammed or destroyed, the expression of VEGF-A and VEGF-C was descent, those mean that SPT can detain rudimental tumor cell transferring to other part by the way of blood and lymphatic vessel, and prevent tumor from proliferation and transfer. (2 )SPT can the proliferation of spleen lymphatic cell, arouse the activity of NK cell and huge-spit cell, enlarge latter secretion of IL-4 IFN and TNF-and then strengthen immunity function of organism (3) SPT can prohibit cellular proliferation, change cellular cycle, and induce cellular apoptosis by descending the expression ratio of Bcl-2/Bax to release the apoptosis factors,.Moreover, this paper analyses SPT's mechanism in killing tumor cell and inducing cellular apoptosis. (1) With ANASYS electromagnetic field analysis software and finite element method (FEM), electric field intensity (EFI) distribution in symmetrical medium is calculated. Combined with rabbit liver experiment, we find the relationship between electrode size distance between different electrode and electrode array arrangement and killing efficiency, select the EFI threshold leading liver cell to irreversible breakdown. (2) Single cell model is built to calculate the transmembrane potentials(TMP) in polar points. TMP curve follows exponential attenuation rule, the more narrow pulse width is, the faster attenuation pace is. During the electroporation, membrane conductivity raises, cellular radius prolongs, membrane thickness is thinner, because of these change, ascend time of TMP is shortened and attenuation pace slows down. (3) Compared with square pulse, SPT owns the more superior ultra high frequency (VHF) killing effect on organelle after frequency spectrum analysis, which means that SPT can induce cellular apoptosis, prevent organelle drifting away from destroyed membrane, stop the tumor transferring or recurring. The more narrow pulse width is, the higher killing effect of VHF part is. With these results, we can control freely the killing effect of SPT in proper scope with the best curative effect.
引文
[1] 彭黎明．王曾礼著．细胞凋亡的基础与临床．人民卫生出版社．2000年7月．第1版
[2] 姚陈果．可控陡脉冲对恶性肿瘤细胞不可逆性电击穿的实验和机理研究．博士学位论文．重庆大学．2003年6月
[3] 汤钊猷著．现代肿瘤学．上海．上海医科大学出版社，1993年
[4] 于洪升．费从合．沈方臻等．低剂量辐射联合环磷酰胺对肿瘤细胞凋亡、细胞周期以及骨髓增殖的影响．中华放射医学与防护杂志．2004．24(2)：117-119
[5] 林永丽．高军．低剂量辐射对机体免疫效应的研究现状．中华航海医学与高气压医学杂志 2004．11(1)：53-55
[6] 刘树铮．刘伟宏．齐进．低剂量辐射增强免疫的细胞机制．中华放射医学与防护杂志．1992．12：299-305．
[7] 刘树铮．张迎春．苏旭．低剂量辐射对TCR/CD3和CD25在小鼠胸腺细胞浆膜表达的影响．中国病理生理杂志．1995．11：2-5．6．
[8] Ipetite C. Wchter T. Sge E. et al. Use of the Ikline comet assay to detect DN repair deficiencies in human fibroblasts exposed to UVC. UVB. UV and gamma-rays. Int. J Radit Biol. 1996. 69: 359-369.
[9] 潘敏求．黎月恒．陈宁．中华肿瘤治疗大全[M]．河北科学技术出版社．1996．
[10] 李向华．李慧．现代肿瘤医学．2004年2月．12(1)：54-55．
[11] 郭海燕．刘贺之．郭晓明等．花灵香云胶囊对小鼠免疫功能的调节及对肿瘤的抑制作用．解放军药学学报．2004．20(1)：5-8
[12] Tsukiok Y. Mtsumur Y. Hmguchi T. et al. Complete response chieved following ministration of S-1 in patient with drenl gland metastsis of 5FU resistant gastic cancer: case report [J]. Jpn J Clin Oncol. 2001. 31(9): 450-453.
[13] Osugi H. Tkd N. Tkemur M. et al. Oral fluoropy rimidine nticancer drug TS-1 for gastric cancer patients with peritonel dissemintion [J]. Oncol Rep. 2002. 9(4): 811-815.
[14] I whshi M. Nkmori M. Tni M. et al. Complete response of highly dvanced gastric cancer with peritonel dissemintion ofter new combined chemotherpy of S-1 nd low dose cisplatin: report of case [J]. Oncology. 2001. 61(1): 6 22.
[15] 林世寅．李瑞英．现代肿瘤热疗学．北京．学苑出版社．1997．
[16] 王智彪．顾美礼．凌萝达等．一种用于超声波生物学效应实验研究的聚能器．重庆医科大学学报．1994．19(4)：298～300．311．
[17] 涂刚．乔天愚．何士元等．高强度聚焦超声治疗兔肾VX2肿瘤的实验研究．中华泌尿外科杂 志．1999．20(8)：456～458．
[1
[18] 邹建中．伍烽．李佩希等．超声监控超声聚焦刀治疗肝癌及疗效评价研究．中国超声医学 杂志．2000．16(10)：766～768．
[19] 伍烽．王智彪．白晋等．高强度聚焦超声体外治疗肝肿瘤的剂量学研究．中华物理医学与康复杂志．2000．22(5)：267～269．
[20] Yang R. Sanghvi NT. Rescorla FJ. et al. Liver vancer ablation with extracorporeal high intensity focused ultrasound [J]. Eur Urol. 1993; 23(suppl 1): 17.
[21] Vazey S. Martin R. Schmiedl U. et al. Liver hemostasis using high intensity focused ultrasound [J]. Ultrasound Med Biol. 1997. 23(9): 1413.
[22] 吴琴．曹友德．伍烽．王智彪．HIFU对兔VX_2乳腺肿瘤毛细淋巴管的破坏效应．临床超声医学杂志．2002，4(1)：1-3．
[23] Yang R. Reilly C R. Rescorla F J. et al. Effect of high intensity focused ultrasound in the treatment of experimental neruro blastoma. J Pediatr Surg. 1992. 27: 246—251.
[24] 贾瑞鹏．周性明．张忠林等．高能聚焦超声对小鼠移植性膀胱肿瘤的杀伤效应及免疫功能的影响．中华泌尿外科杂志．1998年6月．19(6)：270-272．
[25] 武文森．韩月明．尹克铮等．小鼠膀胱移行细胞癌细胞株的建立及其生物学特性．南京铁道医学院学报．1994．13：132-134．
[26] 伍烽．王智彪．陈文直等．高强度聚焦超声破坏体外原发性肝癌的病理学观察[J]．中华肿瘤杂志．2001．23(3)：2208．
[27] 伍烽．陈文直．白晋等．高强度聚焦超声治疗原发性肝癌的初步临床研究[J]．中华超声影像学杂志．1999．8(4)：213．
[28] 吴昱．姜南艳．程庆书等．射频治疗肺癌患者免疫淋巴细胞检测．第四军医大学学报．2004．25(7)：671-672．
[29] 张沪生．叶晖．张传清等．超低频脉冲磁场抑制癌瘤和提高细胞免疫功能的实验研究．中国科学(C辑)．1997．27(2)：173～178．
[30] 曾繁清．郑从义．张新晨等．超低频脉冲磁场诱导癌细胞凋亡和抑制癌细胞生长实验研究．中国科学(C辑)．2001．31(5)：453～457．
[31] 杨逢瑜．磁场对肿瘤细胞的抑制作用．生物电磁．2004．1：1-4．
[32] 曹晓哲．赵梅兰．王德文等．高能电磁．脉冲诱导肺癌细胞株GLC-82凋亡的研究．癌症．2002．21(9)：929-933．
[33] 曹晓哲．赵梅兰．王德文．电磁脉冲诱导肺癌细胞株A549凋亡的研究．细胞与分子免疫学杂志．2002．18(3)：285-289．
[34] 辛育龄．癌症的电化学治疗．北京．人民卫生出版社．1995．
[35] 刘继彦．魏于全．罗锋等．恶性肿瘤电化学治疗前后细胞周期分析及病理学改变．华西医科大 学学报．2000．31(1)：104～106．
[3
[36] 唐步坚．李力．巴卡里·卡马拉等．电化学治疗对宫颈癌杂志Bcl-2、p53、C-myc和Rf基因表达的影响．实用肿瘤学．1998年．12(3)：209-210．
[37] 阎永家．超晓航．吴文．细胞凋亡与癌基因．生物化学生物进展．1994．21(3)：222-224
[38] 王慧．摩若然．宫颈癌中C-erB2、C-myc、P53基因变化及临床意义．国外医学妇产科学分册．1996．23(5)：272-281．
[39] J. H. Sale and W. A. Hamilton. Effects of electric fields on microorganizms I killing of bacteri and yests. Biochimic et Biophysical ct. 1967. 118: 781-788.
[40] E. Neumnn and K. Rosenheck. Permebility changes included by electrical pulse in vesicular membranes. Journal of Membrane Biology. 1972. 10: 279～290.
[41] K. J. Kinosit and T. Y. Tsong. Voltage includes formation and hemolysis of human erythocytes. Biochimic et Biophysical ct. 1979. 471: 227～242.
[42] G. Hofmann and G. Evans. Electronic genetic-Physicl and biological aspects of cellular electromanipulation. IEEE Engineering of Medical Biology. 1986. 5(4): 6～25.
[43] J. C. Weaver. Electroporation: dramatic. nonthermal electric field phenomenon. In Proceedings of the First World Congress for Electricity and Magnetism in Biology and Medicine. Lke Buen Vist. Florid. academic Press. 1992.
[44] Lluis M. Mir. Stephne Orlowski. Mechanisms of Electrochemotherapy. dvnced Drug Delivery Reviews. 1999. (35): 107-118.
[45] Richrd Heller. Richrd Gilbert. Mrk J. Jroszeski. Clinical applictions of Electrochemotherapy. advanced Drug Delivery Reviews. 1999. (35): 119-129.
[46] L. M Mir. Electrochemotherapy polentition of ntitumor effect of bleomycin by electric pulses. European Journal of Cancer. 1991. 27(1): 68～72.
[47] W. R. Pnje. M. P. Hier. G. R. Grmn. et al. Electroporation therapy of head and neck cancer, nn. Otol. Rhinol. Lryngol. 1998. 107: 779～785.
[48] W. R. Panje. M. P. Hier. G. R. Garman. et al. Electroporation therapy of head and neck cancer. Ann. Otol. Rhinol. Laryngol. 1998. 107: 779～785.
[49] M. M. Kekez. P. Svic. B. F. Johnson. Contribution to the biophysics of lethal effects of electric field on microorganisms. Biochimic et Biophysic ct. 1996. 79～88.
[50] L H Rmirez. Electrochemotherapy on liver tumors in rabbits. British Journal of Cancer. 1998. 77(12). 2104～2111.
[51] 孙敬儒．王子淑．刘一勇等．电穿孔诱发细胞凋亡和提高抗癌药物细胞毒性的研究．四川大学学报(自然科学版)．2002．39增刊：170-174．
[52] Sersa G. Kotnik V. Ceramzr M. et al. Electrochemotherapy with bleomycin in S-1 tumor-bearing mice natural resistance and immune responsiveness. anticancer Drugs. 1996; 7(7): 785-791.
[5
[53] Miyazki S. Gunji Y. Mtsubr H. et al. Possible involvement of antitumor immunity in the eradiction of colon 26 induced by low-voltage electrochemotherapy with bleomycin Surg Tody. 2003; 33(1): 39-44.
[54] Engstrom PE Medical applications of electroporation. IEEE Transactions on Plasma Science. 2000. 28 (1): 206-223.
[55] 郭伟剑．宋明志．于尔辛．恶性肿瘤的电化学疗法．国外医学肿瘤学册．1996．23 (6)：349-351．
[56] DeBruin K. Krassowska W. Modeling electroporation in single cell Ⅰ Effects of field strength and rest potential [J]. Biophys-J. 1999. 77(3): 1213. [48]Ktherine. Debrnin. and Krassowska. Modeling electroporation in single cell[J]. Biophysical. 1999. 77: 1225.
[57] Anna O. Bilska, Katherine A. DeBruin, Wanda Krassowska. Theoretical modeling of the effects of shock duration, frequency, and strength on the degree of electroporation. Bioelectrochemistry, 2000, 51, 133-143
[58] Okino M. Optimal electric condictions in electrical impulse chemotherapy. Japanese Journal of Cancer Research. 1992. 83(10): 1095～1101.
[59] Ev Nilsson. Jk Berendson. Edurdo Fontes. Development of Dosge Method for Electrochemical Treatment of Tumours: Simplified Mathematical Model. Bioelectrochemistry and Bioenergetics. 1998. 42 (7): 11-18.
[60] Ev Nilsson. Jk Bereodson. Edurdo Fontes. Electrochemical Treatment of Tumours: Simplified Mathematical Model. Journal of Electronlytical Chemistry. 1999. (460): 88-99.
[61] Ev Nilsson. Edurdo Fontes. Mthematical Modeling of Physicochemical Reactions and Transport Processing Occurring round Platinum Cathode during the Electrochemical Treatment of Tumours. Bioelectrochemistry. 2001. (53): 213-224.
[62] Kostadin Brandiaky. Ivan Daskalov. Electrical Field and Current Distributions in Electrochemotherapy. Bioelectrochemistry and Bioenergetics. 1999. (48): 201-208.
[63] Dr. D. Rabussay and Dr. S. Kornhauser. Frequenfly Asked Questions about Electroporation Therapy. American Journal of Electromedicine. 1998: 64～68.
[64] Dmijn Miklvcic. Dejn Semrov. Hlim Mekid. Lluis M. Mir. Validated Model of in Vivo Electric Field Distribution in Tissues for Electrochemotherapy and for DN Electrotransfer for Gene Therapy. Biochimic et Biophysic ct. 2000. (1523): 73-83.
[65] Julie Gehl. Thyge H. Sφrensen, Kurt Nielsen. In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution. Biochimica et Biophysica Acta. 2000. (1428). 233-240.
[66] Belehradek J Jr. Orlowski S. Ramirez LH. et al. Electropermeabilization of cells in tissues assessed by the qualitative and quantitative electroloading of bleomycin.Biochim Biophys Acta,1994.1190{l).155-163.
[67] Sukhendu B.Dev.Dietmr P.Rabussy.Georg Wider.et al.Medical applications of Electroporation IEEE Transactions On Plasma Science.Vol.28.No.1.FEBRURY 2000:206-223.
[68] D.Semrov.D.Miklvcic.Calculation of the Electrical Parameters in Electrochemotherapy of Solid Tumours in Mice.Computers in Biology and Medicine. 1998. (28): 439-448.
[69] H.P.Schwan.Electrical properties of tissue and cell suspensions, adv. Biol. Med. Phys. 1957. 5:147-209.
[70] Tjitske Heida*.Joost B.M.Wgenr.Wim L.C.Rutten .Investigating Membrane Breakdown of Neuronl Cells Exposed to Nonuniform Electric Fields by Finite-Element Modeling nd Experiments.IEEE Trnsctions On Biomedicl Engineering.2002.49910:1195.
[71] Dev, S.B.Rabussay, D.P.Widera, GHofmann, GA. Medical applications of electroporation.IEEE Transactions on Plasma Science. 2000.28 (1): 206 - 223.
[72] Lee RC. Electrical injury mechanisms: Electrical breakdown of cell membranes. Plast Reconstr Surg. 1987.80:672-679.
[73] kevin T P.Jmes C W.Transient qaueous pores in bilayer membranes: statistical theory{J}.Bioelectrochem Bioenergetics.l986.15:211-227.
[74] Bier M.Hnner SM.Cvdy DJ.et al.Kinetics of sealing for transient electropores in isolated mammlin skeletal muscle cells.Bioelectromgneics.l999.20(3): 94.
[75] J.Teissie .M.P.Rols.an experimental evalution of the critical potential difference inducing cell membrane electropermeabiliztion.Biophys.J.65 (1993): 409-413.
[76] T.Y.Tsong.Electroporation of cell membrane.Biophys.J.60(1991):297-306.
[77] James C.Weaver.Electroporation of Biological Membranes from Multicellular to Nano Scales.IEEE Transactions on Dielectrics and Electrical Insultion.2003.10(5) :754-768.
[78] Gorzd Pucihr.Tdej Kotnik.Masa Kanduser .et al.The influence of medium conductivity on electorpermeabiliztion and survival of cells in vitro.Bioelectrochemistry 54(2001):107-115.
[79] J.C.Weaver.Electroporation: A dramatic.nonthermal electric field phenomenon.In Proceedings of the First World Congress for Electricity and Magnetism in Biology and Medicine.Lake Buena Vista.FloridaAcademic Press.1992.
[80] E.Neumnn..E.Sowers and C.Jordan.Eds.Electroporation and Electrofusion in Cell Biology.New York.Plenum.1989.
[81] K.H.Schoenbch.mr.bou-Ghzl.Terry.Vithoulks.et al.Effect of pulsed electrical fields on biological cells.Digest of Technical Papers-IEEE Interntional Pulsed Power Conference.l997.(1) 2: 73-78.
[82] Sersa G. Tumor blood flow change induced by application of electrical pulses. European Journal of Cancer. 1999. 35(4): 672～677.
[83] Stephen J. Beebe. Pul Fox. Lur Rec. et al. Nanosecond Pulsed Electric Field Effects On Human Cells. 20012. 652-656.
[84] Stephen J. Beebe. P. M. Fox. L. J. Rec. et al Nanosecond Pulsed Electric Field (nsPEF) Effects on Cells and Tissues: apoptosis Induction and Tumor Growth Inhibition. IEEE TRANSACTIONS ON PLASMA SCIENCE. 2002. 30(1): 286-292.
[85] Taylor, M. J. Measurement of the properties of plasma from ETC capillary plasma generators. IEEE Transactions on Magnetics. 200137(1): 194 - 198.
[86] Bischof, J. C. Bhowmick, S.; Lulloff, L. et al Thermal therapy in the Dunning AT-1 prostate tumor using a wet electrode RF probe [Engineering in Medicine and Biology, 1999. 21st Annual Conf. and the 1999 Annual Fall Meeting of the Biomedical Engineering Soc.] BMES/EMBS Conference, 1999. Proceedings of the First Joint. 1999. 2: 1282
[87] Lee RC. Electrical injury mechanisms: Electrical breakdown of cell membranes. Plast Reconstr Surg. 1987. 80: 672～679.
[88] E. Stephen Buescher. Krl H. Schoenbch.. Effects of Submicrosecond. High Intensity Pulsed Electric Fields on Living Cells_Intracellular Electromanipulation. IEEE Transactions on Dielectrics and Electrical Insulation Vol.10.No.5; October 2003.788-794.
[89] 吴扬兰．王远亮．肿瘤新生血管抑制剂——血管抑素和内皮抑素．重庆大学学报．2003．26(10)：72-75．
[90] 王杰．田晓峰．韩雪春．肿瘤组织中的血管生成及抗血管治疗医师进修杂志(外科版)．2003．26(11)：1-3．
[91] 李军．俞兰．VEGF、肿瘤血管再生及抗肿瘤血管生成治疗．医师进修杂志(外科版)2004．27(4)：52-54．
[92] Folkman M J. Cotrans. Relation of vascular proliferation to tumor growth [J]. Int Rev Exp Pathol. 1976. 16: 207-215.
[93] Folkman M J. Fighting cancer by attacking its blood supply [J] Sci AM. 1996. 275: 150-154.
[94] 吴沛宏．李立．抗血管治疗联合抗血管生成治疗恶性肿瘤．中华放射学杂志 2003．37(12)．Chin J Radiol. 2003. 37(12)：1061．
[95] 赵敏．彭芝兰．赵霞．抗肿瘤血管治疗的新进展．山西医药杂志．2003．32(2)：91-94．
[96] 何振辉．梁念慈．以VEGF和bFGFF及其受体为靶点的抗肿瘤血管治疗．国外医学·生理、病理科学与临床分册．2004．24(2)：162-165．
[97] 李建生．阎锡蕴．．以肿瘤血管为靶的抗体导向治疗．科学通报 1997．19：2031-2039．
[98] Kumar H. Heer K. Lee P W. et al. Preoperative serum vascular endothelial growth factor can psedict stage in colorectal cancer[J]. ClinCancerRes. 1998. 4(5): 1279-1285.
[9
[99] Hyodo I. Doi T. Endo H. et al. Clinical significance of plasma vascular endothelial growth factor in gastro intestinal cancer [J]. EurJCancer. 1998. 34(13): 2041-2045.
[100] 彭小萍．李俊东．李孟达等．妇科恶性肿瘤患者血清中血管内皮生长因子测定的临床意义．癌症．2002．21(2)：181-185．
[101] 李秋梨．陈福进．血管内皮生长因子—C、-D与肿瘤淋巴道转移研究进展．癌症．2002．21(6)：696-700．
[102] VEGF-C和flt-4在肺腺癌中的表达及其临床意义．中国肿瘤临床与康复．2004．11(2)：112-114．
[103] 吕学诜．王朝辉．生物的防卫功能—生物具有维护自身的存在和正常生长发育繁殖以及适应环境的能力．黑龙江医药科学．2003．26(5)：1-3．
[104] Miyazaki S. Gunji Y. Matsubara H. et al. Possible involvement of antitumor immunity in the eradication of colon 26 induced by low-voltage electrochemotherapy with bleomycin. Surg Today. 2003. 33(1): 39-44.
[105] 张丙忠．邝健全．化疗对卵巢癌患者N K细胞活性的影响．中国实用妇科与产科杂志 2004．20(3)：155-157．
[106] 鞠秀丽．丁红芳．沈柏均．自然杀伤细胞与肿瘤免疫治疗的研究进展．国外医学儿科学分册．2004．31(2)：93-95．
[107] 余丽丽．王伯龄．刘玉芝．乳腺癌患者血清I L-6．F A和T N F联检的临床意义．放射免疫学杂志．2004．17(1)：41-42．
[108] 刘志伟．张晨．郭勇．肿瘤坏死因子及其基因工程研究进展．嘉应大学学报．2002．20(6)：32-35．
[109] 邓衔柏．王小莺．陈红平等．细胞因子与动物免疫．江西农业大学学报(自然科学版)．25(1)：137-141．
[110] 周滨．姜志尧．冯作化．体内IFN-γ基因转染巨噬细胞对化疗小鼠免疫功能的影响．华中科技大学学报(医学版)．1998．27(2)：94-97．
[111] Lucci A. Turner RR. Morton DL. Carbon dye as an adjunct to isosulfan blue dye for sentinel lympha node dissection. Surgery. 1999. 126(1): 48-53.
[112] Klimberg VS. Rubio IT. Henry R. Subareolar versus peritumoral injection for location of the sentinel lymph node. Ann Surg. 1999. 229(6): 860-865.
[113] 廖新波．唐慰萍．赵颖海等．5-核苷酸碱性磷酸酶双重染色法在淋巴管研究中的应用．中国组织化学与细胞化学杂志．1996．29(1)：15-19．
[114] Kato S. Itonaga I. Ji RC. Enzyme triple staining for differentiation of lymphatics from venous and arterial capillaries. Lymphology. 1996. 29(1) : 15-19.
[1
[115] 何金生．李瑞珠．宗庭益．MTT还原法检测NK细胞活性的方法学研究．中国免疫学杂志．1996．12：356．
[116] 李爱玲．田志刚等．NK细胞系细胞毒效应MTT比色法优化条件探讨．中国免疫学杂志．2002．18(10)：687-687．689．
[117] Kerr J F. Wyllie A H. Currie AR. Apoptosis: a basic biologic phenomenon with wide ranging implications in tissue kinetics [J]. Br J Cancer. 1972. 26: 2392.
[118] 潘耀谦．高丰．成军．细胞凋亡与细胞坏死比较的研究进展．动物医学进展．2000．21(4)：5-8．
[119] 付永锋．樊廷俊Bcl-2家族蛋白与细胞凋亡．生物化学与生物物理学报．2002．34(4)：389-394．
[120] 杨鲁．细胞因子及其受体系统．生命的化学．1995．3：15-17．
[121] 熊绍银．金亚丽．刘素清．张秋红．肿瘤坏死因子抗癌研究现状．中国生化药物杂志．2000．2：101-103．
[122] 张丽杰．赵振军．细胞凋亡与肿瘤发生及治疗新策略．临床荟萃．2003．18(7)：416-417．
[123] 罗斌．相磊．伍新尧．何韵．部分心血管疾病细胞凋亡的分子生物学研究进展．中国法医学杂志．2002．1：57-60．
[124] 彭枫．魏于全．细胞凋亡应用于肿瘤诊断治疗的新进展．华西医学．2000．2：258-259．
[125] 苏宝山．徐汉卿．刘丹亚．张磐谏．细胞凋亡的检测方法．临床与实验病理学杂志．1997．03：283．
[116] 杨录军．Nuesse Michael．敖琳．曹佳．昆明山海棠碱诱导Jurkat淋巴瘤细胞核DNA链断裂和DNA片段化．第三军医大学学报．2003．17：1515-1518．
[127] 李江．王文亮．王文勇．王春杰．李玉松．TUNEL技术在检测肝组织细胞凋亡中的应用．临床与实验病理学杂志．1998．4．401-402．
[128] 岳晓红．唐荣银．席清平．五倍子水提取物对LPS抑制人牙龈成纤维细胞DNA合成和对细胞周期改变的影响．牙体牙髓牙周病学杂志．2003．12：．696-699．
[129] 盛剑霓．工程电磁场数值分析．西安交通大学出版社．1991．320-324．
[130] 冯慈璋．静态电磁场．西安．西安交通大学出版社．1988．
[131] 冯慈璋．电磁场．北京．高等教育出版社．1994．
[132] 梁萍．董宝玮．于晓玲等．双电极植入式微波辐射三维热场的研究．中华超声影像学杂志．1999．8(4)：255-256．
[133] 史锋义．何荣涛．汪枫等．静电场数值计算与精度分析．沈阳工业大学学报．1999．21(6)：512-514．
[134] 杨溢．李朗如．大型铝电解槽磁场的有限元法综合分析．有色金属．2002．54(3)：66-70．
[135] H. Steinbigler. D. Haller. Comparative Analysis of Methods for Computing 2-D and 3-D Electric Fields. IEEE Transactions on Electrical Insulation. 1991. 28(3): 529-536.
[136] 翟国富．毕勇．许峰．刘茂恺．采用有限元法分析电网谐波对断路器动作特性的影响．中国电机工程学报．2003．23(1)：112-116．
[137] 王世山，王德林，李彦明．有限元软件ANSYS电磁学科的使用及其在电力变压器分析中的应用．西安石油学院学报(自然科学版)．2002．17(5)：66-71
[138] 王泽忠．李成榕．李鹏等．用球形三维电场探头测量变电站瞬态电场．华北电力大学学报．2002．29(3)：16-19．
[139] 尉伟．王勇．周洪军．场发射结构的有限元模拟．真空电子技术．2003．1：27-29．
[140] 王国强．实用工程数值模拟技术及其在ANSYS上的实践．西安．西北工业大学出版社．1999．
[141] 唐兴伦．范群波．张朝晖．ANSYS工程应用教程热与电磁学篇．中国铁道出版社．2003．1．第1版．
[142] 欧阳宇．有限元分析——ANSYS理论与应用．电子工业出版社．2003．6．第1版．
[143] 嘉木工作室．ANSYS5.7有限元实例分析教程．机械工业出版社．2002．4．第1版．
[144] T. Kotnik. D. Miklavi. T. Slivnik. Time course of trnsmembrane voltage induced by time-varying electric fields-method for theoretical analysis and its ppliction. Bioelectrochem. Bioenerge. 45(1998): 3-16.
[145] 凌诒萍．细胞生物学．北京．人民卫生出版社．2001．
[146] 杨建一．医学细胞生物学．北京．科学出版社．2000．
[147] 刘长军．王保义．张弘．李丰群等．脉冲电磁场对细胞模型特异性作用机理研究．生物医学工程学杂志．1998．15(3)：294～297．
[148] 刘长军．王保义．张弘．王子淑等．低强度快速电磁脉冲导致细胞电穿孔的研究．科学通报．1999．44(11)：1157～1161．
[149] 刘长军．张弘．王保义．瞬态电磁脉冲对细胞跨膜电位的影响．四川大学学报(自然科学版)．1999．36(5)：969～972．
[150] 赵南明．蒲慕明．细胞膜组分的原位电泳理论．清华大学学报．1983．23(4)：47～57．
[151] 牛中奇．细胞膜上的自电场应力．中国生物医学工程学报．1994．13(1)：90～95．
[152] Noha Hassan. Indira Chatterjee. Nelson G. Publicover. et al. Mapping Membrane-Potential Perturbations of Chromaffin Cells Exposed to Electric Fields. IEEE TRANSACTIONS ON PLASMA SCIENCE. 2002. 30(4): 1516-1524.
[2] 姚陈果．可控陡脉冲对恶性肿瘤细胞不可逆性电击穿的实验和机理研究．博士学位论文．重庆大学．2003年6月
[3] 汤钊猷著．现代肿瘤学．上海．上海医科大学出版社，1993年
[4] 于洪升．费从合．沈方臻等．低剂量辐射联合环磷酰胺对肿瘤细胞凋亡、细胞周期以及骨髓增殖的影响．中华放射医学与防护杂志．2004．24(2)：117-119
[5] 林永丽．高军．低剂量辐射对机体免疫效应的研究现状．中华航海医学与高气压医学杂志 2004．11(1)：53-55
[6] 刘树铮．刘伟宏．齐进．低剂量辐射增强免疫的细胞机制．中华放射医学与防护杂志．1992．12：299-305．
[7] 刘树铮．张迎春．苏旭．低剂量辐射对TCR/CD3和CD25在小鼠胸腺细胞浆膜表达的影响．中国病理生理杂志．1995．11：2-5．6．
[8] Ipetite C. Wchter T. Sge E. et al. Use of the Ikline comet assay to detect DN repair deficiencies in human fibroblasts exposed to UVC. UVB. UV and gamma-rays. Int. J Radit Biol. 1996. 69: 359-369.
[9] 潘敏求．黎月恒．陈宁．中华肿瘤治疗大全[M]．河北科学技术出版社．1996．
[10] 李向华．李慧．现代肿瘤医学．2004年2月．12(1)：54-55．
[11] 郭海燕．刘贺之．郭晓明等．花灵香云胶囊对小鼠免疫功能的调节及对肿瘤的抑制作用．解放军药学学报．2004．20(1)：5-8
[12] Tsukiok Y. Mtsumur Y. Hmguchi T. et al. Complete response chieved following ministration of S-1 in patient with drenl gland metastsis of 5FU resistant gastic cancer: case report [J]. Jpn J Clin Oncol. 2001. 31(9): 450-453.
[13] Osugi H. Tkd N. Tkemur M. et al. Oral fluoropy rimidine nticancer drug TS-1 for gastric cancer patients with peritonel dissemintion [J]. Oncol Rep. 2002. 9(4): 811-815.
[14] I whshi M. Nkmori M. Tni M. et al. Complete response of highly dvanced gastric cancer with peritonel dissemintion ofter new combined chemotherpy of S-1 nd low dose cisplatin: report of case [J]. Oncology. 2001. 61(1): 6 22.
[15] 林世寅．李瑞英．现代肿瘤热疗学．北京．学苑出版社．1997．
[16] 王智彪．顾美礼．凌萝达等．一种用于超声波生物学效应实验研究的聚能器．重庆医科大学学报．1994．19(4)：298～300．311．
[17] 涂刚．乔天愚．何士元等．高强度聚焦超声治疗兔肾VX2肿瘤的实验研究．中华泌尿外科杂 志．1999．20(8)：456～458．
[1
[18] 邹建中．伍烽．李佩希等．超声监控超声聚焦刀治疗肝癌及疗效评价研究．中国超声医学 杂志．2000．16(10)：766～768．
[19] 伍烽．王智彪．白晋等．高强度聚焦超声体外治疗肝肿瘤的剂量学研究．中华物理医学与康复杂志．2000．22(5)：267～269．
[20] Yang R. Sanghvi NT. Rescorla FJ. et al. Liver vancer ablation with extracorporeal high intensity focused ultrasound [J]. Eur Urol. 1993; 23(suppl 1): 17.
[21] Vazey S. Martin R. Schmiedl U. et al. Liver hemostasis using high intensity focused ultrasound [J]. Ultrasound Med Biol. 1997. 23(9): 1413.
[22] 吴琴．曹友德．伍烽．王智彪．HIFU对兔VX_2乳腺肿瘤毛细淋巴管的破坏效应．临床超声医学杂志．2002，4(1)：1-3．
[23] Yang R. Reilly C R. Rescorla F J. et al. Effect of high intensity focused ultrasound in the treatment of experimental neruro blastoma. J Pediatr Surg. 1992. 27: 246—251.
[24] 贾瑞鹏．周性明．张忠林等．高能聚焦超声对小鼠移植性膀胱肿瘤的杀伤效应及免疫功能的影响．中华泌尿外科杂志．1998年6月．19(6)：270-272．
[25] 武文森．韩月明．尹克铮等．小鼠膀胱移行细胞癌细胞株的建立及其生物学特性．南京铁道医学院学报．1994．13：132-134．
[26] 伍烽．王智彪．陈文直等．高强度聚焦超声破坏体外原发性肝癌的病理学观察[J]．中华肿瘤杂志．2001．23(3)：2208．
[27] 伍烽．陈文直．白晋等．高强度聚焦超声治疗原发性肝癌的初步临床研究[J]．中华超声影像学杂志．1999．8(4)：213．
[28] 吴昱．姜南艳．程庆书等．射频治疗肺癌患者免疫淋巴细胞检测．第四军医大学学报．2004．25(7)：671-672．
[29] 张沪生．叶晖．张传清等．超低频脉冲磁场抑制癌瘤和提高细胞免疫功能的实验研究．中国科学(C辑)．1997．27(2)：173～178．
[30] 曾繁清．郑从义．张新晨等．超低频脉冲磁场诱导癌细胞凋亡和抑制癌细胞生长实验研究．中国科学(C辑)．2001．31(5)：453～457．
[31] 杨逢瑜．磁场对肿瘤细胞的抑制作用．生物电磁．2004．1：1-4．
[32] 曹晓哲．赵梅兰．王德文等．高能电磁．脉冲诱导肺癌细胞株GLC-82凋亡的研究．癌症．2002．21(9)：929-933．
[33] 曹晓哲．赵梅兰．王德文．电磁脉冲诱导肺癌细胞株A549凋亡的研究．细胞与分子免疫学杂志．2002．18(3)：285-289．
[34] 辛育龄．癌症的电化学治疗．北京．人民卫生出版社．1995．
[35] 刘继彦．魏于全．罗锋等．恶性肿瘤电化学治疗前后细胞周期分析及病理学改变．华西医科大 学学报．2000．31(1)：104～106．
[3
[36] 唐步坚．李力．巴卡里·卡马拉等．电化学治疗对宫颈癌杂志Bcl-2、p53、C-myc和Rf基因表达的影响．实用肿瘤学．1998年．12(3)：209-210．
[37] 阎永家．超晓航．吴文．细胞凋亡与癌基因．生物化学生物进展．1994．21(3)：222-224
[38] 王慧．摩若然．宫颈癌中C-erB2、C-myc、P53基因变化及临床意义．国外医学妇产科学分册．1996．23(5)：272-281．
[39] J. H. Sale and W. A. Hamilton. Effects of electric fields on microorganizms I killing of bacteri and yests. Biochimic et Biophysical ct. 1967. 118: 781-788.
[40] E. Neumnn and K. Rosenheck. Permebility changes included by electrical pulse in vesicular membranes. Journal of Membrane Biology. 1972. 10: 279～290.
[41] K. J. Kinosit and T. Y. Tsong. Voltage includes formation and hemolysis of human erythocytes. Biochimic et Biophysical ct. 1979. 471: 227～242.
[42] G. Hofmann and G. Evans. Electronic genetic-Physicl and biological aspects of cellular electromanipulation. IEEE Engineering of Medical Biology. 1986. 5(4): 6～25.
[43] J. C. Weaver. Electroporation: dramatic. nonthermal electric field phenomenon. In Proceedings of the First World Congress for Electricity and Magnetism in Biology and Medicine. Lke Buen Vist. Florid. academic Press. 1992.
[44] Lluis M. Mir. Stephne Orlowski. Mechanisms of Electrochemotherapy. dvnced Drug Delivery Reviews. 1999. (35): 107-118.
[45] Richrd Heller. Richrd Gilbert. Mrk J. Jroszeski. Clinical applictions of Electrochemotherapy. advanced Drug Delivery Reviews. 1999. (35): 119-129.
[46] L. M Mir. Electrochemotherapy polentition of ntitumor effect of bleomycin by electric pulses. European Journal of Cancer. 1991. 27(1): 68～72.
[47] W. R. Pnje. M. P. Hier. G. R. Grmn. et al. Electroporation therapy of head and neck cancer, nn. Otol. Rhinol. Lryngol. 1998. 107: 779～785.
[48] W. R. Panje. M. P. Hier. G. R. Garman. et al. Electroporation therapy of head and neck cancer. Ann. Otol. Rhinol. Laryngol. 1998. 107: 779～785.
[49] M. M. Kekez. P. Svic. B. F. Johnson. Contribution to the biophysics of lethal effects of electric field on microorganisms. Biochimic et Biophysic ct. 1996. 79～88.
[50] L H Rmirez. Electrochemotherapy on liver tumors in rabbits. British Journal of Cancer. 1998. 77(12). 2104～2111.
[51] 孙敬儒．王子淑．刘一勇等．电穿孔诱发细胞凋亡和提高抗癌药物细胞毒性的研究．四川大学学报(自然科学版)．2002．39增刊：170-174．
[52] Sersa G. Kotnik V. Ceramzr M. et al. Electrochemotherapy with bleomycin in S-1 tumor-bearing mice natural resistance and immune responsiveness. anticancer Drugs. 1996; 7(7): 785-791.
[5
[53] Miyazki S. Gunji Y. Mtsubr H. et al. Possible involvement of antitumor immunity in the eradiction of colon 26 induced by low-voltage electrochemotherapy with bleomycin Surg Tody. 2003; 33(1): 39-44.
[54] Engstrom PE Medical applications of electroporation. IEEE Transactions on Plasma Science. 2000. 28 (1): 206-223.
[55] 郭伟剑．宋明志．于尔辛．恶性肿瘤的电化学疗法．国外医学肿瘤学册．1996．23 (6)：349-351．
[56] DeBruin K. Krassowska W. Modeling electroporation in single cell Ⅰ Effects of field strength and rest potential [J]. Biophys-J. 1999. 77(3): 1213. [48]Ktherine. Debrnin. and Krassowska. Modeling electroporation in single cell[J]. Biophysical. 1999. 77: 1225.
[57] Anna O. Bilska, Katherine A. DeBruin, Wanda Krassowska. Theoretical modeling of the effects of shock duration, frequency, and strength on the degree of electroporation. Bioelectrochemistry, 2000, 51, 133-143
[58] Okino M. Optimal electric condictions in electrical impulse chemotherapy. Japanese Journal of Cancer Research. 1992. 83(10): 1095～1101.
[59] Ev Nilsson. Jk Berendson. Edurdo Fontes. Development of Dosge Method for Electrochemical Treatment of Tumours: Simplified Mathematical Model. Bioelectrochemistry and Bioenergetics. 1998. 42 (7): 11-18.
[60] Ev Nilsson. Jk Bereodson. Edurdo Fontes. Electrochemical Treatment of Tumours: Simplified Mathematical Model. Journal of Electronlytical Chemistry. 1999. (460): 88-99.
[61] Ev Nilsson. Edurdo Fontes. Mthematical Modeling of Physicochemical Reactions and Transport Processing Occurring round Platinum Cathode during the Electrochemical Treatment of Tumours. Bioelectrochemistry. 2001. (53): 213-224.
[62] Kostadin Brandiaky. Ivan Daskalov. Electrical Field and Current Distributions in Electrochemotherapy. Bioelectrochemistry and Bioenergetics. 1999. (48): 201-208.
[63] Dr. D. Rabussay and Dr. S. Kornhauser. Frequenfly Asked Questions about Electroporation Therapy. American Journal of Electromedicine. 1998: 64～68.
[64] Dmijn Miklvcic. Dejn Semrov. Hlim Mekid. Lluis M. Mir. Validated Model of in Vivo Electric Field Distribution in Tissues for Electrochemotherapy and for DN Electrotransfer for Gene Therapy. Biochimic et Biophysic ct. 2000. (1523): 73-83.
[65] Julie Gehl. Thyge H. Sφrensen, Kurt Nielsen. In vivo electroporation of skeletal muscle: threshold, efficacy and relation to electric field distribution. Biochimica et Biophysica Acta. 2000. (1428). 233-240.
[66] Belehradek J Jr. Orlowski S. Ramirez LH. et al. Electropermeabilization of cells in tissues assessed by the qualitative and quantitative electroloading of bleomycin.Biochim Biophys Acta,1994.1190{l).155-163.
[67] Sukhendu B.Dev.Dietmr P.Rabussy.Georg Wider.et al.Medical applications of Electroporation IEEE Transactions On Plasma Science.Vol.28.No.1.FEBRURY 2000:206-223.
[68] D.Semrov.D.Miklvcic.Calculation of the Electrical Parameters in Electrochemotherapy of Solid Tumours in Mice.Computers in Biology and Medicine. 1998. (28): 439-448.
[69] H.P.Schwan.Electrical properties of tissue and cell suspensions, adv. Biol. Med. Phys. 1957. 5:147-209.
[70] Tjitske Heida*.Joost B.M.Wgenr.Wim L.C.Rutten .Investigating Membrane Breakdown of Neuronl Cells Exposed to Nonuniform Electric Fields by Finite-Element Modeling nd Experiments.IEEE Trnsctions On Biomedicl Engineering.2002.49910:1195.
[71] Dev, S.B.Rabussay, D.P.Widera, GHofmann, GA. Medical applications of electroporation.IEEE Transactions on Plasma Science. 2000.28 (1): 206 - 223.
[72] Lee RC. Electrical injury mechanisms: Electrical breakdown of cell membranes. Plast Reconstr Surg. 1987.80:672-679.
[73] kevin T P.Jmes C W.Transient qaueous pores in bilayer membranes: statistical theory{J}.Bioelectrochem Bioenergetics.l986.15:211-227.
[74] Bier M.Hnner SM.Cvdy DJ.et al.Kinetics of sealing for transient electropores in isolated mammlin skeletal muscle cells.Bioelectromgneics.l999.20(3): 94.
[75] J.Teissie .M.P.Rols.an experimental evalution of the critical potential difference inducing cell membrane electropermeabiliztion.Biophys.J.65 (1993): 409-413.
[76] T.Y.Tsong.Electroporation of cell membrane.Biophys.J.60(1991):297-306.
[77] James C.Weaver.Electroporation of Biological Membranes from Multicellular to Nano Scales.IEEE Transactions on Dielectrics and Electrical Insultion.2003.10(5) :754-768.
[78] Gorzd Pucihr.Tdej Kotnik.Masa Kanduser .et al.The influence of medium conductivity on electorpermeabiliztion and survival of cells in vitro.Bioelectrochemistry 54(2001):107-115.
[79] J.C.Weaver.Electroporation: A dramatic.nonthermal electric field phenomenon.In Proceedings of the First World Congress for Electricity and Magnetism in Biology and Medicine.Lake Buena Vista.FloridaAcademic Press.1992.
[80] E.Neumnn..E.Sowers and C.Jordan.Eds.Electroporation and Electrofusion in Cell Biology.New York.Plenum.1989.
[81] K.H.Schoenbch.mr.bou-Ghzl.Terry.Vithoulks.et al.Effect of pulsed electrical fields on biological cells.Digest of Technical Papers-IEEE Interntional Pulsed Power Conference.l997.(1) 2: 73-78.
[82] Sersa G. Tumor blood flow change induced by application of electrical pulses. European Journal of Cancer. 1999. 35(4): 672～677.
[83] Stephen J. Beebe. Pul Fox. Lur Rec. et al. Nanosecond Pulsed Electric Field Effects On Human Cells. 20012. 652-656.
[84] Stephen J. Beebe. P. M. Fox. L. J. Rec. et al Nanosecond Pulsed Electric Field (nsPEF) Effects on Cells and Tissues: apoptosis Induction and Tumor Growth Inhibition. IEEE TRANSACTIONS ON PLASMA SCIENCE. 2002. 30(1): 286-292.
[85] Taylor, M. J. Measurement of the properties of plasma from ETC capillary plasma generators. IEEE Transactions on Magnetics. 200137(1): 194 - 198.
[86] Bischof, J. C. Bhowmick, S.; Lulloff, L. et al Thermal therapy in the Dunning AT-1 prostate tumor using a wet electrode RF probe [Engineering in Medicine and Biology, 1999. 21st Annual Conf. and the 1999 Annual Fall Meeting of the Biomedical Engineering Soc.] BMES/EMBS Conference, 1999. Proceedings of the First Joint. 1999. 2: 1282
[87] Lee RC. Electrical injury mechanisms: Electrical breakdown of cell membranes. Plast Reconstr Surg. 1987. 80: 672～679.
[88] E. Stephen Buescher. Krl H. Schoenbch.. Effects of Submicrosecond. High Intensity Pulsed Electric Fields on Living Cells_Intracellular Electromanipulation. IEEE Transactions on Dielectrics and Electrical Insulation Vol.10.No.5; October 2003.788-794.
[89] 吴扬兰．王远亮．肿瘤新生血管抑制剂——血管抑素和内皮抑素．重庆大学学报．2003．26(10)：72-75．
[90] 王杰．田晓峰．韩雪春．肿瘤组织中的血管生成及抗血管治疗医师进修杂志(外科版)．2003．26(11)：1-3．
[91] 李军．俞兰．VEGF、肿瘤血管再生及抗肿瘤血管生成治疗．医师进修杂志(外科版)2004．27(4)：52-54．
[92] Folkman M J. Cotrans. Relation of vascular proliferation to tumor growth [J]. Int Rev Exp Pathol. 1976. 16: 207-215.
[93] Folkman M J. Fighting cancer by attacking its blood supply [J] Sci AM. 1996. 275: 150-154.
[94] 吴沛宏．李立．抗血管治疗联合抗血管生成治疗恶性肿瘤．中华放射学杂志 2003．37(12)．Chin J Radiol. 2003. 37(12)：1061．
[95] 赵敏．彭芝兰．赵霞．抗肿瘤血管治疗的新进展．山西医药杂志．2003．32(2)：91-94．
[96] 何振辉．梁念慈．以VEGF和bFGFF及其受体为靶点的抗肿瘤血管治疗．国外医学·生理、病理科学与临床分册．2004．24(2)：162-165．
[97] 李建生．阎锡蕴．．以肿瘤血管为靶的抗体导向治疗．科学通报 1997．19：2031-2039．
[98] Kumar H. Heer K. Lee P W. et al. Preoperative serum vascular endothelial growth factor can psedict stage in colorectal cancer[J]. ClinCancerRes. 1998. 4(5): 1279-1285.
[9
[99] Hyodo I. Doi T. Endo H. et al. Clinical significance of plasma vascular endothelial growth factor in gastro intestinal cancer [J]. EurJCancer. 1998. 34(13): 2041-2045.
[100] 彭小萍．李俊东．李孟达等．妇科恶性肿瘤患者血清中血管内皮生长因子测定的临床意义．癌症．2002．21(2)：181-185．
[101] 李秋梨．陈福进．血管内皮生长因子—C、-D与肿瘤淋巴道转移研究进展．癌症．2002．21(6)：696-700．
[102] VEGF-C和flt-4在肺腺癌中的表达及其临床意义．中国肿瘤临床与康复．2004．11(2)：112-114．
[103] 吕学诜．王朝辉．生物的防卫功能—生物具有维护自身的存在和正常生长发育繁殖以及适应环境的能力．黑龙江医药科学．2003．26(5)：1-3．
[104] Miyazaki S. Gunji Y. Matsubara H. et al. Possible involvement of antitumor immunity in the eradication of colon 26 induced by low-voltage electrochemotherapy with bleomycin. Surg Today. 2003. 33(1): 39-44.
[105] 张丙忠．邝健全．化疗对卵巢癌患者N K细胞活性的影响．中国实用妇科与产科杂志 2004．20(3)：155-157．
[106] 鞠秀丽．丁红芳．沈柏均．自然杀伤细胞与肿瘤免疫治疗的研究进展．国外医学儿科学分册．2004．31(2)：93-95．
[107] 余丽丽．王伯龄．刘玉芝．乳腺癌患者血清I L-6．F A和T N F联检的临床意义．放射免疫学杂志．2004．17(1)：41-42．
[108] 刘志伟．张晨．郭勇．肿瘤坏死因子及其基因工程研究进展．嘉应大学学报．2002．20(6)：32-35．
[109] 邓衔柏．王小莺．陈红平等．细胞因子与动物免疫．江西农业大学学报(自然科学版)．25(1)：137-141．
[110] 周滨．姜志尧．冯作化．体内IFN-γ基因转染巨噬细胞对化疗小鼠免疫功能的影响．华中科技大学学报(医学版)．1998．27(2)：94-97．
[111] Lucci A. Turner RR. Morton DL. Carbon dye as an adjunct to isosulfan blue dye for sentinel lympha node dissection. Surgery. 1999. 126(1): 48-53.
[112] Klimberg VS. Rubio IT. Henry R. Subareolar versus peritumoral injection for location of the sentinel lymph node. Ann Surg. 1999. 229(6): 860-865.
[113] 廖新波．唐慰萍．赵颖海等．5-核苷酸碱性磷酸酶双重染色法在淋巴管研究中的应用．中国组织化学与细胞化学杂志．1996．29(1)：15-19．
[114] Kato S. Itonaga I. Ji RC. Enzyme triple staining for differentiation of lymphatics from venous and arterial capillaries. Lymphology. 1996. 29(1) : 15-19.
[1
[115] 何金生．李瑞珠．宗庭益．MTT还原法检测NK细胞活性的方法学研究．中国免疫学杂志．1996．12：356．
[116] 李爱玲．田志刚等．NK细胞系细胞毒效应MTT比色法优化条件探讨．中国免疫学杂志．2002．18(10)：687-687．689．
[117] Kerr J F. Wyllie A H. Currie AR. Apoptosis: a basic biologic phenomenon with wide ranging implications in tissue kinetics [J]. Br J Cancer. 1972. 26: 2392.
[118] 潘耀谦．高丰．成军．细胞凋亡与细胞坏死比较的研究进展．动物医学进展．2000．21(4)：5-8．
[119] 付永锋．樊廷俊Bcl-2家族蛋白与细胞凋亡．生物化学与生物物理学报．2002．34(4)：389-394．
[120] 杨鲁．细胞因子及其受体系统．生命的化学．1995．3：15-17．
[121] 熊绍银．金亚丽．刘素清．张秋红．肿瘤坏死因子抗癌研究现状．中国生化药物杂志．2000．2：101-103．
[122] 张丽杰．赵振军．细胞凋亡与肿瘤发生及治疗新策略．临床荟萃．2003．18(7)：416-417．
[123] 罗斌．相磊．伍新尧．何韵．部分心血管疾病细胞凋亡的分子生物学研究进展．中国法医学杂志．2002．1：57-60．
[124] 彭枫．魏于全．细胞凋亡应用于肿瘤诊断治疗的新进展．华西医学．2000．2：258-259．
[125] 苏宝山．徐汉卿．刘丹亚．张磐谏．细胞凋亡的检测方法．临床与实验病理学杂志．1997．03：283．
[116] 杨录军．Nuesse Michael．敖琳．曹佳．昆明山海棠碱诱导Jurkat淋巴瘤细胞核DNA链断裂和DNA片段化．第三军医大学学报．2003．17：1515-1518．
[127] 李江．王文亮．王文勇．王春杰．李玉松．TUNEL技术在检测肝组织细胞凋亡中的应用．临床与实验病理学杂志．1998．4．401-402．
[128] 岳晓红．唐荣银．席清平．五倍子水提取物对LPS抑制人牙龈成纤维细胞DNA合成和对细胞周期改变的影响．牙体牙髓牙周病学杂志．2003．12：．696-699．
[129] 盛剑霓．工程电磁场数值分析．西安交通大学出版社．1991．320-324．
[130] 冯慈璋．静态电磁场．西安．西安交通大学出版社．1988．
[131] 冯慈璋．电磁场．北京．高等教育出版社．1994．
[132] 梁萍．董宝玮．于晓玲等．双电极植入式微波辐射三维热场的研究．中华超声影像学杂志．1999．8(4)：255-256．
[133] 史锋义．何荣涛．汪枫等．静电场数值计算与精度分析．沈阳工业大学学报．1999．21(6)：512-514．
[134] 杨溢．李朗如．大型铝电解槽磁场的有限元法综合分析．有色金属．2002．54(3)：66-70．
[135] H. Steinbigler. D. Haller. Comparative Analysis of Methods for Computing 2-D and 3-D Electric Fields. IEEE Transactions on Electrical Insulation. 1991. 28(3): 529-536.
[136] 翟国富．毕勇．许峰．刘茂恺．采用有限元法分析电网谐波对断路器动作特性的影响．中国电机工程学报．2003．23(1)：112-116．
[137] 王世山，王德林，李彦明．有限元软件ANSYS电磁学科的使用及其在电力变压器分析中的应用．西安石油学院学报(自然科学版)．2002．17(5)：66-71
[138] 王泽忠．李成榕．李鹏等．用球形三维电场探头测量变电站瞬态电场．华北电力大学学报．2002．29(3)：16-19．
[139] 尉伟．王勇．周洪军．场发射结构的有限元模拟．真空电子技术．2003．1：27-29．
[140] 王国强．实用工程数值模拟技术及其在ANSYS上的实践．西安．西北工业大学出版社．1999．
[141] 唐兴伦．范群波．张朝晖．ANSYS工程应用教程热与电磁学篇．中国铁道出版社．2003．1．第1版．
[142] 欧阳宇．有限元分析——ANSYS理论与应用．电子工业出版社．2003．6．第1版．
[143] 嘉木工作室．ANSYS5.7有限元实例分析教程．机械工业出版社．2002．4．第1版．
[144] T. Kotnik. D. Miklavi. T. Slivnik. Time course of trnsmembrane voltage induced by time-varying electric fields-method for theoretical analysis and its ppliction. Bioelectrochem. Bioenerge. 45(1998): 3-16.
[145] 凌诒萍．细胞生物学．北京．人民卫生出版社．2001．
[146] 杨建一．医学细胞生物学．北京．科学出版社．2000．
[147] 刘长军．王保义．张弘．李丰群等．脉冲电磁场对细胞模型特异性作用机理研究．生物医学工程学杂志．1998．15(3)：294～297．
[148] 刘长军．王保义．张弘．王子淑等．低强度快速电磁脉冲导致细胞电穿孔的研究．科学通报．1999．44(11)：1157～1161．
[149] 刘长军．张弘．王保义．瞬态电磁脉冲对细胞跨膜电位的影响．四川大学学报(自然科学版)．1999．36(5)：969～972．
[150] 赵南明．蒲慕明．细胞膜组分的原位电泳理论．清华大学学报．1983．23(4)：47～57．
[151] 牛中奇．细胞膜上的自电场应力．中国生物医学工程学报．1994．13(1)：90～95．
[152] Noha Hassan. Indira Chatterjee. Nelson G. Publicover. et al. Mapping Membrane-Potential Perturbations of Chromaffin Cells Exposed to Electric Fields. IEEE TRANSACTIONS ON PLASMA SCIENCE. 2002. 30(4): 1516-1524.