能量可控陡脉冲对肿瘤细胞膜功能的影响及安全性研究
|
摘要
陡脉冲电场对细胞膜的不可逆性电击穿导致的细胞死亡成为了恶性肿瘤低创或微创物理治癌的新方式,而其对机体的安全性以及对周边正常组织有否影响是保证其安全治疗的前提。细胞膜作为生物膜在维持细胞稳定性中具有重要的作用。细胞膜电位是作为细胞膜最重要的生物物理特性之一,它在细胞的正常生命活动中亦起着重要的作用,调节着许多重要的细胞功能。膜电位的变化必然会改变细胞膜离子通道状态,导致细胞内离子浓度变化。而离子浓度的改变还可能影响细胞缝隙连接功能,影响肿瘤细胞的增殖和活性。因此本研究拟通过三个部分的研究进行陡脉冲对细胞膜功能的影响及其对机体的安全性作深入的探讨,对陡脉冲研制中某些关键问题作定性及定量的研究。
第一部分能量可控陡脉冲对细胞内钙离子浓度及膜电位的影响
目的:探讨不同剂量陡脉冲对细胞内游离Ca~(2+)浓度([Ca~(2+)]i)和细胞膜电位的影响,为进一步研究其治疗恶性肿瘤的机制奠定基础。
方法:将乳腺癌细胞MDA-MB-231分为对照组和5个不同剂量ECSP处理组,分别用荧光探针Fluo-3/AM标记Ca~(2+)、DiBAC4(3)标
The steep pulse which electric field can make the cell death by destroying the cell membrane with irreversible electroporation is a new low and micro trauma method in the treatment of malignant tumor. The safety and the influence of steep pulse on surrounding normal tissue are the prerequisite of it in the treatment. The cell membrane as a biomembrane has very important role in maintaining the stability of cell. The cell membrane potential is one of the most important biophysical characteristics in cell membrane. It has very important function in the cellular normal vital movement, regulating many important cell functions. The changes of cell membrane potential certainly alter the states of ion channel in cellular membrane, which induce the changes of ionic concentration. The changes of ionic concentration may influence the function of intercellular gap junction, which affects the proliferation and activity of tumor cells. So in this succession, we plan to further investigate the influence of ECSP on cellular membrane function and its safety on transplanted tumor rabbit, also give qualitation and quantitation analysis in some key issues concerning the development of ECSP.
第一部分能量可控陡脉冲对细胞内钙离子浓度及膜电位的影响
目的:探讨不同剂量陡脉冲对细胞内游离Ca~(2+)浓度([Ca~(2+)]i)和细胞膜电位的影响,为进一步研究其治疗恶性肿瘤的机制奠定基础。
方法:将乳腺癌细胞MDA-MB-231分为对照组和5个不同剂量ECSP处理组,分别用荧光探针Fluo-3/AM标记Ca~(2+)、DiBAC4(3)标
The steep pulse which electric field can make the cell death by destroying the cell membrane with irreversible electroporation is a new low and micro trauma method in the treatment of malignant tumor. The safety and the influence of steep pulse on surrounding normal tissue are the prerequisite of it in the treatment. The cell membrane as a biomembrane has very important role in maintaining the stability of cell. The cell membrane potential is one of the most important biophysical characteristics in cell membrane. It has very important function in the cellular normal vital movement, regulating many important cell functions. The changes of cell membrane potential certainly alter the states of ion channel in cellular membrane, which induce the changes of ionic concentration. The changes of ionic concentration may influence the function of intercellular gap junction, which affects the proliferation and activity of tumor cells. So in this succession, we plan to further investigate the influence of ECSP on cellular membrane function and its safety on transplanted tumor rabbit, also give qualitation and quantitation analysis in some key issues concerning the development of ECSP.
引文
[1] Zimmernann U, Friedrich U, Mussauer H, et al. Electromanipulation of mammalian cells: fundamentals and application[J]. IEEE Transaction on Plasma Science, 2000, 28(1): 72-82
[2] Sukhendu BD, Dietmar PR, Georg W, et al. Medical applications of electroporation [J]. IEEE Transaction on Plasma Science, 2000, 28(1): 206-223
[3] Nilsson E, von Euler H, Berendson J, et al. Electrochemical treatment of tumours [J]. Bioelectrochemistry, 2000, 51(1): 1-11
[4] Sersa G, Stabuc B, Cemazar M, et al. Electrochemotherapy with cisplatin: potentation of local cisplatin antitumour effectiveness by application of electric pulses in cancer patients[J]. Eur J Cancer, 1998, 34(8): 1213-1218
[5] Engstrom PE, Persson BR, Brun A, et al. A new antitumour treatment combining radiation and electric pulses[J]. Anticancer Res, 2001, 21(3B): 1809-1815
[6] Toru Horikoshi, Hirofumi Naganuma, Yasuhiro Ohashi, et al. Enhancing effect of electric stimulation on cytotoxicity of anticancer agents against rat and human glioma cells[J]. Brain Research Bulletin, 2000, 51(5): 371-378
[7] Cemazar M, Miklavcic D, Mir LM, et al. Electrochemotherapy of tumors resistant to cisplatin: a study in a murine tumour model[J]. Eur J Cancer, 2001, 37(9): 1166-1172
[8] Jaroszeski MJ, Coppoda D, Pottinger C, et al. Treatment of hepatocellular carcinoma in a rat model using electrochemotherapy[J]. Eur J Cancer, 2001, 37(3): 422-430
[9] Weaver JC. Electroporation: a general phenomenon for manipulating cells and tissues[J]. J Cell Biochem, 1993, 51(4): 426-435
[10] Hofmann GA, Evans G. Electronic genetic-physical and biological aspects ofcellular electromanipulation[J]. IEEE Eng. Med. Biol, Mag, 1986, 5(4): 6-25
[11] Hofmann GA, Dev SB, Dimmer S, et al. Electroporation therapy: a new approach for the treatment of head and neck cancer[J]. IEEE Trans. On Biomedical Engineering, 1999, (46) 6: 752-759
[12] 李大强, 熊兰, 胡丽娜, 等. 能量可控陡脉冲对离体肿瘤组织杀伤作用的观察[J]. 重庆医科大学学报, 2001, 26(4): 413-415
[13] 孙才新, 姚陈果, 熊兰, 等. 陡脉冲电场对恶性肿瘤细胞杀伤效应的研究[J]. 生物物理学报, 2002, 18(4): 474-477
[14] 熊兰, 孙才新, 胡丽娜, 等. 能量可控陡脉冲杀伤肿瘤的离体试验研究[J].生物医学工程学杂志, 2002, 19(3): 440-443
[15] 胡娅, 胡丽娜, 熊兰, 等. 能量可控陡脉冲对荷瘤小鼠生存转归的影响[J].实用肿瘤杂志, 2005, 20(4): 305-307
[16] Parkman HP, Pagano AP, Martin JS, et al. Electric field stimulation geuinea pig gallbladder contraction: role of calcium channels in acetycholine release[J]. Digestive Disease and Sciences, 1997, 142(9): 1919-1925
[17] Berridge MJ. Inositol trisphosphate and calcium signalling[J]. Nature, 1993, 36(28): 315-325
[18] Kolaja KL, Engelken DT, Klaassen CD. Inhibition of gap-junctional- intercellular communication in intact rat liver by non-genotoxic hepatocarcinogens[J]. Toxicology, 2000, 146(1): 15-22
[19] Saunders MM, Seraj MJ, Li Z, et al. Breast cancer metastatic potential correlates with a breakdown in homospecific and heterospecific gap junctional intercellular communication[J]. Cancer Res, 2001, 61(5): 1765-1767
[20] Esinduy C, Chang CC, Trosko JE. In vitro growth inhibition of neoplastically transformed cells by non-transformed cells: requirement for gap junctional intercellular communication[J]. Carcinogenesis, 1995, 16(4): 915-921
[21] Mehta PP, Perez-Stable C, Nadji M, et al. Suppression of human prostate cancer cell growth by forced expression of connexin genes[J]. Dev Genet, 1999, 24 (1): 91-110
[22] 张晓峰,李百祥. 细胞间隙连接通讯与肿瘤关系的研究进展[J]. 卫生毒理学杂志,2002, 16(3): 185-187
[23] Lai H, Singh NP. Acute exposure to a 60 Hz magnetic field increase DNA strand breaks in rat brain cell[J]. Bioelectromagnetics, 1997, 18(2): 156-165
[1] 胡娅, 胡丽娜, 米彦等. 能量可控陡脉冲对人卵巢癌细胞的体外作用[J].第三军医大大学学报, 2003, 25(16): 1441-1445
[2] 姚陈果, 孙才新, 米彦等. 陡脉冲对恶性肿瘤细胞不可逆性电击穿的实验研究[J].中国生物医学工程学报, 2004, 23(1): 92-97
[3] 米彦, 孙才新, 姚陈果等. 陡脉冲肿瘤治疗仪的研制及应用[J].重庆大学学报(自然科学版),2003, 26(2):12-14
[4] 张薇, 朴英杰, 鲍永耀,等. 粘附式细胞仪测定巨噬细胞内游离钙的方法[J]. 第一军医大学学报,1994, 14 (1):43-45
[5] Manning TJ, Sontheimer H. Recording of intracellular Ca~(2+), Cl2,pH and membrane potential in cultured astrocytes using a fluorescence plate reader[J]. J Neurosci Methods, 1999, 91(122): 73-81
[6] Gordienko DV, Zholos AV, Bolton TB. Membrane ion channels as physiological targets for local Ca~(2+) signalling[J]. J Microsc, 1999,196(Pt 3): 305-316
[7] Asada Y, Yamazawa T, Hirose K, et al. Dynamic Ca~(2+) signaling in rat arterial smooth muscle cells under the control of local reninangiotensin system[J] . J Physiol Lond, 1999, 521( Pt 2): 497-505
[8] Tsien RY. Measuring and manipulating cytosolic Ca~(2+) with trapped indicators [J]. Kroc Found Ser, 1984, 17: 147-155
[9] Distelhorst CW,Duhyak G.. Role of calcium in glucocorticosterione immunal apotosis of thycocyte and lymphoma cells: resumecole of old theroies by new findings[J]. Blood, 1998, 91(3): 731-734
[10] Wang HG, Pathan Y, Ethell IM, el al. Ca~(2+) induced apoptosis through calcineurin dephosphocylin of BAD[J]. Science, 1999, 284(5412): 339-343
[11] Chattopadhyay N, Ye CP, Yamaguchi T, et al. Extracellular calcium-sensingreceptor induces cellular proliferation and activation non-selective cation channel in U373 astrocytoma cells[J]. Brain Res, 1999, 851(1-2): 116-124
[12] 梁润酶, 董惠文. 钙通道[J]. 生命的化学, 1994, 14(5): 23-25
[13] Dolmetsch RE, Lewis RS, Goodnows CC, et al. Differential activation of transcription factors induced by Ca~(~(2+)) response amplitude and duration[J]. Nature, 1997, 386(6627): 855-858
[14] Walleczek J. Electromagnetic field effects on cells of the immune system: the role of calcium signaling[J]. FASEB, 1992, 6(13): 3177-3185
[15] Blackman CF, Benane SG, Radinowitz JR, et al. A role for the magnetic field in the radiation induced efflux of calcium ions from brain tissue in vitro[J]. Bioelectromagnetics, 1985, 6(4): 327-337
[16] Beani L, Tomasini C, Govoni BM, et al. Fluorimetric determination of electrically evoked increase in intracellular calcium in cultures cerebellar granule cells[J]. J Neurosci Methods, 1994, 51(1): 1-7
[17] Parkman HP, Pagano AP, Martin JS, et al. Electric field stimulation geuinea pig gallbladder contractions: role of calcium channels in acetycholine release[J]. Digestive Diseases and Sciences, 1997, 142(9): 1919-1925
[18] Eichwald C, Kaiser F. Model for external influences on cellular signal transductin pathway including cytosolic calcium oscillations [J]. Bioelectromagnetics, 1995, 16(2): 75-85
[19] Berridge MJ. Inositol trisphosphate and calcium signalling[J]. Nature, 1993, 361(28): 315-325
[20] Dibirdik I, Kristupaitis D, Kurosaki T, et al. Stimulation of Src family protein tyrosine kinases as a proximal and mandatory step for SYK kinase-dependent phospholipase Cy2 activation in lymphoma B cells exposed to low energy electromagnetic fields[J]. J Biol Chem, 1998, 273 (7): 4035-4039
[21] Kristupaitis D, Dibirdik I, Vassilev A, et al. Electromagnetic field-induced stimulation of Bruton’s tyrosine kinase[J]. J Biol Chem, 1998, 273(20): 12397-12401
[22] Miller SC, Furniss MJ. Bruton’s tyrosine kinase activity and inositol 1,4,5- trisphosphate production are not altered in DT40 lymphoma B cells exposed to power line frequency magnetic fields[J]. J Biol Chem, 1998, 273(49): 32618-32626
[23] 熊兰, 孙才新, 米彦, 等.陡脉冲诱导在体瘤细胞凋亡的实验及分析.重庆大学学报(自然科学版), 2004, 27(11): 22-25
[24] 王萍玲, 胡丽娜, 李聪, 等.能量可控陡脉冲联合 H-ras 干扰性 RNA 治疗卵巢癌裸鼠皮下移植瘤的实验研究.第三军医大学学报, 2005,27(6): 490-493
[25] Schiffenbauer YS, Trubniykov E, Zacharia BT, et al. Tumor sensitivity to anti-cancer drugs predicted by changes in fluorescence intensity and polarization in vitro[J]. Anticancer Res, 2002, 22(5): 2663-2669
[26] Matarrese P, Gamdbardella L, Gassone A, et al. Mitochondrial membrane hyperpolarization hijacks activated T lymphocytes toward the apoptotic-probe phenotype: homeostatic mechanisms of HIV protease inhibitors[J]. J Immunol, 2003, 170(12): 6006-6015
[27] Radosevoic K, Schut TC, Van Graft M, et al. A flow cytometric study of the membrane potential natural killer and k562 cells during the cytotoxic process[J]. J Immunol Methods, 1993,161 (1-2): 119
[28] Taichman NS, Iwase M, Lally ET, et al. Early changes in cytosolic calcium and membrane potential induced by actinobacillus actinomyce-temcomitans leukotoxin insusceptible and resistant target cells[J]. J Immunol, 1991, 147(10): 3587.
[1] Zhang JT, Nicholson BJ. The topological structure of connexin 26 and its distribution compared to connexin 32 in hepatic gap junctions[J]. J Membr Biol, 1994, 139(1): 15-29
[2] Naus CC, Zhu D, Todd SD, et al. Characteristics of C6 glioma cells overexpression a gap junction protein [J]. Cell Mol Neuroboil, 1992, 12 (2): 163-175
[3] Paul DL. New functions for gap junctions [J]. Curr Opin Cell Biol, 1995, 7(5): 665-672
[4] Noguchi M, Nomata K, Watanabe J, et al. Changes in the gap junctional intercellular communication inrenal tubular epithelial cells in vitro treated with renal carcinogens [J]. Cancer Lett, 1998, 122 (1-2): 77- 84
[5] 孙才新, 姚陈果, 熊兰, 等. 陡脉冲电场对恶性肿瘤细胞杀伤效应的研究[J].生物物理学报, 2002,18(4):474-477
[6] Kolaja KL, Engelken DT, Klaassen CD. Inhibition of gap-junctional -intercellular communication in intact rat liver by non-genotoxic hepatocarcinogens[J]. Toxicology, 2000, 146(1): 15-22
[7] Ruch RJ. The role of gap junctional intercellular communication in neoplasia [J]. Ann Clin Lab Sci, 1994, 24 (3): 216-223.
[8] Lee SW, Tomasetto C, Paul D, et al. Transcriptional downregulation of gap junction proteins blocks junctional communication in human mammary tumor cell lines [J]. J Cell Bio1, 1992, 118 (5): 1213-1221
[9] Hirschi KK, Xu CE, Tsukamoto T, et al. Gap junction genes Cx26 and Cx43 individually suppress the cancer phenotype of human mammary carcinoma cells and restore differentiation potential [J]. Cell Growth Differ, 1996, 7 (7): 861- 870
[10] Saunders MM, Seraj MJ, Li Z, et al. Breast cancer metastatic potential correlates with a breakdown in homospecific and heterospecific gap junctional intercellular communication[J]. Cancer Res. 2001,61(5): 1765-1767
[11] Esinduy C, Chang CC, Trosko JE. In vitro growth inhibition of neoplastically transformed cells by non-transformed cells: requirement for gap junctional intercellular communication[J]. Carcinogenesis, 1995, 16(4): 915-921
[12] Mehta PP, Perez-Stable C, Nadji M, et al. Suppression of human prostate cancer cell growth by forced expression of connexin genes[J]. Dev Genet, 1999, 24 (1-2): 91-110
[13] Yao C, Sun C, Xiong L, et al. Effect of steep pulsed electric fields on survival of tumour-bearing mice[J]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2004, 21(3): 433-435
[14] 王萍玲, 胡丽娜, 李聪, 等. 能量可控陡脉冲联合 H-ras 干扰性 RNA 治疗卵巢癌裸鼠皮下移植瘤的实验研究[J]. 第三军医大学学报, 2005, 27(6): 490-493
[15] 张晓峰, 李百祥. 细胞间隙连接通讯与肿瘤关系的研究进展[J]. 卫生毒理学杂志, 2002, 16(3): 185-187
[16] Fang M, Zhang H, Xue S. Intracellular calcium distribution in apoptosis of HL260 cells induced by harringtonine: intranuclear accumulation and regionalization [J]. Cancer Lett, 1998, 127(122): 113-121
[17] Bruzzone R, White TW, Paul DL. Connections with connexins: the molecular basis of direct intercellular signaling[J]. Eur J Biolchem, 1996, 238(1): 1-27
[18] Hofer T. Model of intercellular calcium oscillations in hepatocytes: Synchronization of heterogeneous cells[J]. Biophysical J, 1999, 77(3): 1244- 1256
[19] Bevans CG, Kordel M, Rhee SK, et al. Isoform conposition of connectionchannels determines selectivity among second messenger and uncharged molecular[J]. J Biol Chem, 1988, 273(5): 2808-2816
[20] Niessen H, Harz H, Bedner P, et al. Selective permeability of different connexin channels to the second messenger inositol 1,4,5-trisphossphate[J]. J Cell Sci, 2000, 118(pt8): 1365-1372
[21] 卢绮萍, 史陈让, 吴笑春. 用 Fura-2 和显微荧光术定量检测活性肝细胞胞内游离钙离子[J]. 中国病理生理杂志, 1996, 12(4): 446-448
[22] Pfahnl A, Dahl G. Gating of cx46 gap junction hemichannels by calcium and voltage[J]. Pfhugers Arch, 1999, 437(3): 345-353
[23] Jansen LA, Vrije T, Jongen WM. Differences in the calcium mediated regulation of gap junctional intercellular communication between a cell line consisting of initiated cellls and a carcinoma derived cell line[J]. Carcinogenesis, 1996,17(11): 2311-2319
[24] Toyofuku T, Yabuki M, Otsu K, et al. Intercellular calcium signaling via gap junction in connexin43 transfected cells[J]. J Biol Chem, 1998, 273(3): 1519-1528
[26] 李靖, 迟彦邦. Ca~(2+)与肝细胞损伤[J]. 国外医学生理病理学与临床分册, 1996, 16(3): 159-161
[1] Gothelf A,Mir LM,Gehl J. Electrochemotherapy: results of cancer treatment using enhanced silivery of bleomycin by electroporation[J]. Cancer Treat Rev, 2003, 29(5): 371-387
[2] Yao C, Sun C, Xiong L, et al. Effect of steep pulsed electric fields on survival of tumour-bearing mice[J]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2004, 21(3): 433-435
[3] 李大强, 熊兰, 胡丽娜, 等. 能量可控陡脉冲对离体肿瘤组织杀伤作用的观察[J]. 重庆医科大学学报, 2001, 26(4): 413-415
[4] 米彦, 孙才新, 姚陈果等. 陡脉冲肿瘤治疗仪的研制及应用[J]. 重庆大学学报(自然科学版), 2003, 26(2): 12-14
[5] 吴传新, 刘长安, 乔天愚, 等. 兔乳腺移植性鳞癌模型的建立及其生物学特征的观察[J]. 重庆医科大学学报, 1999, 24(2): 137-140
[6] Singh NP, McCoy MT, Tice RR, et al. A simple technique for quantitation of low levels of DNA damage in individual cells[J]. Exp Cell Res, 1988, 175 (1): 184-191
[7] Hermann M, Lorenz HM, Voll K, et al. A rapid and simple method for the isolation of apoptotic DNA fragments[J]. Nuleic Acids Research, 1994, 22(24): 5506-5507
[8] 姚陈果, 孙才新, 米彦. 陡脉冲对恶性肿瘤细胞不可逆性电击穿的实验研究[J]. 中国生物医学工程学报, 2004, 23(1): 92-97
[9] 胡娅, 胡丽娜, 熊兰, 等. 能量可控陡脉冲对荷瘤小鼠生存转归的影响[J].实用肿瘤杂志, 2005, 20(4): 305-307
[10] 恽时锋. 健康新西兰兔心电图的测定与分析[J]. 畜牧与兽医, 1998, 30(1): 29-30
[11] Miklavcic D, Semrov D, Mekid H, et al. A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy[J]. Biochem Biophys Acta, 2000, 1523(1): 73-83
[12] Lai H, Singh NP. Acute exposure to a 60 Hz magnetic field increase DNA strand breaks in rat brain cell[J]. Bioelectromagnetics, 1997, 18(2): 156-165
[13] Olive PL, Banath JP, Fjell CD. DNA strand breakage and DNA structure influence staining with propidium iodide using the alkaline comet assay. Cytometry, 1994, 16(4): 305-312
[1] Jalife J, Morley GE, Vaidya D, et al. Connexins and impulse propagation in mouse heart [J]. J Cardiovasc Eletrophysiol, 1999, 10(11): 1649-1663
[2] Bloor DJ, Wilson Y, Kibschull M, et al. Expression of connexins in human preimplantation embryos in vitro[J]. Reprod Biol Endocrinol, 2004, 2(1): 25-30
[3] Liao Y, Day KH, Damon DN, et al. Endothelial cell-specific knock-out of connexin 43 causes hypotention bradycardiain mice[J]. Proc Natl Acad Sci, 2001, 98(17): 9989-9994
[4] Bruzzone R. Learning the language of cell-cell communication through connexin channels[J]. Genome Biol, 2001, 2 (11): 4027
[5] Huang XD, Sandushy GE, Zipes DP. Heterogeneous loss of Cx43 protein in ischemic dog heats [J]. J Cardiovasc Eletrophysiol, 1999, 10(1): 79-91
[6] Azzam EI, de Toledo SM, Little JB. Direct evidence for the participation of gap junction mediated intercellular communication in the transmission of damage signals fromα-particle irradiated to nonirradiated cells[J]. Proc Natl Acad Sci, 2001, 98(2): 473-478
[7] Brink PR, Cronin K, Banach K, et al. Evidnce for heteromeric gap junction channels formed from rat connexin43 and human connexin37[J]. Am J Physiol, 1997, 273(4Pt1): C1386-1396
[8] Wang Y, Rose B. Clustering of Cx43 cell to cell channels into gap junction plaques: regulation by cAMP and microfilaments[J]. J Cell Sci, 1995, 108(Pt 11): 3501-3508
[9] Cooper CD, Solan JL, Dolejsi MK, et al. Analysis of connexin phosphorylation sites[J]. Methods, 2000, 20(2): 196-204
[10] Ren P, Mehta PP, Ruch RJ. Inhibition of gap junctional intercellularcommuniction by tumor promoters in connexin43 and connexin32 expressing liver cells: cell specificity and role of protein kinase C[J]. Carcinogenesis, 1998, 19(1): 169-175
[11] Hossain MZ, Jagdale AB, Ao P, et al. Mitogen activated protein kinase and phosphorylation of connexin43 are not sufficient for the disruption of gap junctional communication by platelet-derived growth factor and tetradecanoy phorbol acetate[J]. J Cell Physiol, 1999, 179(1): 87-96
[12] Atkinson MM, Lampe PD, Lin HH, et al. Cyclic AMP modifies the cellular distribution of connexin43 and induces a persistent increase in the junctional permeability of mouse mammary tumor cells [J]. J Cell Sci, 1995, 108(Pt 19): 3079-3090
[13] Wang Y, Rose B. An inhibition of gap junctional communication by cadherins[J]. J Cell Sci, 1997,110 (Pt3): 301-309
[14] Krutovskikh VA, Troyanovsky SM, Piccoli C, et al. Differential effect of subcellular localization of communication impairing gap junction protein connexin43 on tumor cell growth in vivo [J]. Oncogen, 2000, 19 (4): 505-513
[15] Su YA, BittnerML, Chen Y, et al. Identification of tumor suppressor genes using human melanoma cell lines UACC903, UACC903 (+6), and SRS3 by comparison of expression profiles[J]. Mol Carcinog, 2000, 28(2): 119-127
[16] Huang RP, Hossain MZ, Sehgal A, et al. Reduced connexin 43 expression in high grade human brain gliome cells[J]. J Surg Oncol, 1999, 70(1): 21-24
[17] Murray SA, Davis K, Fishman LM, et al. Alphal connexin43 gap junctions are decreased in human adrenocortical tumors[J]. J Clin Endocrinol Metab, 2000, 85(2): 890-895
[18] Laird DW, Fisturis P, Batist G, et al. Deficiency of connexin43 gap junctions is an independent marker for breast tumors[J]. Cancer Res, 1999, 59(16): 4104-4110
[19] Cesen Cummings K, Fernstrom MJ, Malkinson AM, et al. Frequent reduction of gap junctional intercellular communication and connexin43 expression in human and mouse lung carcinoma cells[J]. Carcinogenesis, 1998,19(1): 61-67
[20] Hanna EA, Umhauer S, Roshong SL, et al. Gap junctional intercellular communication and connexin43 expression in human ovarian surface epithelial cells and ovarian carcinomas in vivo and in vitro[J]. Carcinogenesis, 1999, 20(7): 1369- 1373.
[21] 胡叶青, 刘元姣. 在卵巢上皮性肿瘤组织中的表达及临床意义[J]. 癌症, 2005, 24(1): 104-109
[22] Omori Y, Yamasaki H. Mutated connexin43 proteins inhibit rat glioma cell growth suppression mediated by wild type connexin43 in a domiant negative manner[J]. Int J Cancer, 1998, 78(4): 446-453
[23] Hattori Y, Maitani Y. Folate-linked nanoparticle-mediated suicide gene therapy in human prostate cancer and nasopharyngeal cancer with herpes simplex virus thymidine kinase[J]. Cancer Gene Ther, 2005, 12(10): 796-809
[24] Shinoura N, Chen L, Wani MA, et al. Protein and messenger RNA expression of connexin43 in astrocytomas: implications in brain tumor gene therapy[J]. J Neurosurg, 1996, 84(5): 839-845
[25] Shirakawa T, Gardner TA, Ko SC, et al. Cytotoxicity of adenoviral mediated cytosine deaminase plus 5-fluorocytosine gene therapy is superior to thymidine kinase plus acyclovir in a human renal cell carcinoma mode[J]. J Urol, 1999, 162 (3pt1): 949-954
[26] 刘颖斌, 许斌, 王建伟, 等. 全反式维甲酸对肝癌细胞连接蛋白基因表达及细胞间隙连接通讯功能的影响[J].中华医学杂志, 2005, 85(20): 1414-1418
[27] King TJ, Bertram JS. Connexins as targets for cancer chemoprevention andchemotherapy[J]. Biochim Biophys Acta, 2005, 1719(1-2): 146-60.
[28] Clairmont A, Sies H. Evidence for a posttranscriptional effect of retinoicacid on connexin43 gene expression via the 3-untranslated region[J]. FEBS Lett, 1997, 419(223): 268-270
[2] Sukhendu BD, Dietmar PR, Georg W, et al. Medical applications of electroporation [J]. IEEE Transaction on Plasma Science, 2000, 28(1): 206-223
[3] Nilsson E, von Euler H, Berendson J, et al. Electrochemical treatment of tumours [J]. Bioelectrochemistry, 2000, 51(1): 1-11
[4] Sersa G, Stabuc B, Cemazar M, et al. Electrochemotherapy with cisplatin: potentation of local cisplatin antitumour effectiveness by application of electric pulses in cancer patients[J]. Eur J Cancer, 1998, 34(8): 1213-1218
[5] Engstrom PE, Persson BR, Brun A, et al. A new antitumour treatment combining radiation and electric pulses[J]. Anticancer Res, 2001, 21(3B): 1809-1815
[6] Toru Horikoshi, Hirofumi Naganuma, Yasuhiro Ohashi, et al. Enhancing effect of electric stimulation on cytotoxicity of anticancer agents against rat and human glioma cells[J]. Brain Research Bulletin, 2000, 51(5): 371-378
[7] Cemazar M, Miklavcic D, Mir LM, et al. Electrochemotherapy of tumors resistant to cisplatin: a study in a murine tumour model[J]. Eur J Cancer, 2001, 37(9): 1166-1172
[8] Jaroszeski MJ, Coppoda D, Pottinger C, et al. Treatment of hepatocellular carcinoma in a rat model using electrochemotherapy[J]. Eur J Cancer, 2001, 37(3): 422-430
[9] Weaver JC. Electroporation: a general phenomenon for manipulating cells and tissues[J]. J Cell Biochem, 1993, 51(4): 426-435
[10] Hofmann GA, Evans G. Electronic genetic-physical and biological aspects ofcellular electromanipulation[J]. IEEE Eng. Med. Biol, Mag, 1986, 5(4): 6-25
[11] Hofmann GA, Dev SB, Dimmer S, et al. Electroporation therapy: a new approach for the treatment of head and neck cancer[J]. IEEE Trans. On Biomedical Engineering, 1999, (46) 6: 752-759
[12] 李大强, 熊兰, 胡丽娜, 等. 能量可控陡脉冲对离体肿瘤组织杀伤作用的观察[J]. 重庆医科大学学报, 2001, 26(4): 413-415
[13] 孙才新, 姚陈果, 熊兰, 等. 陡脉冲电场对恶性肿瘤细胞杀伤效应的研究[J]. 生物物理学报, 2002, 18(4): 474-477
[14] 熊兰, 孙才新, 胡丽娜, 等. 能量可控陡脉冲杀伤肿瘤的离体试验研究[J].生物医学工程学杂志, 2002, 19(3): 440-443
[15] 胡娅, 胡丽娜, 熊兰, 等. 能量可控陡脉冲对荷瘤小鼠生存转归的影响[J].实用肿瘤杂志, 2005, 20(4): 305-307
[16] Parkman HP, Pagano AP, Martin JS, et al. Electric field stimulation geuinea pig gallbladder contraction: role of calcium channels in acetycholine release[J]. Digestive Disease and Sciences, 1997, 142(9): 1919-1925
[17] Berridge MJ. Inositol trisphosphate and calcium signalling[J]. Nature, 1993, 36(28): 315-325
[18] Kolaja KL, Engelken DT, Klaassen CD. Inhibition of gap-junctional- intercellular communication in intact rat liver by non-genotoxic hepatocarcinogens[J]. Toxicology, 2000, 146(1): 15-22
[19] Saunders MM, Seraj MJ, Li Z, et al. Breast cancer metastatic potential correlates with a breakdown in homospecific and heterospecific gap junctional intercellular communication[J]. Cancer Res, 2001, 61(5): 1765-1767
[20] Esinduy C, Chang CC, Trosko JE. In vitro growth inhibition of neoplastically transformed cells by non-transformed cells: requirement for gap junctional intercellular communication[J]. Carcinogenesis, 1995, 16(4): 915-921
[21] Mehta PP, Perez-Stable C, Nadji M, et al. Suppression of human prostate cancer cell growth by forced expression of connexin genes[J]. Dev Genet, 1999, 24 (1): 91-110
[22] 张晓峰,李百祥. 细胞间隙连接通讯与肿瘤关系的研究进展[J]. 卫生毒理学杂志,2002, 16(3): 185-187
[23] Lai H, Singh NP. Acute exposure to a 60 Hz magnetic field increase DNA strand breaks in rat brain cell[J]. Bioelectromagnetics, 1997, 18(2): 156-165
[1] 胡娅, 胡丽娜, 米彦等. 能量可控陡脉冲对人卵巢癌细胞的体外作用[J].第三军医大大学学报, 2003, 25(16): 1441-1445
[2] 姚陈果, 孙才新, 米彦等. 陡脉冲对恶性肿瘤细胞不可逆性电击穿的实验研究[J].中国生物医学工程学报, 2004, 23(1): 92-97
[3] 米彦, 孙才新, 姚陈果等. 陡脉冲肿瘤治疗仪的研制及应用[J].重庆大学学报(自然科学版),2003, 26(2):12-14
[4] 张薇, 朴英杰, 鲍永耀,等. 粘附式细胞仪测定巨噬细胞内游离钙的方法[J]. 第一军医大学学报,1994, 14 (1):43-45
[5] Manning TJ, Sontheimer H. Recording of intracellular Ca~(2+), Cl2,pH and membrane potential in cultured astrocytes using a fluorescence plate reader[J]. J Neurosci Methods, 1999, 91(122): 73-81
[6] Gordienko DV, Zholos AV, Bolton TB. Membrane ion channels as physiological targets for local Ca~(2+) signalling[J]. J Microsc, 1999,196(Pt 3): 305-316
[7] Asada Y, Yamazawa T, Hirose K, et al. Dynamic Ca~(2+) signaling in rat arterial smooth muscle cells under the control of local reninangiotensin system[J] . J Physiol Lond, 1999, 521( Pt 2): 497-505
[8] Tsien RY. Measuring and manipulating cytosolic Ca~(2+) with trapped indicators [J]. Kroc Found Ser, 1984, 17: 147-155
[9] Distelhorst CW,Duhyak G.. Role of calcium in glucocorticosterione immunal apotosis of thycocyte and lymphoma cells: resumecole of old theroies by new findings[J]. Blood, 1998, 91(3): 731-734
[10] Wang HG, Pathan Y, Ethell IM, el al. Ca~(2+) induced apoptosis through calcineurin dephosphocylin of BAD[J]. Science, 1999, 284(5412): 339-343
[11] Chattopadhyay N, Ye CP, Yamaguchi T, et al. Extracellular calcium-sensingreceptor induces cellular proliferation and activation non-selective cation channel in U373 astrocytoma cells[J]. Brain Res, 1999, 851(1-2): 116-124
[12] 梁润酶, 董惠文. 钙通道[J]. 生命的化学, 1994, 14(5): 23-25
[13] Dolmetsch RE, Lewis RS, Goodnows CC, et al. Differential activation of transcription factors induced by Ca~(~(2+)) response amplitude and duration[J]. Nature, 1997, 386(6627): 855-858
[14] Walleczek J. Electromagnetic field effects on cells of the immune system: the role of calcium signaling[J]. FASEB, 1992, 6(13): 3177-3185
[15] Blackman CF, Benane SG, Radinowitz JR, et al. A role for the magnetic field in the radiation induced efflux of calcium ions from brain tissue in vitro[J]. Bioelectromagnetics, 1985, 6(4): 327-337
[16] Beani L, Tomasini C, Govoni BM, et al. Fluorimetric determination of electrically evoked increase in intracellular calcium in cultures cerebellar granule cells[J]. J Neurosci Methods, 1994, 51(1): 1-7
[17] Parkman HP, Pagano AP, Martin JS, et al. Electric field stimulation geuinea pig gallbladder contractions: role of calcium channels in acetycholine release[J]. Digestive Diseases and Sciences, 1997, 142(9): 1919-1925
[18] Eichwald C, Kaiser F. Model for external influences on cellular signal transductin pathway including cytosolic calcium oscillations [J]. Bioelectromagnetics, 1995, 16(2): 75-85
[19] Berridge MJ. Inositol trisphosphate and calcium signalling[J]. Nature, 1993, 361(28): 315-325
[20] Dibirdik I, Kristupaitis D, Kurosaki T, et al. Stimulation of Src family protein tyrosine kinases as a proximal and mandatory step for SYK kinase-dependent phospholipase Cy2 activation in lymphoma B cells exposed to low energy electromagnetic fields[J]. J Biol Chem, 1998, 273 (7): 4035-4039
[21] Kristupaitis D, Dibirdik I, Vassilev A, et al. Electromagnetic field-induced stimulation of Bruton’s tyrosine kinase[J]. J Biol Chem, 1998, 273(20): 12397-12401
[22] Miller SC, Furniss MJ. Bruton’s tyrosine kinase activity and inositol 1,4,5- trisphosphate production are not altered in DT40 lymphoma B cells exposed to power line frequency magnetic fields[J]. J Biol Chem, 1998, 273(49): 32618-32626
[23] 熊兰, 孙才新, 米彦, 等.陡脉冲诱导在体瘤细胞凋亡的实验及分析.重庆大学学报(自然科学版), 2004, 27(11): 22-25
[24] 王萍玲, 胡丽娜, 李聪, 等.能量可控陡脉冲联合 H-ras 干扰性 RNA 治疗卵巢癌裸鼠皮下移植瘤的实验研究.第三军医大学学报, 2005,27(6): 490-493
[25] Schiffenbauer YS, Trubniykov E, Zacharia BT, et al. Tumor sensitivity to anti-cancer drugs predicted by changes in fluorescence intensity and polarization in vitro[J]. Anticancer Res, 2002, 22(5): 2663-2669
[26] Matarrese P, Gamdbardella L, Gassone A, et al. Mitochondrial membrane hyperpolarization hijacks activated T lymphocytes toward the apoptotic-probe phenotype: homeostatic mechanisms of HIV protease inhibitors[J]. J Immunol, 2003, 170(12): 6006-6015
[27] Radosevoic K, Schut TC, Van Graft M, et al. A flow cytometric study of the membrane potential natural killer and k562 cells during the cytotoxic process[J]. J Immunol Methods, 1993,161 (1-2): 119
[28] Taichman NS, Iwase M, Lally ET, et al. Early changes in cytosolic calcium and membrane potential induced by actinobacillus actinomyce-temcomitans leukotoxin insusceptible and resistant target cells[J]. J Immunol, 1991, 147(10): 3587.
[1] Zhang JT, Nicholson BJ. The topological structure of connexin 26 and its distribution compared to connexin 32 in hepatic gap junctions[J]. J Membr Biol, 1994, 139(1): 15-29
[2] Naus CC, Zhu D, Todd SD, et al. Characteristics of C6 glioma cells overexpression a gap junction protein [J]. Cell Mol Neuroboil, 1992, 12 (2): 163-175
[3] Paul DL. New functions for gap junctions [J]. Curr Opin Cell Biol, 1995, 7(5): 665-672
[4] Noguchi M, Nomata K, Watanabe J, et al. Changes in the gap junctional intercellular communication inrenal tubular epithelial cells in vitro treated with renal carcinogens [J]. Cancer Lett, 1998, 122 (1-2): 77- 84
[5] 孙才新, 姚陈果, 熊兰, 等. 陡脉冲电场对恶性肿瘤细胞杀伤效应的研究[J].生物物理学报, 2002,18(4):474-477
[6] Kolaja KL, Engelken DT, Klaassen CD. Inhibition of gap-junctional -intercellular communication in intact rat liver by non-genotoxic hepatocarcinogens[J]. Toxicology, 2000, 146(1): 15-22
[7] Ruch RJ. The role of gap junctional intercellular communication in neoplasia [J]. Ann Clin Lab Sci, 1994, 24 (3): 216-223.
[8] Lee SW, Tomasetto C, Paul D, et al. Transcriptional downregulation of gap junction proteins blocks junctional communication in human mammary tumor cell lines [J]. J Cell Bio1, 1992, 118 (5): 1213-1221
[9] Hirschi KK, Xu CE, Tsukamoto T, et al. Gap junction genes Cx26 and Cx43 individually suppress the cancer phenotype of human mammary carcinoma cells and restore differentiation potential [J]. Cell Growth Differ, 1996, 7 (7): 861- 870
[10] Saunders MM, Seraj MJ, Li Z, et al. Breast cancer metastatic potential correlates with a breakdown in homospecific and heterospecific gap junctional intercellular communication[J]. Cancer Res. 2001,61(5): 1765-1767
[11] Esinduy C, Chang CC, Trosko JE. In vitro growth inhibition of neoplastically transformed cells by non-transformed cells: requirement for gap junctional intercellular communication[J]. Carcinogenesis, 1995, 16(4): 915-921
[12] Mehta PP, Perez-Stable C, Nadji M, et al. Suppression of human prostate cancer cell growth by forced expression of connexin genes[J]. Dev Genet, 1999, 24 (1-2): 91-110
[13] Yao C, Sun C, Xiong L, et al. Effect of steep pulsed electric fields on survival of tumour-bearing mice[J]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2004, 21(3): 433-435
[14] 王萍玲, 胡丽娜, 李聪, 等. 能量可控陡脉冲联合 H-ras 干扰性 RNA 治疗卵巢癌裸鼠皮下移植瘤的实验研究[J]. 第三军医大学学报, 2005, 27(6): 490-493
[15] 张晓峰, 李百祥. 细胞间隙连接通讯与肿瘤关系的研究进展[J]. 卫生毒理学杂志, 2002, 16(3): 185-187
[16] Fang M, Zhang H, Xue S. Intracellular calcium distribution in apoptosis of HL260 cells induced by harringtonine: intranuclear accumulation and regionalization [J]. Cancer Lett, 1998, 127(122): 113-121
[17] Bruzzone R, White TW, Paul DL. Connections with connexins: the molecular basis of direct intercellular signaling[J]. Eur J Biolchem, 1996, 238(1): 1-27
[18] Hofer T. Model of intercellular calcium oscillations in hepatocytes: Synchronization of heterogeneous cells[J]. Biophysical J, 1999, 77(3): 1244- 1256
[19] Bevans CG, Kordel M, Rhee SK, et al. Isoform conposition of connectionchannels determines selectivity among second messenger and uncharged molecular[J]. J Biol Chem, 1988, 273(5): 2808-2816
[20] Niessen H, Harz H, Bedner P, et al. Selective permeability of different connexin channels to the second messenger inositol 1,4,5-trisphossphate[J]. J Cell Sci, 2000, 118(pt8): 1365-1372
[21] 卢绮萍, 史陈让, 吴笑春. 用 Fura-2 和显微荧光术定量检测活性肝细胞胞内游离钙离子[J]. 中国病理生理杂志, 1996, 12(4): 446-448
[22] Pfahnl A, Dahl G. Gating of cx46 gap junction hemichannels by calcium and voltage[J]. Pfhugers Arch, 1999, 437(3): 345-353
[23] Jansen LA, Vrije T, Jongen WM. Differences in the calcium mediated regulation of gap junctional intercellular communication between a cell line consisting of initiated cellls and a carcinoma derived cell line[J]. Carcinogenesis, 1996,17(11): 2311-2319
[24] Toyofuku T, Yabuki M, Otsu K, et al. Intercellular calcium signaling via gap junction in connexin43 transfected cells[J]. J Biol Chem, 1998, 273(3): 1519-1528
[26] 李靖, 迟彦邦. Ca~(2+)与肝细胞损伤[J]. 国外医学生理病理学与临床分册, 1996, 16(3): 159-161
[1] Gothelf A,Mir LM,Gehl J. Electrochemotherapy: results of cancer treatment using enhanced silivery of bleomycin by electroporation[J]. Cancer Treat Rev, 2003, 29(5): 371-387
[2] Yao C, Sun C, Xiong L, et al. Effect of steep pulsed electric fields on survival of tumour-bearing mice[J]. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi, 2004, 21(3): 433-435
[3] 李大强, 熊兰, 胡丽娜, 等. 能量可控陡脉冲对离体肿瘤组织杀伤作用的观察[J]. 重庆医科大学学报, 2001, 26(4): 413-415
[4] 米彦, 孙才新, 姚陈果等. 陡脉冲肿瘤治疗仪的研制及应用[J]. 重庆大学学报(自然科学版), 2003, 26(2): 12-14
[5] 吴传新, 刘长安, 乔天愚, 等. 兔乳腺移植性鳞癌模型的建立及其生物学特征的观察[J]. 重庆医科大学学报, 1999, 24(2): 137-140
[6] Singh NP, McCoy MT, Tice RR, et al. A simple technique for quantitation of low levels of DNA damage in individual cells[J]. Exp Cell Res, 1988, 175 (1): 184-191
[7] Hermann M, Lorenz HM, Voll K, et al. A rapid and simple method for the isolation of apoptotic DNA fragments[J]. Nuleic Acids Research, 1994, 22(24): 5506-5507
[8] 姚陈果, 孙才新, 米彦. 陡脉冲对恶性肿瘤细胞不可逆性电击穿的实验研究[J]. 中国生物医学工程学报, 2004, 23(1): 92-97
[9] 胡娅, 胡丽娜, 熊兰, 等. 能量可控陡脉冲对荷瘤小鼠生存转归的影响[J].实用肿瘤杂志, 2005, 20(4): 305-307
[10] 恽时锋. 健康新西兰兔心电图的测定与分析[J]. 畜牧与兽医, 1998, 30(1): 29-30
[11] Miklavcic D, Semrov D, Mekid H, et al. A validated model of in vivo electric field distribution in tissues for electrochemotherapy and for DNA electrotransfer for gene therapy[J]. Biochem Biophys Acta, 2000, 1523(1): 73-83
[12] Lai H, Singh NP. Acute exposure to a 60 Hz magnetic field increase DNA strand breaks in rat brain cell[J]. Bioelectromagnetics, 1997, 18(2): 156-165
[13] Olive PL, Banath JP, Fjell CD. DNA strand breakage and DNA structure influence staining with propidium iodide using the alkaline comet assay. Cytometry, 1994, 16(4): 305-312
[1] Jalife J, Morley GE, Vaidya D, et al. Connexins and impulse propagation in mouse heart [J]. J Cardiovasc Eletrophysiol, 1999, 10(11): 1649-1663
[2] Bloor DJ, Wilson Y, Kibschull M, et al. Expression of connexins in human preimplantation embryos in vitro[J]. Reprod Biol Endocrinol, 2004, 2(1): 25-30
[3] Liao Y, Day KH, Damon DN, et al. Endothelial cell-specific knock-out of connexin 43 causes hypotention bradycardiain mice[J]. Proc Natl Acad Sci, 2001, 98(17): 9989-9994
[4] Bruzzone R. Learning the language of cell-cell communication through connexin channels[J]. Genome Biol, 2001, 2 (11): 4027
[5] Huang XD, Sandushy GE, Zipes DP. Heterogeneous loss of Cx43 protein in ischemic dog heats [J]. J Cardiovasc Eletrophysiol, 1999, 10(1): 79-91
[6] Azzam EI, de Toledo SM, Little JB. Direct evidence for the participation of gap junction mediated intercellular communication in the transmission of damage signals fromα-particle irradiated to nonirradiated cells[J]. Proc Natl Acad Sci, 2001, 98(2): 473-478
[7] Brink PR, Cronin K, Banach K, et al. Evidnce for heteromeric gap junction channels formed from rat connexin43 and human connexin37[J]. Am J Physiol, 1997, 273(4Pt1): C1386-1396
[8] Wang Y, Rose B. Clustering of Cx43 cell to cell channels into gap junction plaques: regulation by cAMP and microfilaments[J]. J Cell Sci, 1995, 108(Pt 11): 3501-3508
[9] Cooper CD, Solan JL, Dolejsi MK, et al. Analysis of connexin phosphorylation sites[J]. Methods, 2000, 20(2): 196-204
[10] Ren P, Mehta PP, Ruch RJ. Inhibition of gap junctional intercellularcommuniction by tumor promoters in connexin43 and connexin32 expressing liver cells: cell specificity and role of protein kinase C[J]. Carcinogenesis, 1998, 19(1): 169-175
[11] Hossain MZ, Jagdale AB, Ao P, et al. Mitogen activated protein kinase and phosphorylation of connexin43 are not sufficient for the disruption of gap junctional communication by platelet-derived growth factor and tetradecanoy phorbol acetate[J]. J Cell Physiol, 1999, 179(1): 87-96
[12] Atkinson MM, Lampe PD, Lin HH, et al. Cyclic AMP modifies the cellular distribution of connexin43 and induces a persistent increase in the junctional permeability of mouse mammary tumor cells [J]. J Cell Sci, 1995, 108(Pt 19): 3079-3090
[13] Wang Y, Rose B. An inhibition of gap junctional communication by cadherins[J]. J Cell Sci, 1997,110 (Pt3): 301-309
[14] Krutovskikh VA, Troyanovsky SM, Piccoli C, et al. Differential effect of subcellular localization of communication impairing gap junction protein connexin43 on tumor cell growth in vivo [J]. Oncogen, 2000, 19 (4): 505-513
[15] Su YA, BittnerML, Chen Y, et al. Identification of tumor suppressor genes using human melanoma cell lines UACC903, UACC903 (+6), and SRS3 by comparison of expression profiles[J]. Mol Carcinog, 2000, 28(2): 119-127
[16] Huang RP, Hossain MZ, Sehgal A, et al. Reduced connexin 43 expression in high grade human brain gliome cells[J]. J Surg Oncol, 1999, 70(1): 21-24
[17] Murray SA, Davis K, Fishman LM, et al. Alphal connexin43 gap junctions are decreased in human adrenocortical tumors[J]. J Clin Endocrinol Metab, 2000, 85(2): 890-895
[18] Laird DW, Fisturis P, Batist G, et al. Deficiency of connexin43 gap junctions is an independent marker for breast tumors[J]. Cancer Res, 1999, 59(16): 4104-4110
[19] Cesen Cummings K, Fernstrom MJ, Malkinson AM, et al. Frequent reduction of gap junctional intercellular communication and connexin43 expression in human and mouse lung carcinoma cells[J]. Carcinogenesis, 1998,19(1): 61-67
[20] Hanna EA, Umhauer S, Roshong SL, et al. Gap junctional intercellular communication and connexin43 expression in human ovarian surface epithelial cells and ovarian carcinomas in vivo and in vitro[J]. Carcinogenesis, 1999, 20(7): 1369- 1373.
[21] 胡叶青, 刘元姣. 在卵巢上皮性肿瘤组织中的表达及临床意义[J]. 癌症, 2005, 24(1): 104-109
[22] Omori Y, Yamasaki H. Mutated connexin43 proteins inhibit rat glioma cell growth suppression mediated by wild type connexin43 in a domiant negative manner[J]. Int J Cancer, 1998, 78(4): 446-453
[23] Hattori Y, Maitani Y. Folate-linked nanoparticle-mediated suicide gene therapy in human prostate cancer and nasopharyngeal cancer with herpes simplex virus thymidine kinase[J]. Cancer Gene Ther, 2005, 12(10): 796-809
[24] Shinoura N, Chen L, Wani MA, et al. Protein and messenger RNA expression of connexin43 in astrocytomas: implications in brain tumor gene therapy[J]. J Neurosurg, 1996, 84(5): 839-845
[25] Shirakawa T, Gardner TA, Ko SC, et al. Cytotoxicity of adenoviral mediated cytosine deaminase plus 5-fluorocytosine gene therapy is superior to thymidine kinase plus acyclovir in a human renal cell carcinoma mode[J]. J Urol, 1999, 162 (3pt1): 949-954
[26] 刘颖斌, 许斌, 王建伟, 等. 全反式维甲酸对肝癌细胞连接蛋白基因表达及细胞间隙连接通讯功能的影响[J].中华医学杂志, 2005, 85(20): 1414-1418
[27] King TJ, Bertram JS. Connexins as targets for cancer chemoprevention andchemotherapy[J]. Biochim Biophys Acta, 2005, 1719(1-2): 146-60.
[28] Clairmont A, Sies H. Evidence for a posttranscriptional effect of retinoicacid on connexin43 gene expression via the 3-untranslated region[J]. FEBS Lett, 1997, 419(223): 268-270