新肿瘤标志物的筛选及功能初步研究
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摘要
第一章肿瘤标志物的生物信息学筛选及其表达谱初步分析
目的:采用生物信息学方法筛选肿瘤差异表达基因,并对筛选得到的结果进行表达谱初步分析。
方法:利用CGAP网站提供的cDNA xProfiler工具,以人类正常组织和肿瘤组织EST数据库为基础,筛选肿瘤差异表达基因,并对筛选得到的68个基因进行染色体定位。采用电子杂交以及RT-PCR的方法对筛选得到的结果进行表达谱初步分析。
结果:通过生物信息学筛选得到在肿瘤组织中特异性表达的基因或EST片段2801个,其中已知基因68个,未知基因2733个。在这68个已知基因中,40个基因的功能已基本明确。在这40个基因中5个基因已经实验证实为肿瘤特异性基因,占12.5%。对筛选得到的68个基因进行染色体定位,发现在7号和10号染色体上筛选得到的肿瘤特异性基因较少,而在8号、21号以及X染色体中肿瘤特异性基因出现的频率明显多于其他染色体。进一步对筛选得到的2801个肿瘤特异性表达基因或EST片段进行电子杂交分析,9个基因结果较理想。RT-PCR检测这9个基因在不同细胞株中的表达,7个基因在被检测的11个细胞株中未得到目的片段,而GABRA3基因与HTA基因在肿瘤细胞中表达特异。
结论:生物信息学筛选肿瘤差异表达基因是一种高效的方法。肿瘤特异性基因在某些染色体上相对“活跃”。
第二章GABRA3基因的表达谱分析及功能研究
目的:对GABRA3基因进行表达谱分析及功能初步研究。检测GABAA受体各亚单位在肿瘤组织中的表达。
方法:采用RT-PCR以及免疫组化法分析GABRA3的表达谱。通过RNAi以及药物处理对GABRA3基因的功能进行初步研究。
结果:在被检测的11株细胞株中,GABRA3基因在肝癌细胞株HepG2,乳腺癌细胞株MCF-7,MDA-MB-231和胶质瘤细胞株U251中表达,而在其他肿瘤细胞株以及正常细胞株中无表达。在被检测的20种正常组织中,该基因除在脑组织,子宫内膜,胎盘以及前列腺中有表达外,在其他正常组织中均未被检测到。在18例新鲜肺癌组织标本中GABRA3表达阳性率为66.67%,而对应的18例肺癌癌旁组织中均未检测到该基因。采用免疫组化的方法,分析GABRA3在60例肺癌及10例癌旁组织中的表达。10例癌旁组织均未染色,而60例肺癌组织标本中GABRA3蛋白表达的阳性率为41.67%,肺癌组织中细胞阳性染色主要见于胞质和胞膜。通过对GABRA3蛋白在肺癌组织中表达量与临床资料的相关性分析,发现GABRA3蛋白的表达量肺癌的病理分级密切相关(p＜0.05)。随着肿瘤恶性程度的增高,GABRA3蛋白表达的阳性率和表达量有增高的趋势。在8例肝癌组织标本中,共6例表达GABRA3基因,阳性率为65%。而在所有对应的癌旁组织中均未扩增得到该基因目的片断。在肺癌和肝癌组织中,还检测了GABAA受体其他亚单位的表达情况,除α3亚单位外还有GABAA受体α6、β3、γ2、δ、θ、ε和π亚单位的表达。
在肝癌细胞株HepG2细胞中,检测到GABA生成过程中的关键酶GAD67表达。通过细胞增殖能力研究发现,GABA对肝癌细胞株HepG2具有促增殖的作用。当GABRA3基因被沉默后HepG2细胞的增殖能力明显降低。对GABRA3基因被沉默的HepG2细胞给予GABA药物处理,结果发现其增殖能力非但没有增强,反而有减弱的趋势。
结论:GABRA3基因在肺癌和肝癌中表达上调,其表达量与肿瘤的分化程度密切相关。在肝癌中,肝癌细胞可经GAD67催化产生GABA;GABA发挥了促肿瘤细胞增殖的作用,其作用是通过上调表达的GABRA3介导的。除GABRA3外,肝癌和肺癌组织中还有GABAA受体其他亚单位的表达,当GABRA3被沉默时,GABA通过这些亚单位发挥了抑制肿瘤细胞增殖的作用。
第三章HTA基因的表达谱分析及功能研究
目的:对HTA基因进行生物信息学分析,并对该基因进行表达谱分析及功能初步研究。
方法:采用RT-PCR法分析HTA基因的表达谱,通过RNAi对该基因的功能进行初步研究,采用各种在线工具软件对该基因进行生物信息学分析。
结果:通过RT-PCR检测到HTA基因在人肝癌细胞株HepG2以及多种肿瘤组织中表达,在肝癌中表达阳性率较高,而在正常肝细胞株L-0以及20种正常组织标本均无表达。采用RNAi技术抑制HTA基因在肝癌HepG2细胞中的表达,通过细胞生长曲线、细胞倍增时间、软琼脂集落形成实验、细胞周期检测以及裸鼠成瘤实验研究发现,HTA基因被沉默后HepG2细胞的增殖能力降低。经生物信息学分析,HTA定位于人类染色体16q22.3,包含了3个外显子和2个内含子。其编码的蛋白质为一个分子量较小的碱性亲水性蛋白,定位于细胞核和细胞浆的可能性较大,可能含有7个磷酸化位点、6个糖基化位点以及4个抗原表位。HTA编码蛋白的二级结构中α-螺旋为33.70%,β-折叠为5.43%,属于混合蛋白。
结论:HTA基因特异性表达于肿瘤组织,在肝癌中表达阳性率较高,可能是一种肿瘤特异性基因。该基因具有促进肝癌细胞增殖的作用。
Part 1 In Silico Identification of Tumor Markers and the Expression Patterns of the Candidate Genes
Objectives:To screen tumor markers through whole genome in silico.
Methods:To identify the genes,which are differentially expressed in tumors compared with their corresponding normal tissues,a search was performed using the CGAP cDNA xProfiler based on EST data. E-Northern and RT-PCR was used to analyze the expression profiles of the identified tumor unique genes.
Results:According to the cDNA xProfiler results,there were 2801 genes or ESTs unique in tumor tissues,68 of which were known and 2733 of which were unknown.The functions of 40 genes are clear.5 genes among the 40 genes were tumor-associated genes.On chromosome 7 and 10,few tumor markers were identified;while on chromosome 8,21 and X,much more markers were identified.Then,we performed E-Northern to analyze the expression profiles of the 2801 tumor unique genes.9 genes seemed like ideal.We then performed RT-PCR to verify the expression of these 9 genes in tumor and normal cell lines.7 of them could not be detected in 11 cell lines.GABRA3 and HTA were expressed specifically in cancer cells.
Conclusions:In silico identification is an excellent and time-saving approache to identify genes that could be used as tumor diagnostic markers,prognostic indicators,and suitable targets for various forms of therapeutic intervention.Tumor associated genes were more "active" on some chromosomes.
Part 2 Expression Profile and Function of GABRA3
Objectives:To study the expression profile and function of GABRA3 gene and to detect the expression of GABAA receptor subunits in tumors.
Methods:RT-PCR and immunohistochemistry were used to analyze the expression profile of GABRA3 gene.RNAi and GABA were used to study the function of GABRA3.
Results:GABRA3 was highly expressed in hepatocellular carcinoma line HepG2,and weakly detected in glioma cell line U251 and breast cancer cell lines MCF-7 and MDA-MB-231.In normal tissues, GABRA3 was strongly expressed in brain and placenta,and weakly detected in endometrium and prostate,but undetectable in other tissues. More importantly,the expression of GABRA3 in cancers was rare or less abundant but with the exception of glioma,endometrial cancer,lung caner and liver cancer.By RT-PCR,GABRA3 was detected in 12 out of 18 lung cancer samples(66.67%),but not expressed in corresponding adjacent noncancerous lung tissues.By immunohistochemistry,GABRA3 was detected in 25 out of 60 lung cancer samples(41.67%),but not in 10 corresponding adjacent noncancerous lung tissues.The experimental results demonstrated cytoplasmic and membrane staining.The results further showed the correlation between GABRA3 protein expression and clinical-pathologic variables in lung cancers.GABRA3 protein expression was significantly higher in lower grade of lung cancer (p＜0.05).GABRA3 was also detected in 6 out of 8 liver cancer samples (65%),while not in corresponding adjacent noncancerous liver tissues. We also detected the other subunits of GABAA receptor in lung cancer and liver cancer by RT-PCR.In those samples GABAA-α6,β3,γ2,δ,θ,εandπsubunits were also expressed.GABRA3 may compose functional GABAA receptors with them.
In liver cancer cell line HepG2,GAD67 were detected,suggesting that GABA could function in an autocrine/paracrine manner in HCC cells and promote cell growth.GABA promoted the proliferation of HepG2 cells.Knockdown of endogenous GABRA3 expression in HepG2 attenuated HCC cell growth.GABA enhanced the growth of GABRA3 expressing HepG2 cell.On the other hand,the proliferating ability of GABRA3-knockdown HepG2 was not enhanced but lowered by GABA.
Conclusions:GABRA3 is overexpressed in lung cancer and hepatoma.GABRA3 protein expression was significantly higher in lower grade of cancer.HepG2 cells could produce GABA.GABA promoted the proliferation of HepG2 cells through GABRA3.In lung cancers and liver cancers,some other GABAA receptor subunits were also expressed. When GABRA3 was knocken down,GABA inhibited the proliferative ability of HepG2 cells through those subunits.
Part 3 Expression Profile and Function of HTA
Objectives:To study the expression profile and function of HTA.
Methods:RT-PCR was used to analyze the expression profile of HTA gene and RNAi was used to study the function of it.
Results:HTA was a tumor-specific gene,especially in hepatoma.It was detected in liver cancer cell line HepG2,some liver cancer tissue samples(75%) and some other cancer tissues.But in the normal tissues it was not detected.Knockdown of endogenous HTA gene was performed by small interfering RNA in malignant hepatocyte HepG2.Then we tested the cell proliferative ability of these cells in vitro and in vivo.The results showed that HTA could promote HCC cell growth.HTA is located on chromosome 16q22.3,including 3 exons and 2 introns.The encoded protein is an alkaline hydrophilic protein,whose molecular weight is 10KD,PI is 10.9.This protein may play an important role in signal conduction because it may contain 7 phosphorylation sites and 6 glycosylation sites.The secondary structure of the protein contains 33.7%α-helix and 5.43%β-sheet.HTA encoded protein may contains 4 antigen epitope,which are located at 4-14aa,37-43aa,54-60aa and 65-89aa.
Conclusions:HTA was a tumor-specific gene,especially in hepatoma.It plays an important role in HCC cell viability and is a sustained event in the tumorigenic process.
目的:采用生物信息学方法筛选肿瘤差异表达基因,并对筛选得到的结果进行表达谱初步分析。
方法:利用CGAP网站提供的cDNA xProfiler工具,以人类正常组织和肿瘤组织EST数据库为基础,筛选肿瘤差异表达基因,并对筛选得到的68个基因进行染色体定位。采用电子杂交以及RT-PCR的方法对筛选得到的结果进行表达谱初步分析。
结果:通过生物信息学筛选得到在肿瘤组织中特异性表达的基因或EST片段2801个,其中已知基因68个,未知基因2733个。在这68个已知基因中,40个基因的功能已基本明确。在这40个基因中5个基因已经实验证实为肿瘤特异性基因,占12.5%。对筛选得到的68个基因进行染色体定位,发现在7号和10号染色体上筛选得到的肿瘤特异性基因较少,而在8号、21号以及X染色体中肿瘤特异性基因出现的频率明显多于其他染色体。进一步对筛选得到的2801个肿瘤特异性表达基因或EST片段进行电子杂交分析,9个基因结果较理想。RT-PCR检测这9个基因在不同细胞株中的表达,7个基因在被检测的11个细胞株中未得到目的片段,而GABRA3基因与HTA基因在肿瘤细胞中表达特异。
结论:生物信息学筛选肿瘤差异表达基因是一种高效的方法。肿瘤特异性基因在某些染色体上相对“活跃”。
第二章GABRA3基因的表达谱分析及功能研究
目的:对GABRA3基因进行表达谱分析及功能初步研究。检测GABAA受体各亚单位在肿瘤组织中的表达。
方法:采用RT-PCR以及免疫组化法分析GABRA3的表达谱。通过RNAi以及药物处理对GABRA3基因的功能进行初步研究。
结果:在被检测的11株细胞株中,GABRA3基因在肝癌细胞株HepG2,乳腺癌细胞株MCF-7,MDA-MB-231和胶质瘤细胞株U251中表达,而在其他肿瘤细胞株以及正常细胞株中无表达。在被检测的20种正常组织中,该基因除在脑组织,子宫内膜,胎盘以及前列腺中有表达外,在其他正常组织中均未被检测到。在18例新鲜肺癌组织标本中GABRA3表达阳性率为66.67%,而对应的18例肺癌癌旁组织中均未检测到该基因。采用免疫组化的方法,分析GABRA3在60例肺癌及10例癌旁组织中的表达。10例癌旁组织均未染色,而60例肺癌组织标本中GABRA3蛋白表达的阳性率为41.67%,肺癌组织中细胞阳性染色主要见于胞质和胞膜。通过对GABRA3蛋白在肺癌组织中表达量与临床资料的相关性分析,发现GABRA3蛋白的表达量肺癌的病理分级密切相关(p＜0.05)。随着肿瘤恶性程度的增高,GABRA3蛋白表达的阳性率和表达量有增高的趋势。在8例肝癌组织标本中,共6例表达GABRA3基因,阳性率为65%。而在所有对应的癌旁组织中均未扩增得到该基因目的片断。在肺癌和肝癌组织中,还检测了GABAA受体其他亚单位的表达情况,除α3亚单位外还有GABAA受体α6、β3、γ2、δ、θ、ε和π亚单位的表达。
在肝癌细胞株HepG2细胞中,检测到GABA生成过程中的关键酶GAD67表达。通过细胞增殖能力研究发现,GABA对肝癌细胞株HepG2具有促增殖的作用。当GABRA3基因被沉默后HepG2细胞的增殖能力明显降低。对GABRA3基因被沉默的HepG2细胞给予GABA药物处理,结果发现其增殖能力非但没有增强,反而有减弱的趋势。
结论:GABRA3基因在肺癌和肝癌中表达上调,其表达量与肿瘤的分化程度密切相关。在肝癌中,肝癌细胞可经GAD67催化产生GABA;GABA发挥了促肿瘤细胞增殖的作用,其作用是通过上调表达的GABRA3介导的。除GABRA3外,肝癌和肺癌组织中还有GABAA受体其他亚单位的表达,当GABRA3被沉默时,GABA通过这些亚单位发挥了抑制肿瘤细胞增殖的作用。
第三章HTA基因的表达谱分析及功能研究
目的:对HTA基因进行生物信息学分析,并对该基因进行表达谱分析及功能初步研究。
方法:采用RT-PCR法分析HTA基因的表达谱,通过RNAi对该基因的功能进行初步研究,采用各种在线工具软件对该基因进行生物信息学分析。
结果:通过RT-PCR检测到HTA基因在人肝癌细胞株HepG2以及多种肿瘤组织中表达,在肝癌中表达阳性率较高,而在正常肝细胞株L-0以及20种正常组织标本均无表达。采用RNAi技术抑制HTA基因在肝癌HepG2细胞中的表达,通过细胞生长曲线、细胞倍增时间、软琼脂集落形成实验、细胞周期检测以及裸鼠成瘤实验研究发现,HTA基因被沉默后HepG2细胞的增殖能力降低。经生物信息学分析,HTA定位于人类染色体16q22.3,包含了3个外显子和2个内含子。其编码的蛋白质为一个分子量较小的碱性亲水性蛋白,定位于细胞核和细胞浆的可能性较大,可能含有7个磷酸化位点、6个糖基化位点以及4个抗原表位。HTA编码蛋白的二级结构中α-螺旋为33.70%,β-折叠为5.43%,属于混合蛋白。
结论:HTA基因特异性表达于肿瘤组织,在肝癌中表达阳性率较高,可能是一种肿瘤特异性基因。该基因具有促进肝癌细胞增殖的作用。
Part 1 In Silico Identification of Tumor Markers and the Expression Patterns of the Candidate Genes
Objectives:To screen tumor markers through whole genome in silico.
Methods:To identify the genes,which are differentially expressed in tumors compared with their corresponding normal tissues,a search was performed using the CGAP cDNA xProfiler based on EST data. E-Northern and RT-PCR was used to analyze the expression profiles of the identified tumor unique genes.
Results:According to the cDNA xProfiler results,there were 2801 genes or ESTs unique in tumor tissues,68 of which were known and 2733 of which were unknown.The functions of 40 genes are clear.5 genes among the 40 genes were tumor-associated genes.On chromosome 7 and 10,few tumor markers were identified;while on chromosome 8,21 and X,much more markers were identified.Then,we performed E-Northern to analyze the expression profiles of the 2801 tumor unique genes.9 genes seemed like ideal.We then performed RT-PCR to verify the expression of these 9 genes in tumor and normal cell lines.7 of them could not be detected in 11 cell lines.GABRA3 and HTA were expressed specifically in cancer cells.
Conclusions:In silico identification is an excellent and time-saving approache to identify genes that could be used as tumor diagnostic markers,prognostic indicators,and suitable targets for various forms of therapeutic intervention.Tumor associated genes were more "active" on some chromosomes.
Part 2 Expression Profile and Function of GABRA3
Objectives:To study the expression profile and function of GABRA3 gene and to detect the expression of GABAA receptor subunits in tumors.
Methods:RT-PCR and immunohistochemistry were used to analyze the expression profile of GABRA3 gene.RNAi and GABA were used to study the function of GABRA3.
Results:GABRA3 was highly expressed in hepatocellular carcinoma line HepG2,and weakly detected in glioma cell line U251 and breast cancer cell lines MCF-7 and MDA-MB-231.In normal tissues, GABRA3 was strongly expressed in brain and placenta,and weakly detected in endometrium and prostate,but undetectable in other tissues. More importantly,the expression of GABRA3 in cancers was rare or less abundant but with the exception of glioma,endometrial cancer,lung caner and liver cancer.By RT-PCR,GABRA3 was detected in 12 out of 18 lung cancer samples(66.67%),but not expressed in corresponding adjacent noncancerous lung tissues.By immunohistochemistry,GABRA3 was detected in 25 out of 60 lung cancer samples(41.67%),but not in 10 corresponding adjacent noncancerous lung tissues.The experimental results demonstrated cytoplasmic and membrane staining.The results further showed the correlation between GABRA3 protein expression and clinical-pathologic variables in lung cancers.GABRA3 protein expression was significantly higher in lower grade of lung cancer (p＜0.05).GABRA3 was also detected in 6 out of 8 liver cancer samples (65%),while not in corresponding adjacent noncancerous liver tissues. We also detected the other subunits of GABAA receptor in lung cancer and liver cancer by RT-PCR.In those samples GABAA-α6,β3,γ2,δ,θ,εandπsubunits were also expressed.GABRA3 may compose functional GABAA receptors with them.
In liver cancer cell line HepG2,GAD67 were detected,suggesting that GABA could function in an autocrine/paracrine manner in HCC cells and promote cell growth.GABA promoted the proliferation of HepG2 cells.Knockdown of endogenous GABRA3 expression in HepG2 attenuated HCC cell growth.GABA enhanced the growth of GABRA3 expressing HepG2 cell.On the other hand,the proliferating ability of GABRA3-knockdown HepG2 was not enhanced but lowered by GABA.
Conclusions:GABRA3 is overexpressed in lung cancer and hepatoma.GABRA3 protein expression was significantly higher in lower grade of cancer.HepG2 cells could produce GABA.GABA promoted the proliferation of HepG2 cells through GABRA3.In lung cancers and liver cancers,some other GABAA receptor subunits were also expressed. When GABRA3 was knocken down,GABA inhibited the proliferative ability of HepG2 cells through those subunits.
Part 3 Expression Profile and Function of HTA
Objectives:To study the expression profile and function of HTA.
Methods:RT-PCR was used to analyze the expression profile of HTA gene and RNAi was used to study the function of it.
Results:HTA was a tumor-specific gene,especially in hepatoma.It was detected in liver cancer cell line HepG2,some liver cancer tissue samples(75%) and some other cancer tissues.But in the normal tissues it was not detected.Knockdown of endogenous HTA gene was performed by small interfering RNA in malignant hepatocyte HepG2.Then we tested the cell proliferative ability of these cells in vitro and in vivo.The results showed that HTA could promote HCC cell growth.HTA is located on chromosome 16q22.3,including 3 exons and 2 introns.The encoded protein is an alkaline hydrophilic protein,whose molecular weight is 10KD,PI is 10.9.This protein may play an important role in signal conduction because it may contain 7 phosphorylation sites and 6 glycosylation sites.The secondary structure of the protein contains 33.7%α-helix and 5.43%β-sheet.HTA encoded protein may contains 4 antigen epitope,which are located at 4-14aa,37-43aa,54-60aa and 65-89aa.
Conclusions:HTA was a tumor-specific gene,especially in hepatoma.It plays an important role in HCC cell viability and is a sustained event in the tumorigenic process.
引文
[1]统计显示:恶性肿瘤已成城乡居民首要死因。医药与保健,2007年05期。
[2]Giorgio P,Marialuisa S,Chiara C,et al.T-cell response to unique and shared antigens and vaccination of cancer patients.Cancer Immunity,2002,2:6.
[3]Renkvist N,Castelli C,Robbins PF,et al.A listing of human tumor antigens recognized by T cells.Cancer Immunol Immunother,2001,50:3-15.
[4]Ruf P,Jager M,Ellwart J,et al.Two new trifunctional antibodies for the therapy of human malignant melanoma.Int J Cancer,2004,108(5):725-732.
[5]Chao Zhang.Structural principles that govern the peptide-binding motifs of class I MHC molecules.J Mol Biol,1998,281(5):929-947.
[6]Dunnion DJ,Cywinski AL,Tucker VC,et al.Human antigen- presenting cell/tumor cell hybrids stimulate strong allogenic responses and present tumorassociated antigens to cytotoxic T cells in vitro.Immunology,1999,98(4):541-550.
[7]张翠玲,高霞,孔庆友。胃液CEA测定对胃癌诊断的临床意义。医师进修杂志,2000年8月第23卷第8期。
[8]高杰,吕淑兰,程险峰。AFP-mRNA在原发性肝癌患者外周血的检测及其意义。哈尔滨医科大学学报,2004年4月第38卷第2期。
[9]李子文,刘观斌,封建凯,等。C-12蛋白芯片检测12种肿瘤标记物的血清学表达情况。齐鲁医学检验,2005年第16卷第06期。
[10]Yaziji H,Gown AM.Immunohistochemical markers of melanocytic tumors.Int J Surg Pathol,2003,11(1):11-5.
[11]Roessler K,M(o|¨)nig SP,Schneider PM,et al.Co-expression of CDX2 and MUC2in gastric carcinomas:correlations with clinico-pathological parameters and prognosis.World J Gastroenterol,2005,11(21):3182-8.
[12]Reynolds SR,Oratz R,Shapiro RL,et al.Stimulation of CD8~+ T cell responses to MAGE-3 and MelanA/MART-1 by immunization to a polyvalent melanoma vaccine.Int J Cancer,1997,72(6):72-76.
[13]Parkhurst MR,Salgaller ML,Southwood S,et al.Improved induction of melanoma- reactive CTL with peptides from the melanoma antigen gp100modified at HLA-A ~*0201-binding residues.J Immunol,1996,157(6): 2539-2548.
[14] Rosenberg SA, Yang JC, Schwartzentruber DJ, et al. Impact of cytokine administration on the generation of antitumor reactivity in patients with metastatic melanoma receiving a peptide vaccine. J Immunol, 1999, 163 (3): 1690-5.
[15] Bergman P J, McKnight J, Novosad A, et al. Long-term survival of dogs with advanced malignant melanoma after DNA vaccination with xenogeneic human tyrosinase: a phase I trial. Clin Cancer Res, 2003,9 (4): 1284-1290.
[16] Yu JS, Liu G, Ying H, et al. Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res, 2004,64(14): 4973-4979.
[17] Liu KJ, Wang CC, Chen LT, et al. Generation of carcinoembryonic antigen (CEA)-specific T-cell responses in HLA-A*0201 and HLA-A*2402 late-stage colorectal cancer patients after vaccination with dendritic cells loaded with CEA peptides. Clin Cancer Res, 2004,10(8): 2645-2651.
[18] Gong JL, Najm Osama N , Chen DS, et al. Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity. J Immunol, 2000,165 (3): 1705-1711.
[19] Gong JL, David A, Chen DS, et al. Activation of antitumor cytotoxic T lymphocytes by fusion of human dendritic cells and breast carcinoma cells. Proc Nat Acad Sci, 2000,97 (6): 2715-2718.
[20] Gong JL, Chen DS, Masahiro K, et al. Induct ion of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nat Med, 1997, 3 (13): 558-561.
[21] Morse MA, Clay TM, Hobeika AC, et al. Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules. Clin Cancer Res, 2005,11(8): 3017-3024.
[22] Martin J, Stribbling SM, Poon GK. Antibody-directed enzyme prodrug therapy: pharmacokinetics and plasma levels of prodrug and drug in a phase I clinical trial. Cancer Chemother Pharmacol, 1997,40(3): 189-201.
[23] Kawakami YS, Eliyahu CH, Delgado PF, et al. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor.Proc Natl Acad Sci USA,1994,91:3515-3519.
[24]Kawakami YS,Eliyahu CH,Delgado PF,et al.Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection.Proc Natl Acad Sci USA,1994b,91:6458-6462.
[25]Robbins PF,el-Gamil M,Kawakami Y,et al.Recognition of tyrosinase by tumor-infiltrating lymphocytes from a patient responding to immunotherapy.Cancer Res,1994,54:3124-3126.
[26]Tureci O,Sahin U,Schobert I,et al.The SSX-2 gene,which is involved in the t(X;18) translocation of synovial sarcomas,codes for the human tumor antigen HOM-MEL-40.Cancer Res,1996,56:4766-4772.
[27]Chen YT,Scanlan MJ,Sahin U,et al.A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening.Proc Natl Acad Sci USA,1997,94:1914-1918.
[28]Tureci O,Sahin U,Zwick C,et al.Identification of a meiosis-specific protein as a member of the class of cancer/testis antigens.Proc Natl Acad Sci USA,1998,95:5211-5216.
[29]Chen YT,Gure AO,Tsang S,et al.Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library.Proc Natl Acad Sci USA,1998,95:6919-6923.
[30]Dupuy A,Simon RM.Critical review of published microarray studies for cancer outcome and guidelines on statistical analysis and reporting.J Natl Cancer Inst,2007,99(2):147-157.
[31]Pitzer C,Stassar M,Zoller M.Identification of renal cell carcinoma related cDNA clones by suppression subtractive hybridization.Cancer Res Clin Oncol,1999,125:487-492.
[32]湛凤凰,江宁,曹利,等。应用代表性差异分析法筛选人癌候选抑癌基因。生物化学与生物物理进展,1999;26(2)。
[33]Vonderheide RH,Hahn WC,Schultze JL,et al.The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes.Immunity,1999,10:673-679.
[34]Kao H,Marto JA,Hoffmann TK,et al.Identification of cyclin B1 as a shared human epithelial tumor-associated antigen recognized by T cells.J Exp Med,2001b,194:1313-1323.
[35]Howley PM.Role of the human papilomavirus in human cancer.Cancer Res,1991,51:5019-5022.
[36]Zhang JX,Chen HL,Zong YS,et al.Epstein-Barr virus expression within keratinizing nasopharyngeal carcinoma.J Med Virol,1998,55(3):227-33.
[37]Zhon XG,Hamlton-Dutoit SJ,Yan QH,et al.The association between Epstein-Barr virus and Chinese Hodgkin disease.Int J Cancer,1993,55:359-363.
[38]Deyrup AT.Epstein-Barr virus-associated epithelial and mesenchymal neoplasms.Hum Pathol,2008,39(4):473-83.
[39]Larouze B,Blumberg BS,London WT,et al.Forecasting the development of primary hepatocellular carcinoma by the use of risk factors:studied in West Africa.J Natl Cancer Inst,1977,58(6):1557-61.
[40]Okuda K.The research of capacity of HCV to primary liver cancer.Hepatology,1992,15(5):948.
[41]Daniela S,Mautice PD,David MB,et al.Cancer Gene Discovery Using Digital Differential Display.Cancer Res,2000,60(15):4037-43.
[42]Dong XY,Su YR,Qian XP,et al.Identification of two novel CT antigens and their capacity to elicit antibody response in hepatocellular carcinoma patients.British Journal of Cancer,2003,89:291-297.
[43]Song J,Yang W,Shih IeM,et al.Identification of BCOX1,a novel gene overexpressed in breast cancer.Biochim Biophys Acta,2006,1760(1):62-9.Epub 2005 Oct 25.
[44]孙立军,陈忠平,黄强。基因差异表达的高通量分析及其在肿瘤研究中的应用。癌症,2002,21(5):571-575。
[45]Nakamura TM,Morin GB,Chapman KB,et al.Telomerase catalytic subunit homologs from fission yeast and human.Science,1997,277:955-959.
[46]Brinkmann U,Vasmatzis G,Lee B,et al.Novel genes in the PAGE and GAGE family of tumor antigens found by homology walking in the dbEST database. Cancer Res, 1999, 59: 1445-1448.
[47] Loging WT, Lal A, Siu IM, Loney TL, et al. Identifying potential tumor markers and antigens by database mining and rapid expression screening. Genome Res, 2000,10: 1393-1402.
[48] Scheurle D, DeYoung MP, Binninger DM, et al. Cancer gene discovery using digital differential display. Cancer Res, 2000, 60: 4037-4043.
[49] Elek J, Pinzon W, Park KH, et al. Relevant genomics of neurotensin receptor in cancer. Anticancer Res, 2000,20: 53-58.
[50] Schmitt AO, Specht T, Beckmann G, et al. Exhaustive mining of EST libraries for genes differentially expressed in normal and tumour tissues. Nucleic Acids Res, 1999,27:4251-4260.
[51] Hough CD, Sherman-Baust CA, Pizer ES, et al. Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer. Cancer Res, 2000,60: 6281-6287.
[52] Spieker N, van Sluis P, Beitsma M, et al. The MEIS1 oncogene is highly expressed in neuroblastoma and amplified in cell line IMR32. Genomics, 2001, 71:214-221. [53] Argani P, Rosty C, Reiter RE, et al. Discovery of new markers of cancer through serial analysis of gene expression: prostate stem cell antigen is overexpressed in pancreatic adenocarcinoma. Cancer Res, 2001, 61: 4320-4324.
[54] Cho-Vega JH, Troncoso P, Do KA, et al. Combined laser capture microdissection and serial analysis of gene expression from human tissue samples. Mod Pathol, 2005,18(4):577-584.
[55] Bredenbeck A, Hollstein VM, Trefzer U, et al. Coordinated expression of clustered cancer/testis genes encoded in a large inverted repeat DNA structure. Gene, 2008,415(1-2): 68-73. Epub 2008 Feb 29.
[56] Oba-Shinjo SM, Caballero OL, Jungbluth AA, et al. Cancer-testis (CT) antigen expression in medulloblastoma. Cancer Immun, 2008, 8:7.
[57] Heidebrecht HJ, Claviez A, Kruse ML, et al. Characterization and expression of CT45 in Hodgkin's lymphoma. Clin Cancer Res, 2006,12(16):4804-11.
[58]G(u|¨)re AO,Wei IJ,Old LJ,Chen YT.The SSX gene family:characterization of 9complete genes.Int J Cancer,2002,101(5):448-53.
[59]Hofmann O,Caballero OL,Stevenson BJ,et al.Genome-wide analysis of cancer/testis gene expression.Proc Natl Acad Sci USA,2008,105(51):20422-7.Epub 2008 Dec 16.
[60]Aouacheria A,Navratil V,Barthelaix A,et al.Bioinformatic screening of human ESTs for differentially expressed genes in normal and tumor tissues.BMC Genomics,2006,7:94.
[61]Scheurle D,DeYoung MP,Binninger DM,et al.Cancer gene discovery using digital differential display.Cancer Res,2000,60(15):4037-43.
[62]Baranova AV,Lobashev AV,Ivanov DV,et al.In silico screening for tumour-specific expressed sequences in human genome.FEBS Lett,2001,508(1):143-8.
[63]Schmitt AO,Specht T,Beckmann G,et al.Exhaustive mining of EST libraries for genes differentially expressed in normal and turnout tissues.Nucleic Acids Res,1999,27(21):4251-4260.
[64]Imyanitov EN,Togo AV,Hanson KP.Searching for cancer-associated gene polymorphisms:promises and obstacles.Cancer Lett,2004,204(1):3-14.
[65]Qiu P,Wang L,Kostich M,et al.Genome wide in silico SNP-tumor association analysis.BMC Cancer,2004,4(1):4.
[66]Essrich C,Lorez M,Benson JA,et al.Postsynaptic clustering of major GABAA receptor subtypes requires the α 2 subunit and gephyrin.Nat Neurosci,1998,1:563-571.
[67]Johnston GA,Chebib M,Hanrahan JR,et al.GABAC receptors as drug targets.Curr Drug Targ CNS Neurol Disord,2003,2(4):260-268.
[68]Rosahl TW,Atack JR.Preface.Curr Drug Targ CNS Neurol Disord,2003,2(4):1-3.
[69]Kash TL,Trudell JR,Harison NL.Structural dements involved in activation of the γ aminobutyrie acid type A(GABAA) receptor.Biochem Soc Trans,2004,32(3):540-547.
[70]Zhang G,Raol YH,Hsu FC,et al.Effects of status epilepticus on hippocampal GABAA receptors are age-dependent.Neurosci,2004,125:299-303.
[71]张瑞华,李丽琴,王惠芳。GABAA受体药理学研究进展。中国药理通讯,2003,20(3):18-19。
[72]Tretter V,Ehya N,Fuchs K,et al.Stoichiometry and assembly of a recombinant GABAA receptor subtype.J Neurosci,1997,17:2728-2737.
[73]Thompson SA,Wafford K.Mechanism of action of general anaesthetics new information from molecular pharmacology.Curr Opin Pharmacol,2001,1:78-83.
[74]Minuk GY,Zhang M,Gong Y,et al.Decreased hepatocyte membrane potential differences and GABAA-beta3 expression in human hepatocellular carcinoma.Hepatology,2007,45(3):735-45.
[75]Takehara A,Hosokawa M,Eguchi H,et al.Gamma-aminobutyrie acid(GABA)stimulates pancreatic cancer growth through overexpressing GABAA receptor pi subunit.Cancer Res,2007,67(20):9704-12.
[76]Johnson SK,Haun RS.The gamma-aminobutyric acid A receptor pi subunit is overexpressed in pancreatic adenocarcinomas.JOP,2005,6(2):136-42.
[77]Laurie DJ,Wisden W,Seeburg PH.The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain.Ⅲ.Embryonic and postnatal development.J Neurosci,1992,12:4151-4172.
[78]Neelands TR,Zhang J,Macdonald RL.GABAA receptors expressed in undifferentiated human teratocarcinoma NT2 cells differ from those expressed by differentiated NT2-N cells.J Neurosci,1999,19:7057-7065.
[79]Barker JL,Behar T,Li YX,et al.GABAergic cells and signals in CNS development.Perspect.Dev Neurobiol,1998,5:305-322.
[80]Waagepetersen HS,Sonnewald U,Schousboe A.The GABA paradox:Multiple roles as metabolite,neurotransmitter,and neurodifferentiative agent.J Neurochem,1999,73:1335-1342.
[81]Ben-Ari Y.Excitatory actions of gaba during development:the nature of the nurture.Nat Rev Neurosci,2002,3:728-739.
[82]Ben-Yaakov G,Golan H.Cell proliferation in response to GABA in postnatal hippocampal slice culture.Int J Dev Neurosci,2003,21:153-157.
[83]Owens DF,Kriegstein AR.Is there more to GABA than synaptic inhibition? Nat Rev Neurosci,2002,3:715-727.
[84]Meier E,Hertz L,Schousboe A.Neurotransmitters as developmental signals.Neurochem Int,1991,19:1-15.
[85]LoTurco JJ,Owens DF,Heath MJS,et al.GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis.Neuron,1995,15:1287-1298.
[86]Borodinsky LN,Fiszman ML.Extracellular potassium concentration regulates proliferation of immature cerebellar granule cells.Brain Res Dev Brain Res,1998,107:43-48.
[87]Cui H,Bulleit RF.Potassium chloride inhibits proliferation of cerebellar granule neuron progenitors.Brain Res Dev Brain Res,1998,106:129-135.
[88]Haydar TF,Wang F,Schwartz ML,et al.Differential modulation of proliferation in the neocortical ventricular and subventricular zones.J Neurosci,2000,20:5764-5774.
[89]Watanabe M,Maemura K,Kanbara K,et al.GABA and GABA receptors in the central nervous system and other organs.Int Rev Cytol,2002,213:1-47.
[90]Geigerseder C,Doepner RF,Thalhammer A,et al.Stimulation of TM3 Leydig cell proliferation via GABA(A) receptors:a new role for testicular GABA.Reprod Biol Endocrinol,2004,2:13.
[91]Erlitzki R,Gong Y,Zhang M,et al.Identification of gaminobutyric acid receptor subunit types in human and rat liver.Am J Physiol Gastroint Liver Physiol,2000,279:G733-G739.
[92]Minuk GY,Gauthier T.The effect of g-aminobutyric acid on hepatic regenerative activity following partial hepatectomy in rats.Gastroenterology,1993,104:217-221.
[93]Zhang M,Song G,Minuc GY.Effects of hepatic stimulator substance,herbal medicine selenium/vitamin E,and ciprofloxacin on cirrhosis in the rat.Gastroenterology,1996,110:1150-1155.
[94]Kaita KDE,Assy N,Gauthier T,et al.The beneficial effects of ciprofloxacin on survival and hepatic regenerative activity in a rat model of fulminant hepatic failure. Hepatology, 1998,27: 533-536.
[95] Kleinrok Z, Matuszek M, Jesipowicz J, et al. GABA content and GAD activity in colon tumors taken from patients with colon cancer or from xenografted human colon cancer cells growing as s.c. tumors in athymic nu/nu mice. J Physiol Pharmacol, 1998,49: 303-310.
[96] Wang FY, Maemura K, Hirata I, et al. Immunohistochemical study on GABAergic system in rat and human large intestine. Bull Osaka Med, 2000, 46: 25-34.
[97] Maemura K, Yamauchi H, Hayasaki H, et al. Y-Amino-butyric acid immunoreactivity in intramucosal colonic tumors. J Gastroenterol Hepatol, 2003,18:1089-1094.
[98] Mazurkiewicz M, Opolski A, Wietrzyk J, et al. GABA level and GAD activity in human and mouse normal and neoplastic mammary gland. J Exp Clin Cancer Res, 1999,18:247-253.
[99] Opolski A, Mazurkiewicz M, Wietrzyk J, et al. The role of GABA-ergic system in human mammary gland pathology and in growth of transplantable murine mammary cancer. J Exp Clin Cancer Res, 2000,19: 383-390.
[100] Azuma H, Inamoto T, Sakamoto T, et al. g-aminobutyric acid as a promoting factor of cancer metastasis; induction of matrix metalloproteinase production is potentially its underlying mechanism. Cancer Res, 2003,63: 8090-8098.
[101] Hu Y, Ippolito JE, Garabedian EM, et al. Molecular characterization of a metastatic neuroendocrine cell cancer arising in the prostates of transgenic mice. J Biol Chem, 2001,277: 44462-44474.
[102] Matuszek M, Jesipowicz M, Kleinrok Z. GABA content and GAD activity in gastric cancer. Med Sci Monit, 2001, 7: 377-381.
[103]Bianchi L, De Micheli E, Bricolo A, et al. Extracellular levels of amino acids and choline in human high grade gliomas: an intraoperative microdialysis study. Neurochem Res, 2004,29: 325-334.
[104] Roberts SS, Mori M, Pattee P, et al. GABAergic system gene expression predicts clinical outcome in patients with neuroblastoma. J Clin Oncol, 2004, 22: 4127-4134.
[105]Biju MP,Pyroja S,Rajeshkumar NV,et al.Enhanced GABA(B) receptor in neoplastic rat liver:induction of DNA synthesis by baclofen in hepatocyte cultures.J Biochem Mol Biol Biophys,2002,6:209-214.
[106]Jiang Y,Harlocker SL,Molesh DA,et al.Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarrays.Oncogene,2002,21:2270-2282.
[107]Tatsuta M,Iishi H,Baba M,et al.Inhibition by gamma-amino-n-butyric acid and baclofen of gastric carcinogenesis induced by N-methyl-N'-nitro-Nnitrosoguanidine in Wistar rats.Cancer Res,1990,50:4931-4934.
[108]Tatsuta M,Iishi H,Baba M,et al.Effect of gamma-butyrolactone on baclofen inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-Nnitrosoguanidine in Wistar rats.Oncology,1992,49:123-126.
[109]Wang JM,Johnston PB,Ball BG,et al.The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates call-cycle gene and protein expression.J Neurosci,2005,25:4706-4718.
[110]Leinekugel X,Tseeb V,Ben-Ari Y,et al.Synaptic GABAA activation induces Ca2+ rise in pyramidal cells and interneurons from rat neonatal hippocampal slices.J Physiol,1995,487:319-329.
[111]Gao XB,van den Pol AN.GABA,not glutamate,a primary transmitter driving action potentials in developing hypothalamic neurons.J Neurophysiol,2001,85:425-434.
[112]Ashworth R,Bolsover SR.Spontaneous activityindependent intracellular calcium signals in the developing spinal cord of the zebra fish embryo.Brain Res Dev Brain Res,2002,139:131-137.
[113]Deisseroth K,Singla S,Toda H,et al.Excitation-neurogenesis coupling in adult neural stem/progenitor cells.Neuron,2004,42:535-552.
[114]Fiszman ML,Borodinski LN,Neale JH.GABA induces proliferation of immature cerebellar granule cells growth in vitro.Dev Brain Res,1999,115:1-18.
[115]Roberts E,Harman PJ,Frankel S.gamma Aminobutyric acid content and glutamic decarboxylase activity in developing mouse brain.Proc Soc Exp Biol Med,1951,78(3):799-803.
[116]Asada H,Kawamura Y,Maruyama K,et al.Mice lacking the 65 kDa isoform of glutamic acid decarboxylase(GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to seizures.Biochem Biophys Res Commun,1996,229(3):891-5.
[117]Asada H,Kawamura Y,Maruyama K,et al.Cleft palate and decreased brain gamma-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase.Proc Natl Acad Sci USA,1997,94(12):6496-9.
[118]Parkin DM,Bray F,Ferlay J,et al.Global cancer statistics,2002.CA Cancer J Clin,2005,55(2):74-108.
[119]Stewart WB,Kleihues P.World cancer report.Lyon:IARC,2003:1-351.
[120]El-serag HB,Mason AC.Rising incidence of hepatocellular carcinoma in the United States.N Engl J Med,1999,340(10):745-750.
[121]Jemal A,Murray T,Word E,et al.Cancer statistics,2005.CA Cancer J Clin,2005,55(2):10-30.
[122]Parkin DM,Bray F,Ferlay J,et al.Estimating the world cancer burden:globocan 2000.Int J Cancer,2001,94(2):153-156.
[123]Yang L,Parkin DM,Stewart BW,et al.Estimates of cancer incidence in China for 2000 and p rojections for 2005.Cancer Epidemid Biomark Prev,2005,14(1):243-250.
[124]陈建国,宋新明。中国肝癌发病水平的估算与分析。中国肿瘤,2005,14(5):302-306。
[125]Fire A,Xu S,Montgomery MK,et al.Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.Nature,1998,391:806-811.
[126]Aravin AA,Klenov MS,Vagin VV,et al.Role of double-stranded RNA in eukarotie gene silencing.Mol Biol(Mosk),2002,36:240-251.
[127]McManus MT,Sharp PA.Gene silencing in mammals by small interfering RNAs.Nat Rev Genet,2002,3:737-747.
[128]Ketting RF,Fischer SE,Bernstein E,et al.Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C.elegans.Genes Dev,2001,15:2654-2659.
[129]Hannon GJ.RNA interference.Nature,2002,418:244-251.
[130]Tan FL,Yin JQ.RNAi,a new therapeutic strategy against viral infection.Cell Res,2004,14:460-466.
[131]Pomerantz RJ.RNA interference:a potential novel therapeutic combating HIV-1 in the central nervous system.Arch Immunol Ther Exp(Warsz),2004,52:401-409.
[132]Yano J,Hirabayashi K,Nakaawa S,et al.Antitumor activity of small interfering RNA/cationic liposome complex in mouse models of cancer.Clin Cancer Res,2004,10:7721-7726.
[133]Lee NS,Dohjima T,Bauer G,et al.Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells.Nat Biotechnol,2002,20:500-505.
[134]Park YN,Chae KJ,Kim YB,et al.Apoptosis and proliferation in hepatoearcinogenesis related to cirrhosis.Cancer,2001,92:2733-2738.
[135]Barlow DJ,Edwards MS,Thornton JM.Continuous and discontinuous protein antigenic determinants.Nature,1986,322(6081):747.
[136]De Groot AS,Sbai H,Aubin CS,et al.Immumoinformatics:Mining genomes for vaccine components.Immunol Cel Biol,2002,80:255-269.
[137]B(o|¨)er E,Steinbom G,Kunze G,et al.Yeast expression platforms.Appl Microbiol Biotechnol,2007,77(3):513-523.
[138]Cregg JM.Introduction:Distinctions Between Pichia pastoris and Other Expression Systems.Methods Mol Biol,2007,389:1-10.
[139]McCormick AA,Reinl SJ,Cameron TI,et al.Individualized human seFv vaccines produced in plants:humoral anti-idiotype responses in vaccinated mice confirm relevance to the tumor Ig.J Immunol Methods,2003,278(1-2):95-104.
[140]Liu Y,DeCarolis N,Beck N,et al.Protein production with recombinant baculoviruses in lepidopteran larvae.Methods Mol Biol,2007,388:267-280.
[141]Condreay JP,Kost TA.Baculovirus expression vectors for insect and mammalian cells.Curr Drag Targets,2007,8(10):1126-1131.
[142]Fraisier C,Arnarson H,Barbezange C,et al.Expression of the gpl50 maedi visna virus envelope precursor protein by mammalian expression vectors.J Virol Methods,2007,146(1-2):363-367.
[1]Barker J.L.,Behar T.,Li Y.X.,Liu Q.Y.,Ma W.,Maric D.,Maric I.,Schaffner A.E.,Serafini R.,Smith S.V.,Somogyi R.,Vautrin J.Y.,Wen X.L.and Xian H.(1998).GABAergic cells and signals in CNS development.Perspect.Dev.Neurobiol.5,305-322.
[2]Ben-Ari Y.(2002).Excitatory actions of gaba during development:the nature of the nurture.Nat.Rev.Neurosci.3,728-739.
[3]Waagepetersen H.S.,Sonnewald U.and Schousboe A.(1999).The GABA paradox:Multiple roles as metabolite,neurotransmitter,and neurodifferentiative agent.J.Neurochem.73,1335-1342.
[4]Ben-Yaakov G.and Golan H.(2003).Cell proliferation in response to GABA in postnatal hippocampal slice culture.Int.J.Dev.Neurosci.21,153-157.
[5]Owens D.F.and Kriegstein A.R.(2002).Is there more to GABA than synaptic inhibition? Nat.Rev.Neurosci.3,715-727.
[6]Watanabe M.,Maemura K.,Kanbara K.,Tamayama T.and Hayasaki H.(2002).GABA and GABA receptors in the central nervous system and other organs.Int.Rev.Cytol.213,1-47.
[7]Ding R.,Tsunekawa N.and Obata K.(2004).Cleft palate by picrotoxin or 3-MP and palatal shelf elevation in GABA-deficient mice.Neurotoxicol.Teratol.26,587-592.
[8]Gilon P.,Reusens-Billen B.,Remacle C.,Janssens de Varebeke P.,Pauwels G.and Hoet J.J.(1987).Localization of high-affinity GABA uptake and GABA content in the rat duodenum during development.Cell Tissue.Res.249,593-600.
[9]Wang F.Y.,Watanabe M.,Zhu R.M.and Maemura K.(2004).Characteristic expression of g-aminobutyric acid and glutamate decarboxylase in rat jejunum and its relation to differentiation of epithelial cells.World J.Gastroenterol 10,3608-3611.
[10]Gilon P.,Remacle C.,Janssens de Varebeke P.,Pauwels G.and Hoet J.J.(1987).GABA content and localisation of high-affinity GABA uptake during the development of the rat pancreas.Cell.Mol.Biol.33,573-585.
[11]Minuk G.Y.and Gauthier T.(1993).The effect of g-aminobutyric acid on hepatic regenerative activity following partial hepatectomy in rats.Gastroenterology 104,217-221.
[12]Minuk G.Y.,Kren B.T.,Xu R.,Zhang X.K.,Burczynski F.J.,Mulrooney N.P.,Fan G.and Steer C.J.(1997).The effect of changes in hepatocyte membrane potential on immediate-early protooncogene expression following partial hepatectomy in rats.Hepatology 25,1123-1127.
[13]Fujimod S.,Hinoi E.and Yoneda Y.(2002).Functional GABAB receptors expressed in cultured calvarial osteoblasts.Biochem.Biophys.Res.Commun.293,1445-1452.
[14]Tamayama T.,Maemura K.,Kanbara K.,Hayasaki H.,Yabumoto Y.,Yuasa M.and Watanabe M.(2005).Expression of GABAA and GABAB receptors in rat growth plate chondrocytes:Activation of the GABA receptors promotes proliferation of mouse chondrogenic ATDC5 cells.Mol.Cell.Biochem.273,117-126.
[15]Geigerseder C.,Doepner R.F.,Thalhammer A.,Krieger A.and Mayerhofer A.(2004).Stimulation of TM3 Leydig cell proliferation via GABA(A) receptors:a new role for testieular GABA.Reprod.Biol.Endocrinol.2,13.
[16]Kanbara K.,Okamoto K.,Nomura S.,Kaneko T.,Shigemoto R.,Azuma H.,Katsuoka Y.and Watanabe M.(2005).Cellular localization of GABA and GABAB receptor subunit proteins during spermatogenesis in rat testis.J.Androl.26,485-493.
[17]Bouch(?) N.,Lacombe B.and Fromm H.(2003).GABA signaling:a conserved and ubiquitous mechanism.Trends Cell.Biol.13,607- 610.
[18]Ma H.(2003).Plant reproduction:GABA gradient,guidance and growth.Curr.Biol.13,R834-836.
[19]Palanivelu R.,Brass L.,Edlund A.F.and Preuss D.(2003).Pollen tube growth and guidance is regulated by POP2,an Arabidopsis gene that controls GABA levels.Cell 114,47-59.
[20]Yang Z.(2003).GABA,a new player in the plant mating game.Dev.Cell 5,185-186.
[21]Azuma H.,Inamoto T.,Sakamoto T.,Kiyama S.,Ubai T.,Shinohara Y.,Maemura K.,Tsuji M.,Segawa N.,Masuda H.,Takahara K.,Katsuoka Y.and Watanabe M.(2003).g-aminobutyric acid as a promoting factor of cancer metastasis;induction of matrix metalloproteinase production is potentially its underlying mechanism.Cancer Res.63,8090-8098.
[22]Maemura K.,Yamauchi H.,Hayasaki H.,Kanbara K.,Tamayama T.,Hirata I.and Watanabe M.(2003).g-Amino-butyric acid immunoreactivity in intramucosal colonic tumors.J.Gastroenterol.Hepatol.18,1089-1094.
[23]McKerman R.M.and Whiting P.J.(1996).Which GABAA-receptor subtypes really occur in the brain? Trends Neurosci.19,139-143.
[24] Erlitzki R., Gong Y., Zhang M. and Minuk G. (2000). Identification of g-aminobutyric acid receptor subunit types in human and rat liver. Am. J. Physiol. Gastroint. Liver Physiol. 279, G733-G739.
[25] Hedblom E. and Kirkness E.F. (1997). A novel class of GABAA receptor subunit in tissues of the reproductive system. J. Biol. Chem. 272,15346-15350.
[26] Bolmann J. (2000). The 'ABC of GABA receptors. Trends. Pharmacol. Sci. 21, 16-19.
[27] Steward EC., Thompson J.F. and Dent C.E. (1949). g-aminobutyric acid: a constituent of the potato tuber? Science 110,439-440.
[28] Baum G., Lev-Yadun S., Fridmann Y., Arazi T., Katsnelson H., Zik M. and Fromm H. (1996). Calmodulin binding to glutamate decarboxilase is required for regulation of glutamate and GABA metabolism and normal development in plants. EMBO J. 15,2988-2996.
[29] Wolff J.R., Jo(?) F. and Dames W. (1978). Plasticity in dendrites shown by continuous GABA administration in superior cervical ganglion of adult rat. Nature 274,72-74.
[30] Meier E., Hertz L. and Schousboe A. (1991). Neurotransmitters as developmental signals. Neurochem. Int. 19,1-15.
[31] Leinekugel X., Tseeb V., Ben-Ari Y. and Bregestovski P. (1995). Synaptic GABAA activation induces Ca2+ rise in pyramidal cells and interneurons from rat neonatal hippocampal slices. J. Physiol. 487,319-329.
[32] Lin M.H., Takahashi M.P., Takahashi Y. and Tsumoto T. (1994). Intracellular calcium increase induced by GABA in visual cortex of fetal and neonatal rats and its disappearance with development. Neurosci. Res. 20, 85-94.
[33] Cui H. and Bulleit R.F. (1998). Potassium chloride inhibits proliferation of cerebellar granule neuron progenitors. Brain Res. Dev. Brain Res. 106,129-135.
[34] Haydar T.F., Wang F., Schwartz M.L. and Rakic P. (2000). Differential modulation of proliferation in the neocortical ventricular and subventricular zones. J. Neurosci. 20, 5764-5774.
[35] Behar T.N., Li Y.X., Tran H.T., Ma W, Dunlap V., Scott C. and Barker J.L. (1996). GABA stimulates chemotaxis and chemokinesis of embryonic cortical neurons via calcium-dependent mechanisms. J. Neurosci. 16,1808-1818.
[36] Behar T.N., Schafmer A.E., Scott C.A., Greene C.L. and Barker J.L. (2000).GABA receptor antagonists modulate postmitotic cell migration in slice cultures of embryonic rat cortex.Cereb.Cortex 10,899-909.
[37]Barbin G.,Pollard H.,Gaiarsa J.L.and Ben-Ari Y.(1993).Involvement of GABAA receptors in the outgrowth of cultured hippocampal neurons.Neurosci.Lett.152,150-154.
[38]Maric D.,Liu Q.Y.,Marie I.,Chaudry S.,Chang Y.H.,Smith S.V.,Sieghart W.,Fritschy J.M.and Barker J.L.(2001).GABA expression dominates neuronal lineage progression in the embryonic rat neocortex and facilitates neurite outgrowth via GABA(A) autoreceptor/Cl-channels.J.Neurosci.21,2343-2360.
[39]Tamayama T.,Kanbara K.,Maemura K.,Kuno M.and Watanabe M.(2001).Localization of GABA,GAD65,GAD67 in rat epiphyseal growth plate chondrocytes.Acta.Histochem.Cytochem.34,201-206.
[40]Tamayama T.,Maemura K.,Kanbara K.,Hayasaki H.,Yabumoto Y.,Yuasa M.and Watanabe M.(2005).Expression of GABAA and GABAB receptors in rat growth plate chondrocytes:Activation of the GABA receptors promotes proliferation of mouse chondrogenic ATDC5 cells.Mol.Cell.Biochem.273,117-126.
[41]Opolsld A.,Mazurkiewicz M.,Wietrzyk J.,Kleinrok Z.and Radzikowski C.(2000).The role of GABA-ergic system in human mammary gland pathology and in growth of transplantable murine mammary cancer.J.Exp.Clin.Cancer Res.19,383-390.
[42]Matuszek M.,Jesipowicz M.and Kleinrok Z.(2001).GABA content and GAD activity in gastric cancer.Med.Sci.Monit.7,377-381.
[43]Bianchi L.,De Micheli E.,Bricolo A.,Ballini C.,Fattori M.,Venturi C.,Pedata F.,Tipton K.F.and Della Corte L.(2004).Extracellular levels of amino acids and choline in human high grade gliomas:an intraoperative microdialysis study.Neurochem.Res.29,325-334.
[44]Roberts S.S.,Mori M.,Pattee P.,Lapidus J.,Mathews R.,O'Malley J.P.,Hsieh Y.C.,Turner MA.,Wang Z.,Tian Q.,Rodland M.J.,Reynolds C.P.,Seeger RC.and Nagalla S.R.(2004).GABAergic system gene expression predicts clinical outcome in patients with neuroblastoma.J.Clin.Oncol.22,4127-4134.
[45]Biju M.P.,Pyroja S.,Rajeshkumar N.V.and Paulose C.S.(2002).Enhanced GABA(B) receptor in neoplastic rat liver:induction of DNA synthesis by baclofen in hepatocyte cultures.J.Biochem.Mol.Biol.Biophys.6,209-214.
[46]Jiang Y.,Harlocker S.L.,Molesh D.A.,Dillon D.C.,Stolk J.A.,Houghton R.L.,Repasky E.A.,Badaro R.,Reed S.G.and Xu J.(2002).Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarrays.Oncogene.21,2270-2282.
[47]Sehuller H.M.,A1-Wadei H.A.,Majidi M.(2008).GABA B receptor is a novel drug target for pancreatic cancer.Cancer.112,767-78.
[48]Takehara A.,Hosokawa M.,Eguchi H.,Ohigashi H.,Ishikawa O.,Nakamura Y.,Nakagawa H.(2007).Gamma-aminobutyric acid(GABA) stimulates pancreatic cancer growth through overecpressing GABAA receptor pi subunit.Cancer.Res.67,9704-12.
[49]Liu Y.,Guo F.,Dai M.,Wang D.,Tong Y.,Huang J.,Hu J,Li G.(2008).Gammaaminobutyric Acid A Receptor Alpha 3 Subunit is Overexpressed in Lung Cancer.Pathol.Oncol.Res.2008 Dec 2.[Epub ahead of print]
[50]Liu Y,Li Y.H.,Guo F.J.,Wang J.J.,Sun R.L.,Hu J.Y.,Li G.C..(2008)Gamma-aminobutyric acid promotes human hepatoeellular carcinoma growth through overexpressed gamma-aminobutyric acid A receptor alpha3 subunit.World.J.Gastroenterol.14,7175-82.
[51]Zhang M.,Gong Y.,Assy N.and Minuk Y.(2000).Increased GABAergie activity inhibits a-fetoprotein mRNA expression and the proliferation activity of the HepG2human hepatocellular carcinoma cell line.J.Hepatol.32,85-91.
[52]Tatsuta M.,Iishi H.,Baba M.,Nakaizumi A.,Ichii M.and Taniguchi H.(1990).Inhibition by gamma-amino-n-butyric acid and baelofen of gastric carcinogenesis induced by N-methyl-N'-nitro-Nnitrosoguanidine in Wistar rats.Cancer Res.50,4931-4934.
[53]Tatsuta M.,Iishi H.,Baba M.,Nakaizumi A.,Uehara H.and Taniguchi H.(1992).Effect of gamma-butyrolactone on baclofen inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-Nnitrosoguanidine in Wistar rats.Oncology 49,123-126
[54]Entsehladen F.,Lang K.,Drell T.L.,Joseph J.and Zaenker K.S.(2002).Neurotransmitters are regulators for the migration of tumor cells and leukocytes.Cancer Immunol.Immunother.51,467-482.
[55]Joseph J.,Niggemann B.,Zaenker K.S.and Entschladen F.(2002).The neurotransmitter gamma-aminobutyric acid is an inhibitory regulator for the migration of SW 480 colon carcinoma cells.Cancer Res.62,6467-6469.
[56]Garib V.,Niggemann B.,Zanker K.S.,Brandt L.and Kubens B.S.(2002).Influence of non-volatile anesthetics on the migration behavior of the human breast cancer cell line MDA-MB-468.Acta Anaesthesiol.Scand.46,836-844.
[57]Wang J.M.,Johnston P.B.,Ball B.G.and Brinton R.D.(2005).The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates cell-cycle gene and protein expression.J.Neurosci.25,4706-4718.
[58]Gao X.B.and van den Pol A.N.(2001).GABA,not glutamate,a primary transmitter driving action potentials in developing hypothalamic neurons.J.Neurophysiol.85,425-434.
[59]Ashworth R.and Bolsover S.R.(2002).Spontaneous activityindependent intracellular calcium signals in the developing spinal cord of the zebra fish embryo.Brain Res.Dev.Brain Res.139,131-137.
[60]Deisseroth K.,Singla S.,Toda H.,Monje M.,Palmer T.D.and Malenka R.C.(2004).Excitation-neurogenesis coupling in adult neural stem/progenitor calls.Neuron 42,535-552.
[61]Rosen L.B.,Ginty D.D.,Weber M.J.and Greenberg M.E.(1994).Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of Ras.Neuron 12,1207-1221.
[62]Fiszman M.L.,Borodinski L.N.and Neale J.H.(1999).GABA induces proliferation of immature cerebellar granule cells growth in vitro.Dev.Brain.Res.115,1-18.
[63]Yarden Y.(2001).The EGFR family and its ligands in human cancer:signaling mechanisms and therapeutic opportunities.Eur.J.Cancer 37,S3-S8.
[64]Daub H.,Weiss F.U.,Wallasch C.and Ullrich A.(1996).Role of transactivation of the EGF receptor in signaling by G-proteincoupled receptors.Nature 379,557-560.
[65]Alderton F.,Sambi B.,Tate R.,Pyne N.J.and Pyne S.(2001).Assessment of agonism at G-protein coupled receptors by phosphatidic acid and lysophosphatidic acid in human embryonic kidney 293 calls.Brit.J.Pharmacol.134,6-9.
[66]Daub H.,Wallasch C.,Lankenau A.,Herrlich A.and Ullrich A.(1997).Signal characteristics of G protein-transactivated EGF receptor.EMBO J.16,7032-7044.
[67]Zwick E.,Hackel P.O.,Prenzel N.and Ullrich A.(1999).The EGF receptor as central transducer of heterologous signaling systems.Trends Pharmacol.Sci.20,408-412.
[68]Nilssen L.S.,Odegard J.,Thoresen G.H.,Molven A.,Sandnes D.and Christoffersen T.(2004).G protein-coupled receptor agoniststimulated expression of ATF3/LRF-1 and c-myc and comitogenic effects in hepatocytes do not require EGF receptor transactivation.J.Cell.Physiol.201,349-358.
[69]Koon H.W.,Zhao D.,Na X.,Moyer M.P.and Pothoulakis C.(2004).Metalloproteinases and transforming growth factor-alpha mediate substance P-induced mitogen-activated protein kinase activation and proliferation in human colonocytes.J.Biol.Chem.279,45519-45527.
[70]Prenzel N.,Zwick E.,Daub H.,Leserer M.,Abraham R.,Wallasch C.and Ullrich A.(1999).EGF receptor transactivation by G-proteincoupled receptors requires metalloproteinase cleavage of proHBEGF.Nature 402,884-888.
[71]Yan Y.,Shirakabe K.and Werb Z.(2002).The metalloprotease Kuzubanian (ADAM10) mediates the transactivation of EGF receptor by G protein-coupled receptors.J.Cell Biol.158,221-226.
[2]Giorgio P,Marialuisa S,Chiara C,et al.T-cell response to unique and shared antigens and vaccination of cancer patients.Cancer Immunity,2002,2:6.
[3]Renkvist N,Castelli C,Robbins PF,et al.A listing of human tumor antigens recognized by T cells.Cancer Immunol Immunother,2001,50:3-15.
[4]Ruf P,Jager M,Ellwart J,et al.Two new trifunctional antibodies for the therapy of human malignant melanoma.Int J Cancer,2004,108(5):725-732.
[5]Chao Zhang.Structural principles that govern the peptide-binding motifs of class I MHC molecules.J Mol Biol,1998,281(5):929-947.
[6]Dunnion DJ,Cywinski AL,Tucker VC,et al.Human antigen- presenting cell/tumor cell hybrids stimulate strong allogenic responses and present tumorassociated antigens to cytotoxic T cells in vitro.Immunology,1999,98(4):541-550.
[7]张翠玲,高霞,孔庆友。胃液CEA测定对胃癌诊断的临床意义。医师进修杂志,2000年8月第23卷第8期。
[8]高杰,吕淑兰,程险峰。AFP-mRNA在原发性肝癌患者外周血的检测及其意义。哈尔滨医科大学学报,2004年4月第38卷第2期。
[9]李子文,刘观斌,封建凯,等。C-12蛋白芯片检测12种肿瘤标记物的血清学表达情况。齐鲁医学检验,2005年第16卷第06期。
[10]Yaziji H,Gown AM.Immunohistochemical markers of melanocytic tumors.Int J Surg Pathol,2003,11(1):11-5.
[11]Roessler K,M(o|¨)nig SP,Schneider PM,et al.Co-expression of CDX2 and MUC2in gastric carcinomas:correlations with clinico-pathological parameters and prognosis.World J Gastroenterol,2005,11(21):3182-8.
[12]Reynolds SR,Oratz R,Shapiro RL,et al.Stimulation of CD8~+ T cell responses to MAGE-3 and MelanA/MART-1 by immunization to a polyvalent melanoma vaccine.Int J Cancer,1997,72(6):72-76.
[13]Parkhurst MR,Salgaller ML,Southwood S,et al.Improved induction of melanoma- reactive CTL with peptides from the melanoma antigen gp100modified at HLA-A ~*0201-binding residues.J Immunol,1996,157(6): 2539-2548.
[14] Rosenberg SA, Yang JC, Schwartzentruber DJ, et al. Impact of cytokine administration on the generation of antitumor reactivity in patients with metastatic melanoma receiving a peptide vaccine. J Immunol, 1999, 163 (3): 1690-5.
[15] Bergman P J, McKnight J, Novosad A, et al. Long-term survival of dogs with advanced malignant melanoma after DNA vaccination with xenogeneic human tyrosinase: a phase I trial. Clin Cancer Res, 2003,9 (4): 1284-1290.
[16] Yu JS, Liu G, Ying H, et al. Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. Cancer Res, 2004,64(14): 4973-4979.
[17] Liu KJ, Wang CC, Chen LT, et al. Generation of carcinoembryonic antigen (CEA)-specific T-cell responses in HLA-A*0201 and HLA-A*2402 late-stage colorectal cancer patients after vaccination with dendritic cells loaded with CEA peptides. Clin Cancer Res, 2004,10(8): 2645-2651.
[18] Gong JL, Najm Osama N , Chen DS, et al. Fusions of human ovarian carcinoma cells with autologous or allogeneic dendritic cells induce antitumor immunity. J Immunol, 2000,165 (3): 1705-1711.
[19] Gong JL, David A, Chen DS, et al. Activation of antitumor cytotoxic T lymphocytes by fusion of human dendritic cells and breast carcinoma cells. Proc Nat Acad Sci, 2000,97 (6): 2715-2718.
[20] Gong JL, Chen DS, Masahiro K, et al. Induct ion of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nat Med, 1997, 3 (13): 558-561.
[21] Morse MA, Clay TM, Hobeika AC, et al. Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules. Clin Cancer Res, 2005,11(8): 3017-3024.
[22] Martin J, Stribbling SM, Poon GK. Antibody-directed enzyme prodrug therapy: pharmacokinetics and plasma levels of prodrug and drug in a phase I clinical trial. Cancer Chemother Pharmacol, 1997,40(3): 189-201.
[23] Kawakami YS, Eliyahu CH, Delgado PF, et al. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor.Proc Natl Acad Sci USA,1994,91:3515-3519.
[24]Kawakami YS,Eliyahu CH,Delgado PF,et al.Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection.Proc Natl Acad Sci USA,1994b,91:6458-6462.
[25]Robbins PF,el-Gamil M,Kawakami Y,et al.Recognition of tyrosinase by tumor-infiltrating lymphocytes from a patient responding to immunotherapy.Cancer Res,1994,54:3124-3126.
[26]Tureci O,Sahin U,Schobert I,et al.The SSX-2 gene,which is involved in the t(X;18) translocation of synovial sarcomas,codes for the human tumor antigen HOM-MEL-40.Cancer Res,1996,56:4766-4772.
[27]Chen YT,Scanlan MJ,Sahin U,et al.A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening.Proc Natl Acad Sci USA,1997,94:1914-1918.
[28]Tureci O,Sahin U,Zwick C,et al.Identification of a meiosis-specific protein as a member of the class of cancer/testis antigens.Proc Natl Acad Sci USA,1998,95:5211-5216.
[29]Chen YT,Gure AO,Tsang S,et al.Identification of multiple cancer/testis antigens by allogeneic antibody screening of a melanoma cell line library.Proc Natl Acad Sci USA,1998,95:6919-6923.
[30]Dupuy A,Simon RM.Critical review of published microarray studies for cancer outcome and guidelines on statistical analysis and reporting.J Natl Cancer Inst,2007,99(2):147-157.
[31]Pitzer C,Stassar M,Zoller M.Identification of renal cell carcinoma related cDNA clones by suppression subtractive hybridization.Cancer Res Clin Oncol,1999,125:487-492.
[32]湛凤凰,江宁,曹利,等。应用代表性差异分析法筛选人癌候选抑癌基因。生物化学与生物物理进展,1999;26(2)。
[33]Vonderheide RH,Hahn WC,Schultze JL,et al.The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes.Immunity,1999,10:673-679.
[34]Kao H,Marto JA,Hoffmann TK,et al.Identification of cyclin B1 as a shared human epithelial tumor-associated antigen recognized by T cells.J Exp Med,2001b,194:1313-1323.
[35]Howley PM.Role of the human papilomavirus in human cancer.Cancer Res,1991,51:5019-5022.
[36]Zhang JX,Chen HL,Zong YS,et al.Epstein-Barr virus expression within keratinizing nasopharyngeal carcinoma.J Med Virol,1998,55(3):227-33.
[37]Zhon XG,Hamlton-Dutoit SJ,Yan QH,et al.The association between Epstein-Barr virus and Chinese Hodgkin disease.Int J Cancer,1993,55:359-363.
[38]Deyrup AT.Epstein-Barr virus-associated epithelial and mesenchymal neoplasms.Hum Pathol,2008,39(4):473-83.
[39]Larouze B,Blumberg BS,London WT,et al.Forecasting the development of primary hepatocellular carcinoma by the use of risk factors:studied in West Africa.J Natl Cancer Inst,1977,58(6):1557-61.
[40]Okuda K.The research of capacity of HCV to primary liver cancer.Hepatology,1992,15(5):948.
[41]Daniela S,Mautice PD,David MB,et al.Cancer Gene Discovery Using Digital Differential Display.Cancer Res,2000,60(15):4037-43.
[42]Dong XY,Su YR,Qian XP,et al.Identification of two novel CT antigens and their capacity to elicit antibody response in hepatocellular carcinoma patients.British Journal of Cancer,2003,89:291-297.
[43]Song J,Yang W,Shih IeM,et al.Identification of BCOX1,a novel gene overexpressed in breast cancer.Biochim Biophys Acta,2006,1760(1):62-9.Epub 2005 Oct 25.
[44]孙立军,陈忠平,黄强。基因差异表达的高通量分析及其在肿瘤研究中的应用。癌症,2002,21(5):571-575。
[45]Nakamura TM,Morin GB,Chapman KB,et al.Telomerase catalytic subunit homologs from fission yeast and human.Science,1997,277:955-959.
[46]Brinkmann U,Vasmatzis G,Lee B,et al.Novel genes in the PAGE and GAGE family of tumor antigens found by homology walking in the dbEST database. Cancer Res, 1999, 59: 1445-1448.
[47] Loging WT, Lal A, Siu IM, Loney TL, et al. Identifying potential tumor markers and antigens by database mining and rapid expression screening. Genome Res, 2000,10: 1393-1402.
[48] Scheurle D, DeYoung MP, Binninger DM, et al. Cancer gene discovery using digital differential display. Cancer Res, 2000, 60: 4037-4043.
[49] Elek J, Pinzon W, Park KH, et al. Relevant genomics of neurotensin receptor in cancer. Anticancer Res, 2000,20: 53-58.
[50] Schmitt AO, Specht T, Beckmann G, et al. Exhaustive mining of EST libraries for genes differentially expressed in normal and tumour tissues. Nucleic Acids Res, 1999,27:4251-4260.
[51] Hough CD, Sherman-Baust CA, Pizer ES, et al. Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer. Cancer Res, 2000,60: 6281-6287.
[52] Spieker N, van Sluis P, Beitsma M, et al. The MEIS1 oncogene is highly expressed in neuroblastoma and amplified in cell line IMR32. Genomics, 2001, 71:214-221. [53] Argani P, Rosty C, Reiter RE, et al. Discovery of new markers of cancer through serial analysis of gene expression: prostate stem cell antigen is overexpressed in pancreatic adenocarcinoma. Cancer Res, 2001, 61: 4320-4324.
[54] Cho-Vega JH, Troncoso P, Do KA, et al. Combined laser capture microdissection and serial analysis of gene expression from human tissue samples. Mod Pathol, 2005,18(4):577-584.
[55] Bredenbeck A, Hollstein VM, Trefzer U, et al. Coordinated expression of clustered cancer/testis genes encoded in a large inverted repeat DNA structure. Gene, 2008,415(1-2): 68-73. Epub 2008 Feb 29.
[56] Oba-Shinjo SM, Caballero OL, Jungbluth AA, et al. Cancer-testis (CT) antigen expression in medulloblastoma. Cancer Immun, 2008, 8:7.
[57] Heidebrecht HJ, Claviez A, Kruse ML, et al. Characterization and expression of CT45 in Hodgkin's lymphoma. Clin Cancer Res, 2006,12(16):4804-11.
[58]G(u|¨)re AO,Wei IJ,Old LJ,Chen YT.The SSX gene family:characterization of 9complete genes.Int J Cancer,2002,101(5):448-53.
[59]Hofmann O,Caballero OL,Stevenson BJ,et al.Genome-wide analysis of cancer/testis gene expression.Proc Natl Acad Sci USA,2008,105(51):20422-7.Epub 2008 Dec 16.
[60]Aouacheria A,Navratil V,Barthelaix A,et al.Bioinformatic screening of human ESTs for differentially expressed genes in normal and tumor tissues.BMC Genomics,2006,7:94.
[61]Scheurle D,DeYoung MP,Binninger DM,et al.Cancer gene discovery using digital differential display.Cancer Res,2000,60(15):4037-43.
[62]Baranova AV,Lobashev AV,Ivanov DV,et al.In silico screening for tumour-specific expressed sequences in human genome.FEBS Lett,2001,508(1):143-8.
[63]Schmitt AO,Specht T,Beckmann G,et al.Exhaustive mining of EST libraries for genes differentially expressed in normal and turnout tissues.Nucleic Acids Res,1999,27(21):4251-4260.
[64]Imyanitov EN,Togo AV,Hanson KP.Searching for cancer-associated gene polymorphisms:promises and obstacles.Cancer Lett,2004,204(1):3-14.
[65]Qiu P,Wang L,Kostich M,et al.Genome wide in silico SNP-tumor association analysis.BMC Cancer,2004,4(1):4.
[66]Essrich C,Lorez M,Benson JA,et al.Postsynaptic clustering of major GABAA receptor subtypes requires the α 2 subunit and gephyrin.Nat Neurosci,1998,1:563-571.
[67]Johnston GA,Chebib M,Hanrahan JR,et al.GABAC receptors as drug targets.Curr Drug Targ CNS Neurol Disord,2003,2(4):260-268.
[68]Rosahl TW,Atack JR.Preface.Curr Drug Targ CNS Neurol Disord,2003,2(4):1-3.
[69]Kash TL,Trudell JR,Harison NL.Structural dements involved in activation of the γ aminobutyrie acid type A(GABAA) receptor.Biochem Soc Trans,2004,32(3):540-547.
[70]Zhang G,Raol YH,Hsu FC,et al.Effects of status epilepticus on hippocampal GABAA receptors are age-dependent.Neurosci,2004,125:299-303.
[71]张瑞华,李丽琴,王惠芳。GABAA受体药理学研究进展。中国药理通讯,2003,20(3):18-19。
[72]Tretter V,Ehya N,Fuchs K,et al.Stoichiometry and assembly of a recombinant GABAA receptor subtype.J Neurosci,1997,17:2728-2737.
[73]Thompson SA,Wafford K.Mechanism of action of general anaesthetics new information from molecular pharmacology.Curr Opin Pharmacol,2001,1:78-83.
[74]Minuk GY,Zhang M,Gong Y,et al.Decreased hepatocyte membrane potential differences and GABAA-beta3 expression in human hepatocellular carcinoma.Hepatology,2007,45(3):735-45.
[75]Takehara A,Hosokawa M,Eguchi H,et al.Gamma-aminobutyrie acid(GABA)stimulates pancreatic cancer growth through overexpressing GABAA receptor pi subunit.Cancer Res,2007,67(20):9704-12.
[76]Johnson SK,Haun RS.The gamma-aminobutyric acid A receptor pi subunit is overexpressed in pancreatic adenocarcinomas.JOP,2005,6(2):136-42.
[77]Laurie DJ,Wisden W,Seeburg PH.The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain.Ⅲ.Embryonic and postnatal development.J Neurosci,1992,12:4151-4172.
[78]Neelands TR,Zhang J,Macdonald RL.GABAA receptors expressed in undifferentiated human teratocarcinoma NT2 cells differ from those expressed by differentiated NT2-N cells.J Neurosci,1999,19:7057-7065.
[79]Barker JL,Behar T,Li YX,et al.GABAergic cells and signals in CNS development.Perspect.Dev Neurobiol,1998,5:305-322.
[80]Waagepetersen HS,Sonnewald U,Schousboe A.The GABA paradox:Multiple roles as metabolite,neurotransmitter,and neurodifferentiative agent.J Neurochem,1999,73:1335-1342.
[81]Ben-Ari Y.Excitatory actions of gaba during development:the nature of the nurture.Nat Rev Neurosci,2002,3:728-739.
[82]Ben-Yaakov G,Golan H.Cell proliferation in response to GABA in postnatal hippocampal slice culture.Int J Dev Neurosci,2003,21:153-157.
[83]Owens DF,Kriegstein AR.Is there more to GABA than synaptic inhibition? Nat Rev Neurosci,2002,3:715-727.
[84]Meier E,Hertz L,Schousboe A.Neurotransmitters as developmental signals.Neurochem Int,1991,19:1-15.
[85]LoTurco JJ,Owens DF,Heath MJS,et al.GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis.Neuron,1995,15:1287-1298.
[86]Borodinsky LN,Fiszman ML.Extracellular potassium concentration regulates proliferation of immature cerebellar granule cells.Brain Res Dev Brain Res,1998,107:43-48.
[87]Cui H,Bulleit RF.Potassium chloride inhibits proliferation of cerebellar granule neuron progenitors.Brain Res Dev Brain Res,1998,106:129-135.
[88]Haydar TF,Wang F,Schwartz ML,et al.Differential modulation of proliferation in the neocortical ventricular and subventricular zones.J Neurosci,2000,20:5764-5774.
[89]Watanabe M,Maemura K,Kanbara K,et al.GABA and GABA receptors in the central nervous system and other organs.Int Rev Cytol,2002,213:1-47.
[90]Geigerseder C,Doepner RF,Thalhammer A,et al.Stimulation of TM3 Leydig cell proliferation via GABA(A) receptors:a new role for testicular GABA.Reprod Biol Endocrinol,2004,2:13.
[91]Erlitzki R,Gong Y,Zhang M,et al.Identification of gaminobutyric acid receptor subunit types in human and rat liver.Am J Physiol Gastroint Liver Physiol,2000,279:G733-G739.
[92]Minuk GY,Gauthier T.The effect of g-aminobutyric acid on hepatic regenerative activity following partial hepatectomy in rats.Gastroenterology,1993,104:217-221.
[93]Zhang M,Song G,Minuc GY.Effects of hepatic stimulator substance,herbal medicine selenium/vitamin E,and ciprofloxacin on cirrhosis in the rat.Gastroenterology,1996,110:1150-1155.
[94]Kaita KDE,Assy N,Gauthier T,et al.The beneficial effects of ciprofloxacin on survival and hepatic regenerative activity in a rat model of fulminant hepatic failure. Hepatology, 1998,27: 533-536.
[95] Kleinrok Z, Matuszek M, Jesipowicz J, et al. GABA content and GAD activity in colon tumors taken from patients with colon cancer or from xenografted human colon cancer cells growing as s.c. tumors in athymic nu/nu mice. J Physiol Pharmacol, 1998,49: 303-310.
[96] Wang FY, Maemura K, Hirata I, et al. Immunohistochemical study on GABAergic system in rat and human large intestine. Bull Osaka Med, 2000, 46: 25-34.
[97] Maemura K, Yamauchi H, Hayasaki H, et al. Y-Amino-butyric acid immunoreactivity in intramucosal colonic tumors. J Gastroenterol Hepatol, 2003,18:1089-1094.
[98] Mazurkiewicz M, Opolski A, Wietrzyk J, et al. GABA level and GAD activity in human and mouse normal and neoplastic mammary gland. J Exp Clin Cancer Res, 1999,18:247-253.
[99] Opolski A, Mazurkiewicz M, Wietrzyk J, et al. The role of GABA-ergic system in human mammary gland pathology and in growth of transplantable murine mammary cancer. J Exp Clin Cancer Res, 2000,19: 383-390.
[100] Azuma H, Inamoto T, Sakamoto T, et al. g-aminobutyric acid as a promoting factor of cancer metastasis; induction of matrix metalloproteinase production is potentially its underlying mechanism. Cancer Res, 2003,63: 8090-8098.
[101] Hu Y, Ippolito JE, Garabedian EM, et al. Molecular characterization of a metastatic neuroendocrine cell cancer arising in the prostates of transgenic mice. J Biol Chem, 2001,277: 44462-44474.
[102] Matuszek M, Jesipowicz M, Kleinrok Z. GABA content and GAD activity in gastric cancer. Med Sci Monit, 2001, 7: 377-381.
[103]Bianchi L, De Micheli E, Bricolo A, et al. Extracellular levels of amino acids and choline in human high grade gliomas: an intraoperative microdialysis study. Neurochem Res, 2004,29: 325-334.
[104] Roberts SS, Mori M, Pattee P, et al. GABAergic system gene expression predicts clinical outcome in patients with neuroblastoma. J Clin Oncol, 2004, 22: 4127-4134.
[105]Biju MP,Pyroja S,Rajeshkumar NV,et al.Enhanced GABA(B) receptor in neoplastic rat liver:induction of DNA synthesis by baclofen in hepatocyte cultures.J Biochem Mol Biol Biophys,2002,6:209-214.
[106]Jiang Y,Harlocker SL,Molesh DA,et al.Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarrays.Oncogene,2002,21:2270-2282.
[107]Tatsuta M,Iishi H,Baba M,et al.Inhibition by gamma-amino-n-butyric acid and baclofen of gastric carcinogenesis induced by N-methyl-N'-nitro-Nnitrosoguanidine in Wistar rats.Cancer Res,1990,50:4931-4934.
[108]Tatsuta M,Iishi H,Baba M,et al.Effect of gamma-butyrolactone on baclofen inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-Nnitrosoguanidine in Wistar rats.Oncology,1992,49:123-126.
[109]Wang JM,Johnston PB,Ball BG,et al.The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates call-cycle gene and protein expression.J Neurosci,2005,25:4706-4718.
[110]Leinekugel X,Tseeb V,Ben-Ari Y,et al.Synaptic GABAA activation induces Ca2+ rise in pyramidal cells and interneurons from rat neonatal hippocampal slices.J Physiol,1995,487:319-329.
[111]Gao XB,van den Pol AN.GABA,not glutamate,a primary transmitter driving action potentials in developing hypothalamic neurons.J Neurophysiol,2001,85:425-434.
[112]Ashworth R,Bolsover SR.Spontaneous activityindependent intracellular calcium signals in the developing spinal cord of the zebra fish embryo.Brain Res Dev Brain Res,2002,139:131-137.
[113]Deisseroth K,Singla S,Toda H,et al.Excitation-neurogenesis coupling in adult neural stem/progenitor cells.Neuron,2004,42:535-552.
[114]Fiszman ML,Borodinski LN,Neale JH.GABA induces proliferation of immature cerebellar granule cells growth in vitro.Dev Brain Res,1999,115:1-18.
[115]Roberts E,Harman PJ,Frankel S.gamma Aminobutyric acid content and glutamic decarboxylase activity in developing mouse brain.Proc Soc Exp Biol Med,1951,78(3):799-803.
[116]Asada H,Kawamura Y,Maruyama K,et al.Mice lacking the 65 kDa isoform of glutamic acid decarboxylase(GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to seizures.Biochem Biophys Res Commun,1996,229(3):891-5.
[117]Asada H,Kawamura Y,Maruyama K,et al.Cleft palate and decreased brain gamma-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase.Proc Natl Acad Sci USA,1997,94(12):6496-9.
[118]Parkin DM,Bray F,Ferlay J,et al.Global cancer statistics,2002.CA Cancer J Clin,2005,55(2):74-108.
[119]Stewart WB,Kleihues P.World cancer report.Lyon:IARC,2003:1-351.
[120]El-serag HB,Mason AC.Rising incidence of hepatocellular carcinoma in the United States.N Engl J Med,1999,340(10):745-750.
[121]Jemal A,Murray T,Word E,et al.Cancer statistics,2005.CA Cancer J Clin,2005,55(2):10-30.
[122]Parkin DM,Bray F,Ferlay J,et al.Estimating the world cancer burden:globocan 2000.Int J Cancer,2001,94(2):153-156.
[123]Yang L,Parkin DM,Stewart BW,et al.Estimates of cancer incidence in China for 2000 and p rojections for 2005.Cancer Epidemid Biomark Prev,2005,14(1):243-250.
[124]陈建国,宋新明。中国肝癌发病水平的估算与分析。中国肿瘤,2005,14(5):302-306。
[125]Fire A,Xu S,Montgomery MK,et al.Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans.Nature,1998,391:806-811.
[126]Aravin AA,Klenov MS,Vagin VV,et al.Role of double-stranded RNA in eukarotie gene silencing.Mol Biol(Mosk),2002,36:240-251.
[127]McManus MT,Sharp PA.Gene silencing in mammals by small interfering RNAs.Nat Rev Genet,2002,3:737-747.
[128]Ketting RF,Fischer SE,Bernstein E,et al.Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C.elegans.Genes Dev,2001,15:2654-2659.
[129]Hannon GJ.RNA interference.Nature,2002,418:244-251.
[130]Tan FL,Yin JQ.RNAi,a new therapeutic strategy against viral infection.Cell Res,2004,14:460-466.
[131]Pomerantz RJ.RNA interference:a potential novel therapeutic combating HIV-1 in the central nervous system.Arch Immunol Ther Exp(Warsz),2004,52:401-409.
[132]Yano J,Hirabayashi K,Nakaawa S,et al.Antitumor activity of small interfering RNA/cationic liposome complex in mouse models of cancer.Clin Cancer Res,2004,10:7721-7726.
[133]Lee NS,Dohjima T,Bauer G,et al.Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells.Nat Biotechnol,2002,20:500-505.
[134]Park YN,Chae KJ,Kim YB,et al.Apoptosis and proliferation in hepatoearcinogenesis related to cirrhosis.Cancer,2001,92:2733-2738.
[135]Barlow DJ,Edwards MS,Thornton JM.Continuous and discontinuous protein antigenic determinants.Nature,1986,322(6081):747.
[136]De Groot AS,Sbai H,Aubin CS,et al.Immumoinformatics:Mining genomes for vaccine components.Immunol Cel Biol,2002,80:255-269.
[137]B(o|¨)er E,Steinbom G,Kunze G,et al.Yeast expression platforms.Appl Microbiol Biotechnol,2007,77(3):513-523.
[138]Cregg JM.Introduction:Distinctions Between Pichia pastoris and Other Expression Systems.Methods Mol Biol,2007,389:1-10.
[139]McCormick AA,Reinl SJ,Cameron TI,et al.Individualized human seFv vaccines produced in plants:humoral anti-idiotype responses in vaccinated mice confirm relevance to the tumor Ig.J Immunol Methods,2003,278(1-2):95-104.
[140]Liu Y,DeCarolis N,Beck N,et al.Protein production with recombinant baculoviruses in lepidopteran larvae.Methods Mol Biol,2007,388:267-280.
[141]Condreay JP,Kost TA.Baculovirus expression vectors for insect and mammalian cells.Curr Drag Targets,2007,8(10):1126-1131.
[142]Fraisier C,Arnarson H,Barbezange C,et al.Expression of the gpl50 maedi visna virus envelope precursor protein by mammalian expression vectors.J Virol Methods,2007,146(1-2):363-367.
[1]Barker J.L.,Behar T.,Li Y.X.,Liu Q.Y.,Ma W.,Maric D.,Maric I.,Schaffner A.E.,Serafini R.,Smith S.V.,Somogyi R.,Vautrin J.Y.,Wen X.L.and Xian H.(1998).GABAergic cells and signals in CNS development.Perspect.Dev.Neurobiol.5,305-322.
[2]Ben-Ari Y.(2002).Excitatory actions of gaba during development:the nature of the nurture.Nat.Rev.Neurosci.3,728-739.
[3]Waagepetersen H.S.,Sonnewald U.and Schousboe A.(1999).The GABA paradox:Multiple roles as metabolite,neurotransmitter,and neurodifferentiative agent.J.Neurochem.73,1335-1342.
[4]Ben-Yaakov G.and Golan H.(2003).Cell proliferation in response to GABA in postnatal hippocampal slice culture.Int.J.Dev.Neurosci.21,153-157.
[5]Owens D.F.and Kriegstein A.R.(2002).Is there more to GABA than synaptic inhibition? Nat.Rev.Neurosci.3,715-727.
[6]Watanabe M.,Maemura K.,Kanbara K.,Tamayama T.and Hayasaki H.(2002).GABA and GABA receptors in the central nervous system and other organs.Int.Rev.Cytol.213,1-47.
[7]Ding R.,Tsunekawa N.and Obata K.(2004).Cleft palate by picrotoxin or 3-MP and palatal shelf elevation in GABA-deficient mice.Neurotoxicol.Teratol.26,587-592.
[8]Gilon P.,Reusens-Billen B.,Remacle C.,Janssens de Varebeke P.,Pauwels G.and Hoet J.J.(1987).Localization of high-affinity GABA uptake and GABA content in the rat duodenum during development.Cell Tissue.Res.249,593-600.
[9]Wang F.Y.,Watanabe M.,Zhu R.M.and Maemura K.(2004).Characteristic expression of g-aminobutyric acid and glutamate decarboxylase in rat jejunum and its relation to differentiation of epithelial cells.World J.Gastroenterol 10,3608-3611.
[10]Gilon P.,Remacle C.,Janssens de Varebeke P.,Pauwels G.and Hoet J.J.(1987).GABA content and localisation of high-affinity GABA uptake during the development of the rat pancreas.Cell.Mol.Biol.33,573-585.
[11]Minuk G.Y.and Gauthier T.(1993).The effect of g-aminobutyric acid on hepatic regenerative activity following partial hepatectomy in rats.Gastroenterology 104,217-221.
[12]Minuk G.Y.,Kren B.T.,Xu R.,Zhang X.K.,Burczynski F.J.,Mulrooney N.P.,Fan G.and Steer C.J.(1997).The effect of changes in hepatocyte membrane potential on immediate-early protooncogene expression following partial hepatectomy in rats.Hepatology 25,1123-1127.
[13]Fujimod S.,Hinoi E.and Yoneda Y.(2002).Functional GABAB receptors expressed in cultured calvarial osteoblasts.Biochem.Biophys.Res.Commun.293,1445-1452.
[14]Tamayama T.,Maemura K.,Kanbara K.,Hayasaki H.,Yabumoto Y.,Yuasa M.and Watanabe M.(2005).Expression of GABAA and GABAB receptors in rat growth plate chondrocytes:Activation of the GABA receptors promotes proliferation of mouse chondrogenic ATDC5 cells.Mol.Cell.Biochem.273,117-126.
[15]Geigerseder C.,Doepner R.F.,Thalhammer A.,Krieger A.and Mayerhofer A.(2004).Stimulation of TM3 Leydig cell proliferation via GABA(A) receptors:a new role for testieular GABA.Reprod.Biol.Endocrinol.2,13.
[16]Kanbara K.,Okamoto K.,Nomura S.,Kaneko T.,Shigemoto R.,Azuma H.,Katsuoka Y.and Watanabe M.(2005).Cellular localization of GABA and GABAB receptor subunit proteins during spermatogenesis in rat testis.J.Androl.26,485-493.
[17]Bouch(?) N.,Lacombe B.and Fromm H.(2003).GABA signaling:a conserved and ubiquitous mechanism.Trends Cell.Biol.13,607- 610.
[18]Ma H.(2003).Plant reproduction:GABA gradient,guidance and growth.Curr.Biol.13,R834-836.
[19]Palanivelu R.,Brass L.,Edlund A.F.and Preuss D.(2003).Pollen tube growth and guidance is regulated by POP2,an Arabidopsis gene that controls GABA levels.Cell 114,47-59.
[20]Yang Z.(2003).GABA,a new player in the plant mating game.Dev.Cell 5,185-186.
[21]Azuma H.,Inamoto T.,Sakamoto T.,Kiyama S.,Ubai T.,Shinohara Y.,Maemura K.,Tsuji M.,Segawa N.,Masuda H.,Takahara K.,Katsuoka Y.and Watanabe M.(2003).g-aminobutyric acid as a promoting factor of cancer metastasis;induction of matrix metalloproteinase production is potentially its underlying mechanism.Cancer Res.63,8090-8098.
[22]Maemura K.,Yamauchi H.,Hayasaki H.,Kanbara K.,Tamayama T.,Hirata I.and Watanabe M.(2003).g-Amino-butyric acid immunoreactivity in intramucosal colonic tumors.J.Gastroenterol.Hepatol.18,1089-1094.
[23]McKerman R.M.and Whiting P.J.(1996).Which GABAA-receptor subtypes really occur in the brain? Trends Neurosci.19,139-143.
[24] Erlitzki R., Gong Y., Zhang M. and Minuk G. (2000). Identification of g-aminobutyric acid receptor subunit types in human and rat liver. Am. J. Physiol. Gastroint. Liver Physiol. 279, G733-G739.
[25] Hedblom E. and Kirkness E.F. (1997). A novel class of GABAA receptor subunit in tissues of the reproductive system. J. Biol. Chem. 272,15346-15350.
[26] Bolmann J. (2000). The 'ABC of GABA receptors. Trends. Pharmacol. Sci. 21, 16-19.
[27] Steward EC., Thompson J.F. and Dent C.E. (1949). g-aminobutyric acid: a constituent of the potato tuber? Science 110,439-440.
[28] Baum G., Lev-Yadun S., Fridmann Y., Arazi T., Katsnelson H., Zik M. and Fromm H. (1996). Calmodulin binding to glutamate decarboxilase is required for regulation of glutamate and GABA metabolism and normal development in plants. EMBO J. 15,2988-2996.
[29] Wolff J.R., Jo(?) F. and Dames W. (1978). Plasticity in dendrites shown by continuous GABA administration in superior cervical ganglion of adult rat. Nature 274,72-74.
[30] Meier E., Hertz L. and Schousboe A. (1991). Neurotransmitters as developmental signals. Neurochem. Int. 19,1-15.
[31] Leinekugel X., Tseeb V., Ben-Ari Y. and Bregestovski P. (1995). Synaptic GABAA activation induces Ca2+ rise in pyramidal cells and interneurons from rat neonatal hippocampal slices. J. Physiol. 487,319-329.
[32] Lin M.H., Takahashi M.P., Takahashi Y. and Tsumoto T. (1994). Intracellular calcium increase induced by GABA in visual cortex of fetal and neonatal rats and its disappearance with development. Neurosci. Res. 20, 85-94.
[33] Cui H. and Bulleit R.F. (1998). Potassium chloride inhibits proliferation of cerebellar granule neuron progenitors. Brain Res. Dev. Brain Res. 106,129-135.
[34] Haydar T.F., Wang F., Schwartz M.L. and Rakic P. (2000). Differential modulation of proliferation in the neocortical ventricular and subventricular zones. J. Neurosci. 20, 5764-5774.
[35] Behar T.N., Li Y.X., Tran H.T., Ma W, Dunlap V., Scott C. and Barker J.L. (1996). GABA stimulates chemotaxis and chemokinesis of embryonic cortical neurons via calcium-dependent mechanisms. J. Neurosci. 16,1808-1818.
[36] Behar T.N., Schafmer A.E., Scott C.A., Greene C.L. and Barker J.L. (2000).GABA receptor antagonists modulate postmitotic cell migration in slice cultures of embryonic rat cortex.Cereb.Cortex 10,899-909.
[37]Barbin G.,Pollard H.,Gaiarsa J.L.and Ben-Ari Y.(1993).Involvement of GABAA receptors in the outgrowth of cultured hippocampal neurons.Neurosci.Lett.152,150-154.
[38]Maric D.,Liu Q.Y.,Marie I.,Chaudry S.,Chang Y.H.,Smith S.V.,Sieghart W.,Fritschy J.M.and Barker J.L.(2001).GABA expression dominates neuronal lineage progression in the embryonic rat neocortex and facilitates neurite outgrowth via GABA(A) autoreceptor/Cl-channels.J.Neurosci.21,2343-2360.
[39]Tamayama T.,Kanbara K.,Maemura K.,Kuno M.and Watanabe M.(2001).Localization of GABA,GAD65,GAD67 in rat epiphyseal growth plate chondrocytes.Acta.Histochem.Cytochem.34,201-206.
[40]Tamayama T.,Maemura K.,Kanbara K.,Hayasaki H.,Yabumoto Y.,Yuasa M.and Watanabe M.(2005).Expression of GABAA and GABAB receptors in rat growth plate chondrocytes:Activation of the GABA receptors promotes proliferation of mouse chondrogenic ATDC5 cells.Mol.Cell.Biochem.273,117-126.
[41]Opolsld A.,Mazurkiewicz M.,Wietrzyk J.,Kleinrok Z.and Radzikowski C.(2000).The role of GABA-ergic system in human mammary gland pathology and in growth of transplantable murine mammary cancer.J.Exp.Clin.Cancer Res.19,383-390.
[42]Matuszek M.,Jesipowicz M.and Kleinrok Z.(2001).GABA content and GAD activity in gastric cancer.Med.Sci.Monit.7,377-381.
[43]Bianchi L.,De Micheli E.,Bricolo A.,Ballini C.,Fattori M.,Venturi C.,Pedata F.,Tipton K.F.and Della Corte L.(2004).Extracellular levels of amino acids and choline in human high grade gliomas:an intraoperative microdialysis study.Neurochem.Res.29,325-334.
[44]Roberts S.S.,Mori M.,Pattee P.,Lapidus J.,Mathews R.,O'Malley J.P.,Hsieh Y.C.,Turner MA.,Wang Z.,Tian Q.,Rodland M.J.,Reynolds C.P.,Seeger RC.and Nagalla S.R.(2004).GABAergic system gene expression predicts clinical outcome in patients with neuroblastoma.J.Clin.Oncol.22,4127-4134.
[45]Biju M.P.,Pyroja S.,Rajeshkumar N.V.and Paulose C.S.(2002).Enhanced GABA(B) receptor in neoplastic rat liver:induction of DNA synthesis by baclofen in hepatocyte cultures.J.Biochem.Mol.Biol.Biophys.6,209-214.
[46]Jiang Y.,Harlocker S.L.,Molesh D.A.,Dillon D.C.,Stolk J.A.,Houghton R.L.,Repasky E.A.,Badaro R.,Reed S.G.and Xu J.(2002).Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarrays.Oncogene.21,2270-2282.
[47]Sehuller H.M.,A1-Wadei H.A.,Majidi M.(2008).GABA B receptor is a novel drug target for pancreatic cancer.Cancer.112,767-78.
[48]Takehara A.,Hosokawa M.,Eguchi H.,Ohigashi H.,Ishikawa O.,Nakamura Y.,Nakagawa H.(2007).Gamma-aminobutyric acid(GABA) stimulates pancreatic cancer growth through overecpressing GABAA receptor pi subunit.Cancer.Res.67,9704-12.
[49]Liu Y.,Guo F.,Dai M.,Wang D.,Tong Y.,Huang J.,Hu J,Li G.(2008).Gammaaminobutyric Acid A Receptor Alpha 3 Subunit is Overexpressed in Lung Cancer.Pathol.Oncol.Res.2008 Dec 2.[Epub ahead of print]
[50]Liu Y,Li Y.H.,Guo F.J.,Wang J.J.,Sun R.L.,Hu J.Y.,Li G.C..(2008)Gamma-aminobutyric acid promotes human hepatoeellular carcinoma growth through overexpressed gamma-aminobutyric acid A receptor alpha3 subunit.World.J.Gastroenterol.14,7175-82.
[51]Zhang M.,Gong Y.,Assy N.and Minuk Y.(2000).Increased GABAergie activity inhibits a-fetoprotein mRNA expression and the proliferation activity of the HepG2human hepatocellular carcinoma cell line.J.Hepatol.32,85-91.
[52]Tatsuta M.,Iishi H.,Baba M.,Nakaizumi A.,Ichii M.and Taniguchi H.(1990).Inhibition by gamma-amino-n-butyric acid and baelofen of gastric carcinogenesis induced by N-methyl-N'-nitro-Nnitrosoguanidine in Wistar rats.Cancer Res.50,4931-4934.
[53]Tatsuta M.,Iishi H.,Baba M.,Nakaizumi A.,Uehara H.and Taniguchi H.(1992).Effect of gamma-butyrolactone on baclofen inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-Nnitrosoguanidine in Wistar rats.Oncology 49,123-126
[54]Entsehladen F.,Lang K.,Drell T.L.,Joseph J.and Zaenker K.S.(2002).Neurotransmitters are regulators for the migration of tumor cells and leukocytes.Cancer Immunol.Immunother.51,467-482.
[55]Joseph J.,Niggemann B.,Zaenker K.S.and Entschladen F.(2002).The neurotransmitter gamma-aminobutyric acid is an inhibitory regulator for the migration of SW 480 colon carcinoma cells.Cancer Res.62,6467-6469.
[56]Garib V.,Niggemann B.,Zanker K.S.,Brandt L.and Kubens B.S.(2002).Influence of non-volatile anesthetics on the migration behavior of the human breast cancer cell line MDA-MB-468.Acta Anaesthesiol.Scand.46,836-844.
[57]Wang J.M.,Johnston P.B.,Ball B.G.and Brinton R.D.(2005).The neurosteroid allopregnanolone promotes proliferation of rodent and human neural progenitor cells and regulates cell-cycle gene and protein expression.J.Neurosci.25,4706-4718.
[58]Gao X.B.and van den Pol A.N.(2001).GABA,not glutamate,a primary transmitter driving action potentials in developing hypothalamic neurons.J.Neurophysiol.85,425-434.
[59]Ashworth R.and Bolsover S.R.(2002).Spontaneous activityindependent intracellular calcium signals in the developing spinal cord of the zebra fish embryo.Brain Res.Dev.Brain Res.139,131-137.
[60]Deisseroth K.,Singla S.,Toda H.,Monje M.,Palmer T.D.and Malenka R.C.(2004).Excitation-neurogenesis coupling in adult neural stem/progenitor calls.Neuron 42,535-552.
[61]Rosen L.B.,Ginty D.D.,Weber M.J.and Greenberg M.E.(1994).Membrane depolarization and calcium influx stimulate MEK and MAP kinase via activation of Ras.Neuron 12,1207-1221.
[62]Fiszman M.L.,Borodinski L.N.and Neale J.H.(1999).GABA induces proliferation of immature cerebellar granule cells growth in vitro.Dev.Brain.Res.115,1-18.
[63]Yarden Y.(2001).The EGFR family and its ligands in human cancer:signaling mechanisms and therapeutic opportunities.Eur.J.Cancer 37,S3-S8.
[64]Daub H.,Weiss F.U.,Wallasch C.and Ullrich A.(1996).Role of transactivation of the EGF receptor in signaling by G-proteincoupled receptors.Nature 379,557-560.
[65]Alderton F.,Sambi B.,Tate R.,Pyne N.J.and Pyne S.(2001).Assessment of agonism at G-protein coupled receptors by phosphatidic acid and lysophosphatidic acid in human embryonic kidney 293 calls.Brit.J.Pharmacol.134,6-9.
[66]Daub H.,Wallasch C.,Lankenau A.,Herrlich A.and Ullrich A.(1997).Signal characteristics of G protein-transactivated EGF receptor.EMBO J.16,7032-7044.
[67]Zwick E.,Hackel P.O.,Prenzel N.and Ullrich A.(1999).The EGF receptor as central transducer of heterologous signaling systems.Trends Pharmacol.Sci.20,408-412.
[68]Nilssen L.S.,Odegard J.,Thoresen G.H.,Molven A.,Sandnes D.and Christoffersen T.(2004).G protein-coupled receptor agoniststimulated expression of ATF3/LRF-1 and c-myc and comitogenic effects in hepatocytes do not require EGF receptor transactivation.J.Cell.Physiol.201,349-358.
[69]Koon H.W.,Zhao D.,Na X.,Moyer M.P.and Pothoulakis C.(2004).Metalloproteinases and transforming growth factor-alpha mediate substance P-induced mitogen-activated protein kinase activation and proliferation in human colonocytes.J.Biol.Chem.279,45519-45527.
[70]Prenzel N.,Zwick E.,Daub H.,Leserer M.,Abraham R.,Wallasch C.and Ullrich A.(1999).EGF receptor transactivation by G-proteincoupled receptors requires metalloproteinase cleavage of proHBEGF.Nature 402,884-888.
[71]Yan Y.,Shirakabe K.and Werb Z.(2002).The metalloprotease Kuzubanian (ADAM10) mediates the transactivation of EGF receptor by G protein-coupled receptors.J.Cell Biol.158,221-226.