摘要
背景
腺样囊性癌是一种恶性肿瘤,它起源于腺体,在颜面部的涎腺中发生最多,其次是泪腺。泪腺腺样囊性癌是泪腺上皮性肿瘤中最为常见并且恶性程度最高的肿瘤,其发生率居于第二位,仅次于多形性腺瘤。泪腺腺样囊性癌进展快,预后差,且其发病机制不明,除了手术外尚无有效治疗方法。从基因和蛋白质水平探讨泪腺腺样囊性癌的发生机制,寻找与其发生相关的生物学标记物成为研究的一个热点。分子生物学方面的研究认为,肿瘤是一类由于某些染色体上的DNA损伤引起细胞内某些基因异常表达,以致细胞生长失去控制、缺乏分化及异常增生的一类复杂的基因疾病。现代医学认为,在肿瘤的发生发展过程中,与其相关的特征基因在不同组织(如癌、瘤、正常组织)的表达具有差异性。探索发现这些表达差异的特征基因,对进一步了解肿瘤的发病机制、提高治疗的针对性、做好早期预防及预后有着重大意义。Survivn和Livin是新近发现的IAPs家族中两种最具有表达特异性的凋亡抑制蛋白,能够直接或间接抑制Caspase-3凋亡信号转导过程中相关因子的活性,成为研究的重点。另外,在现代抗肿瘤药物中,中药占居重要的地位,其中银杏叶提取物有明显的抗肿瘤活性及辅助化疗作用,其能够通过调节凋亡基因的表达来抑制肿瘤细胞增殖和加速细胞凋亡,且对正常组织细胞的不良反应较少,近年来在临床上的应用越来越广泛。然而,目前Survivin、Livin和Caspase-3在泪腺腺样囊性癌中的表达分析,及银杏叶提取物在泪腺腺样囊性癌发生发展中的作用很少有报道。
目的
通过比较Survivin、Livin和Caspase-3在泪腺腺样囊性癌、泪腺多形性腺瘤和正常泪腺组织中的表达差异,探讨其在泪腺腺样囊性癌发生、发展中的作用及与临床预后之间的关系；探讨中药银杏叶提取物对人泪腺腺样囊性癌细胞株增殖、凋亡及Survivin、Livin和Survivin Caspase-3表达的影响,为明确泪腺腺样囊性癌的发病机理及探索新的治疗方向提供一定的理论基础。
方法
1.采用RT-PCR、免疫印迹及免疫组化的方法检测Survivin、Livin和Caspase-3在泪腺腺样囊性癌、泪腺多形性腺瘤及正常泪腺组织中的表达情况,利用数学算法探讨基因间表达的相关性。
2.通过体外培养人泪腺腺样囊性癌ACC-2细胞株,应用MTT法检测细胞增殖,Annexin V/PI双染色流式细胞仪检测细胞凋亡和细胞周期；免疫印迹法检测蛋白表达来分析银杏叶提取物(EGB)对泪腺腺样囊性癌ACC-2细胞增殖、凋亡及Survivin、Livin和Caspase-3蛋白表达的影响。
结果
1. Livin和Survivin在正常泪腺组织中低表达或者不表达,在多形性腺瘤和泪腺腺样囊性癌中高表达,并且随着肿瘤恶性程度的增加表达量不断增加。Caspase-3在正常泪腺组织中高表达,在泪腺多形性腺瘤和泪腺腺样囊性癌中的表达量随肿瘤恶性程度的增加而下降。
2. Livin和Survivin在泪腺腺样囊性癌中的表达均与Caspase-3呈负相关,但是二者之间没有相关性。Caspase-3和Livin在泪腺腺样囊性癌中的表达与其临床分期、病理类型和转移有关系,Survivin仅与肿瘤的大小及转移有关系。
3.不同浓度的EGB对人泪腺腺样囊性癌ACC-2细胞的体外增殖均有一定的抑制作用,并且随着EGB浓度的升高,抑制作用增强,量效关系显著(P<0.01)。EGB的加入能够使ACC-2细胞Go-G1期逐渐增加,G2-M期和S期逐渐减少,并且随着剂量的增加,ACC-2细胞凋亡率明显增加。EGB不同浓度对ACC-2细胞Livin和Survivin基因均有一定的抑制作用,并且随着EGB浓度的升高,抑制作用增强。与之相反,Caspase-3基因的相对含量则随着EGB给药剂量的加大而逐渐增高。
结论
1.泪腺腺样囊性癌的发病可能与Livin和Survivin基因的表达异常上调及Caspase-3基因的表达下调有关。Caspase-3、Livin的表达与泪腺腺样囊性癌的临床分期、病理类型和转移有关,Survivin与肿瘤大小及是否转移有关。
2. Livin和Survivin在泪腺腺样囊性癌中的表达均与Caspase-3呈负相关,但是二者之间没有相关性。
3.银杏叶提取物能够抑制人腺样囊性癌ACC-2细胞的体外增殖、促进细胞凋亡,对Caspase-3基因的表达有一定的促进作用,而对Livin和Survivin基因的表达有一定的抑制作用,并且随剂量的增加,其促进或抑制效应增强。
Background
Adenoid cystic carcinoma (ACC) is a kind of malignant tumor originated from glandular organ. In the maxillofacial region, the salivary glands are particularly affected by ACC and, less frequently, the lacrimal glands. ACC of the lacrimal gland, the incidence rate of which ranked the second place (only after pleomorphic tumor) in lacrimal gland epithelial tumor, is the most common and malignant tumor in lacrimal gland epithelial tumor. The invasive biological behaviour is the main reason for the poor prognosis of this disease. At present, operation is the main conventional therapy for this disease, and radiotherapy plays an important role in the prevention of postoperative recurrence. Molecular biology believes that tumor is a kind of complex genetic disease with uncontrolled cell growth, lack of cell differentiation and cell dysplasia which were resulted from abnormal expression of genes caused by DNA damage in some chromosomes.Modern medcine thinks that the expression of tumor-related feature genes in different tissues (such as cancer, tumor and normal tissues) has difference in the process of the generation and development of tumors. The exploration and discovery of these feature genes with expression difference is critical for the further understanding of tumor pathogenesis, the improvement of targeted therapy and the early prevention and prognosis work. Survivn and Livin gene are two newly found anti-apoptosis proteins with expression specificity in IAPs family. They can directly or indirectly inhibit the activity of related factors in the process of Caspase-3apoptotic signal transduction, which is a focus of study. In addition, traditional Chinese medicine occupies an important position in modern anti-tumor drugs. Having obvious anti-tumor activity and function of adjuvant chemotherapy, extract of ginkgo biloba can inhibit the proliferation of tumor cell and accelerate the apoptosis of cell through regulating the expression of apoptotic gene; Moreover, it has less adverse effect on the cell in normal tissue. Extract of ginkgo biloba has been more and more widely applied in clinic.There have not been reports about the expression of Survivin, Livin and Caspase-3gene in ACC of the lacrimal gland and the effect of Ginkgo biloba extrac on the development and progression of LGCC till now.
Objective
This study devoted to find the expression differences of Survivin, Livin and Caspase-3in the ACC, pleomorphic adenoma and the normal tissue of the lacrimal gland and investigate the role that these three genes play in the tumorigenesis and development of ACC of the lacrimal gland, as well as the relationship between the clinical prognosis of this disease and these genes.We also devoted to determine the influence of EGB on the proliferation, apoptosis of ACC-2cell and the expression of Caspase-3,Livin and Survivin, which can provide certain theoretical basis for clarifying the pathogenesis of adenoid cystic carcinoma and exploring new direction of treatment.
Methods
1. RT-PCR, immunoblotting and immunohistochemistry were used to detect the expression of Survivin, Livin and Caspase-3in the ACC, pleomorphic adenoma and the normal tissue of the lacrimal gland.Then, mathematic algorithm was utilized to establish models about the expression correlation between genes
2. The ACC-2cells of adenoid cystic carcinoma of the lacrimal gland were incubated in vitro. Cell proliferation was tested by MTT method. Annexin V/PI double-staining flow cytometer was used to detect cell apoptosis and cell cycle. Protein expression was measured by immunoblotting method in order to analyze the influence of EGB on the proliferation and apoptosis of ACC-2cells and the protein expression of Caspase-3, Livin and Survivin.
Results
1. Livin and Survivin were low or not expressed in the normal lacrimal gland tissue and highly expressed in pleomorphic adenoma and ACC of the lacrimal gland, and the expression amount increased with the increase of the malignant degree. Caspase-3was highly expressed in the normal lacrimal gland tissue, and the expression amount of which decreased with the increase of the malignant degree of pleomorphic adenoma and ACC of the lacrimal gland.
2. The expressions of Livin and Survivin in the ACC of the lacrimal gland were negatively correlated with Caspase-3, but there was no correlation between the former two. The expressions of Caspase-3and Livin were closely related to the clinical stage, pathological type and metastasis of the ACC of the lacrimal gland, while Survivin was only related to tumor size and metastasis.
3. EGB in different concentration had certain inhibitory effect on the in vitro proliferation of ACC-2cells, and the inhibitory effect increased with the increase of the EGB concentration. The dose-effect relationship was significant (P<0.01). EGB can gradually increase ACC-2cells in G0-G1stage and decrease it in G2-M and S stage. With the increase of dose, the apoptosis rate of ACC-2cell obviously increased. EGB in different concentration had certain inhibitory effect on the Livin and Survivin gene of ACC-2cells, and the inhibitory effect increased with the increase of the EGB concentration. On the contrary, the relative amount of Caspase-3gene gradually increased with the increase of the administration dosage of EGB.
Conclusion
1. The incidence of the ACC of the lacrimal gland may be related to the abnormal up-regulation of Livin and Survivin gene and the down-regulation of Caspase-3gene. The expressions of Caspase-3and Livin were closely related to the clinical stage, pathological type and metastasis of the ACC of the lacrimal gland, and Survivin was related to the tumor size and metastasis.
2. The expressions of Livin and Survivin in the ACC of the lacrimal gland were negatively correlated with Caspase-3, but there was no correlation between the former two.
3. EGB can inhibit the in vitro multiplication of ACC-2cells and promote the apoptosis. It has certain promotion effect on Caspase-3gene expression while some inhibtory effect on the expression of Livin and Survivin gene, and the promotion or inhibtory effect increases with the increase of dose.
引文
[1]王磊峰.泪腺腺样囊性癌的研究现状[J].眼科研究,2007,6：477-480.
[2]夏勇.涎腺恶性肿瘤治疗方法的研究进展[J].国际口腔医学杂志,2009,36(1)：46-50.
[3]Mellissa L, Meldrum MD, David T, et al. Neoadjuvant intracarotid chemotherapy for treatment of advanced adenocystic carcinoma of the lacrimal gland[J]. Arch Ophthalmol, 1998,116(3):315-321.
[4]Sato M, Harada K, Yura Y,et al. Induction of tumor differentiation and apoptosis and LeY antigen expression in treatment with differentiation-inducing agent, vesnarinone, of a patient with salvary adenoid carcinoma[J]. Apoptosis,1997,2(1):106-113.
[5]Sun CX, He RG, Cheng LK, et al. The biological behavior of human adenoid cystic carcinoma cells transduced with interleukin-2 gene[J]. Int J Oral Maxillofac Surg,2002, 31(6):650-656.
[6]Camp ER, Wang C, Little EC, et al. Transferrin receptor targeting nanomedicine delivering wild-type p53 gene sensitizes pancreatic cancer to gemcitabine therapy[J]. Cancer Gene Ther,2013[Epub ahead of print].
[7]Zhang H, Qian Y, Liu Y, et al. Celastrus orbiculatus extract induces mitochondrial-mediated apoptosis in human hepatocellular carcinoma cells [J]. J Tradit Chin Med,2012, 32(4):621-626.
[8]谢三祥.Livin-. Caspase-3在涎腺腺样囊性癌中的表达及意义[D].[硕士学位论文].武汉；华中科技大学,2009.
[9]潘涛.Survivin和Caspase-3在口腔鳞状细胞癌中的表达及意义[D].[硕士学位论文].合肥：安徽医科大学,2005.
[10]Kasof GM, Gomes BC.Livin, a novel inhibitor of apoptosis protein family member[J]. J Biol Chem,2001,276(5):3238-3246.
[11]阮晶.凋亡抑制因子Livin的研究进展[J].广东医学院学报,2008,26(1)：68-82.
[12]柴春艳.Livin基因与肿瘤的研究进展[J].陕西医学杂志,2010,39(1)：107-110.
[13]王秀峰,马瑞阳,景作乾,等.银杏叶提取物抗肿瘤机制研究进展[J].微生物学杂志,2011,31(6)：76-79.
[14]郑海平.银杏叶提取物对AFB1大鼠肝癌抑制作用的研究[D].[硕士学位论文].南宁：广西医科大学,2009.
[1]Konno R, Yamakawa H, Utsunomiya H, et al. Expression of surviving and bcl-2 in the normal human endometrium[J]. Mol Hum Reprod,2000,6(6):529-534.
[2]D.C. Altieri. Validating survivin as a cancer therapeutic target[J]. Nat Rev Cancer,2003,3(1): 46-54.
[3]F. Li. Survivin study:what is the next wave? [J]. J Cell Physiol,2003,197 (1):8-29.
[4]Sampath J, Pelus LM. Alternative splice variants of surviving as potential targets in cancers[J]. Curr Drug Discov Technol,2007,4(3):174-191.
[5]Mesri M, Wall NR, Li J, et al. Cancer gene therapy using a surviving mutant adenovirus[J]. J Clin Invest,2001,108:981-90.
[6]Blanc-Brude OP, Mesri M, Wall NR, et al. Therapeutic targeting of the survivin pathway in cancer initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis[J]. Clin Cancer Res,2003,9:2683-2692.
[7]Wall NR, O'Connor DS, Plescia J, et al. Suppression of survivin phosphorrylation on Thr34 by flavopiridol enhances tumor cell apoptosis[J]. Cancer Res,2003,63:230-235.
[8]Zhang M, Latham DE, Delaney MA, et al. Survivin mediates resistance to antiandrogen therapy in prostate cancer[J]. Oncogene,2005,24:2474-2482.
[9]Hayashi N, Asano K, Suzuki H, et al. Adenoviral infection of surviving antisense sensitizes prostate cancer cells to etoposide in vivo[J]. Prostate,2005,65:10-19.
[10]Uchida H, Tanaka T, Sasaki K, et al. Adenovirus-mediated transfer of siRNA against survivin induced apoptosis and attenuated tumor cell growth in vitro and in vivo[J]. Mol Ther,2004, 10:162-171.
[11]Kanwar JR, Shen WP, Kanwar RK, et al. Effects of surviving antagonists on growth of established tumors and B7-1 immunogene therapy[J]. J Natl Cancer Inst,2001,93: 1541-1552.
[12]Caldas H, Holloway MP, Hall BM, et al. Survivin-directed RNA interference cocktail is a potent suppressor of tumor growth in vivo[J]. J Med Genet,2006,43:119-128.
[13]Tu SP, Cui JT, Liston P, et al. Gene therapy for colon cancer by adenoassociated viral vector-mediated transfer of survivin Cys84Ala mutant[J]. Gastroenterology,2005, 128:361-375.
[14]Plescia J, Salz W, Xia F, et al. Rational design of shepherdin, a novel anticancer agent[J]. Cancer Cell,2005,7:457-468.
[15]Kasof GM, Gomes BC.Livin,a novel inhibitor of apoptosis protein family member[J], J Biol Chem,2001,276(5):3238-3246.
[16]Bin Liu, Mei Han, Jin-Kun Wen, et al. Livin/ML-IAP as a new target for cancer treatment[J]. Cancer Letters,2007,250(2):168-176.
[17]Chang H, Schimmer AD. Livin/melanoma inhibitor of apoptosis protein as a potential therapeutic target for the treatment of malignancy[J]. Mol Cancer Ther,2007,6(1):24-30.
[18]Song QZ, Leesmiller SP, Kumar S, et al. DNA-dependent protein kinase catalytic subunit:A target for an ICE-like protease in apoptosis[J]. EMBO J,1996,15(13):3238-3246.
[19]Tamm I, Wang Y, Sausville E, et al. IAP-family protein surviving inhibits caspase activity and apoptosis induced by Fas(CD95),Bax,caspases,and anticancer drugs[J]. Cancer Res, 1998,58(23):5315-5320.
[20]黄丽萍,彭安邦.凋亡抑制蛋白Livin与消化道肿瘤关系的研究进展[J].基层医学论坛,2012,16(4)：507-508.
[21]Cascioa-Rosen L, Nicholson DW, Chong T, et al. Apopain/CPP32 cleaves proteins that are essential for cellular repair:A fundamental principle of apoptotic death[J]. J Exp Med,1996, 183(5):1957-1964.
[22]Waterhouse N, Kumar S, Song QH, et al.Heteronuclear ribonucleoproteins C1 and C2, components of the spliceosome, are specific targets of interleukin 1 beta-converting enzyme-like proteases in apoptosis[J]. J Biol Chem,1996,271(46):29335-29341.
[23]Kumar S. Caspase function in programmed cell death[J]. Cell Death and Differentiation, 2007,14:32-43.
[24]Cottrez F, Auriault C, Apron A, et al. Quantitative PCR:validation of the use of multispecific internal control[J]. Nucleic Acida Res,1994,22(1):2712-2713.
[25]边杉,王颖,于涛,等.聚丙烯酰胺凝胶银染技术在半定量RT-PCR中的应用[J].中国药科大学学报,2004,2：178-182.
[26]Grasso YZ, Gupta MK, Levin HS, et al. Combined nested RT-PCR assay for prostate cancer patients:correlation with pathological stage[J]. Cancer Res,1998,58(7):1456-1459.
[27]刘宏伟,谢风,刘刚,等RT-PCR法检测非小细胞肺癌患者外周血Lunx mRNA的表达及临床意义[J].2008,8(12)：1007-1011.
[28]李剑,刘新平,林树新,等.一种新的抑癌候选基因-NDR2在人类正常组织及相应肿瘤中的表达[J].生物化学与生物物理进展,2002,29(2)：223-231.
[29]Kumkum J, Mridula S, Manoj P. Survivin expression and targeting in breast cancer[J]. Surgical Oncology,2012,21(2):125-131.
[30]Tsuburaya A, Noguchi Y. An anti-apoptosis gene,surviving and telomerase expression in gastric cancer[J]. Hepato-Gastroenterology,2002,49:1150-1152.
[31]Hariu H, Hirohashi Y, Torigoe T, et al. Aberrant expression and potency as a cancer immunotherapy target of inhibitor of apoptosis protein family, Livin/ML-IAP in lung cancer[J]. Clin Cancer Res,2005, 11(3):1000-1009.
[32]史淑红,刘英丽,教伟,等.乳腺癌中Livin的表达与癌细胞凋亡相关性的研究[J].现代肿瘤医学,2009,17(12)：2320-2323。
[331黄培堂.分子克隆实验指南,第3版[M].北京：科学出版社,2005：245.
[34]徐彬,徐浩,李月琴,等.生长抑素2型受体在12株肿瘤细胞中的表达[J].广东医学,2006,27(3)：324-326.
[35]Hofmann HS, Simm A, Hammer A, et al. Expression of inhibitors of apoptosis(IAP) protein in non-small human lung cancer[J]. J Cancer Res Clin Oncol,2002,128(10):554-560.
[36]Li DW, Zhou L, Jin B,et al. Expression and significance of hypoxia-inducible factor-la and surviving in laryngeal carcinoma tissue and cells[J]. Otolaryngol Head Neck Surg,2013, 148(1):75-81
[37]Balakier H, Xiao R, Zhao J, et al. Expression of surviving in human oocytes and preimplantation embryos[J]. Fertil Steril,2013,99(2):518-525.
[38]何剪太,李珍发,张阳德,等.凋亡抑制因子Livin在大肠癌中的表达意义[J].中国现代医学杂志,2007,17(6)：654-657.
[39]Gazzaniga P, Gradilone A, Guliani L, et al. Expression and prognostic significance of livin,surviving and other apoptosis related genes in the progression of superficial bladder cancer[J]. Ann Oncol,2003,14(1):85-90.
[40]Chen YS, Li HR, Miao Y. Local injection of lentivirus-delivered livin shRNA suppresses lung adenocarcinoma growth by inducing a G0/G1 phase cell cycle arrest[J]. Int J Clin Exp Pathol,2012,5(8):796-805.
[41]Oh BY, Lee RA, Kim KH. siRNA targeting livin decreases tumor in a xenograft model for colon cancer[J]. World J Gastroenterol,2011,17(20):2563-2571.
[42]Olie RA, Simoes-Wust AP,Baumann B, et al.A novel antisense oligonucleotide targeting surviving expression induces apoptosis and sensitizes lung cancer cells to chemotherapy [J]. Cancer Res,2000,60(11):2805-2809.
[43]Mesri M, Wall NR, Li J,et al. Cancer gene therapy using a survivin mutant adenovirus[J]. Clin Invest,2001,108(7):981-990.
[1]Perzin KH,Bridge MF.Adenomatous and carcinomatous changes in hamartomatous polyps of the small intestine(Peutz-Jeghers syndrome):report of case and review of the literature[J]. Cancer,1982,49(5):971-983.
[2]Ringertz N. Pathology of malignant tumors arising in the nasal and paranasal cavities and. maxilla[J]. Acta Otolaryngol [Suppl] (Stockh),1938,27:1-405.
[3]Eneroth CM. Adenoid cystic carcinoma of the palate. Acta Otolaryngol.1968;66:248-260.
[4]赵国元.头颈部圆柱瘤型腺癌45例病理分析[J].中国肿瘤临床,1980.2.
[5]刘复生,刘彤华.肿瘤病理学,第1版[M].北京：中国协和医科大学联合出版社,1991,418.
[6]Szanto,PA,Luna MA,Tortoledo ME,et al.Histologic grading of adenoid cystic carcinoma of the salivery glands[J].Cancer,1984,54:1062-1069.
[7]Gondivkar SM,Gadbail AR,Chole R,et al.Adenoid cystic carcinoma:a rare clinical entity and literature review[J].Oral Oncol,2011,47(4):231-236.
[8]Friedrich RE, Bleckmann V. Adenoid cystic carcinoma of salivary and lacrimal gland origin:localization, classification, clinical pathological correlation, treatment results and long-term follow-up control in 84 patientsf J]. Anticancer Res,2003,23:931-940
[9]Zimmerman LE. Histological typ ing of the eye and its adexa.International histological classification of tumor [S]. Geneva:WHO,1980.112-116.
[10]金国瑛.试析免疫组化技术在病理诊断中的应用[J].医学信息,2011,6：2482.
[11]高艳,吴永红,张成岗,等.整合平均光密度和面积比两种参数用于显微图像定量分析的初步研究[J].军事医学科学院院刊,2009,33(5)：405409.
[12]Rachel N.Winter,Andrew Kramer, Andrew Borkowski,et al.Loss of Caspase-1 and Caspase-3 protein expression in human prostate cancer [J].Cancer Res,2001,61(3):1227-1232.
[13]王智明,赵志国,管新明,等Survivin mRNA、Caspase-3 mRNA在舌鳞癌中的表达及相关性[J].上海口腔医学,2007,16(6)：582-586.
[14]Maryla K,Hong-wang,Stainslaw K,et al. Immunohistochemical analysis of in vivo patterns of expression of CPP32(Caspase-3),a cell death protease[J].Cancer Res,1997,57:1605-1613.
[15]Liao Y,Zeng H,Wang X,et al.Expression patterns and prognostic significance of inhibitor of apoptosis proteins in adenoid cystic carcinoma and pleomorphic adenoma of lachrymal gland[J].Exp Eye Res,2009,88(1):4-11.
[16]Chang H,Schimmer AD.Livin/melanoma inhibitor of apoptosis protein as a potential therapeutic target for the treatment of malignancy[J].Mol Cancer Ther,2007,6(1):24-30.
[17]Yagihashi A,Ohmura T,Asanuma K,et al.Detection of autoantibodies to surviving and livin in sera from patients with breast cancer[J].Clin Chim Acta,2005,362(2):125-130.
[18]Grzybowska-Izydorczyk O, Smolewski P. The role of the inhibitor of apoptosis protein (LAP) family in hematological malignancies[J]. Postepy Hig Med Dosw,2008,62:55-63.
[19]Tanabe H, Yagihashi A, Tsuji N, et al. Expression of survivin mRNA and Livin mRNA in non-small-cell lung cancer [J]. Lung Cancer,2004,46(3):299-304.
[20]Lopes RB, Gangeswaran R, McNeish IA, et al. Expression of the IAP protein family is dysregulated in pancreatic cancer cells and is important for resistance to Chemotherapy [J]. Int J Cancer,2007,120(11):2344-2352.
[21]Kempkensteffen C, Hinz S, Christoph F, et al. Expression of the apoptosis inhibitor livin in renal cell carcinomas:correlations with pathology and outcome[J]. Tumour Biol,2007, 28(3):132-138.
[22]宗志红,尚德浩,孙长伏.Livin基因及其蛋白在人口腔鳞癌中的表达[J].上海口腔医学,2007,16(3)：315-318.
[23]Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene, surviving, expressed in cancer and lymphomal[J]. Nat Med,1997,3(8):917-921.
[24]Kami K, Doi R, Koizumi M, et al. Survivin expression is a prognostic marker in pancreatic cancer patients[J]. Surgery,2004,136(2):443-448.
[25]Ambrosini G, Adida C, Altieri DC. A novel anti-apoptosis gene survivin,expressed in cancer and lymphoma[J]. Nat Med,1997,3(8):917-921.
[26]Satoh K, KaneKo, Hirota M, et al. Expression of Survivin is correlated with cancer cell apoptosis and is involved in the development of human pancreatic duct carcinoma [J]. Cancer,2001,92(2):271-278.
[27]王红霞,魏锐利.Survivin在眼部肿瘤预后评估中的作用[J].眼科新进展,2009,29(6)：477-479.
[28]Liao Y, Zeng H, Wang X, et al. Expression patterns and prognostic significance of inhibitor of apoptosis proteins in adenoid cystic carcinoma and pleomorphic adenoma of lachrymal gland [J]. Exp Eye Res,2009,88(1):4-11.
[29]Lee MA, Park G, Lee H, et al. Survivin expression and its clinical significance in pancreatic cancer[J]. BMC Cancer,2005,5:127.
[30]Wang ZN, Xu HM, Jiang L, et al.Expression of surviving in primary and metastatic gastric cancer cells obtained by laser capture microdissection[J]. World J Gastroenterol,2004, 10(21):3094-3098.
[31]Takai N, Miyazaki T, Nishida M, et al. Survivin expression correlates with clinical stage, histological grade, invasive behavior and survival rate in endometrial carcinoma[J]. Cancer Lett,2002,84(1):105-116.
[32]武阳Bax、Livin、Survivin在非小细胞肺癌组织中的表达及其意义[D].[博士学位论文].石家庄：河北医科大学,2009.
[33]孙建建.XIAP、Survivin和Caspase-3在胰腺癌组织中的表达及预后价值[D].[硕士学位论文].石家庄：河北医科大学,2011.
[34]Hauser HP, Bardaroff M, Pyrowolakis G, et al. A giant ubiquitin conjugating enzyme related to IAP apoptosis in inhibitors[J]. J Cell Biol,1998,141:1415-1422.
[35]BOAZ N, YAQOUB A, VERED B, et al. Caspase-mediated cleavage converts livin from an antiapoptotic to a proapoptotic factor[J]. Cancer Research,2003,63:6340-6349.
[36]赵树鹏,靳彩玲,赵新利,等.Livin、Survivin和Caspase-3在星形细胞瘤中的表达[J].新乡医学院学报,2012,29(2)：99-102.
[37]王亚利,王中卫,王西京,等.Livin、survivin在乳腺癌中的表达及其与caspase-3和临床病理的相关性[J].西安交通大学学报,2009,30(4)：466-472.
[38]吴文新,刘惠民,崔爱荣.Livin和Caspase-3在散发性大肠管状腺瘤癌变过程中的表达及相关性研究[J].中国全科医学,2012,15(18)：2050-2054.
[39]高英超.Livin和Caspase-3在结直肠癌和腺瘤中的表达及其临床意义[D].[硕士学位论文].石家庄：河北医科大学,2008.
[40]王永,宋怡才,尹作文,等.Livin和Caspase-3在结直肠腺瘤-癌序列中的表达及相关性研究[J].华西医学,2011,26(6)：878-882.
[41]Survivin、Caspase-3和Bcl-2在肺癌中的表达及意义[J].中国癌症杂志,2009,19(1)：25-31.
[42]于红丽,郑建华,赵宏敏.Survivin、Caspase-3及PCNA在卵巢上皮性肿瘤中表达的临床意义[J].中国实用妇科与产科杂志,2007,23(12)：948-951.
[43]张生军,刘敏丽,魏晓丽.大肠癌中Survivin、Caspase-3基因的表达与生物学特性分析[J].中国现代医学杂志,2007,17(9)：1073-1077.
[44]Li SX, Chai L, Cai ZG, et al. Expression of surviving and caspase-3 in oral squamous cell carcinoma and peritumoral tissue[J]. Asian Pac J Cancer Prev,2012,13(10):5027-5031.
[45]高波,郝敏.Livin、survivin、caspase-3在子宫内膜异位症中的表达及其意义[J].武警医学,2011,22(7)：602-606.
[46]Yagihashi A, Asanuma K, Kobayashi D, et al. Detection of autoantibodies to Livin and Survivin in sera from lung cancer patients[J]. Lung Cancer,2005,48(2):217-221.
[47]Kalungi S, Wabinga H, Bostad L. Expression of apoptosis associated proteins Survivin、 Livin and Thrombospondin-1 in Burkitt lymphoma[J]. APMIS,2013,121(3):239-245.
[48]张久荣,李田,陈石.Survivin和Livin蛋白在非小细胞肺癌中的表达及临床意义[J].临床肺科杂志,2012,17(1)：101-103.
[49]Nam S, Buettner R, Turkson J, et al.Indirubin derivatives inhibit Stat3 signaling and induce apoptosis in human cancer cells[J]. Proc Natl Acad Sci USA,2005,102(17):5998-6003.
[50]Vucic D, Franklin MC, Wallweber HJ, et al.Engineering ML-IAP to produce an extraordinarily potent caspase-9 inhibitor:implications for Smac-dependent anti-apoptotic activity of ML-IAP[J]. Biochem J,2005,385(1):11-20.
[51]Smolewski P, Robak T. Inhibitors of apoptosis proteins(IAPs) as potential molecular targets for therapy of hematological malignancies[J]. Curr Mol Med,2011,11(8):633-649.
[52]Xi RC, Sheng YR, Chen WH, et al. Expression of surviving and livin predicts early recurrence in non-muscle invasive bladder cancer[J]. J Surg Oncol,2012, [Epub ahead of print]
[1]王光兰.20(S)-人参皂甙Rg3诱导肺癌细胞NCI-H460凋亡及其机制的研究[D].[硕士学位论文].长春：吉林大学,2007.
[2]Oh M, Choi YH, Choi S, et al. Anti-proliferating effects of ginsenoside Rh2 on McF-7 human breast cancer cells[J]. Int J Oncol,1999,14(5):869-875.
[3]王鹂,吴军,李敏,等.华蟾毒精抑制Hela细胞增殖作用机制的探讨[J].中华肿瘤杂志,2005,27(12)：717-719.
[4]张俊文,王丕龙.木黄酮对人胃癌细胞SGC-7901作用的研究[J].胃肠病学和肝病学杂志,2004,13(2)：154-157.
[5]陈铁军,哈敏文,孙丽萍,等.大蒜素诱导人胃癌SGC-7901细胞M期阻滞及其机制研究[J].中国医科大学学报,2007,36(6)：686-688.
[6]佟丽,黄添友.刺五加多糖抗肿瘤作用与机理的实验研究[J].中国药理学通报,1994,2：105-109.
[7]刘诗平,陈尚猛,朱卫东.槲皮素及其衍生物的生物活性研究进展[J].中草药,1991；22(4)：182-184.
[8]Borobia FG, Figueras J, Escriba JM, et al.Platelet-activating factor antagonist BN52021 improves survival in normothermic liver ischemia in rat[J].Transplant Proc,1993,25(4): 2543-2544.
[9]叶其正,沈明勤,石磊,等.银杏叶提取物对血瘀模型家兔血液流变性的影响[J].中国中医药科技,2003,10(5)：288-289.
[10]张磊艺,王学翔,杨景云.银杏叶提取物对高脂血症调脂机制的新探[J].中国微生态学,2003,15(6)：342-344.
[11]黑子清,吴伟康,孙惠兰,等.银杏叶提取物对高脂胆固醇喂养家兔血管神经酰胺含量和泡沫细胞凋亡的影响[J].中国实验方剂学杂志,2005,11(2)：60-63.
[12]梁新剑,董少红.银杏叶提取物诱导血管平滑肌细胞凋亡的实验研究[J].广东医学,2004,25(6)：640-641.
[13]蒿艳蓉,杨芳,曹骥,等.银杏叶提取物对AFB1致HepG2细胞毒性保护作用的观察[J].中华肿瘤防治杂志,2008,15(23)：1796-1799.
[14]蒿艳蓉,曹骥,李媛,等.银杏叶提取物阻断AFB1致大鼠肝癌及其机制研究[J].中药材,2009,32(1)：92-96.
[15]Papadopoulos V, Kapsis A, Li H, et al. Drug-induced inhibition of the peripheral-type benzodiazepine receptor expression and cell proliferation in human breast cancer cells [J]. Anticancer Res,2000,20(5A):2835-2847.
[16]Li W, Pretner E, Shen L, et al. Common gene targets of Ginkgo biloba extract in human tumor cells:relation to cell growth [J]. Cell Mol Biol (Noisy legrand),2002, 48(6):655-662.
[17]Rodfiguez M, Ringstad L, Schafer P, et al. Reduction of atherosclerotic nanoplaque formation and size by Ginkgo biloba (EGb761) in cardiovascular high risk patients [J]. Atherosclerosis,2007,192(2):438-444.
[18]Luo Y. Alzheimer's disease, the nematode Caenorhabditis elegans, and ginkgo biloba leaf extract [J]. Life Sci,2006,78(18):2066-2072.
[19]Agha AM, El-Fattah AA, Al-Zuhair HH, et al. Chemoprevenrive effect of Ginkgo biloba extract against benzo (a) pyrene-induced forestomach carcinogenesis in mice: amelioration of doxorubicin cardiotoxicity [J]. J Exp Clin Cancer Res,2001,20(1):39-50.
[20]Dias MC, Rodrigues MA, Reimberg MC, et al. Protective effects of Ginkgo biloba against rat liver carcinogenesis [J]. Chem Biol Interact,2008,173(1):32-42.
[21]Chen XH, Miao YX, Wang XJ, et al. Effects of Ginkgo biloba extract EGb761 on human colon adenocarcinoma cells [J]. Cell Physiol Biochem,2011,27(3):227-232.
[22]Biggs ML, Sorkin BC, Nahin RL, et al. Ginkgo biloba and risk of cancer secondary analysis of the Ginkgo Evaluation of Memory (GEM) Study [J]. Pharmacoepidemiol Drug Saf,2010,19(7):694-698.
[23]张媛英,张凤珍,孙凌云,等.泰山医学院学报[J],2004,5(25)：433-435.
[24]Wang SY, Zhang DS, Wu JL, et al. Experimental study on the expression of NF-κB-P65 protein and apoptosis of adenoid cystic carcinoma cells after radiation treatment [J]. Shanghai Kou Qiang Yi Xue,2011,20(2):125-130.
[25]Otsuki T, Kanno T, Fujita Y, et al. A (3) Adenosine Receptor-Mediated p53-Dependent Apoptosis in Lu-65 Human Lung Cancer Cells [J]. Cell Physiol Biochem,2012,30(1): 210-220.
[26]Harris AW, Boding SE, Warnce BJ, et al. Cyclin D1 as the putative bell oncogene[J].Curr Top Microbiol Immunol,1995,194(3):347-353.
[27]苟文,肖丽华p16、cyclinD1与肿瘤[J].实用肿瘤学杂志,2007,21(1)：75-77.
[28]Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell cycle control causing specific inhibition of cyclin D/CDK4 [J]. Nature,1993,366 (6456):704-707.
[29]Kamb A, Gruis NA, Weaver-Feldhaus J, et al.A cell cycle regulator potentially involved in genesis of many tumor types [J]. Science,1994,264(5157):436-440.
[30]Reed JC. Apoptosis-targeted therapies for cancer [J]. Cancer Cell,2003,3(1):17-22.
[31]Kawasaki H, Altieri DC, Lu CD, et al. Inhibition of apoptosis by surviving predicts shorter survival rates in colorectal cancer [J]. Cancer Res,1998,58(22):5071-5074.
[32]汪朝阳,黄秀榕,祁明信,等.中医中药对细胞凋亡的影响研究进展[J].中国中西医结合杂志,2000,20(9)：712-714.
[33]谢广茹,吴雄志.中药诱导肝癌细胞凋亡的研究进展[J].临床肿瘤学杂志,2007,12(3)：225-227.
[34]章圣辉,俞康,吴建波,等.苦参碱诱导RPMI8226细胞凋亡及其对Bcl-2、增殖细胞核抗原蛋白表达的影响[J].中国临床药理学与治疗学,2007,12(5)：566-570.
[35]黑静雅,黄凌燕,张建中.Caspase、bcl-2蛋白在乳腺癌中表达的临床病理研究[J].宁夏医学杂志,2010,32(1)：17-19.
[36]Olie RA, Simoes Wust AF, Baumann B, et al. A novel antisense oligonucleotide targeting surviving expression induce apoptosis and sensitisize lung cancer cells to chemotherapy [J]. Cancer Res,2000,60(11):2805-2809.
[37]Mita AC, Mita MM, Nawrocki ST, et al. Survivin:key regulator of mitosis and apoptosis and novel target for cancer therapeuitcs [J]. Clin Cnacer Res,2008,14(16):5000-5005.
[38]石梅,王平,张霞,等.肝癌细胞凋亡中TIP30对Bcl-2蛋白家族的表达的调节[J].中德临床肿瘤学杂志,2005,4(1)：11-15.
[1]Foote FW, Frazell EL. Tumors of the major salivary glands [J]. Cancer,1953,6:1065-1133.
[2]Conley J, Dingman D L. Adenoid cystic careinoma in the head and neck [J]. Arch Otolaryngol,1974,100:81-90.
[3]Clark JM, Triana RJ, Meredith SD. Uncontrolled central adenoid cystic carcinoma:case report [J]. Ear Nose Throat J,2000,79:785-786.
[4]Mithani SK, Shao C, Tan M, et al. Mitochondrial mutations in adenoid cystic carcinoma of the salivary glands [J]. PLoS One,2009,4(12):e8493.
[5]Persson M, Andren Y, Mark J, et al. Recurrent fusion of MYB and NFB transcription factor genes in carcinomas of the breast and head and neck [J]. Proc Natl Acad Sci USA, 2009,106(44):18740-18744.
[6]Lupinetti AD, Roherts DB, Williams MD, et al.Sinonnasal adenoid cystic carcinoma:the M. D. Anderson Cancer Center experience [J]. Cancer,2007,110(12):2726-2731.
[7]Liu TR, Yang AK, Guo X, et al. Adenoid cystic carcinoma of the nasopharynx; 27-year experience[J] Laryngoscope,2008,118(11):1981-1988.
[8]Luna-Ortiz K, Carmona- Luna T, Cano-Valdez AM, et al. Adenoid cystic carcinoma of the tongue; clinicopathological study and survival analysis [J]. Head Neck Oncol,2009,1:15
[9]Garcia de Marcos JA, Calderon-Polanco J, Poblet E, et al.Primary adenoid cystic carcinoma of the mandible:case report and review of the literature[J]. J Oral Maxillofac Surg,2008,66(12):2609-2615.
[10]Lee JI, Kim YZ, Lee EH, et al. Skull base invasion of adenoid cystic carcinoma of the lacrimal gland:a case report [J]. J Korean Neurosurg Soc,2008,44(4):273-276.
[11]Lin SC, Kau HC, Yang CF, et al. Adenoid cystic carcinoma arising in the inferior orbit without evidence of lacrimal gland involvement[J]. Ophthal Plast Reconstr Surg,2008, 24(1):74-76.
[12]Dong F, Gidley PW, Ho T, et al. Adenoid cystic carcinoma of the external auditory canal[J]. Laryngoscope,2008,118(9):1591-1596.
[13]Glazebrook KN, Reynolds C, Smith RL, et al.Adenoid cystic carcinoma of the breast [J]. AJRAm J Roentgenol,2010,194(5):1391-1396.
[14]Seth A, Agarwal A. Adenoid cystic carcinoma of uterine cervix in a young patient [J]. Indian J Pathol Microbiol,2009,52(4):543-545.
[15]Sahincioglu O, Berker B, Gungor M, et al. Adenoid cystic carcinoma of the Bartholin's gland:a rare tumor unmarked by persistent vulvar pain in a postmenopausal woman. Arch Gynecol Obstet,2008,278 (5):473-476.
[16]Kim UR, Shah AD, Shanti R, et al. Primary adenoid cystic carcinoma of the eyelid. Ophthal Plast Reconstr Surg,2010,26(2):134-136.
[17]Singh A, Ramesh V. Primary cutaneous adenoid cystic carcinoma with distant metastasis:a case report and brief literature review [J]. Indian J Dermatol Venereol Leprol,2010,76(2):176-179.
[18]Dores GM, Huycke MM, Devesa SS, et al. Primary cutaneous adenoid cystic carcinoma in the United States:incidence, survival, and associated cancers,1976 to 2005[J]. J Am Acad Dermatol,2010,63 (1):71-78.
[19]Iczkowski KA, Ferguson KL, Grier DD, et al. Adenoid cystic/basal cell carcinoma of the prostate:clinicopathologic findings in 19 cases [J]. Am J Surg Pathol,2003,27(12): 1523-1529.
[20]赵文川,章魁华.涎腺腺样囊性癌ras, myc, erbB1和sis癌基因的表达[J].华西口腔医学杂志,1993,11(3)：167-169.
[21]Sasahira T, Oue N, Kirita T, et al. RegⅣ expression is associated with cell growth and prognosis of adenoid cystic carcinoma in the salivary gland[J]. Histopathology,2008, 53(6):667-675.
[22]Yu Y, Chen W, Zhang Y, et al. Suppression of salivary adenoid cystic carcinoma growth and metastasis by ErbB3 binding protein Ebpl transfer [J].Int J Cancer,2007, 120(9):1909-1913.
[23]Kulbe H, Levinson NR, Balkwill F, et al. The chemokine network in cancer-much more than directing cell movement [J]. Int J Dev Biol,2004,48(5-6):489-496.
[24]Xu XG, Lu CT, Zhou ZH. Expressions of chemokine receptor CXCR4 and its ligand CXCL12 in salivary adenoid cystic carcinoma [J]. Journal of Medical Colleges of PLA, 2004,19(4):225-228.
[25]Zushi Y, Noguchi K, Hashitani S, et al.Relations among expression of CXCR4, histological patterns, and metastatic potential in adenoid cystic carcinoma of the head and neck [J].Int J Oncol,2008,33(6):1133-1139.
[26]彭歆,俞光岩,高岩,等.肿瘤转移抑制基因nnm23在涎腺腺样囊性癌表达的研究[J].现代口腔医学杂志.2001,15(2)：94-96.
[27]刘秀明,蔡以理,徐骚,等.ADAM9和ADAM10基因沉默对腺样囊性癌高转移潜能细胞生物学行为的影响[J].中国口腔颌面外科杂志,2009,7(3)：249-256.
[28]Mcdonld NQ. New protein fold revealnd by 2.3A' crystal structure of NGF[J]. Nature, 1991,35(4):411-414.
[29]Kowalski PJ, Paulind AF.Pefineural invasion in adenoid cystic carcinoma:its causation/ promotion by brain-derived neurotrephic factor[J]. Hum Pathol,2002,33(9):933-936.
[30]李媛,金岩,聂鑫,等.神经营养因子与腺样囊性癌肿瘤生物学特性的关系[J].第四军医大学学报,2002,23(24)：2299-2301.
[31]李昊,农晓琳,陈琦,等.神经生长因子、血管内皮生长因子在腺样囊性癌侵袭转移中的作用[J].实用口腔医学杂志,2008,24(4)：555-559.
[32]孙沫逸,王磊,陆斌酪,等.酪氨酸激酶C与涎腺腺样囊性癌嗜颅神经侵袭的关系 [J].中华神经外科疾病研究,2004,12(5)：388-390.
[33]Ferrara N, Henzel WJ.Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells [J]. Biochem Biophys Res Commun,1989, 16(1):851-858.
[34]Deneckamp J, et al. Endothelial proliferation in tumors and normall tissue:continuous labeling studies [J]. Br J Cancer,1984,49(4):405-413.
[35]Weidner N. Tumoral vascularity as a prognostic factor in cancer patients:the evidence continues to growth [J]. J Pathol,1998,184(2):119-122.
[36]宋琦,李萍,谢文扬.涎腺腺样囊性癌组织中层粘连蛋白及血管内皮生长因子表达的研究[J].实用口腔医学杂志,2004,20(4)：451-453.
[37]Gospodarowicz D. Localisation of a fibroblast growth factor and its effect alone and with hydrocortisone on NT3 cell growth [J]. Nature,1974,24(9):123-127.
[38]Boelaert K, McCabe CJ, Tannahill LA, et al.Pituitary tumor transforming gene and fibroblast growth factor-2 expression:potential prognostic indicators in differentiated thyroid cancer[J]. J Clin Endocrinol Metab,2003,88:2341-2347.
[39]Alzheimer C, Werner S. Fibroblast growth factors and neuroprotection [J]. Adv Exp Med Biol,2002,51(3):335-351.
[40]Kayton RJ, Aktas RG.Electron microscopic immunolocalization of basic fibroblast growth factor in peripheral nerves [J]. Histochem Cell Biol,2000,114(5):413-419.
[41]He JF, Ge MH, Zhu X, et al. Expression of Runx3 in salivary adenoid cystic carcinoma: implications for tumor progression and prognosis [J]. Cancer Sci,2008,99(7):1334-1340.
[42]肖胤,杨军,肖林,等.Survivin基因在人涎腺腺样囊性癌中的表达[J].临床口腔医学杂志,2007,23(4)：209-214.
[43]Friedrich RE, Bleckmann V. Adenoid cystic carcinoma of salivary and lacrimal gland origin:localization, classification, clinical pathological correlation, treatment results and long term follow-up control in 84 patients [J]. Anticancer Res,2003,23:931-940.
[44]Lee DA, Campbell RJ, Waller RR, et al. A clinicopathologic study of primary adenoid cystic carcinoma of the lacrimal gland [J]. Ophthalmology 1985,92:1281-1284.
[45]Ducrey N, Villemure JG, JaquesB, et al. Cystic adenocarcinomas of the lacrimal gland [J]. Klin Monatsbl Augenheilkd,2002,219 (4):231-234
[46]Font RL, Gamel JW. Adenoid cystic carcinoma of the lacrimal gland. A clinicopathologic study of 79 cases [M]. Ocular Pathology Update. New York:Masson Publishing; 1980:277-283.
[47]Jakobiec FA. Discussion of Henderson JW. Adenoid cystic carcinoma of the lacrimal gland:Is there a cure? [J]Trans Am Ophthalmol Soc 1987,85:314-317
[48]Zimmerman LE. Histological typing of the eye and its adexa. International histological classification of tumor [S]. Geneva:WHO,1980.112-116.
[49]TelladoMV, McLean I, SpechtCS, et al. Adenoid cystic carcinomas of the lacrimal gland in childhood and adolescence [J]. Ophthalmology,1997,104(10):1622-1625
[50]王毅,李冬梅,康莉等.泪腺腺样囊性癌的组织病理学特征[J].眼科.2009,18(3)：194-198.
[51]Mercer WE, Avignolo C, Basterga R. Role of the p53 protein in cell proliferation as studied by microinjection of monoclonal antibodies [J]. Mol Cell Biol,1985,5:2851.
[52]Kastan MB, Onyekwere O, Sidransky D, et al. Participation of p53 protein in the cellular response to DNA damageCancer Res,1991,51:6304-6311.
[53]Hall PA, Ray A, Lemoine NR, et al. p53 immonostaining as a marker of malignant disease in diagnosis cytopathology [J]. Lancet,1991,338(8765):513
[54]Helen P, Sydney D, Finkelstein SD, et al. The role of p53 mutation and protein expression in primary and recurrence adenoid cystic carcinoma [J]. Hum Pathol,1996,27:567-568.
[55]郑磊,何淑芳,范忠义.泪腺腺样囊性癌p53表达的研究[J].眼科研究,1996,14(4)：252-253.
[56]郭素珍,宋国祥,田文芳,等.泪腺肿瘤中p53蛋白表达的意义[J].眼科新进展,1997,17(4)：197-199.
[57]张红梅,周晓冬.凋亡相关基因在眼眶腺样囊性癌组织中的表达意义[J].国际眼科杂志,2006,6(4)：799-801.
[58]郭素珍,宋国祥,王炳亮,等.泪腺肿瘤中bcl-2蛋白表达的意义[J].中国肿瘤临床,1998,25(123)：905.
[59]Albelda SM, Buck CA, Muller WA, et al. Integrins and other cell adhesion molecules [J]. FASEB J,1990,4:2868-2880.
[60]Tempfer G, Gitsch G, Haeusler G, et al. Prognostic value of immonohistochemically detected expression in patients with carcinoma of the vulva [J]. Cancer,1996,78:273-277.
[61]陈刚,赵春利,翁秀琴,等.CD54, CD44在涎腺腺样囊性癌中的表达及意义[J].中国肿瘤,2001,10(3)：159-160.
[62]牛膺筠,刘夫玲,杨文毅,等.泪腺肿瘤中细胞黏附分子CD44变异体及纤维连接蛋白的表达与预后相关性探讨[J].中华眼科杂志,2004,40(9)：620-624.
[63]Tepass U, Truong K, Godt D, et al. Cadherins in embryonic and neural morphogenesis [J]. Nat Rev Mol Cell Biol,2000, 1(2):91-100.
[64]Y ilmaz M, Christofori G. EMT, the cytoskeleton and cancer cell invasion [J]. Cancer Metast Rev,2009,28 (1-2):15-33.
[65]刘辉,李永平,张文忻,等.E-cadherin和β-catenin在泪腺多形性腺瘤和腺样囊性癌中的表达[J].眼科研究,2010,28(9)：821-826.
[66]杨娜p63、Ki-67及Laminin在泪腺上皮性肿瘤的表达及意义[D].[硕士学位论文].石家庄：河北医科大学,2009.
[67]Santo PA, Luna MA, Tortoledo MF, et al. Histologic glading of adenoid cystic carcinoma of the salivary gland[J]. Cancer,1984,54(6):1062-1069.
[68]Kerr JF, Wyllie AH, Currie AR. Apoptosis:a basic biological phenomenon with wide-ranging implications in tussue kinetics [J].Br J Cancer,1972,26(4):239-257.
[69]Garewal H, Bernstein H, Bernstein C, et al. Reduced bile acidinduced apoptosis in"normal" colorectal mucosa:a poteintial biological marker for cancer risk [J]. Cancer Res,1996,56(7):1480-1483.
[70]胡野,凌志强,善小云.细胞凋亡的分子医学[M].北京：军事医学出版社,2002：48-76.
[71]Alnemri E S, Livingston D J, Nieholson D W, et al. Human ICE/CED-3 protease nomenclature [J]. Cell,1996,87:171-172.
[72]Bratton S B, MaeFarlane M, Cain K, et al. Protein complexes activate distinct caspase cascades in death receptor and stresss-induced apoptosis [J]. Exp Cell Res,2000, 256:27-33.
[73]熊世勤,来锡华.Caspase激活与调控的分子机制[J].生物化学与生物物理进展,2002,27(10)：33-36.
[74]王筱冰,张小翠,夏妙红,等.Caspase的活化机制[J].现代生物医学进展,2006,6(3)：53-55.
[75]Chang HY et al. Proteases for cell suicide:Function and Regulation of Caspase. Microbiol [J], Mol Biol Rev,2000,64:821-846.
[76]尹芳,张端莲,熊彦娥等.高糖诱导小鼠囊胚Caspase-3的表达及其意义[J].中国组织化学与细胞化学杂志.2005,14(5)：544-546.
[77]Harrington HA, Ho KL, Ghosh S, Tung KC. Construction and analysis of a modular model of caspase activation in apoptosis[J]. Theor Biol Med Model,2008,5(1):26-30
[78]Maryla K, Hong wang, Stanislaw K, et al. Immunohistochemical analysis of in vivo patterns of expression of CPP32 (caspase-3), a cell death protease[J]. Cancer Res,1997, 57:16051613.
[79]Rachel N. Winter, Andrew Kramer, Andrew Borkowski, et al. Loss of Caspase-1 and Caspase-3 protein expression in Human Prostate cancer[J]. Cancer Res 2001, 61:1227-1232.
[80]孟凡生,高珊,徐勤.Caspase-3蛋白在喉鳞癌组织中表达及与喉癌细胞凋亡的对比研究[J].临床和实验医学杂志,2013,4.
[81]王智明,赵志国,管新明,等.Survivin mRNA、Caspase-3 mRNA在舌鳞癌中的表达及相关性[J].上海口腔医学,2007,16(6)：582-586.
[82]Yoo NJ, Kim HS, Kim SY, et al. Stomach cancer highly expresses both initiator and effector caspases:an immunohistochemical study [J]. APMIS,2002,110(11):825-832.
[83]Wang TS, Ding QQ, Guo RH, et al. Expression of livin in gastric cancer and induction of apoptosis in SGC-7901 cells by shRNA mediated silencing of livin gene[J].Biomed Pharmacother,2010,64(5):333-338.
[84]Hauck L, Hansmann G, Dietz R, et al. Inhibition of hypoxia-induced apoptosis by modulation of retinoblastoma protein-dependent signaling in cardiomyocytes [J]. Circ Res, 2002,91:782-789.
[85]周舟,小华,朱光旭,等.氧诱导心肌细胞凋亡与Caspase-3激活及细胞内钙超载的关系[J].应用生理学,2005,1(1)：10-14.
[86]Porter AG, Janicke RU (February 1999). Emerging roles of caspase-3 in apoptosis [J]. Cell Death Differ.6 (2):99-104.
[87]Ambrosini G, Adida C, Altieri DC, et al. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma [J]. Nat Med,1997,3(8):917-921
[88]Yamamoto T, Tanigaxa N. The role of surviving as a new target of diagnosis and treatment in human cancer [J]. Med Eleetron Microsc.2001 Dec:34(4):207-212
[89]Ambrosini G, Adida C, Sirugo G et al. Induction of apoptosis and inhibition of cell proliferation by surviving gene targeting [J]. J Biol Chem,1998:273(111):77-82.
[90]Catalona WJ, Beiser JA, Smith DS. Serum free prostate specific antigen and prostate specific antigen density measurements for predicting cancer in men with prior negative prostatic biopsies [J]. J Urol 1997,158(216):2-7
[91]Mikolajezyk SD, Millar LS, Wang TJ, et al. A precursor form of prostate-specific antigen is more highly elevated in prostate cancer compared with benign transition zone prostate tissue [J]. Cancer Res 2000,60:756-759
[92]Tamm I, Wang Y, Sansville E, et al. IAP-family protein surviving inhibits caspase activity and apoptosis induced by Fas(CD95), Bax, and anticancer drugs[J]. Cancer Res, 1998,58(23):5315-5320.
[93]Hauser HP, Bardroff M, Pyrowolakis G, et al. A giant ubiquitin-conjugating enzyme related to LAP apoptosis inhibitors [J]. J Cell Biol,1998,141(6):1415-1422.
[94]Li F, Ambrosini G, Chu EY, et al. Control of apoptosis and mitotic spindle checkpoint by Survivin [J]. Nature,1998,396:580-584.
[95]Shin S, Sung BJ, Cho YS, et al. An Aneli-apoptotic protein human survivin is a direct inhibitor surviving with different anti-apoptosis properties [J]. Cancer Res,1999, 59(24):6097-6012.
[96]Grossman D, McNif JM, Li F et al. Expression of the apoptosis inhibitor, surviving, in nonmelanoma skin cancer and gene targeting in a keratinocyte cell line [J]. Lab Invest, 1999,79:1121-1126.
[97]Adida C, Berebi D, Peucbmaur M, et al. Anti-apoptosis gene, surviving, and prognosis of neuroblastoma [J]. Lancet,1998,351:882-883.
[98]Yamamoto T, Tanigaxa N. The role of surviving as a new target of diagnosis and treatment in human cancer [J]. Med Electron Microsc,2001,34(4):207-212
[99]Oconnor DS, Grossman D, Plescia J, et al. Regulation of apoptosis at cell division by p34 cdc-2 phosphorylation of surviving[J]. Proc Natl Acad Sci,2000,97(24):13103-13107
[100]Grossman D, Kim PJ, Schechner JS, et al. Inhibition of melanoma tumor growth in vivo by surviving targeting [J]. Proc Natl Acad Sci,2001,98(2):635-640.
[101]Miller WE, Cheshire JI, Baldwin AS Jr. The NPC derived C15 LMP1 protein confers enhanced activation of NF-Kappa B and induction of the EGFR in epithelial cells[J]. Oncogene,1998,16(14):1869-1877.
[102]Frost M, Jarboe EA, Orlicky D, et al. Immunohistochemical localization of surviving in benign cervical mucosa, cervical dysplasis, and invasive squamous cell carcinoma [J]. Am J Clin Pathol,2002,117(5):738-774.
[103]Anthony Sandler, David Scott, Shgeru Takamizawa, et al. The survivin:Fas ratio is predictive of recurrent disease in neuroblastoma [J]. Journal of Pediatric Surgery.2002, 37(3):507-511.
[104]Smith SD, Wheeler AM, Plescia J, et al. Urine detection of Survivin and diagnosis of bladder cancer[J]. JAMA,2001,285(3):324-328.
[105]Shin S, Sung BJ, Cho YS.An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and-7 [J]. Biochemistry,2001,40(4):1117-1123.
[106]Sohn J, Khauostov VI, Xie Q. Survivin expression and the effects of ursodeoxcholic acid on the survivin in thapsigargin-induced apoptosis[J]. Cancer Letters,2003,191:83-92.
[107]Soria JC, Rodriguez M, Liu DD, et al. Aberrant promoter methylation of multiple genes in bronchial brush samples former cigarette smokers [J]. Cancer Res,2002,62:351-355.
[108]Suzuki A, Hayashida M, Ito T, et al. Survivin initiates cell cycle entry by the competitive interaction with CDK4/p16(INK 4a)and CDK4/cyclinE complex activation[J]. Oncogene, 2000,19(29):3225-3234.
[109]Suzuki A, To T, Kawano H, et al. Survivin initiates procapase-3/P21 complex formation as a result of interaction with CDK4 to resist Fas-mediated cell death [J]. Oncogene,2000, 19(10):1346-1353.
[110]Suzuki A, Hayashida M, Ito T, et al. Survivin initiates cell cycle entry by the competitive interaction with CDK4/pl6(INK 4a) and CDK4/cyclinE complex activation[J]. Oncogene,2000,19(29):3225-3234.
[111]Guo F, Nimmanapalli R, Paranawithana S, et al. Ectopic overexpression of second mitochondria-derived activator of caspases(smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothflone B derivative-(BSM 247550)and Apo-2L/TRAIL-induced apoptosis[J]. Blood,2002,99:3419-3426.
[112]Du C, Fang M, Li Y Smac, a mitochondrial protein that promotes cytochrome C-dependent caspase activation by eliminating 1AP inhibition[J]. Cell,2000,102:33-42.
[113]Tamawski AS, Smabo I.Apoptosis-progarammed cell death and its relevance to gastrointestinal epithelium:survival signal from the mahix [J]. Castroenterology,2001, 120(1),244-299.
[114]Mesri M, Wall NR, Li J, et al. Cancer gene therapy using a surviving mutant adenovirus[J]. J Clin Invest 2001,108:981-990.
[115]Arbab IA, Looi CY, Abdul AB, et al. Dentatin induces apoptosis in prostate cancer cells via bcl-2.bcl-xL, surviving downregulation, caspase-9,-3/7 activation, and NF-kB inhibition [J]. Evid Based Complement Alternat Med,2012[Epub 2012 Oct3].
[116]O'Connor DS, Grossman D, Plescia J, et al.Regulation of apoptosis at cell division by p34cdc2 phosphorylation of surviving[J]. ProcNatl Acad Sci USA,2000,97:3103-3107.
[117]Guo LD, Chen XJ, Hu YH, et al. Curcumin inhibits proferation and induces apoptosis of human colorectal cancer cells by activating the mitochondria apoptotic pathway [J]. Phytother Res,2013,27(3):422-430.
[118]Verhagen AM, Ekert PG, Pakusch M, et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP protein [J]. Cell 2000, 102:43-53.
[119]Jin Y, WeiY, Xiong L, et al. Differential regulation of surviving by P53 contributes to cell cyele dependent apoptosis[J]. Cell Res2005,15:361-370.
[120]Shankar SL, Mani S, O'Guin KN, et al. Survivin inhibition induces human neural tumor cell death through caspase independent and dependent pathways [J]. J Neurochem 2001,79:426-436.
[121]Kasof GM. Gomes BC. Livin, a novel inhibitor of apoptosis protein family member [J]. Biol Chem,2001,276(5):3238-3246.
[122]Lin JH, Deng G, Huang O, et al. KIAP, a novel member of the inhibitor of apoptosis protein famiIy[J]. Biochem Biophys Res Commun,2000,279(3):820-831.
[123]Vucic D, Stennicke HR, Pisabarro MT, et al. ML-IAP, a novel inhibitor of apoptosis that is preferentially expressed in human meIanomas[J]. Curr Biol,2000,10(21):1359-1366.
[124]Ashhab Y, Alian A, PoIIiack A, et al. Two splicing variants of a new inhibitor of apoptosis gene with different biological properties and tissue distribution pattern [J]. FEBS Lett,2001,495(2):56-60.
[125]韩兴涛.Livin、Caspase-3和MVD在膀胱癌中的表达及意义[D].[硕士学位论文].郑州：郑州大学,2009.
[126]江亚军,顾健.Livin与恶性肿瘤的研究进展[J].医学综述,2008,14(15)：2267-2271.
[127]Gong J, Chen N, Zhou Q, et al. Melanoma inhibitor of apoptosis protein is expressed differentially in melanoma and melanocytic naevus but similarly in primary and metastatic melanomas [J]. Clin Pathol,2005,58(10):1081-1085.
[128]Xiang Y, Yao H, Wang S, et al. Prognostic value of surviving and livin in nasopharygeal carcinoma [J]. Laryngoscope,2006,116(1):126-130.
[129]Gazzaniga P,Gradilone A, Ginliani L, et al. Expression and prognostic significance of livin,surviving and other apoptosis related genes in the progression of superficial bladder cancer[J]. Ann Oncol,2003,14(1):85-90.
[130]李中福,王子卫.新的凋亡抑制蛋白Livin的研究及临床意义[J].重庆医学2005,34(12)：1892-1895.
[131]Nachmia SB, Ashhab Y, Buchotz V, et al. Caspase-mediated cleavage converts livin from an antiapoptotic to a proapoptotic factor:implications for drug- resistant melanoma [J]. Cancer Res,2003,63 (19):6340-6349.
[132]Hariu H, Hirohashi Y, Torigoe T, et al. Aberrant expression and potency as a cancer immunotherapy target of inhibitor of apoptosis protein family, Livin /ML-IAP in lung cancer[J]. Clin Cancer Res,2005,11 (3):1000-1009.
[133]Yagihashi A, Asanuma K, Tsuji N, et al. Detection of antilivin antibody in gastroinstestinal cancer patiences[J]. Clin Chem,2003,49(7):1206-1208.
[134]Yagihashi A,Ohmura T, Asanuma K, et al. Detection of autoantibodies to surviving and livin in sera from patients with breast cancer[J]. Clin Chem,2005,12:362(1-2):125-130.
[135]Vucic D, Franklin MC, Wallweber HJ, et al. Engineering ML-IAP to produce an extraordinarily potent caspase-9 inhibitor implications for Smac-dependent anti-apoptotic activity of ML-IAP [J]. Biochem J,2005,385 (1):11-20.
[136]Crnkovic-Mertens I, Semzow J, Hoppe-Seyler F, et al. Isoform-specific silencing of the Livin gene by RNA interference defines Livin beta as key mediator of apoptosis inhibition in Hela cells [J]. J Mol Med,2006,84 (3):232-240.
[137]Liao YC, Zeng H, Wang X J, et al. Expression patterns and prognostic significance of inhibitor of apoptosis proteins in adenoid cystic carcinoma and pleomorphic adenoma of lachrymal gland[J]. Exp Eye Res,2009,88(1):4-11.
[138]王红霞.Survivin和p53在泪腺多形性腺瘤组织中的表达及意义[D].[硕士学位论文]上海：第二军医大学,2008.
[139]李青吉.复发性泪腺上皮性肿瘤临床特征分析及相关凋亡因子研究[D].[博士学位论文].天津：天津医科大学,2008.
[1]何松,左国庆,张燕,等.苦参碱诱导人肝癌细胞分化、凋亡时对G1细胞周期调节因子的调控[J].癌症,2001,20(8)：848-851.
[2]张卫东,赵慧儒,于秉治.斑蝥素对肺癌A549细胞周期阻滞作用机制的观察[J].中国肿瘤临床,2005,31(23)：1372-1374.
[3]李洁,张岱州,马梅芳.白花蛇舌草对肝癌H22荷瘤小鼠抑瘤作用的研究[J].中国中医药科技,2009,16(1):28-29.
[4]Kuo PL, Chiang LC, Lin CC. Resveratrel-induced apoptosis is mediated by p53-dependent pathway in HepG2 cells [J]. Life Sci,2002,72(1):23-34.
[5]袁淑兰,黄韧敏,宋毅.丹参酮HA对HL260细胞系体外诱导分化作用的研究[J].实用肿瘤杂志,1997,12(6)：253-261.
[6]Cui GH, Chen WH, Xue KY, et al. Effects of triptolide and TNF-alpha on the expression of VEGF in Raji cells and on angiogenesis in ECV304 cells [J]. Zhongguo Shi Yan Xue Ye Xue Za Zhi,2006,14(5):1008-1012.
[7]刘丽丽,刘艳娥,房国涛.三七总皂苷逆转乳腺癌细胞MCF-7/ADM多药耐药的实验研究[J].时珍国医国药,2008,19(4)：954-956.
[8]李卫东,任连生,林志彬,等.灵龙颗粒剂的抗肿瘤作用及对免疫功能的影响[J].中国新药杂志,2002,11(12)：928-931.
[9]金春峰,王守岩,蔡玉文,等.中药复方诱导肿瘤细胞凋亡的研究述评[J].辽宁中医学院学报,2004,6(3)：233-234.
[10]关文明,范钰,郭学良,等.β榄香烯对人胃癌细胞SGC-7901细胞凋亡及Survivin表达和Caspase酶活性的影响[J].复旦学报,2003,30(5)：434-438.
[11]梁朝晖,潘智然,李娟,等.复方中药对小鼠肺癌细胞凋亡的影响[J].世界中西医结合杂志,2008,3(11)：643-648.
[12]Jang KJ, Han MH, Lee BH, et al. Induction of apoptosis by ethanol extracts of Ganoderma lucidum in human gastriccarcinoma cells [J]. J Acupunct Meridian Stud,2010,3(1):24-31.
[13]Athar M, Back JH, Kopelovich L, et al. Multiple molecular targets of resveratrol:Anti-carcinogenic mechanisms [J]. Arch Biochem Biophys,2009,486(2):95-102.
[14]Dai ZJ, Gao J, Ji ZZ, et al. Matrine induces apoptosis in gastric carcinoma AGS cells to TRA1L-mediated apoptosis via down-regulation of AKT and activation of caspase-3[J]. Anticancer Res,2009,29(11):4457-4465.
[15]Lin JP, Yang JS, Lee JH, et al. Berberine induces cell cycle arrest and apoptosis in human gastric carcinoma SNU-5 cell line[J]. World J Gastroenterol,2006,12(1):21-28.
[16]刘兰,许东元,杨万山,等.小白菊内酯增强4-HPR诱导肿瘤细胞凋亡[J].中国病理生理杂志,2008,24(9)：1738-1740.
[17]尚西亮,傅华群,刘佳,等.三七总皂苷对人肝癌细胞的抑制作用[J].中国临床康复,2006,10(23)：121-123.
[18]刘军权,陈复兴,黄键,等.银杏叶提取物增强细胞因子诱导的杀伤细胞杀伤肿瘤细胞活性的研究[J].陕西医学杂志,2002,31：469-471.
[19]Tsukada Y, Miyazawa K, Kitamura N, et al. High intensity ERK signal mediates hepatocyte growth factor-induced proliferation inhibition of the human hepatocellular carcinoma cell line HepG2[J]. JBC,2001,276:40968-40976.
[20]Clostre F. Ginkgo biloba extract (Egb761). State of knowledge in the dawn of the year 2000[J]. Ann Pharm Fr,1999,57(1):158-188
[21]Lenoir M, Pedruzzi E, Rais S. Sensitization of human neutropil defense activities through activation of platelet activiating receptors by ginkgolide B, a bioactive component of the Ginkgo biloba extract EGB 761 [J]. Biochempharmacol,2002,63 (7):1241-1249
[22]Akisu M, Kultursay N, Coker J, et al. Platelet activating factor is an important mediator in hypoxic ischemic brain injury in the newborn rat. Flunarizine and Ginkgo biloba extract reduce PAF concentration in the brain[J].Biol Neonate,1998,74(6):439-441
[23]Ni Y, Zhao B, Hou J, et al. Preventive effect of Ginkgo biloba extract on apoptosis in rat cerebellar neuronal cells induced by hydroxyl radicals [J]. Neurosci Lett,1996,214(2-3): 115-118.
[24]Chen C, Wei T, Gao Z. Different effects of the constituents of Egb761 on apoptosis in rat cerebellar granule cells induced by hydroxyl radicals [J].Biochem Mol Biol Int,1999, 47(3):397-405.
[25]Jiang XY, Qian LP, Zheng XJ, et al. Interventional effect of Ginkgo biloba extract on the progression of gastric precancerous lesions in rats [J]. Journal of Digestive Diseases,2009, 10(4):293-299.
[26]Chandrasekaran K, Mehrabian Z, Spinnewyn B, et al. Bilobalide, a component of the Ginkgo biloba extract (EGb 761), protects against neuronal death in global brain ischemia and in glutamate-induced excitotoxicity[J].Cell Mol Biol (Noisylegrand),2002,48(6): 663-669.
[27]Jane CJ. Effects of Ginkgo biloba extract on cytoprotective factors in rats with duodenal ulcer [J]. World J Gastroenterol,2004,10(1):37-41.
[28]Matsushima H, Morimoto K.The modulation of immunological activities in human NK cells by extracts of ginkgo [J]. Environ Health Prev Med,2009,4(9):361-365.
[29]Chen XH, Miao YX, Wang XJ, et al. Effects of Ginkgo Bilobs Extract EGB761 on Human Colon Adenocarcinoma Cells [J]. Cell Physiol Biochem,2011,27(3-4):227-232.
[30]Koltermann A, Liebl J, Furst R, et al. Ginkgo biloba extract EGb 761 exerts anti-angiogenic effects via activation of tyrosine phosphatases[J]. J Chromatogr A,2009, 13(8B):2122-2130.
[31]Li W, Pretner E, Shen L, Drieu K, Papadopoulos V. Common gene targets of Ginkgo biloba extract (EGb 761) in human tumor cells:relation to cell growth[J]. Cell Mol Biol,2002 Sep; 48(6):655-662.
[32]DeFeudis FV, Papadopoulos V, Drieu K. Ginkgo biloba extracts and cancer:a research area in its infancy [J]. Fundam Clin Pharmacol,2003,17(4):405-417.
[33]Chen C, Wei T, Gao Z, et al. Different effects of the constituents of EGb761 on apoptosis in rat cerebellar granule cells in duced by hydroxyl radicals [J]. Biochem Mol Biol Int, 1999; 47:397-405
[34]Papadopoulos V, Kapsis A, Li H, et al. Drug-induced inhibition of the peripheral-type benzodiazepine receptor expression and cell proliferation in human breast cancer cells [J]. Anticancer Res 2000; 20:2835-2847.
[35]Ni Y, Zhao B, Hou J, et al. Preventive eff ect of Ginkgo biloba extract on apoptosis in rat cerebellar neuronal cells induced by hydroxyl radicals [J]. Neurosci Lett,1996,214:115-118
[36]董丽.银杏叶提取物对高脂喂养胰岛素抵抗大鼠胰岛p细胞凋亡的保护作用[D].[硕士学位论文].石家庄：河北医科大学,2007.
[37]张锋,陈润芬,李惠丽,等.银杏叶提取物GBE50对兔心肌组织bcl-2、bcl-xL基因表达的影响[J].中成药2005,27(1)：60-65.
[38]李玉梅,饶明俐,谭岩.新生大鼠缺氧缺血性脑损伤Caspase-3的表达变化及银杏叶制剂的保护作用[J].中风与神经疾病杂志,2006,23(3)：21-25.
[39]洪森荣,尹明华.银杏叶提取物对缺血再灌注小鼠脑细胞凋亡的保护作用[J].中草药,2008,38(12)：1864-1868.