cDNA微矩阵技术的建立及其对人食管鳞状上皮细胞癌基因表达谱的研究
|
摘要
背景与目的：
食管癌(Esophageal Carcinoma)是人类最常见的恶性肿瘤之一，其死亡率在中国位居第四位，严重危害人类健康。随着现代生物技术的发展，食管癌的分子机制研究取得了长足进展，提示食管癌的发生是一个多阶段、多遗传变异累积的过程。尤其是近年来发展起来的cDNA微矩阵(microarray)技术已经将我们带进了食管癌的内部世界，对于阐明其发生过程和癌变机理有重要作用。同时对食管癌基因表达谱的准确定性将成就一个精确的分类系统，产生用于筛选检验的新诊断标记物和新型治疗靶点。目前，利用这项技术已积累了大量文献，但国内的研究其质量与国际先进水平相比尚存在较大差距，具体表现在：(1)、国内迄今为止的所有肿瘤学芯片研究均采用组织匀浆法获取肿瘤组织，无法克服其异质性缺点，这极大地影响了目的细胞基因表达谱的准确性；(2)、难以对小范围病变的目的细胞进行研究；(3)对微量的组织标本，如微小的活检组织无能为力。为缩小与国际先进水平的差距，也为了准确地了解河南籍食管癌基因mRNA水平表达的整体面貌，我们特建立了LCM-GMA(laser captured microdissection—high fidelity
BACKGROUND AND OBJECTIVE:
Esophageal Carcinoma (EC) is one of the major malignancies worldwide and is the fourth most common cause of cancer-related death in China. Advances in modern biological techniques have contributed to discovery of its molecular mechanism, suggesting that EC is a genetic disease arising from the complex multi-step process and the progressive accumulation of multiple genetic alterations. The recent development of cDNA microarray technology provides a platform where one can explore the inner status of EC. The data obtained from the microarray analysis are expected to uncover the important genetic alterations underlying EC development and its clinical behavior. It is likely that cDNA microarray-based expression profiling will substantially facilitate the discovery of new diagnostic and prognostic indicators and biomarkers of therapeutic response, as well as the classification of pathological diagnosis, in EC. There are several
食管癌(Esophageal Carcinoma)是人类最常见的恶性肿瘤之一，其死亡率在中国位居第四位，严重危害人类健康。随着现代生物技术的发展，食管癌的分子机制研究取得了长足进展，提示食管癌的发生是一个多阶段、多遗传变异累积的过程。尤其是近年来发展起来的cDNA微矩阵(microarray)技术已经将我们带进了食管癌的内部世界，对于阐明其发生过程和癌变机理有重要作用。同时对食管癌基因表达谱的准确定性将成就一个精确的分类系统，产生用于筛选检验的新诊断标记物和新型治疗靶点。目前，利用这项技术已积累了大量文献，但国内的研究其质量与国际先进水平相比尚存在较大差距，具体表现在：(1)、国内迄今为止的所有肿瘤学芯片研究均采用组织匀浆法获取肿瘤组织，无法克服其异质性缺点，这极大地影响了目的细胞基因表达谱的准确性；(2)、难以对小范围病变的目的细胞进行研究；(3)对微量的组织标本，如微小的活检组织无能为力。为缩小与国际先进水平的差距，也为了准确地了解河南籍食管癌基因mRNA水平表达的整体面貌，我们特建立了LCM-GMA(laser captured microdissection—high fidelity
BACKGROUND AND OBJECTIVE:
Esophageal Carcinoma (EC) is one of the major malignancies worldwide and is the fourth most common cause of cancer-related death in China. Advances in modern biological techniques have contributed to discovery of its molecular mechanism, suggesting that EC is a genetic disease arising from the complex multi-step process and the progressive accumulation of multiple genetic alterations. The recent development of cDNA microarray technology provides a platform where one can explore the inner status of EC. The data obtained from the microarray analysis are expected to uncover the important genetic alterations underlying EC development and its clinical behavior. It is likely that cDNA microarray-based expression profiling will substantially facilitate the discovery of new diagnostic and prognostic indicators and biomarkers of therapeutic response, as well as the classification of pathological diagnosis, in EC. There are several
引文
1. Hergenhahn M, Kenzelmann M, Grone HJ. Laser-controlled microdissection of tissues opens a window of new opportunities. Pathol Res Pract. 2003; 199(6):419-423.
2. De Preter K, Vandesompele J, Heimann P, et al. Application of laser capture microdissection in genetic analysis of neuroblastoma and neuroblastoma precursor cells. Cancer Lett. 2003 Jul 18; 197(1-2):53-61.
3. Curran S, McKay JA, McLeod HL, et al. Laser capture microscopy. Mol Pathol. 2000 Apr;53(2):64-68.
4. Vecchiotti C, Spaltro G, Bloise D, et al. Demonstration of a gastric bioptic specimen??mix-up by laser capture microdissection (LCM) and DNA fingerprinting. Am J Forensic Med Pathol. 2004 Jun;25(2):113-116.
5. Inoue H, Igari T, Nishikage T, et al. A novel method of virtual histopathology using laser-scanning confocal microscopy in-vitro with untreated fresh specimens from the gastrointestinal mucosa. Endoscopy. 2000 Jun;32(6):439-443.
6. Deng MY, Wang H, Ward GB, et al. Comparison of six RNA extraction methods for the detection of classical swine fever virus by real-time and conventional reverse transcription-PCR. J Vet Diagn Invest. 2005 Nov; 17(6):574-578
7. Warner EE, Dieckgraefe BK. Application of genome-wide gene expression profiling by high-density DNA arrays to the treatment and study of inflammatory bowel disease. Inflamm Bowel Dis. 2002 Mar;8(2): 140-157.
8. Wadenback J, Clapham DH, Craig D, et al. Comparison of standard exponential and linear techniques to amplify small cDNA samples for microarrays. BMC Genomics. 2005 May 4;6(1):61.
9. Patel OV, Suchyta SP, Sipkovsky SS, et al. Validation and application of a high fidelity mRNA linear amplification procedure for profiling gene expression. Vet Immunol Immunopathol. 2005 May 15;105(3-4):331-342.
10. Moll PR, Duschl J, Richter K. Optimized RNA amplification using T7-RNA-polymerase based in vitro transcription. Anal Biochem. 2004 Nov 1 ;334(1):164-174
11. Wan Y. Gene expression-driven diagnostics and pharmacogenomics in cancer. Curr Opin Mol Ther. 2005 Jun;7(3):246-250.
12. Smeds J, Miller LD, Bjohle J, et al. Gene profile and response to treatment. Ann Oncol. 2005;16 Suppl 2:ⅱ 195-202.13. Eisen MB, Spellman PT, Brown PO, et al. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sei, 1998; 95:14863-14868.
14. Yue H, Eastman PS, Wang BB, et al. An evaluation of the performance of cDNA microarray for detecting changes in global mRNA expression. Nucleic Acids Res, 2001; 29: e41-1.
15. Yang Ⅳ, Chen E, Hasseman JP, et al. Within the fold: assessing differential expression measures and reproducibility in mieroarray assays. Genome Biol, 2002;24:3(11): Research 0062.Epub 2002 Oct 24.
16. Zhao H J, Hastie T, Whitfield ML, et al. Optimization and evaluation of T7 based RNA linear amplification protocols for eDNA microarray analysis. BMC Genomics, 2002; 30;3(1): 31.1 Wan Y. Gene expression-driven diagnostics and pharmacogenomics in cancer. Curr Opin Mol Ther. 2005 Jun;7(3):246-250.
2 Kwong KF. Molecular biology of esophageal cancer in the genomics era. Surg Clin North Am. 2005;85(3):539-553.
3 Kyrgidis A, Kountouras J, Zavos C, et al. New molecular concepts of Barrett's esophagus: clinical implications and biomarkers. J Surg Res. 2005; 125(2): 189-212.
4 Sunpaweravong P, Sunpaweravong S, Puttawibul P, et al. Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol.??2005;131(2):111-119.
5 Zhang G, Zhou X, Xue L, et al. Accumulation of cytoplasmic beta-catenin correlates with reduced expression of E-cadherin, but not with phosphorylated Akt in esophageal squamous cell carcinoma: immunohistochemical study. Pathol Int. 2005;55(6):310-317.
6 Teraishi F, Kagawa S, Watanabe T, et al. ZD1839 (Gefitinib, 'Iressa'), an epidermal growth factor receptor-tyrosine kinase inhibitor, enhances the anti-cancer effects of TRAIL in human esophageal squamous cell carcinoma. FEBS Lett. 2005 ;579(19):4069-4075.
7 Lu X, Nechushtan H, Ding F, et al. Distinct IL-4-induced gene expression, proliferation, and intracellular signaling in germinal center B-cell-like and activated B-cell-like diffuse large-cell lymphomas. Blood. 2005;105(7):2924-2932.
8 Poulsen CB, Borup R, Nielsen FC, et al. Microarray-based classification of diffuse large B-cell lymphoma. :Eur J Haematol. 2005;74(6):453-465.
9 Danbara N, Yuri T, Tsujita-Kyutoku M, et al. Enterolactone induces apoptosis and inhibits growth of Colo 201 human colon cancer cells both in vitro and in vivo. Anticancer Res. 2005;25(3B):2269-2276.
10 Blanco-Aparicio C, Pequeno B, Moneo V, et al. Inhibition of phosphatidylinositol-3-kinase synergizes with gemcitabine in low-passage tumor cell lines correlating with Bax translocation to the mitochondria. Anticancer Drugs. 2005;16(9): 977-987.1. Kwong KF. Molecular biology of esophageal cancer in the genomics era. Surg Clin North Am. 2005;85(3):539-553.
2. Wan Y. Gene expression-driven diagnostics and pharmacogenomics in cancer. Curr Opin Mol Ther. 2005 Jun;7(3):246-250.
3. Smeds J, Miller LD, Bjohle J, et al. Gene profile and response to treatment. Ann Oncol. 2005; 16 Suppl 2:ⅱ 195-202.
4. Herrera LJ, EI-Hefnawy T, Queiroz de Oliveira PE, et al. The HGF receptor c-Met is overexpressed in esophageal adenocarcinoma. Neoplasia. 2005 ;7(1):75-84.
5. Cheng TL, Chang MY, Huang SY, et al. Overexpression of Circulating c-Met Messenger RNA Is Significantly Correlated With Nodal Stage and Early Recurrence in Non-Small Cell Lung Cancer. Chest. 2005; 128(3): 1453-1460.
6. Hatano H, Siegel H J, Yamagiwa H, et al. Identification of estrogen-regulated genes during fracture healing, using DNA microarray. J Bone Miner Metab. 2004;22(3):224-235.
7. Poulsen CB, Borup R, Nielsen FC, et al. Microarray-based classification of diffuse large B-cell lymphoma. :Eur J Haematol. 2005;74(6):453-465.
8. Chang MS, Lee HS, Lee BL, et al. Differential protein expression between esophageal squamous cell carcinoma and dysplasia, and prognostic significance of??protein markers. Pathol Res Pract. 2005;201 (6):417-425.
9. Teraishi F, Kagawa S, Watanabe T, et al. ZD1839 (Gefitinib, 'Iressa'), an epidermal growth factor receptor-tyrosine kinase inhibitor, enhances the anti-cancer effects of TRAIL in human esophageal squamous cell carcinoma. FEBS Lett. 2005 ;579(19):4069-4075.1. Zhang H, Chen SH, Li YM. Epidemiological investigation of esophageal carcinoma. World J Gastroenterol. 2004; 10(12): 1834-1835
2. Kwong KF. Molecular biology of esophageal cancer in the genomics era. Surg Clin North Am. 2005;85(3):539-553.
3．秦艳茹，王立东，邝丽芸，等．食管癌原发灶与淋巴结转移灶细胞染色体变化特征的比较[J]．癌症，2005，24(9)：1048-1053．
4. Buckhaults P. Gene expression determinants of clinical outcome. Curr Opin Oncol.2006 Jan; 18(1):57-61.
5. Rennebeck G, Martelli M, Kyprianou N. Anoikis and survival connections in the tumor microenvironment: is there a role in prostate cancer metastasis? Cancer Res. 2005 Dec 15;65(24):11230-11235.
6. Sayed-Ahmad MM, Mohamad MA. Contribution of Nitric Oxide and Epidermal Growth Factor Receptor in Anti-Metastatic Potential of Paclitaxel in Human Liver Cancer Cell (HebG2). J Egypt Natl Cane Inst. 2005;17(1):35-41.
7. Baker EA, Leaper DJ, Hayter JP, et al, The matrix metalloproteinase system in oral squamous cell carcinoma. Br J Oral Maxillofac Surg. 2005; [Epub ahead of print]
8. Zhang G, Zhou X, Xue L, et al. Accumulation of cytoplasmic beta-catenin correlates with reduced expression of E-cadherin, but not with phosphorylated Akt in esophageal squamous cell carcinoma: immunohistochemical study. Pathol Int. 2005;55(6):310-317.
9. Teraishi F, Kagawa S, Watanabe T, et al. ZD1839 (Gefitinib, 'Iressa'), an epidermal growth factor receptor-tyrosine kinase inhibitor, enhances the anti-cancer effects of TRAIL in human esophageal squamous cell carcinoma. FEBS Lett.??2005 ;579(19):4069-4075.
10. Chang MS, Lee HS, Lee BL, et al. Differential protein expression between esophageal squamous cell carcinoma and dysplasia, and prognostic significance of protein markers. Pathol Res Pract. 2005;201 (6):417-425.
11. Danbara N, Yuri T, Tsujita-Kyutoku M, et al. Enterolactone induces apoptosis and inhibits growth of Colo 201 human colon cancer cells both in-vitro and in vivo. Anticancer Res. 2005;25(3B):2269-2276.
12．王新允，刘婷，朱从中，等．应用组织芯片技术检测KAI1、MRP-1、FAK蛋白在肺癌组织中的表达[J]．癌症，2005，24(9)：1091-1095．1. Zhang H, Chen SH, Li YM. Epidemiological investigation of esophageal carcinoma. World J Gastroenterol. 2004;10(12):1834-1835
2. Kwong KF. Molecular biology of esophageal cancer in the genomics era. Surg Clin North Am. 2005;85(3):539-553.
3. Kurokawa S, Arimura Y, Yamamoto H, et al. Tumour matrilysin expression predicts metastatic potential of stage Ⅰ (pT1) colon and rectal cancers. Gut. 2005 Dec;54(12):1751-1758.
4. Besson A, Gurian-West M, Chen X, et al. A pathway in quiescent cells that controls p27Kipl stability, subcellular localization, and tumor suppression. Genes Dev. 2006 Jan 1;20(1):47-64.
5. Muthusamy V, Hobbs C, Nogueira C, et al. Amplification of CDK4 and MDM2 in malignant melanoma. Genes Chromosomes Cancer. 2006 Jan 17; [Epub ahead of print]
6. Xu F, Zhong W, Li J, et al. Predictive value of EphA2 and EphrinA-1??expression in oesophageal squamous cell carcinoma. Anticancer Res. 2005;25(4):2943-2950.
7. Dasgupta S, Bhattacharya-Chatterjee M, O'malley BW Jr, et al. Tumor metastasis in an orthotopic murine model of head and neck cancer: Possible role of TGF-beta 1 secreted by the tumor cells. J Cell Biochem. 2005 Nov 17; [Epub ahead of print]
8. Ren Y, Cao B, Law S, et al. Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clin Cancer Res. 2005 Sep 1;11(17):6190-6197.
9. Xu L, Chen S, Bergan RC. MAPKAPK2 and HSP27 are downstream effectors of p38 MAP kinase-mediated matrix metalloproteinase type 2 activation and cell invasion in human prostate cancer. Oncogene. 2006 Jan 16: [Epub ahead of print]
10. Teraishi F, Kagawa S, Watanabe T, et al. ZD1839 (Gefitinib, 'Iressa'), an epidermal growth factor receptor-tyrosine kinase inhibitor, enhances the anti-cancer effects of TRAIL in human esophageal squamous cell carcinoma. FEBS Lett. 2005;579(19):4069-4075.
11. Zhang G, Zhou X, Xue L, et al. Accumulation of cytoplasmic beta-catenin correlates with reduced expression of E-cadherin, but not with phosphorylated Akt in esophageal squamous cell carcinoma: immunohistochemical study. Pathol Int. 2005;55(6):310-317.
12. Iwaya T, Maesawa C, Kimura T, et al. Infrequent mutation of the human envoplakin gene is closely linked to the tylosis oesophageal cancer??locus in sporadic oesophageal squamous cell carcinomas. Oncol Rep. 2005;13(4):703-707.
13. Custer MC, Risinger JI, Hoover S, et al. Characterization of an antibody that can detect the Kail/CD82 murine metastasis suppressor. Prostate. 2005 Dec 21; [Epub ahead of print]
14. Wan Y. Gene expression-driven diagnostics and pharmacogenomics in cancer. Curr Opin Mol Ther. 2005 Jun;7(3):246-250.1. Buskens C J, Marsman WA, Bosma P J, et al. The current state of cancer gene therapy and its application in esophageal carcinoma. Dig Surg. 2005;22(4):222-233. Epub 2005 Sep 20.2. Naidoo R, Ramburan A, Reddi A, et al. Aberrations in the mismatch repair genes and the clinical impact on oesophageal squamous carcinomas from a high incidence area in South Africa. J Clin Pathol. 2005 Mar;58(3):281-284.
3. Yoshimoto M, de Toledo SR, da Silva NS, et al. Comparative genomic hybridization analysis of pediatric adamantinomatous craniopharyngiomas and a review of the literature. J Neurosurg. 2004 Aug; 101 (1 Suppl):85-90.
4. Oka M. Comparative genomic hybridization analysis for esophageal squamous cell carcinoma. Ann Thorac Cardiovasc Surg. 2004 Oct;10(5):275-276.
5. Knijnenburg J, van der Burg M, Nilsson E et al. Rapid detection of genomic imbalances using micro-arrays consisting of pooled BACs covering all human chromosome arms. Nucleic Acids Res. 2005 Oct 12;33(18):e159.
6. Pang ST, Weng WH, Flores-Morales A, et al. Cytogenetic and expression profiles associated with transformation to androgen-resistant prostate cancer. Prostate. 2005 Sep 19; [Epub ahead of print]1. Dasgupta S, Bhattacharya-Chatterjee M, O'malley BW Jr, et al. Tumor metastasis in an orthotopic murine model of head and neck cancer: Possible role of TGF-beta 1 secreted by the tumor cells. J Cell Biochem. 2005 Nov 17; [Epub ahead of print]
2. Chodorowska G, Chodorowski J, Wysokinski A. Vascular endothelial growth factor (VEGF) in physiological and pathological conditions. Ann Univ Mariae Curie Sklodowska [Meal].2004;59(2):8-14.
3. Ren Y, Cao B, Law S, et al. Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clin Cancer Res. 2005 Sep 1;11(17):6190-6197.
4 Katsuta M, Miyashita M, Makino H, et al. Correlation of hypoxia inducible factor-lalpha with lymphatic metastasis via vascular endothelial growth factor-C in human esophageal cancer. Exp Mol Pathol. 2005 Apr;78(2): 123-30. Epub 2005 Jan 7.
5 Forster Y, Meye A, Albrecht S, et al. Tissue factor and tumor: Clinical and laboratory aspects. Clin Chim Acta. 2005 Sep 1; [Epub ahead of print]
6 Ueda M, Terai Y, Kanda K, et al. Tumor angiogenesis and molecular target therapy in ovarian carcinomas. Hum Cell. 2005 Mar; 18(1): 1-16.1. Herrera LJ, El-Hefnawy T, Queiroz de Oliveira PE, et al. The HGF receptor c-Met is overexpressed in esophageal adenocarcinoma. Neoplasia. 2005;7(1):75-84.
2. Ren Y, Cao B, Law S, et al. Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clin Cancer Res. 2005;11(17):6190-6197.
3. Ren Y, Law S, Huang X, et al. Macrophage migration inhibitory factor stimulates angiogenic factor expression and correlates with??differentiation and lymph node status in patients with esophageal squamous cell carcinoma. Ann Surg. 2005:242(1):55-63.
4. Cheng TL, Chang MY, Huang SY, et al. Overexpression of Circulating c-Met Messenger RNA Is Significantly Correlated With Nodal Stage and Early Recurrence in Non-Small Cell Lung Cancer. Chest. 2005;128(3): 1453-1460.
5. Seiden-Long IM, Brown KR, Shih W, et al. Transcriptional targets of hepatocyte growth factor signaling and Ki-ras oncogene activation in colorectal cancer. Oncogene. 2005; 12; [Epub ahead of print]
6. Dominguez FJ, Jones JL, Zabicki K, et al. Prevalence of hereditary breast/ovarian carcinoma risk in patients with a personal history of breast or ovarian carcinoma in a mammography population. Cancer. 2005; 31; [Epub ahead of print]
7. Dominguez F J, Jones JL, Zabicki K, et al. Prevalence of hereditary breast/ovarian carcinoma risk in patients with a personal history of breast or ovarian carcinoma in a mammography population. Cancer. 2005 Nov 1; 104(9): 1849-1853.
8. Everett EN, Heuser CC, Pastore LM, et al. Predictors of suboptimal surgical cytoreduction in women treated with initial cytoreductive surgery for advanced stage epithelial ovarian cancer. Am J Obstet Gynecol. 2005 Aug;193(2):568-574; discussion 574-6.1. Kenny LM, Vigushin DM, A1-Nahhas A, et al. Quantification of Cellular Proliferation in Tumor and Normal Tissues of Patients with Breast Cancer by [18F]Fluorothymidine-Positron Emission Tomography Imaging: Evaluation of Analytical Methods. Cancer Res. 2005;65(21): 10104-10112.
2. Dahia PL, Hao K, Rogus J,et al. Novel pheochromocytoma susceptibility Loci identified by integrative genomics. Cancer Res. 2005;65(21):9651-9658.
3. Yang F, Foekens JA, Yu J, et al. Laser microdissection and microarray analysis of??breast tumors reveal ER-alpha related genes and pathways. Oncogene. 2005; [Epub ahead of print]
4. Zhu B, Xu F, Baba Y, et al. An evaluation of linear RNA amplification in cDNA microarray gene expression analysis. Mol Genet Metab. 2005; [Epub ahead of print]
5. Yazdi AS, Puchta U, Flaig MJ,et al. Laser-capture microdissection: applications in routine molecular dermatopathology. J Cutan Pathol. 2004;31 (7):465-470.1. Sahar DE, Yang GP, Longaker MT, et al. Surgical application of cDNA microarray technique. Surgery. 2005 Sep;138(3):399-403.
2. Wong ML, Medrano JE Real-time PCR for mRNA quantitation. Biotechniques. 2005 Jul;39(1):75-85.
3. Lux MP, Fasching PA, Beckmann MW. Hereditary breast and ovarian cancer:??review and future perspectives. J Mol Med. 2005 Nov 11; [Epub ahead of print]
4. Chen MS Jr. Cancer health disparities among Asian Americans. Cancer. 2005 Nov 3; [Epub ahead of print]
5. Paik S, Kim CY, Song YK, et al. Technology insight: Application of molecular techniques to formalin-fixed paraffin-embedded tissues from breast cancer. Nat Clin Pract Oncol.2005 May;2(5):246-254.
6. Gruber MP, Geraci MW. Practical cancer genetics, genomics and proteomics. J Insur Med. 2005;37(3): 190-200.
7. Dolnik V, Liu S. Applications of capillary electrophoresis on microchip. J Sep Sci. 2005 Oct;28(15): 1994-2009.
8. Lauerman LH. Advances in PCR technology. Anim Health Res Rev. 2004 Dec;5(2):247-248.1. Mu(?)ozN, Epidemiological aspects of esophageal cancer. Endoscopy 1993; 23:609-612.
2. Lam KY, Law S, Tung PH, Wong J. Esophageal small cell carcinomas: clinicopathoiogic parameters, p53 overexpression, proliferation marker, and their impact on pathogenesis. Arch Pathol Lab Med 2000;124: 228-233.
3. Alfred King Y. Lain. Molecular biology of esophageal squamous cell carcinoma[J]. Critical Reviews in Oncology/Hematology 33(2000)71-91.E.R. Fearon, B. Vogelstein, A genetic model for colorectal tumorigenesis[J]. Cell 61 1990 759-767.
4. A.-M.Mandard, P.Hainaut, M.Holistein. Genetic steps in the development of squamous cell carcinoma of the esophagus[J]. Mutation Research 462(2000) 335-342
5. M. Hollstein, L. Peri, A.-M. Mandard,et al. Genetic analysis of human esophageal tumor from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutations[J]. Cancer Res. 51 1991 4102-4106.
6. Lebman DA, Edmiston JS, Chung TD, Snyder SR. Heterogeneity in the transforming growth factor beta response of esophageal cancer cells, Int J Oncol 2002;20:1241- 1246.
7. Matsumoto M, Natsugoe S, Nakashima S, Okumura H, Sakita H, Baba M, Takao S, Aikou T. Clinical significance and prognostic value of apoptosis related proteins in superficial esophageal squamous cell carcinoma. Ann Surg Oncol 2001;8: 598-604.
8. E.P. Xing, Y. Nie, L.-D. Wang, et al. Yang,Aberrant methylation of p16INK4a and deletion of p15INK5b are frequent events in human esophageal cancer in Linxian,. China, Carcinogenesis 20 1999 77-84.
9. W. Jiang, Y.J. Zhang, S.M. Kahn, et al.Altered expression of the cyclin DI and retinoblastoma genes in human esophageal cancer, Proc. Natl. Acad, Sci. U.S.A. 90 1993 9026-9030.10. Anayama T, Furihata M, Takeuchi T, Sonobe H, Sasaguri S, Matsumoto M, Ohtsuki Y. Insufficient effect of p27(KIP1) to inhibit cyclin D1 in human esophageal cancer in vitro. Int J Oncol 2001;18: 151-155.
11. Pennisi E. How a growth control path takes a wrong turn to cancer. Science 1998;281: 1438-1441.
12. M. Hollstein, A.M. Smits, C. Galiana, H. Yamasaki, J.L.Bos, A. Mandard, C. Partensky, R. Montesano, Amplification of EGF receptor gene but no evidence of ras mutations in primary human esophageal cancers, Cancer Res. 48 1988 5119-5123.
13. S.H. Lu, L.L. Hsieh, F.C. Luo, I.B. Weinstein, Amplification of the EGF receptor and c-myc genes in human esophageal cancers, Int. J. Cancer 42 1988 502-505..12 Okuda T, Shurtleff SA, Valentine MB, Raimondi SC, Head DR, Behm F, Curcio-Brint AM, Liu Q, Pui C-H, Sherr CJ, Beach D, Look AT, Downing JR. Frequent deletion of p16(INK4a)/MTS1 and p15(INK4b)/MTS2 in pediatric acute lymphoblastic leukemia. Blood 1995;85:2321-2330.
14. E.R. Fearon, B. Vogeistein, A genetic model for colorectal tumorigenesis[J]. Cell 61 1990 759-767.
15. Wong FH, Hu CP, Chiu JH, et al. Expression of multiple oncogenes in human esophageal carcinomas. Cancer Invest 1994; 12:121-131.
16. Koppert LB, Wijnhoven BP, van Dekken H, et al. The molecular biology of esophageal adenocarcinoma[J]. J Surg Oncoi. 2005 Dec 1;92(3): 169-190.
17. M. Schuler and D.R. Green, Mechanisms of p53-dependent apoptosis, Biochem. Soc. Trans. 29 (2001) (6), pp. 684-688.
18. Dárcio Matenhauer Lehrbach, Marcelo Eidi Nita, Ivan Cecconello,et al. Molecular aspects of esophageal squamous cell carcinoma carcinogenesis[J]. Arq. Gastroenterol. vol. 40 no.4 out/dez. Oct./Dec. 2003 256-261
19. Fujii S, Tominaga O, Nagawa H, Tsuno N, Nita ME, Tsuruo T, Muto T. Quantitative analysis of the??cyclin expression in human esophageal cancer cell lines. J Exp Clin Cancer Res 1998;17: 491-496.
20. Nakagawa H, Zukerberg L, Togawa K, et al. Human cylin D1 oncogene and esophageal squamous cell carcinoma. Cancer 1995;76:541-549.
21. Jiang W, Kahn SM, Tomita N, et al. Amplification and expression of the human cyclin D gene in esophageal cancer. Cancer Res 1992;52: 2980-2983.
22. Tsuruta H, Sakamoto H, Onda M, et al. Amplification and overexpression of EXP1 and EXP2:cyclin D1 genes in human esophageal carcinomas. Biochem Biophys Res Comm 1993;196: 1529-1536.
23. Adlaide J, Monges G, D(rd(rian C, et al. Esophageal cancer and amplification of the human cyclin D gene CCND1:PRAD1. Br J Cancer 1995;71: 64-68.
24. Iamamura M. Prognostic significance of Cyclin D1 and E-cadherin in patients with esophageal squamous cell carcinoma: multiinstitutional retrospective analysis. J Am Coll Surg 2001;192: 708-718.
25. Kanda Y, Nishiyama Y, Shimada Y, et al. Analysis of gene amplification and over expression in human esophageal carcinoma cell lines. Int J Cancer 1994;58: 291-297.
26. Miyazaki S, Sasano H, Shiga K, et al. Analysis of c-myc oncogene in human esophageal carcinoma: immunohistochemistry, in situ hybridization and Northern and Southern blot studies. Anticancer Res 1992; 12:1747-1756.
27. Tsuboi K, Hirayoshi K, Takeuchi K, et al. Expression of the c-myc gene in human gastrointestinal malignaancies. Biochem Biophys Res Comm 1987;146:699-704.
28. Zhu D, Wang L, Zhang C, et al. No evidence for the amplification of mdm2 and c-myc genes involved in the genetic susceptibility to esophageal cancer in a high-risk area of north China. Cancer Genet Cytogenet 1996;89:184-185.29. Shibagaki I, Tanaka H, Shimada Y, et al. p53 mutation, murine double minute 2 amplification, and human papiliomavirus infection are frequently involved but not associated with each other in esophageal squamous cell carcinoma. Ciin Cancer Res 1995;1: 769-773.
30. Burgess AW, Thumwood CM. The Sixth George Swanson Christie Memorial lecture: growth factors and their receptors: new opportunities for cancer treatment. Pathology 1994;26:453-463
31. Mukaida H, Toi M, Hirai T, et al. Clinical significance of the expression of epidermal growth factor and its receptor in esophageal cancer. Cancer 1991;68:142-148.
32 Itakura Y, Sasano H, Shiga C, et al. Epidermal growth factor receptor overexpression in esophageal carcinoma. Cancer 1994;74: 795-804.
33 Hirai T, Kuwahara M, Yoshida K, et al. Clinical results of transhiatal esophagectomy for carcinoma of the lower thoracic esophagus according to biological markers. Dis Esophagus 1998;11: 221-225.
34 Muller A, Nakagawa H, Rustgi AK. Retinoic acid and N-(4-hydroxy-phenyl) retinamide suppress growth of esophageal squamous carcinoma cell lines. Cancer Lett 1997; 113: 95-101.
35 Kok TC, van der Gaast A, Splinter TAW. 13-cis-retinoic acid and alpha-interferon in advanced squamous cell cancer of the esophagus. Eur J Cancer 1997;33:165-166.
36 Hickey K, Grehan D, Reid IM, et al. Expression of epidermal growth factor receptor and proliferating cell nuclear antigen predicts response of esophageal squamous cell carcinoma to chemoradiotherapy. Cancer 1994;74:1693-1698.
37 Yokota J, Yamamoto T, Toyoshima K, et al. Amplification of c-erbB-2 oncogene in human adenocarcinomas in vivo. Lancet 1986;8484: 765-767.
38 Suwanagool P, Parichatikanond P, Maeda S. Expression of c-erbB-2 oncoprotein in primary human tumors: an immunohistochemistry study. Asain Pac J Allergy lmmunol 1993;11:119-122.
39 Suo Z, Su W, Holm R, Nesland JM. Lack of expression of c-erbB-2 oncoprotein in human??esophageal squamous cell carcinomas. Anticancer Res 1995;15: 2797-2798.
40 Hardwick RH, Barham CP, Ozua, et al. Immunohistochemical detection of p53 and c-erbB-2 in esophageal carcinoma: no correlation with prognosis, Eur J Surg Oncol 1997;23: 30-35.
41 Jones GJ, Heiss NS, Veale RB, et al. Amplification and expression of the TGF-a, EGF receptor and c-myc genes in four human esophageal squamous cell carcinoma lines. Biosci Rep 1993;13:303-312.
42 Wagata T, Ishizaki K, Imammura M, et al. Deletion of 17p and amplification of the int-2 gene in esophageal carcinomas. Cancer Res 1991;51:2113-2117.
43 Kitagawa Y, Ueda M, Ando N, et al. Significance of int-2:hst-1 coamplification as a prognostic factor in patients with esophageal squamous carcinoma. Cancer Res 1991;51:1504-1508.
44 Ikeda Y, Ozawa S, Ando N, et al. Meanings of c-erbB and int-2 amplification in superficial esophageal squamous cell carcinomas. Ann Thorac Surg 1996;62:835-838.
45 Hollstein MC, Peri L, Mandard AM, et al. Genetic analysis of human esophageal tumors from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutation. Cancer Res 1991;51:4102-4106.
46 Lam KY, Shan XC, Dickens P, et al. The expression of H-ras p21 product in esophageal cancer from Hong Kong Chinese. Am J Gastroenterol 1995;90:171-172.
47 Ono H, Takahashi A, Ogoshi S. Relationship between H-ras p21 product and p53 protein or high risk human papillomaviruses in esophageal cancer from Kochi, Japan. Am J Gastroenterol 1994;89:646-647.
48 Hunter T, Pines J. Cyclins and cancer Ⅱ: cyclin D and CDK inhibitors come of age. Cell 1994;79:573-582.
49 Hatano H, Siegel HJ, Yamagiwa H, et al. Identification of estrogen-regulated genes during fracture healing, using DNA microarray. J Bone Miner Metab. 2004;22(3):224-235.
50 T. Kuroki, F. Trapasso and T. Shiraishi et al. Genetic alterations of the tumour suppressor gene WWOX in esophageal squamous cell carcinoma, Cancer Res. 62 (2002), pp. 2258-2260.
51 Lam KY, Loke SL, Chen WZ, et al. Expression of p53 in oesophageal squamous cell carcinoma in Hong Kong Chinese. Eur J Surg Oncol 1995;21:242-247.
52 Casson AG, Tammemagi M, Eskandarian S, et al. p53 alterations in esophageal cancer: associated with clinicopathological features, risk factors, and survival. J Clin Pathol Mol Pathol 1998;51:71-79.
53 Wagata T, Shibagaki I, Imamura M, et al. Loss of 17p mutation of the p53 gene, and overexpression of p53 protein in esophageal squamous cell carcinomas. Cancer Res 1993;53:846-850.
54 Montesano R, Hollstein M, Hainaut P. Genetic alternations in esophageal cancer and their relevance to etiology and pathogenesis: a review. Int J Cancer Pred Oncol 1996;69:225-235.
55 L. Wang, S. Zheng and Z. Zheng et al, Primary adenocarcinomas of lower esophagus, esophagogastric junction and gastric cardia: in special reference to China, World J. Gastroenterol. 9 (2003) (6), pp. 1156-1164
56 Vogelstein B, Kinzler KW. p53 function and dysfunction. Cell 1992;70:523-526
57 el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer E, Kinzler KW, Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell 1993;75:817-825.
58 Sur M, Cooper K. The role of the human papilloma virus in esophageal cancer. Pathology 1998;30:348-354
59 Lam KY, Loke SL, Chen WZ, et al. Expression of p53 in oesophageal squamous cell carcinoma in Hong Kong Chinese. Eur J Surg Oncol 1995;21 -.242-247.
60 Lam KY, Tsao SW, Zhang D, et al. Prevalence and predictive value of p53 mutation in patients with oesophageal squamous cell carcinomas: a prospective clinicopatholgical study and survival analysis of 70 patients. Int J Cancer 1997;74:212-219
61 Boynton R, Blount PL, Yin J, et al. Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers. Proc Natl Acad Sci 1992;89:3385-3388.
62 Hamada M, Naomoto Y, Fujiwara T, et al. Suppressed apoptotic induction in esophageal squamous cell carcinomas expressing extensive p53 protein. Jpn J Clin Oncol 1996;26:398-404.
63 Muro K, Ohtsu A, Boku N, et al. Association of p53 protein expression with responses and survival of patients with locally advanced esophageal carcinoma treated with chemoradiotherapy. Jpn J Clin Oncol 1996;26:65-69.
64 Lam KY, Law S, Ma LT, et al. Pre-operative chemotherapy for squamous cell carcinoma of the oesophagus: do histological assessment and p53 overexpression predict chemo-responsiveness? Eur J Cancer 1997;33:1221-1225.
65 Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW, Vogelstein B. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 1998;282:1497-1501.
66 Hirai T, Kuwahara M, Yoshida K, et al. Clinical results of transhiatal esophagectomy for carcinoma of the lower thoracic esophagus according to biological markers. Dis Esophagus 1998; 11:221-225.
67 Ohashi K, Nemoto T, Eishi Y, et al. Expression of the cyclin dependent kinase inhibitor p21WAF1 :CIP1 in esophageal squamous cell carcinomas. Virchows Arch 1997;430:389-395.
68 Seta T, Imazeki F, Yokosuka O, et al. Expression of p53 and p21WAF1:CIP1 proteins in gastric and esophageal cancers: comparison with mutations of the p53 gene. Dig Dis Sci 1998;43:279-289.
69 Toh Y, Kuwano H, Sonoda K, et al. Correlation between reduced p21WAF1:CIP1 expression and abnormal p53 expression in esophageal carcinomas. Int J Oncol 1997; 11:703-708.70 Shimoyama S, Konishi T, Kawahara N, et al. Expression and alteration of p53 and p21wafl:cipl influence the sensitivity of chemoradiation therapy for esophageal cancer. Hepatogastroenterology 1998;45:1497-1504.
71 Yang G, Zhang Z, Liao J, et al. Immunohistochemical studies on Waflp21, p16 pRb and p53 in human esophageal carcinomas and neighboring epithelia from a high-risk area in northern China. Int J Cancer 1997;72:746-751.
72 Lam K.Y, Law S, Tin L, Tung PHM, Wong J. The clinicopathological significance of p21 and p53 expression in esophageal squamous cell carcinoma: an analysis of 153 patients. Am J Gastroenterol 1999;52:758-760.
73 Anayama T, Furihata M, Ishikawa T, et al. Positive correlation between p27KIPl expression and progression of human esophageal squamous cell carcinoma. Int J Cancer Pred Oncol 1998;79:439-443.
74 Igaki H, Sasaki H, Kishi T, et al. Highly frequent homozygous deletion of the p16 gene in esophageal cancer cell lines. Biochem Biophys Res Comm 1994;203:1090-1095.
75 Tanaka H, Shimada Y, Imamura M, et al. Multiple types of aberrations in the p16 (INK4a) and the p15 (INK4b) genes in 30 esophageal squamous cell carcinoma cell lines. Int J Cancer 1997;70:437-442.
76 Takeuchi H, Ozawa S, Ando N, et al. Altered pl6:MTSl:CDKN2 and cyclin D1:PRAD-1 gene expression is associated with the prognosis of squamous cell carcinoma of the esophagus. Clin Cancer Res 1997;3:2229-2236.
77 Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC, Baylin SB, Sidransky D. 5' CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med 1995; 1:686-692.
78 Shamma A,Dokiy Y,Shiozaki H, et al. Effect of cyclin D1 and associated proteins on proliferation
of esophageal squamous cell carcinoma.Int J Oncol. 1998 Sep; 13(3):455-460.
79 E.P. Xing, G.Lang and L. Wang et al., Loss of hetereozygosity of the Rb gene correlates with pRb protein expression and associates with p53 alteration in human esophageal cancer, Clin. Cancer Res. 5 (1;999), pp. 1231-1240
80 Cheety R, Chetty S. Cyclin D1 and retinoblastoma protein expression in oesophageal squamous cell carcinoma. J Clin Pathol Mol Pathol 1997;50:257-260.
81 Roncalli M, Bosari S, Marchetti A, et al. Cell cycle-related gene abnormalities and product expression in esophageal carcinoma. Lab Invest 1998;78:1049-1057
82 Ashton-Rickardt PG, Wyilie AH, Kovesdi I, et ai. MCC, a candidate familial polyposis gene in 5q.21, shows frequent allele loss in colorectal and lung cancer. Oncogene 1991 ;6:1881-1886.
83 Boynton R, Blount PL, Yin J, et al. Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers. Proc Natl Acad Sci 1992;89:3385-3388.
84 Ogasawara S, Maesawa C, Tamura G, et al. Lack of mutations of the adenomatous polyposis coli gene in esophageal and gastric carcinomas. Virchows Arch 1994;424:607-611.
85 Fearon ER, Cho KR, Nigro JM, et al. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 1990;247:49-56.
86 Backer JM, Mendola CE, Kovesdi I, et al. Chromosomal localization and nucleoside diphosphate kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2. Oncogene 1993;8:497-502.
87 Patel DD, Bhatavdekar JM, Chikhlikar PR, et al. Clinical significance of p53, nm23, and bcl-2 in T3-4N1M0 esophageal carcinoma: an immunohistochemical approach. J Surg Oncol 1997;65:111-116.
88 Ohashi K, Nemoto T, Eishi Y, et al. Proliferative activity and p53 protein accumulation correlate with early invasive trend, and apoptosis correlates with differentiation grade in oesophageal??squamous cell carcinoma. Virchows Arch 1997;430:107-115.
89 Hamada M, Naomoto Y, Fujiwara T, et al. Suppressed apoptotic induction in esophageal squamous cell carcinomas expressing extensive p53 protein. Jpn J Clin Oncol 1996;26:398-404.
90 Shears LL, Ribeiro U, Kane J, et al. Apoptosis in esophageal cancer following induction chemoradiotherapy. J Surg Res 1998;79:20-24.
91 Sarbia M, Stahl M, Fink U, et al. Expression of apoptosis-regulating proteins and outcome of esophageal cancer patients treated by combined therapy modalities. Clin Cancer Res 1998;4:2991-2997.
92 Nita ME, Ono-Nita SK, Tsuno N, Tominaga O, Takenoue T, Sunami E, Kitayama J, Nakamura Y, Nagawa H. Bcl-X(L) antisense sensitizes human colon cancer cell line to 5-fluorouracil. Jpn J Cancer Res 2000;91:825-832.
93 Ohbu M, Saegusa M, Kobayashi N, Tsukamoto H, Mieno H, Kakita A, Okayasu I. Expression of bcl-2 protein in esophageal squamous cell carcinomas and its association with lymph node metastasis. Cancer 1997;79:1287-1293.
94 Nita ME, Nagawa H, Tominaga O, Tsuno N, Hatano K, Kitayama J, Tsuruo T, Domene CE, Muto T. p21Wafl/Cipl expression is a prognostic marker in curatively resected esophageal squamous cell carcinoma, but not p27Kipl, p53, or Rb. Ann Surg Oncol 1999;6:481-488.
95 Nita ME. Role of apoptosis related proteins in digestive tract cancer [thesis]. Tokyo: The University of Tokyo; 2000.
96 D. Coppola, R.H. Shreiber and L. Mora et al., Significance of Fas and restinoblastoma protein expression during progression of Barrett's metaplasia to adenocarcinoma, Ann. Surg. Oncol. 6 (1999) (3), pp. 298-304
97 Y. Li, J.M. Wo and L. Cai et al., Association of metallothionein expression and lack of apoptosis with progression of carcinogenesis in Barrett's Esophagus, Exp. Biol. Med. 228 (2003), pp.??286-287.
98 Yu CCW, Filipe MI. Update on proliferation-associated antibodies applicable to formalin fixed paraffin embedded tissue and their clinical applications. Histochem J 1993;25:843-853.
99 Gerdes J, Schwab U, Lemke H, et al. Production of a monoclonal antibody reactive with a human nuclear antigen associated with a human nuclear antigen associated with cell proliferation. Int J Cancer 1983;31:13-20.
100 Lam KY, Law SYK, So MKP, et al. Prognostic implication of proliferative markers MIB-1 and PC 10 in esophageal sqauamous cell carcinoma. Cancer 1996; 77:7-13.
101 Sarbia M, Bittinger F, Porschen R, et al. The prognostic significance of tumor cell proliferation in squamous cell carcinomas of the esophagus. Br J Cancer 1996;74:1012-1016.
102 Katz AM, Rosenthai D, Sauder DN. Cell adhesion molecules: structure, function, and implication in a variety of cutaneous and other pathologic conditions, Int J Dermatol 1991;30:153-159.
103 Smith MEF, Pignateili M. The molecular histology of neoplasia: the role of the cadherin:catenin complex. Histopathology 1997;31:107-111.
104 Kadowaki T, Shiozaki H, Inoue M, et al. E-cadherin and a-catenin expression in human esophageal cancer. Cancer Res 1994;54:291-296.
105 Tamura S, Shiozaki H, Miyata M, et al. Decreased E-cadherin expression is associated with hematogenous recurrence and poor prognosis in patients with squamous cell carcinoma of the esophagus. Br J Surg 1996;83:1608-1614.
106 Jian WG, Damton SJ, Jenner K, et al. Expression of E-cadherin in oesophageal carcinomas from the UK and China:disparities in prognostic significance. J Clin Pathol 1997;50:640-644.
107 Shima I, Sasaguri Y, Kusukawa J, et al. Production of matrix metailoproteinase 9 (92-kDa gelatinase) by human esophageal squamous cell carcinoma in response to epidermal growth??factor. Br J Cancer 1993;67:721-727.
108 Torzewski M, Sarbia M, Verreet P, et al. Prognostic significance of urokinase-type plasminogen activator expression in squamous cell carcinomas of the esophagus. Clin Cancer Res 1997;3:2263-2268.
109 Baba K, Kuwano H, Kitamura K, et al. Carcinomatous invasion and lymphocyte infiltration in early esophageal carcinoma with special regard to basement membrane: an immunohistochemical study. Hepatogastroenterology 1993;40:226-231.
110 N. Munoz, Epidemiological aspects of oesophageal cancer, Endoscopy 25 (1993), pp. 609-612.
111 Smeds, Miller LD, Bjohle J, et al. Gene profile and response to treatment[J]. Ann Oncol. 2005;16 Suppl 2:ⅱ 195-202.
112 Wan Y. Gene expression-driven diagnostics and pharmacogenomics in cancer[J]. Curr Opin Mol Ther. 2005 Jun;7(3):246-250.
113 赵赞梅，王汉斌。《基因芯片技术及其在医学领域的应用》中国医刊，2005，40(3)30-32．
114 C. D'Ambrosio, L. Gatta, S. Bonini, The future of microarray technology: networking the genome search。 Allergy.2005:60:1219-1226.
115 Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 1975;98:503-517.
116 Velculescu VE, Zhang L, Vogelstein B, et al. Serial analysis of gene expression. Science 1995;270:484-487.
117 Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature 2001;409:860-921.
118 Eisen MB, Spellman PT, Brown PO, et al. Cluster analysis and display of genome-wide expression patterns. Proc Nati Acad Sci USA 1998;95:14863-14868.
119 Ross DT, Scherf U, Eisen MB, et al. Systematic variation in gene expression patterns in human??cancer cell lines. Nat Genet 2000;24:227-235.
120 Schena M, Shalon D, Davis RW, et al. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 1995;270:467-470.
121 Fodor SP, Read JL, Pirrung MC, et al. Light-directed, spatially addressable parallel chemical synthesis. Science 1991;251:767-773.
122 胡蝶，廖静。基因芯片技术在肿瘤研究中的应用。首都医科大学学报。2004，25(1)129-132。
123 Logsdon CD, Simeone DM , Binkley C, et al Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer [J].Cancer Res, 2003,63 (10):264922657.157
124 Gerry NP, Witowski NE, Day Jet ai. Universal DNA microarry method for multiple detection of low abundance point mutations[J]. J Mol Biol, 1999,292(2):251-262.
125 Wen W H , Bernstein L, Lescallett J , et al. Comparison of Tp53 mutations identified by oligonucleotide microarrays and convertionai DNA sequence analysis. Cancer Res, 2000,60 (10):2716～2722.
126 Gong Z, Teixeira C, Xing J Z, et al. Electronic microarray technique for detection of nine Base substitutions including single-nucleotide polymorphisms in the human OGG 1 gene [J]. Cli Chem, 2004,50 (8):14412-1444.
127 王新允，刘婷，朱从中，等．应用组织芯片技术检测KAI1、MRP-1、FAK蛋白在肺癌组织中的表达[J]．癌症，2005，24(9)：1091-1095．
128 Zhang H, Chen SH, Li YM. Epidemiological investigation of esophageal carcinoma[J]. World J Gastroenterol. 2004, 10(12): 1834-1835.
129 Kwong KF. Molecular biology of esophageal cancer in the genomics era[J]. Surg Clin North Am. 2005,85(3):539-53.
2. De Preter K, Vandesompele J, Heimann P, et al. Application of laser capture microdissection in genetic analysis of neuroblastoma and neuroblastoma precursor cells. Cancer Lett. 2003 Jul 18; 197(1-2):53-61.
3. Curran S, McKay JA, McLeod HL, et al. Laser capture microscopy. Mol Pathol. 2000 Apr;53(2):64-68.
4. Vecchiotti C, Spaltro G, Bloise D, et al. Demonstration of a gastric bioptic specimen??mix-up by laser capture microdissection (LCM) and DNA fingerprinting. Am J Forensic Med Pathol. 2004 Jun;25(2):113-116.
5. Inoue H, Igari T, Nishikage T, et al. A novel method of virtual histopathology using laser-scanning confocal microscopy in-vitro with untreated fresh specimens from the gastrointestinal mucosa. Endoscopy. 2000 Jun;32(6):439-443.
6. Deng MY, Wang H, Ward GB, et al. Comparison of six RNA extraction methods for the detection of classical swine fever virus by real-time and conventional reverse transcription-PCR. J Vet Diagn Invest. 2005 Nov; 17(6):574-578
7. Warner EE, Dieckgraefe BK. Application of genome-wide gene expression profiling by high-density DNA arrays to the treatment and study of inflammatory bowel disease. Inflamm Bowel Dis. 2002 Mar;8(2): 140-157.
8. Wadenback J, Clapham DH, Craig D, et al. Comparison of standard exponential and linear techniques to amplify small cDNA samples for microarrays. BMC Genomics. 2005 May 4;6(1):61.
9. Patel OV, Suchyta SP, Sipkovsky SS, et al. Validation and application of a high fidelity mRNA linear amplification procedure for profiling gene expression. Vet Immunol Immunopathol. 2005 May 15;105(3-4):331-342.
10. Moll PR, Duschl J, Richter K. Optimized RNA amplification using T7-RNA-polymerase based in vitro transcription. Anal Biochem. 2004 Nov 1 ;334(1):164-174
11. Wan Y. Gene expression-driven diagnostics and pharmacogenomics in cancer. Curr Opin Mol Ther. 2005 Jun;7(3):246-250.
12. Smeds J, Miller LD, Bjohle J, et al. Gene profile and response to treatment. Ann Oncol. 2005;16 Suppl 2:ⅱ 195-202.13. Eisen MB, Spellman PT, Brown PO, et al. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sei, 1998; 95:14863-14868.
14. Yue H, Eastman PS, Wang BB, et al. An evaluation of the performance of cDNA microarray for detecting changes in global mRNA expression. Nucleic Acids Res, 2001; 29: e41-1.
15. Yang Ⅳ, Chen E, Hasseman JP, et al. Within the fold: assessing differential expression measures and reproducibility in mieroarray assays. Genome Biol, 2002;24:3(11): Research 0062.Epub 2002 Oct 24.
16. Zhao H J, Hastie T, Whitfield ML, et al. Optimization and evaluation of T7 based RNA linear amplification protocols for eDNA microarray analysis. BMC Genomics, 2002; 30;3(1): 31.1 Wan Y. Gene expression-driven diagnostics and pharmacogenomics in cancer. Curr Opin Mol Ther. 2005 Jun;7(3):246-250.
2 Kwong KF. Molecular biology of esophageal cancer in the genomics era. Surg Clin North Am. 2005;85(3):539-553.
3 Kyrgidis A, Kountouras J, Zavos C, et al. New molecular concepts of Barrett's esophagus: clinical implications and biomarkers. J Surg Res. 2005; 125(2): 189-212.
4 Sunpaweravong P, Sunpaweravong S, Puttawibul P, et al. Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol.??2005;131(2):111-119.
5 Zhang G, Zhou X, Xue L, et al. Accumulation of cytoplasmic beta-catenin correlates with reduced expression of E-cadherin, but not with phosphorylated Akt in esophageal squamous cell carcinoma: immunohistochemical study. Pathol Int. 2005;55(6):310-317.
6 Teraishi F, Kagawa S, Watanabe T, et al. ZD1839 (Gefitinib, 'Iressa'), an epidermal growth factor receptor-tyrosine kinase inhibitor, enhances the anti-cancer effects of TRAIL in human esophageal squamous cell carcinoma. FEBS Lett. 2005 ;579(19):4069-4075.
7 Lu X, Nechushtan H, Ding F, et al. Distinct IL-4-induced gene expression, proliferation, and intracellular signaling in germinal center B-cell-like and activated B-cell-like diffuse large-cell lymphomas. Blood. 2005;105(7):2924-2932.
8 Poulsen CB, Borup R, Nielsen FC, et al. Microarray-based classification of diffuse large B-cell lymphoma. :Eur J Haematol. 2005;74(6):453-465.
9 Danbara N, Yuri T, Tsujita-Kyutoku M, et al. Enterolactone induces apoptosis and inhibits growth of Colo 201 human colon cancer cells both in vitro and in vivo. Anticancer Res. 2005;25(3B):2269-2276.
10 Blanco-Aparicio C, Pequeno B, Moneo V, et al. Inhibition of phosphatidylinositol-3-kinase synergizes with gemcitabine in low-passage tumor cell lines correlating with Bax translocation to the mitochondria. Anticancer Drugs. 2005;16(9): 977-987.1. Kwong KF. Molecular biology of esophageal cancer in the genomics era. Surg Clin North Am. 2005;85(3):539-553.
2. Wan Y. Gene expression-driven diagnostics and pharmacogenomics in cancer. Curr Opin Mol Ther. 2005 Jun;7(3):246-250.
3. Smeds J, Miller LD, Bjohle J, et al. Gene profile and response to treatment. Ann Oncol. 2005; 16 Suppl 2:ⅱ 195-202.
4. Herrera LJ, EI-Hefnawy T, Queiroz de Oliveira PE, et al. The HGF receptor c-Met is overexpressed in esophageal adenocarcinoma. Neoplasia. 2005 ;7(1):75-84.
5. Cheng TL, Chang MY, Huang SY, et al. Overexpression of Circulating c-Met Messenger RNA Is Significantly Correlated With Nodal Stage and Early Recurrence in Non-Small Cell Lung Cancer. Chest. 2005; 128(3): 1453-1460.
6. Hatano H, Siegel H J, Yamagiwa H, et al. Identification of estrogen-regulated genes during fracture healing, using DNA microarray. J Bone Miner Metab. 2004;22(3):224-235.
7. Poulsen CB, Borup R, Nielsen FC, et al. Microarray-based classification of diffuse large B-cell lymphoma. :Eur J Haematol. 2005;74(6):453-465.
8. Chang MS, Lee HS, Lee BL, et al. Differential protein expression between esophageal squamous cell carcinoma and dysplasia, and prognostic significance of??protein markers. Pathol Res Pract. 2005;201 (6):417-425.
9. Teraishi F, Kagawa S, Watanabe T, et al. ZD1839 (Gefitinib, 'Iressa'), an epidermal growth factor receptor-tyrosine kinase inhibitor, enhances the anti-cancer effects of TRAIL in human esophageal squamous cell carcinoma. FEBS Lett. 2005 ;579(19):4069-4075.1. Zhang H, Chen SH, Li YM. Epidemiological investigation of esophageal carcinoma. World J Gastroenterol. 2004; 10(12): 1834-1835
2. Kwong KF. Molecular biology of esophageal cancer in the genomics era. Surg Clin North Am. 2005;85(3):539-553.
3．秦艳茹，王立东，邝丽芸，等．食管癌原发灶与淋巴结转移灶细胞染色体变化特征的比较[J]．癌症，2005，24(9)：1048-1053．
4. Buckhaults P. Gene expression determinants of clinical outcome. Curr Opin Oncol.2006 Jan; 18(1):57-61.
5. Rennebeck G, Martelli M, Kyprianou N. Anoikis and survival connections in the tumor microenvironment: is there a role in prostate cancer metastasis? Cancer Res. 2005 Dec 15;65(24):11230-11235.
6. Sayed-Ahmad MM, Mohamad MA. Contribution of Nitric Oxide and Epidermal Growth Factor Receptor in Anti-Metastatic Potential of Paclitaxel in Human Liver Cancer Cell (HebG2). J Egypt Natl Cane Inst. 2005;17(1):35-41.
7. Baker EA, Leaper DJ, Hayter JP, et al, The matrix metalloproteinase system in oral squamous cell carcinoma. Br J Oral Maxillofac Surg. 2005; [Epub ahead of print]
8. Zhang G, Zhou X, Xue L, et al. Accumulation of cytoplasmic beta-catenin correlates with reduced expression of E-cadherin, but not with phosphorylated Akt in esophageal squamous cell carcinoma: immunohistochemical study. Pathol Int. 2005;55(6):310-317.
9. Teraishi F, Kagawa S, Watanabe T, et al. ZD1839 (Gefitinib, 'Iressa'), an epidermal growth factor receptor-tyrosine kinase inhibitor, enhances the anti-cancer effects of TRAIL in human esophageal squamous cell carcinoma. FEBS Lett.??2005 ;579(19):4069-4075.
10. Chang MS, Lee HS, Lee BL, et al. Differential protein expression between esophageal squamous cell carcinoma and dysplasia, and prognostic significance of protein markers. Pathol Res Pract. 2005;201 (6):417-425.
11. Danbara N, Yuri T, Tsujita-Kyutoku M, et al. Enterolactone induces apoptosis and inhibits growth of Colo 201 human colon cancer cells both in-vitro and in vivo. Anticancer Res. 2005;25(3B):2269-2276.
12．王新允，刘婷，朱从中，等．应用组织芯片技术检测KAI1、MRP-1、FAK蛋白在肺癌组织中的表达[J]．癌症，2005，24(9)：1091-1095．1. Zhang H, Chen SH, Li YM. Epidemiological investigation of esophageal carcinoma. World J Gastroenterol. 2004;10(12):1834-1835
2. Kwong KF. Molecular biology of esophageal cancer in the genomics era. Surg Clin North Am. 2005;85(3):539-553.
3. Kurokawa S, Arimura Y, Yamamoto H, et al. Tumour matrilysin expression predicts metastatic potential of stage Ⅰ (pT1) colon and rectal cancers. Gut. 2005 Dec;54(12):1751-1758.
4. Besson A, Gurian-West M, Chen X, et al. A pathway in quiescent cells that controls p27Kipl stability, subcellular localization, and tumor suppression. Genes Dev. 2006 Jan 1;20(1):47-64.
5. Muthusamy V, Hobbs C, Nogueira C, et al. Amplification of CDK4 and MDM2 in malignant melanoma. Genes Chromosomes Cancer. 2006 Jan 17; [Epub ahead of print]
6. Xu F, Zhong W, Li J, et al. Predictive value of EphA2 and EphrinA-1??expression in oesophageal squamous cell carcinoma. Anticancer Res. 2005;25(4):2943-2950.
7. Dasgupta S, Bhattacharya-Chatterjee M, O'malley BW Jr, et al. Tumor metastasis in an orthotopic murine model of head and neck cancer: Possible role of TGF-beta 1 secreted by the tumor cells. J Cell Biochem. 2005 Nov 17; [Epub ahead of print]
8. Ren Y, Cao B, Law S, et al. Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clin Cancer Res. 2005 Sep 1;11(17):6190-6197.
9. Xu L, Chen S, Bergan RC. MAPKAPK2 and HSP27 are downstream effectors of p38 MAP kinase-mediated matrix metalloproteinase type 2 activation and cell invasion in human prostate cancer. Oncogene. 2006 Jan 16: [Epub ahead of print]
10. Teraishi F, Kagawa S, Watanabe T, et al. ZD1839 (Gefitinib, 'Iressa'), an epidermal growth factor receptor-tyrosine kinase inhibitor, enhances the anti-cancer effects of TRAIL in human esophageal squamous cell carcinoma. FEBS Lett. 2005;579(19):4069-4075.
11. Zhang G, Zhou X, Xue L, et al. Accumulation of cytoplasmic beta-catenin correlates with reduced expression of E-cadherin, but not with phosphorylated Akt in esophageal squamous cell carcinoma: immunohistochemical study. Pathol Int. 2005;55(6):310-317.
12. Iwaya T, Maesawa C, Kimura T, et al. Infrequent mutation of the human envoplakin gene is closely linked to the tylosis oesophageal cancer??locus in sporadic oesophageal squamous cell carcinomas. Oncol Rep. 2005;13(4):703-707.
13. Custer MC, Risinger JI, Hoover S, et al. Characterization of an antibody that can detect the Kail/CD82 murine metastasis suppressor. Prostate. 2005 Dec 21; [Epub ahead of print]
14. Wan Y. Gene expression-driven diagnostics and pharmacogenomics in cancer. Curr Opin Mol Ther. 2005 Jun;7(3):246-250.1. Buskens C J, Marsman WA, Bosma P J, et al. The current state of cancer gene therapy and its application in esophageal carcinoma. Dig Surg. 2005;22(4):222-233. Epub 2005 Sep 20.2. Naidoo R, Ramburan A, Reddi A, et al. Aberrations in the mismatch repair genes and the clinical impact on oesophageal squamous carcinomas from a high incidence area in South Africa. J Clin Pathol. 2005 Mar;58(3):281-284.
3. Yoshimoto M, de Toledo SR, da Silva NS, et al. Comparative genomic hybridization analysis of pediatric adamantinomatous craniopharyngiomas and a review of the literature. J Neurosurg. 2004 Aug; 101 (1 Suppl):85-90.
4. Oka M. Comparative genomic hybridization analysis for esophageal squamous cell carcinoma. Ann Thorac Cardiovasc Surg. 2004 Oct;10(5):275-276.
5. Knijnenburg J, van der Burg M, Nilsson E et al. Rapid detection of genomic imbalances using micro-arrays consisting of pooled BACs covering all human chromosome arms. Nucleic Acids Res. 2005 Oct 12;33(18):e159.
6. Pang ST, Weng WH, Flores-Morales A, et al. Cytogenetic and expression profiles associated with transformation to androgen-resistant prostate cancer. Prostate. 2005 Sep 19; [Epub ahead of print]1. Dasgupta S, Bhattacharya-Chatterjee M, O'malley BW Jr, et al. Tumor metastasis in an orthotopic murine model of head and neck cancer: Possible role of TGF-beta 1 secreted by the tumor cells. J Cell Biochem. 2005 Nov 17; [Epub ahead of print]
2. Chodorowska G, Chodorowski J, Wysokinski A. Vascular endothelial growth factor (VEGF) in physiological and pathological conditions. Ann Univ Mariae Curie Sklodowska [Meal].2004;59(2):8-14.
3. Ren Y, Cao B, Law S, et al. Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clin Cancer Res. 2005 Sep 1;11(17):6190-6197.
4 Katsuta M, Miyashita M, Makino H, et al. Correlation of hypoxia inducible factor-lalpha with lymphatic metastasis via vascular endothelial growth factor-C in human esophageal cancer. Exp Mol Pathol. 2005 Apr;78(2): 123-30. Epub 2005 Jan 7.
5 Forster Y, Meye A, Albrecht S, et al. Tissue factor and tumor: Clinical and laboratory aspects. Clin Chim Acta. 2005 Sep 1; [Epub ahead of print]
6 Ueda M, Terai Y, Kanda K, et al. Tumor angiogenesis and molecular target therapy in ovarian carcinomas. Hum Cell. 2005 Mar; 18(1): 1-16.1. Herrera LJ, El-Hefnawy T, Queiroz de Oliveira PE, et al. The HGF receptor c-Met is overexpressed in esophageal adenocarcinoma. Neoplasia. 2005;7(1):75-84.
2. Ren Y, Cao B, Law S, et al. Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clin Cancer Res. 2005;11(17):6190-6197.
3. Ren Y, Law S, Huang X, et al. Macrophage migration inhibitory factor stimulates angiogenic factor expression and correlates with??differentiation and lymph node status in patients with esophageal squamous cell carcinoma. Ann Surg. 2005:242(1):55-63.
4. Cheng TL, Chang MY, Huang SY, et al. Overexpression of Circulating c-Met Messenger RNA Is Significantly Correlated With Nodal Stage and Early Recurrence in Non-Small Cell Lung Cancer. Chest. 2005;128(3): 1453-1460.
5. Seiden-Long IM, Brown KR, Shih W, et al. Transcriptional targets of hepatocyte growth factor signaling and Ki-ras oncogene activation in colorectal cancer. Oncogene. 2005; 12; [Epub ahead of print]
6. Dominguez FJ, Jones JL, Zabicki K, et al. Prevalence of hereditary breast/ovarian carcinoma risk in patients with a personal history of breast or ovarian carcinoma in a mammography population. Cancer. 2005; 31; [Epub ahead of print]
7. Dominguez F J, Jones JL, Zabicki K, et al. Prevalence of hereditary breast/ovarian carcinoma risk in patients with a personal history of breast or ovarian carcinoma in a mammography population. Cancer. 2005 Nov 1; 104(9): 1849-1853.
8. Everett EN, Heuser CC, Pastore LM, et al. Predictors of suboptimal surgical cytoreduction in women treated with initial cytoreductive surgery for advanced stage epithelial ovarian cancer. Am J Obstet Gynecol. 2005 Aug;193(2):568-574; discussion 574-6.1. Kenny LM, Vigushin DM, A1-Nahhas A, et al. Quantification of Cellular Proliferation in Tumor and Normal Tissues of Patients with Breast Cancer by [18F]Fluorothymidine-Positron Emission Tomography Imaging: Evaluation of Analytical Methods. Cancer Res. 2005;65(21): 10104-10112.
2. Dahia PL, Hao K, Rogus J,et al. Novel pheochromocytoma susceptibility Loci identified by integrative genomics. Cancer Res. 2005;65(21):9651-9658.
3. Yang F, Foekens JA, Yu J, et al. Laser microdissection and microarray analysis of??breast tumors reveal ER-alpha related genes and pathways. Oncogene. 2005; [Epub ahead of print]
4. Zhu B, Xu F, Baba Y, et al. An evaluation of linear RNA amplification in cDNA microarray gene expression analysis. Mol Genet Metab. 2005; [Epub ahead of print]
5. Yazdi AS, Puchta U, Flaig MJ,et al. Laser-capture microdissection: applications in routine molecular dermatopathology. J Cutan Pathol. 2004;31 (7):465-470.1. Sahar DE, Yang GP, Longaker MT, et al. Surgical application of cDNA microarray technique. Surgery. 2005 Sep;138(3):399-403.
2. Wong ML, Medrano JE Real-time PCR for mRNA quantitation. Biotechniques. 2005 Jul;39(1):75-85.
3. Lux MP, Fasching PA, Beckmann MW. Hereditary breast and ovarian cancer:??review and future perspectives. J Mol Med. 2005 Nov 11; [Epub ahead of print]
4. Chen MS Jr. Cancer health disparities among Asian Americans. Cancer. 2005 Nov 3; [Epub ahead of print]
5. Paik S, Kim CY, Song YK, et al. Technology insight: Application of molecular techniques to formalin-fixed paraffin-embedded tissues from breast cancer. Nat Clin Pract Oncol.2005 May;2(5):246-254.
6. Gruber MP, Geraci MW. Practical cancer genetics, genomics and proteomics. J Insur Med. 2005;37(3): 190-200.
7. Dolnik V, Liu S. Applications of capillary electrophoresis on microchip. J Sep Sci. 2005 Oct;28(15): 1994-2009.
8. Lauerman LH. Advances in PCR technology. Anim Health Res Rev. 2004 Dec;5(2):247-248.1. Mu(?)ozN, Epidemiological aspects of esophageal cancer. Endoscopy 1993; 23:609-612.
2. Lam KY, Law S, Tung PH, Wong J. Esophageal small cell carcinomas: clinicopathoiogic parameters, p53 overexpression, proliferation marker, and their impact on pathogenesis. Arch Pathol Lab Med 2000;124: 228-233.
3. Alfred King Y. Lain. Molecular biology of esophageal squamous cell carcinoma[J]. Critical Reviews in Oncology/Hematology 33(2000)71-91.E.R. Fearon, B. Vogelstein, A genetic model for colorectal tumorigenesis[J]. Cell 61 1990 759-767.
4. A.-M.Mandard, P.Hainaut, M.Holistein. Genetic steps in the development of squamous cell carcinoma of the esophagus[J]. Mutation Research 462(2000) 335-342
5. M. Hollstein, L. Peri, A.-M. Mandard,et al. Genetic analysis of human esophageal tumor from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutations[J]. Cancer Res. 51 1991 4102-4106.
6. Lebman DA, Edmiston JS, Chung TD, Snyder SR. Heterogeneity in the transforming growth factor beta response of esophageal cancer cells, Int J Oncol 2002;20:1241- 1246.
7. Matsumoto M, Natsugoe S, Nakashima S, Okumura H, Sakita H, Baba M, Takao S, Aikou T. Clinical significance and prognostic value of apoptosis related proteins in superficial esophageal squamous cell carcinoma. Ann Surg Oncol 2001;8: 598-604.
8. E.P. Xing, Y. Nie, L.-D. Wang, et al. Yang,Aberrant methylation of p16INK4a and deletion of p15INK5b are frequent events in human esophageal cancer in Linxian,. China, Carcinogenesis 20 1999 77-84.
9. W. Jiang, Y.J. Zhang, S.M. Kahn, et al.Altered expression of the cyclin DI and retinoblastoma genes in human esophageal cancer, Proc. Natl. Acad, Sci. U.S.A. 90 1993 9026-9030.10. Anayama T, Furihata M, Takeuchi T, Sonobe H, Sasaguri S, Matsumoto M, Ohtsuki Y. Insufficient effect of p27(KIP1) to inhibit cyclin D1 in human esophageal cancer in vitro. Int J Oncol 2001;18: 151-155.
11. Pennisi E. How a growth control path takes a wrong turn to cancer. Science 1998;281: 1438-1441.
12. M. Hollstein, A.M. Smits, C. Galiana, H. Yamasaki, J.L.Bos, A. Mandard, C. Partensky, R. Montesano, Amplification of EGF receptor gene but no evidence of ras mutations in primary human esophageal cancers, Cancer Res. 48 1988 5119-5123.
13. S.H. Lu, L.L. Hsieh, F.C. Luo, I.B. Weinstein, Amplification of the EGF receptor and c-myc genes in human esophageal cancers, Int. J. Cancer 42 1988 502-505..12 Okuda T, Shurtleff SA, Valentine MB, Raimondi SC, Head DR, Behm F, Curcio-Brint AM, Liu Q, Pui C-H, Sherr CJ, Beach D, Look AT, Downing JR. Frequent deletion of p16(INK4a)/MTS1 and p15(INK4b)/MTS2 in pediatric acute lymphoblastic leukemia. Blood 1995;85:2321-2330.
14. E.R. Fearon, B. Vogeistein, A genetic model for colorectal tumorigenesis[J]. Cell 61 1990 759-767.
15. Wong FH, Hu CP, Chiu JH, et al. Expression of multiple oncogenes in human esophageal carcinomas. Cancer Invest 1994; 12:121-131.
16. Koppert LB, Wijnhoven BP, van Dekken H, et al. The molecular biology of esophageal adenocarcinoma[J]. J Surg Oncoi. 2005 Dec 1;92(3): 169-190.
17. M. Schuler and D.R. Green, Mechanisms of p53-dependent apoptosis, Biochem. Soc. Trans. 29 (2001) (6), pp. 684-688.
18. Dárcio Matenhauer Lehrbach, Marcelo Eidi Nita, Ivan Cecconello,et al. Molecular aspects of esophageal squamous cell carcinoma carcinogenesis[J]. Arq. Gastroenterol. vol. 40 no.4 out/dez. Oct./Dec. 2003 256-261
19. Fujii S, Tominaga O, Nagawa H, Tsuno N, Nita ME, Tsuruo T, Muto T. Quantitative analysis of the??cyclin expression in human esophageal cancer cell lines. J Exp Clin Cancer Res 1998;17: 491-496.
20. Nakagawa H, Zukerberg L, Togawa K, et al. Human cylin D1 oncogene and esophageal squamous cell carcinoma. Cancer 1995;76:541-549.
21. Jiang W, Kahn SM, Tomita N, et al. Amplification and expression of the human cyclin D gene in esophageal cancer. Cancer Res 1992;52: 2980-2983.
22. Tsuruta H, Sakamoto H, Onda M, et al. Amplification and overexpression of EXP1 and EXP2:cyclin D1 genes in human esophageal carcinomas. Biochem Biophys Res Comm 1993;196: 1529-1536.
23. Adlaide J, Monges G, D(rd(rian C, et al. Esophageal cancer and amplification of the human cyclin D gene CCND1:PRAD1. Br J Cancer 1995;71: 64-68.
24. Iamamura M. Prognostic significance of Cyclin D1 and E-cadherin in patients with esophageal squamous cell carcinoma: multiinstitutional retrospective analysis. J Am Coll Surg 2001;192: 708-718.
25. Kanda Y, Nishiyama Y, Shimada Y, et al. Analysis of gene amplification and over expression in human esophageal carcinoma cell lines. Int J Cancer 1994;58: 291-297.
26. Miyazaki S, Sasano H, Shiga K, et al. Analysis of c-myc oncogene in human esophageal carcinoma: immunohistochemistry, in situ hybridization and Northern and Southern blot studies. Anticancer Res 1992; 12:1747-1756.
27. Tsuboi K, Hirayoshi K, Takeuchi K, et al. Expression of the c-myc gene in human gastrointestinal malignaancies. Biochem Biophys Res Comm 1987;146:699-704.
28. Zhu D, Wang L, Zhang C, et al. No evidence for the amplification of mdm2 and c-myc genes involved in the genetic susceptibility to esophageal cancer in a high-risk area of north China. Cancer Genet Cytogenet 1996;89:184-185.29. Shibagaki I, Tanaka H, Shimada Y, et al. p53 mutation, murine double minute 2 amplification, and human papiliomavirus infection are frequently involved but not associated with each other in esophageal squamous cell carcinoma. Ciin Cancer Res 1995;1: 769-773.
30. Burgess AW, Thumwood CM. The Sixth George Swanson Christie Memorial lecture: growth factors and their receptors: new opportunities for cancer treatment. Pathology 1994;26:453-463
31. Mukaida H, Toi M, Hirai T, et al. Clinical significance of the expression of epidermal growth factor and its receptor in esophageal cancer. Cancer 1991;68:142-148.
32 Itakura Y, Sasano H, Shiga C, et al. Epidermal growth factor receptor overexpression in esophageal carcinoma. Cancer 1994;74: 795-804.
33 Hirai T, Kuwahara M, Yoshida K, et al. Clinical results of transhiatal esophagectomy for carcinoma of the lower thoracic esophagus according to biological markers. Dis Esophagus 1998;11: 221-225.
34 Muller A, Nakagawa H, Rustgi AK. Retinoic acid and N-(4-hydroxy-phenyl) retinamide suppress growth of esophageal squamous carcinoma cell lines. Cancer Lett 1997; 113: 95-101.
35 Kok TC, van der Gaast A, Splinter TAW. 13-cis-retinoic acid and alpha-interferon in advanced squamous cell cancer of the esophagus. Eur J Cancer 1997;33:165-166.
36 Hickey K, Grehan D, Reid IM, et al. Expression of epidermal growth factor receptor and proliferating cell nuclear antigen predicts response of esophageal squamous cell carcinoma to chemoradiotherapy. Cancer 1994;74:1693-1698.
37 Yokota J, Yamamoto T, Toyoshima K, et al. Amplification of c-erbB-2 oncogene in human adenocarcinomas in vivo. Lancet 1986;8484: 765-767.
38 Suwanagool P, Parichatikanond P, Maeda S. Expression of c-erbB-2 oncoprotein in primary human tumors: an immunohistochemistry study. Asain Pac J Allergy lmmunol 1993;11:119-122.
39 Suo Z, Su W, Holm R, Nesland JM. Lack of expression of c-erbB-2 oncoprotein in human??esophageal squamous cell carcinomas. Anticancer Res 1995;15: 2797-2798.
40 Hardwick RH, Barham CP, Ozua, et al. Immunohistochemical detection of p53 and c-erbB-2 in esophageal carcinoma: no correlation with prognosis, Eur J Surg Oncol 1997;23: 30-35.
41 Jones GJ, Heiss NS, Veale RB, et al. Amplification and expression of the TGF-a, EGF receptor and c-myc genes in four human esophageal squamous cell carcinoma lines. Biosci Rep 1993;13:303-312.
42 Wagata T, Ishizaki K, Imammura M, et al. Deletion of 17p and amplification of the int-2 gene in esophageal carcinomas. Cancer Res 1991;51:2113-2117.
43 Kitagawa Y, Ueda M, Ando N, et al. Significance of int-2:hst-1 coamplification as a prognostic factor in patients with esophageal squamous carcinoma. Cancer Res 1991;51:1504-1508.
44 Ikeda Y, Ozawa S, Ando N, et al. Meanings of c-erbB and int-2 amplification in superficial esophageal squamous cell carcinomas. Ann Thorac Surg 1996;62:835-838.
45 Hollstein MC, Peri L, Mandard AM, et al. Genetic analysis of human esophageal tumors from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutation. Cancer Res 1991;51:4102-4106.
46 Lam KY, Shan XC, Dickens P, et al. The expression of H-ras p21 product in esophageal cancer from Hong Kong Chinese. Am J Gastroenterol 1995;90:171-172.
47 Ono H, Takahashi A, Ogoshi S. Relationship between H-ras p21 product and p53 protein or high risk human papillomaviruses in esophageal cancer from Kochi, Japan. Am J Gastroenterol 1994;89:646-647.
48 Hunter T, Pines J. Cyclins and cancer Ⅱ: cyclin D and CDK inhibitors come of age. Cell 1994;79:573-582.
49 Hatano H, Siegel HJ, Yamagiwa H, et al. Identification of estrogen-regulated genes during fracture healing, using DNA microarray. J Bone Miner Metab. 2004;22(3):224-235.
50 T. Kuroki, F. Trapasso and T. Shiraishi et al. Genetic alterations of the tumour suppressor gene WWOX in esophageal squamous cell carcinoma, Cancer Res. 62 (2002), pp. 2258-2260.
51 Lam KY, Loke SL, Chen WZ, et al. Expression of p53 in oesophageal squamous cell carcinoma in Hong Kong Chinese. Eur J Surg Oncol 1995;21:242-247.
52 Casson AG, Tammemagi M, Eskandarian S, et al. p53 alterations in esophageal cancer: associated with clinicopathological features, risk factors, and survival. J Clin Pathol Mol Pathol 1998;51:71-79.
53 Wagata T, Shibagaki I, Imamura M, et al. Loss of 17p mutation of the p53 gene, and overexpression of p53 protein in esophageal squamous cell carcinomas. Cancer Res 1993;53:846-850.
54 Montesano R, Hollstein M, Hainaut P. Genetic alternations in esophageal cancer and their relevance to etiology and pathogenesis: a review. Int J Cancer Pred Oncol 1996;69:225-235.
55 L. Wang, S. Zheng and Z. Zheng et al, Primary adenocarcinomas of lower esophagus, esophagogastric junction and gastric cardia: in special reference to China, World J. Gastroenterol. 9 (2003) (6), pp. 1156-1164
56 Vogelstein B, Kinzler KW. p53 function and dysfunction. Cell 1992;70:523-526
57 el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer E, Kinzler KW, Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell 1993;75:817-825.
58 Sur M, Cooper K. The role of the human papilloma virus in esophageal cancer. Pathology 1998;30:348-354
59 Lam KY, Loke SL, Chen WZ, et al. Expression of p53 in oesophageal squamous cell carcinoma in Hong Kong Chinese. Eur J Surg Oncol 1995;21 -.242-247.
60 Lam KY, Tsao SW, Zhang D, et al. Prevalence and predictive value of p53 mutation in patients with oesophageal squamous cell carcinomas: a prospective clinicopatholgical study and survival analysis of 70 patients. Int J Cancer 1997;74:212-219
61 Boynton R, Blount PL, Yin J, et al. Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers. Proc Natl Acad Sci 1992;89:3385-3388.
62 Hamada M, Naomoto Y, Fujiwara T, et al. Suppressed apoptotic induction in esophageal squamous cell carcinomas expressing extensive p53 protein. Jpn J Clin Oncol 1996;26:398-404.
63 Muro K, Ohtsu A, Boku N, et al. Association of p53 protein expression with responses and survival of patients with locally advanced esophageal carcinoma treated with chemoradiotherapy. Jpn J Clin Oncol 1996;26:65-69.
64 Lam KY, Law S, Ma LT, et al. Pre-operative chemotherapy for squamous cell carcinoma of the oesophagus: do histological assessment and p53 overexpression predict chemo-responsiveness? Eur J Cancer 1997;33:1221-1225.
65 Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW, Vogelstein B. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 1998;282:1497-1501.
66 Hirai T, Kuwahara M, Yoshida K, et al. Clinical results of transhiatal esophagectomy for carcinoma of the lower thoracic esophagus according to biological markers. Dis Esophagus 1998; 11:221-225.
67 Ohashi K, Nemoto T, Eishi Y, et al. Expression of the cyclin dependent kinase inhibitor p21WAF1 :CIP1 in esophageal squamous cell carcinomas. Virchows Arch 1997;430:389-395.
68 Seta T, Imazeki F, Yokosuka O, et al. Expression of p53 and p21WAF1:CIP1 proteins in gastric and esophageal cancers: comparison with mutations of the p53 gene. Dig Dis Sci 1998;43:279-289.
69 Toh Y, Kuwano H, Sonoda K, et al. Correlation between reduced p21WAF1:CIP1 expression and abnormal p53 expression in esophageal carcinomas. Int J Oncol 1997; 11:703-708.70 Shimoyama S, Konishi T, Kawahara N, et al. Expression and alteration of p53 and p21wafl:cipl influence the sensitivity of chemoradiation therapy for esophageal cancer. Hepatogastroenterology 1998;45:1497-1504.
71 Yang G, Zhang Z, Liao J, et al. Immunohistochemical studies on Waflp21, p16 pRb and p53 in human esophageal carcinomas and neighboring epithelia from a high-risk area in northern China. Int J Cancer 1997;72:746-751.
72 Lam K.Y, Law S, Tin L, Tung PHM, Wong J. The clinicopathological significance of p21 and p53 expression in esophageal squamous cell carcinoma: an analysis of 153 patients. Am J Gastroenterol 1999;52:758-760.
73 Anayama T, Furihata M, Ishikawa T, et al. Positive correlation between p27KIPl expression and progression of human esophageal squamous cell carcinoma. Int J Cancer Pred Oncol 1998;79:439-443.
74 Igaki H, Sasaki H, Kishi T, et al. Highly frequent homozygous deletion of the p16 gene in esophageal cancer cell lines. Biochem Biophys Res Comm 1994;203:1090-1095.
75 Tanaka H, Shimada Y, Imamura M, et al. Multiple types of aberrations in the p16 (INK4a) and the p15 (INK4b) genes in 30 esophageal squamous cell carcinoma cell lines. Int J Cancer 1997;70:437-442.
76 Takeuchi H, Ozawa S, Ando N, et al. Altered pl6:MTSl:CDKN2 and cyclin D1:PRAD-1 gene expression is associated with the prognosis of squamous cell carcinoma of the esophagus. Clin Cancer Res 1997;3:2229-2236.
77 Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC, Baylin SB, Sidransky D. 5' CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med 1995; 1:686-692.
78 Shamma A,Dokiy Y,Shiozaki H, et al. Effect of cyclin D1 and associated proteins on proliferation
of esophageal squamous cell carcinoma.Int J Oncol. 1998 Sep; 13(3):455-460.
79 E.P. Xing, G.Lang and L. Wang et al., Loss of hetereozygosity of the Rb gene correlates with pRb protein expression and associates with p53 alteration in human esophageal cancer, Clin. Cancer Res. 5 (1;999), pp. 1231-1240
80 Cheety R, Chetty S. Cyclin D1 and retinoblastoma protein expression in oesophageal squamous cell carcinoma. J Clin Pathol Mol Pathol 1997;50:257-260.
81 Roncalli M, Bosari S, Marchetti A, et al. Cell cycle-related gene abnormalities and product expression in esophageal carcinoma. Lab Invest 1998;78:1049-1057
82 Ashton-Rickardt PG, Wyilie AH, Kovesdi I, et ai. MCC, a candidate familial polyposis gene in 5q.21, shows frequent allele loss in colorectal and lung cancer. Oncogene 1991 ;6:1881-1886.
83 Boynton R, Blount PL, Yin J, et al. Loss of heterozygosity involving the APC and MCC genetic loci occurs in the majority of human esophageal cancers. Proc Natl Acad Sci 1992;89:3385-3388.
84 Ogasawara S, Maesawa C, Tamura G, et al. Lack of mutations of the adenomatous polyposis coli gene in esophageal and gastric carcinomas. Virchows Arch 1994;424:607-611.
85 Fearon ER, Cho KR, Nigro JM, et al. Identification of a chromosome 18q gene that is altered in colorectal cancers. Science 1990;247:49-56.
86 Backer JM, Mendola CE, Kovesdi I, et al. Chromosomal localization and nucleoside diphosphate kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2. Oncogene 1993;8:497-502.
87 Patel DD, Bhatavdekar JM, Chikhlikar PR, et al. Clinical significance of p53, nm23, and bcl-2 in T3-4N1M0 esophageal carcinoma: an immunohistochemical approach. J Surg Oncol 1997;65:111-116.
88 Ohashi K, Nemoto T, Eishi Y, et al. Proliferative activity and p53 protein accumulation correlate with early invasive trend, and apoptosis correlates with differentiation grade in oesophageal??squamous cell carcinoma. Virchows Arch 1997;430:107-115.
89 Hamada M, Naomoto Y, Fujiwara T, et al. Suppressed apoptotic induction in esophageal squamous cell carcinomas expressing extensive p53 protein. Jpn J Clin Oncol 1996;26:398-404.
90 Shears LL, Ribeiro U, Kane J, et al. Apoptosis in esophageal cancer following induction chemoradiotherapy. J Surg Res 1998;79:20-24.
91 Sarbia M, Stahl M, Fink U, et al. Expression of apoptosis-regulating proteins and outcome of esophageal cancer patients treated by combined therapy modalities. Clin Cancer Res 1998;4:2991-2997.
92 Nita ME, Ono-Nita SK, Tsuno N, Tominaga O, Takenoue T, Sunami E, Kitayama J, Nakamura Y, Nagawa H. Bcl-X(L) antisense sensitizes human colon cancer cell line to 5-fluorouracil. Jpn J Cancer Res 2000;91:825-832.
93 Ohbu M, Saegusa M, Kobayashi N, Tsukamoto H, Mieno H, Kakita A, Okayasu I. Expression of bcl-2 protein in esophageal squamous cell carcinomas and its association with lymph node metastasis. Cancer 1997;79:1287-1293.
94 Nita ME, Nagawa H, Tominaga O, Tsuno N, Hatano K, Kitayama J, Tsuruo T, Domene CE, Muto T. p21Wafl/Cipl expression is a prognostic marker in curatively resected esophageal squamous cell carcinoma, but not p27Kipl, p53, or Rb. Ann Surg Oncol 1999;6:481-488.
95 Nita ME. Role of apoptosis related proteins in digestive tract cancer [thesis]. Tokyo: The University of Tokyo; 2000.
96 D. Coppola, R.H. Shreiber and L. Mora et al., Significance of Fas and restinoblastoma protein expression during progression of Barrett's metaplasia to adenocarcinoma, Ann. Surg. Oncol. 6 (1999) (3), pp. 298-304
97 Y. Li, J.M. Wo and L. Cai et al., Association of metallothionein expression and lack of apoptosis with progression of carcinogenesis in Barrett's Esophagus, Exp. Biol. Med. 228 (2003), pp.??286-287.
98 Yu CCW, Filipe MI. Update on proliferation-associated antibodies applicable to formalin fixed paraffin embedded tissue and their clinical applications. Histochem J 1993;25:843-853.
99 Gerdes J, Schwab U, Lemke H, et al. Production of a monoclonal antibody reactive with a human nuclear antigen associated with a human nuclear antigen associated with cell proliferation. Int J Cancer 1983;31:13-20.
100 Lam KY, Law SYK, So MKP, et al. Prognostic implication of proliferative markers MIB-1 and PC 10 in esophageal sqauamous cell carcinoma. Cancer 1996; 77:7-13.
101 Sarbia M, Bittinger F, Porschen R, et al. The prognostic significance of tumor cell proliferation in squamous cell carcinomas of the esophagus. Br J Cancer 1996;74:1012-1016.
102 Katz AM, Rosenthai D, Sauder DN. Cell adhesion molecules: structure, function, and implication in a variety of cutaneous and other pathologic conditions, Int J Dermatol 1991;30:153-159.
103 Smith MEF, Pignateili M. The molecular histology of neoplasia: the role of the cadherin:catenin complex. Histopathology 1997;31:107-111.
104 Kadowaki T, Shiozaki H, Inoue M, et al. E-cadherin and a-catenin expression in human esophageal cancer. Cancer Res 1994;54:291-296.
105 Tamura S, Shiozaki H, Miyata M, et al. Decreased E-cadherin expression is associated with hematogenous recurrence and poor prognosis in patients with squamous cell carcinoma of the esophagus. Br J Surg 1996;83:1608-1614.
106 Jian WG, Damton SJ, Jenner K, et al. Expression of E-cadherin in oesophageal carcinomas from the UK and China:disparities in prognostic significance. J Clin Pathol 1997;50:640-644.
107 Shima I, Sasaguri Y, Kusukawa J, et al. Production of matrix metailoproteinase 9 (92-kDa gelatinase) by human esophageal squamous cell carcinoma in response to epidermal growth??factor. Br J Cancer 1993;67:721-727.
108 Torzewski M, Sarbia M, Verreet P, et al. Prognostic significance of urokinase-type plasminogen activator expression in squamous cell carcinomas of the esophagus. Clin Cancer Res 1997;3:2263-2268.
109 Baba K, Kuwano H, Kitamura K, et al. Carcinomatous invasion and lymphocyte infiltration in early esophageal carcinoma with special regard to basement membrane: an immunohistochemical study. Hepatogastroenterology 1993;40:226-231.
110 N. Munoz, Epidemiological aspects of oesophageal cancer, Endoscopy 25 (1993), pp. 609-612.
111 Smeds, Miller LD, Bjohle J, et al. Gene profile and response to treatment[J]. Ann Oncol. 2005;16 Suppl 2:ⅱ 195-202.
112 Wan Y. Gene expression-driven diagnostics and pharmacogenomics in cancer[J]. Curr Opin Mol Ther. 2005 Jun;7(3):246-250.
113 赵赞梅，王汉斌。《基因芯片技术及其在医学领域的应用》中国医刊，2005，40(3)30-32．
114 C. D'Ambrosio, L. Gatta, S. Bonini, The future of microarray technology: networking the genome search。 Allergy.2005:60:1219-1226.
115 Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol 1975;98:503-517.
116 Velculescu VE, Zhang L, Vogelstein B, et al. Serial analysis of gene expression. Science 1995;270:484-487.
117 Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature 2001;409:860-921.
118 Eisen MB, Spellman PT, Brown PO, et al. Cluster analysis and display of genome-wide expression patterns. Proc Nati Acad Sci USA 1998;95:14863-14868.
119 Ross DT, Scherf U, Eisen MB, et al. Systematic variation in gene expression patterns in human??cancer cell lines. Nat Genet 2000;24:227-235.
120 Schena M, Shalon D, Davis RW, et al. Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 1995;270:467-470.
121 Fodor SP, Read JL, Pirrung MC, et al. Light-directed, spatially addressable parallel chemical synthesis. Science 1991;251:767-773.
122 胡蝶，廖静。基因芯片技术在肿瘤研究中的应用。首都医科大学学报。2004，25(1)129-132。
123 Logsdon CD, Simeone DM , Binkley C, et al Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer [J].Cancer Res, 2003,63 (10):264922657.157
124 Gerry NP, Witowski NE, Day Jet ai. Universal DNA microarry method for multiple detection of low abundance point mutations[J]. J Mol Biol, 1999,292(2):251-262.
125 Wen W H , Bernstein L, Lescallett J , et al. Comparison of Tp53 mutations identified by oligonucleotide microarrays and convertionai DNA sequence analysis. Cancer Res, 2000,60 (10):2716～2722.
126 Gong Z, Teixeira C, Xing J Z, et al. Electronic microarray technique for detection of nine Base substitutions including single-nucleotide polymorphisms in the human OGG 1 gene [J]. Cli Chem, 2004,50 (8):14412-1444.
127 王新允，刘婷，朱从中，等．应用组织芯片技术检测KAI1、MRP-1、FAK蛋白在肺癌组织中的表达[J]．癌症，2005，24(9)：1091-1095．
128 Zhang H, Chen SH, Li YM. Epidemiological investigation of esophageal carcinoma[J]. World J Gastroenterol. 2004, 10(12): 1834-1835.
129 Kwong KF. Molecular biology of esophageal cancer in the genomics era[J]. Surg Clin North Am. 2005,85(3):539-53.