支气管上皮细胞基因组DNA拷贝数异常对周围型不吸烟肺腺癌患者鉴别诊断价值的初步探讨
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摘要
腺癌发病率逐年提高。周围型肺腺癌为临床诊断的一个难题,目前缺乏有效易行的鉴别诊断手段。有关区域性癌化现象在气道上皮细胞中的研究表明,形态正常的气道上皮细胞分子水平的改变可以用来辅助诊断肺癌,但是针对不吸烟肺腺癌患者的相关研究很少。本课题在实验室已有的稳定的微阵列比较基因组杂交技术(array comparative genome hybridization Array-CGH)平台基础上,研究不吸烟周围型肺腺癌患者与良性周围型疾病患者的支气管上皮细胞基因组DNA拷贝数异常的变化情况,以期获得NSPLAd患者及PBPD患者支气管上皮细胞基因组DNA拷贝数改变谱型；进而揭示NSPLAd患者支气管上皮的特征性改变的基因或DNA片段,并以这些DNA片段的组合来进行NSPLAd患者的鉴别诊断,以指导正确治疗。
首先,应用Agilent Human Genomic CGH 44B芯片,对16例患者(11例NSPLAd,5例PBPD)的32个部位的支气管上皮细胞刷片(每位患者包括健侧叶段支气管上皮细胞-1s及患侧主支气管上皮细胞-2s)基因组DNA进行了Array CGH检测。继而,采用Agilent CGH Analytics 4.0和GeneSpring GX 11.0.1分析软件分析实验数据。结果显示：(1)11个NSPLAd患者支气管上皮细胞基因组DNA拷贝数发生异常的区域较一致,1s发生频率大于45%片段有15个,2s发生频率大于50%的DNA片段有10个。(2) NSPLAd患者与PBPD患者对应的支气管上皮相比,基因组DNA拷贝数变异的区域广,范围大,发生频率高。(3)经过对11例患者2s处Array CGH实验数据的生物信息学分析,初步筛选出34个能用于鉴别诊断NSPLAd患者的DNA片段组合。
综上,本研究表明,NSPLAd患者形态正常的支气管上皮中存在一系列基因组DNA拷贝数变异,2s处基因组DNA拷贝数变异可能用于NSPLAd的辅助诊断,有望通过进一步扩大样本量的深入研究建立起能够用于NSPLAd鉴别诊断的分子模型。
Diagnosis of Non-smoking Peripheral Lung Adenocarcinoma by Bronchial Epithelial Cell Genomic DNA Copy Number Variation
Lung Adenocarcinomas incidence are increasing。Peripheral lung Adenocarcinoma (PLAd) is difficult pclinically。Effective and easy means to differentiate PLAd is not always available. Field cancerization exists in airway epithelial cells, and a series of molecular changes in the airway epithelial cells showed useful in the differential diagnosis of lung cancer. Such researches in non-smoking lung cancer patients are rare. In this study, array comparative genomic hybridization (Array-CGH) was performed on the bronchial epitherial cells of non-smoking patients with peripheral lung adenocarcinoma (NSPLAd) and patients with benign peripheral disease (PBPD),to identify the DNA copy number variation(CNV) profiles that specially related with NSPLAd and PBPD patients, respectively. From these, a set of gain or loss genes/regions could be identified to distinguish the two disease.
The 32 bronchial epithelial cells (including the contralateral bronchial epithelial cells-1s and ipsilateral primary bronchial epithelial cell-2s) derived from 16patients (11 NSPLAd and 5 PBPD)were screened by Agilent Human Genomic CGH 44B array.With analyses by Agilent CGH Analytics 4.0 and GeneSpring GX 11.0.1, the genome-wide CNV profiles of bronchial epithelial cells were obtained.11 NSPLAds showed good accordance in regions of CNV. There were 15 copy number alterations with a frequency of more than 45% in 1s and 10 copy number alterations with a frequency of more than 50% in the NSPLAd. NSPLAd patients showed a much larger scale, much higher frequence in CNV. than PBPD. Bioinformatical analysis was performed with the array CGH data of the 32cases, and 34 genes that could differentiate NSPLAd from PBPD were screened out.
In conclusion, data obtained from a reliable array CGH analysis indicated that there were a series of differences in the genome-wide CNV profiles in the bronchial epithelial cells of the NSPLAd from PBPD. It was promised to build up a molecular model to distinguish NSPLAd from PBPD with bronchial epithelial cells, by further invegestion with an enlarged sample size.
首先,应用Agilent Human Genomic CGH 44B芯片,对16例患者(11例NSPLAd,5例PBPD)的32个部位的支气管上皮细胞刷片(每位患者包括健侧叶段支气管上皮细胞-1s及患侧主支气管上皮细胞-2s)基因组DNA进行了Array CGH检测。继而,采用Agilent CGH Analytics 4.0和GeneSpring GX 11.0.1分析软件分析实验数据。结果显示：(1)11个NSPLAd患者支气管上皮细胞基因组DNA拷贝数发生异常的区域较一致,1s发生频率大于45%片段有15个,2s发生频率大于50%的DNA片段有10个。(2) NSPLAd患者与PBPD患者对应的支气管上皮相比,基因组DNA拷贝数变异的区域广,范围大,发生频率高。(3)经过对11例患者2s处Array CGH实验数据的生物信息学分析,初步筛选出34个能用于鉴别诊断NSPLAd患者的DNA片段组合。
综上,本研究表明,NSPLAd患者形态正常的支气管上皮中存在一系列基因组DNA拷贝数变异,2s处基因组DNA拷贝数变异可能用于NSPLAd的辅助诊断,有望通过进一步扩大样本量的深入研究建立起能够用于NSPLAd鉴别诊断的分子模型。
Diagnosis of Non-smoking Peripheral Lung Adenocarcinoma by Bronchial Epithelial Cell Genomic DNA Copy Number Variation
Lung Adenocarcinomas incidence are increasing。Peripheral lung Adenocarcinoma (PLAd) is difficult pclinically。Effective and easy means to differentiate PLAd is not always available. Field cancerization exists in airway epithelial cells, and a series of molecular changes in the airway epithelial cells showed useful in the differential diagnosis of lung cancer. Such researches in non-smoking lung cancer patients are rare. In this study, array comparative genomic hybridization (Array-CGH) was performed on the bronchial epitherial cells of non-smoking patients with peripheral lung adenocarcinoma (NSPLAd) and patients with benign peripheral disease (PBPD),to identify the DNA copy number variation(CNV) profiles that specially related with NSPLAd and PBPD patients, respectively. From these, a set of gain or loss genes/regions could be identified to distinguish the two disease.
The 32 bronchial epithelial cells (including the contralateral bronchial epithelial cells-1s and ipsilateral primary bronchial epithelial cell-2s) derived from 16patients (11 NSPLAd and 5 PBPD)were screened by Agilent Human Genomic CGH 44B array.With analyses by Agilent CGH Analytics 4.0 and GeneSpring GX 11.0.1, the genome-wide CNV profiles of bronchial epithelial cells were obtained.11 NSPLAds showed good accordance in regions of CNV. There were 15 copy number alterations with a frequency of more than 45% in 1s and 10 copy number alterations with a frequency of more than 50% in the NSPLAd. NSPLAd patients showed a much larger scale, much higher frequence in CNV. than PBPD. Bioinformatical analysis was performed with the array CGH data of the 32cases, and 34 genes that could differentiate NSPLAd from PBPD were screened out.
In conclusion, data obtained from a reliable array CGH analysis indicated that there were a series of differences in the genome-wide CNV profiles in the bronchial epithelial cells of the NSPLAd from PBPD. It was promised to build up a molecular model to distinguish NSPLAd from PBPD with bronchial epithelial cells, by further invegestion with an enlarged sample size.
引文
1. Carretta, A., et al., Surgical treatment of multiple primary adenocarcinomas of the lung. Thorac Cardiovasc Surg,2009.57(1):p.30-4.
2. Greengard, O. and A. Herzfeld, The undifferentiated enzymic composition of human fetal lung and pulmonary tumors. Cancer Res,1977.37(3):p.884-91.
3.陈竺,全国第三次死因回顾抽样调查报告.中国协和医科大学出版社,2008：p.124-133.
4. Jemal, A., et al., Cancer statistics,2008. CA Cancer J Clin,2008.58(2):p.71-96.
5. Jemal, A., et al., Annual report to the nation on the status of cancer,1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst,2008.100(23):p.1672-94.
6. Mountain, C.F., Revisions in the International System for Staging Lung Cancer. Chest,1997.111(6): p.1710-7.
7. Sone, S., et al., Characteristics of small lung cancers invisible on conventional chest radiography and detected by population based screening using spiral CT. Br J Radiol,2000.73(866):p.137-45.
8. Pastorino, U., Lung cancer screening. Br J Cancer,2010.
9. Warner, E., A. Jotkowitz and N. Maimon, Lung cancer screening-are we there yet?. Eur J Intern Med,2010.21(1):p.6-11.
10. Lam, S., et al., Detection of dysplasia and carcinoma in situ with a lung imaging fluorescence endoscope device. J Thorac Cardiovasc Surg,1993.105(6):p.1035-40.
11. Lam, S., et al., Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy. Chest,1998.113(3):p.696-702.
12. Ikeda, N., et al., Histopathological evaluation of fluorescence bronchoscopy using resected lungs in cases of lung cancer. Lung Cancer,2003.41(3):p.303-9.
13. Fearon, E.R. and B. Vogelstein, A genetic model for colorectal tumorigenesis. Cell,1990.61(5):p. 759-67.
14. Colby, T.V., I.I. Wistuba and A. Gazdar, Precursors to pulmonary neoplasia. Adv Anat Pathol,1998. 5(4):p.205-15.
15. Kerr, K.M., Pulmonary preinvasive neoplasia. J Clin Pathol,2001.54(4):p.257-71.
16. Hirsch, F.R., et al., Early detection of lung cancer:clinical perspectives of recent advances in biology and radiology. Clin Cancer Res,2001.7(1):p.5-22.
17. Belinsky, S.A., et al., Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. Cancer Res,2006.66(6):p.3338-44.
18. Prindiville, S.A. and T. Ried, Interphase cytogenetics of sputum cells for the early detection of lung carcinogenesis. Cancer Prev Res (Phila Pa),2010.3(4):p.416-9.
19. Varella-Garcia, M., et al., The detection of chromosomal aneusomy by fluorescence in situ hybridization in sputum predicts lung cancer incidence. Cancer Prev Res (Phila Pa),2010.3(4):p. 447-53.
20. Yu, L., et al., Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int J Cancer,2010.
21. Miyazu, Y.M., et al., Telomerase expression in noncancerous bronchial epithelia is a possible marker of early development of lung cancer. Cancer Res,2005.65(21):p.9623-7.
22. Tsou, J.A., et al., Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma. Mol Cancer,2007.6:p.70.
23. Rivera, M.P. and A.C. Mehta, Initial diagnosis of lung cancer:ACCP evidence-based clinical practice guidelines (2nd edition). Chest,2007.132(3 Suppl):p.131S-148S.
24. SLAUGHTER, D.P., H.W. SOUTHW1CK and W. SMEJKAL, Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer,1953.6(5):p.963-8.
25. Copper, M.P., et al., A panel of biomarkers of carcinogenesis of the upper aerodigestive tract as potential intermediate endpoints in chemoprevention trials. Cancer,1993.71(3):p.825-30.
26. Tabor, M.P., et al., Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res,2001.7(6):p.1523-32.
27. Nakajima, T., et al., Metachronous gastric cancers after endoscopic resection:how effective is annual endoscopic surveillance?. Gastric Cancer,2006.9(2):p.93-8.
28. Kammori, M., et al., Squamous cell carcinomas of the esophagus arise from a telomere-shortened epithelial field. Int J Mol Med,2007.20(6):p.793-9.
29. Heaphy, C.M., J.K. Griffith and M. Bisoffi, Mammary field cancerization:molecular evidence and clinical importance. Breast Cancer Res Treat,2009.118(2):p.229-39.
30. Lou, C., et al., Aberrant DNA methylation profile of hepatocellular carcinoma and surgically resected margin. Cancer Sci,2009.100(6):p.996-1004.
31. Knuchel, R., et al., [Precancerous lesions of the urothelium. From Feulgen staining to single cell CGH]. Pathologe,2008.29(5):p.364-70.
32. Lee, P., et al., Primary lung cancer after treatment of head and neck cancer without lymph node metastasis:is there a role for autofluorescence bronchoscopy?. Lung Cancer,2008.62(3):p.309-15.
33. Franklin, W.A., et al., Widely dispersed p53 mutation in respiratory epithelium. A novel mechanism for field carcinogenesis. J Clin Invest,1997.100(8):p.2133-7.
34. Guo, M., et al., Promoter hypermethylation of resected bronchial margins:a field defect of changes?. Clin Cancer Res,2004.10(15):p.5131-6.
35. Chu, T.Y., et al., Monoclonality and surface lesion-specific microsatellite alterations in premalignant and malignant neoplasia of uterine cervix:a local field effect ofgenomic instability and clonal evolution. Genes Chromosomes Cancer,1999.24(2):p.127-34.
36. Stern, R.S., et al., p53 mutation in nonmelanoma skin cancers occurring inpsoralen ultraviolet a-treated patients:evidence for heterogeneity and field cancerization. J Invest Dermatol,2002. 119(2):p.522-6.
37. Zochbauer-Muller, S., et al., Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers. Int J Cancer,2003.107(4):p.612-6.
38. BJ, B., et al., A genetic explanation of Slaughter's concept of field cancerization:evidence and clinical implications.2003. p.1727-30.
39. Nelson, M.A., J. Wymer and N.J. Clements, Detection of K-ras gene mutations in non-neoplastic lung tissue and lung cancers. Cancer Lett,1996.103(1):p.115-21.
40. Wistuba, I.I., et al., Molecular damage in the bronchial epithelium of current and former smokers. J Natl Cancer Inst,1997.89(18):p.1366-73.
41. Mao, L., et al., Clonal genetic alterations in the lungs of current and former smokers. J Natl Cancer Inst,1997.89(12):p.857-62.
42. Liu, Y., et al., Hypermethylation of p161NK4a in Chinese lung cancer patients:biological and clinical implications. Carcinogenesis,2003.24(12):p.1897-901.
43. Belinsky, S.A., et al., Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum. Br J Cancer,2007.96(8):p.1278-83.
44. Belinsky, S.A., et al., Gene promoter methylation in plasma and sputum increases with lung cancer risk. Clin Cancer Res,2005.11(18):p.6505-11.
45. Belinsky, S.A., et al., Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci USA,1998.95(20):p.11891-6.
46. Charles A. Powell, et al., Loss of Heterozygosity in epithelial Cells Obtained By Bronchial Brushing:Clinical Utility in Lung cancer, in Clinical Cancer Research.1999. p.2025-2034.
47. Spira, A., et al., Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat Med,2007.13(3):p.361-6.
48. Brock, M.V., et al., DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med,2008.358(11):p.1118-28.
49. Belinsky, S.A., J.H. Schiller and C.A. Stidley, DNA methylation biomarkers to assess therapy and chemoprevention for non-small cell lung cancer. Nutr Rev,2008.66 Suppl 1:p. S24-6.
50. von Zeidler, S.V., et al., Hypermethylation of the p16 gene in normal oral mucosa of smokers. Int J Mol Med,2004.14(5):p.807-11.
51. Ayan, N., et al., P53 overexpression in normal oral mucosa of heavy smokers. J Exp Clin Cancer Res, 2000.19(4):p.525-9.
52. Helland, A., et al., Mutations in the TP53 gene and protein expression of p53, MDM 2 and p21/WAF-1 in primary cervical carcinomas with no or low human papillomavirus load. Br J Cancer, 1998.78(1):p.69-72.
53. Colucci, S., et al., p53 mutations and protein expression in primary cultures of normal oral mucosa in smokers and non-smokers. Oral Oncol,1997.33(4):p.240-6.
54. Sridhar, S., et al., Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium. BMC Genomics,2008.9:p.259.
55. Tang, X., et al., EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients. Cancer Res,2005.65(17):p.7568-72.
56. Stearman, R.S., et al., A macrophage gene expression signature defines a field effect in the lung tumor microenvironment. Cancer Res,2008.68(1):p.34-43.
57. Bhutani, M., et al., Oral epithelium as a surrogate tissue for assessing smoking-induced molecular alterations in the lungs. Cancer Prev Res (Phila Pa),2008.1(1):p.39-44.
58. Hackett, N.R., et al., Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers. Am J Respir Cell Mol Biol,2003.29(3 Pt 1):p.331-43.
59. Spira, A., et al., Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci USA,2004.101(27):p.10143-8.
60. Harvey, B.G., et al., Modification of gene expression of the small airway epithelium in response to cigarette smoking. J Mol Med,2007.85(1):p.39-53.
61. Steiling, K., et al., The field of tissue injury in the lung and airway. Cancer Prev Res (Phila Pa),2008. 1(6):p.396-403.
62. Belinsky, S.A., et al., Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. Cancer Res,2006.66(6):p.3338-44.
63.I,I., et al., Tumors of the Chest,2006:Springer Berlin Heidelberg.93-94.
64. Youlden, D.R., S.M. Cramb and P.D. Baade, The International Epidemiology of Lung Cancer: geographical distribution and secular trends. J Thorac Oncol,2008.3(8):p.819-31.
65. Proctor, R.N., Tobacco and the global lung cancer epidemic. Nat Rev Cancer,2001.1 (1):p.82-6.
66. Sanchez-Cespedes, M., et al., Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers. Cancer Res,2001.61(4):p.1309-13.
67. Bhattacharjee, A., et al., Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA,2001.98(24):p.13790-5.
68. MP, W., et al., Primary adenocarcinomas of the lung in nonsmokers show a distinct pattern of allelic imbalance, in Cancer Res.2002. p.4464-8.
69. Wilhelm, M., et al., Array-based comparative genomic hybridization for the differential diagnosis of renal cell cancer. Cancer Res,2002.62(4):p.957-60.
70. Schraml, P., et al., Combined array comparative genomic hybridization and tissue microarray analysis suggest PAK1 at 11q13.5-q14 as a critical oncogene target in ovarian carcinoma. Am J Pathol,2003.163(3):p.985-92.
71. Jain, A.N., et al., Quantitative analysis of chromosomal CGH in human breast tumors associates copy number abnormalities with p53 status and patient survival. Proc Natl Acad Sci USA,2001.98(14): p.7952-7.
72. Hui, A.B., et al., Genome wide detection of oncogene amplifications in nasopharyngeal carcinoma by array based comparative genomic hybridization. Int J Oncol,2002.20(3):p.467-73.
73. Bar-Shira, A., et al., Multiple genes in human 20q13 chromosomal region are involved in an advanced prostate cancer xenograft. Cancer Res,2002.62(23):p.6803-7.
74. Maciejewski, J.P., R.V. Tiu and C. O'Keefe, Application of array-based whole genome scanning technologies as a cytogenetic tool in haematological malignancies. Br J Haematol,2009.146(5):p. 479-88.
75. Shi, Q., et al., Polymorphisms of methionine synthase and methionine synthase reductase and risk of lung cancer:a case-control analysis. Pharmacogenet Genomics,2005.15(8):p.547-55.
76. Hung, R.J., et al., Folate-related genes and the risk of tobacco-related cancers in Central Europe. Carcinogenesis,2007.28(6):p.1334-40.
77. Wilson, B.S., et al., Calcium-dependent clustering of inositol 1,4,5-trisphosphate receptors. Mol Biol Cell,1998.9(6):p.1465-78.
78. Schrodl, K., et al., Altered Ca2+-homeostasis of cisplatin-treated and low level resistant non-small-cell and small-cell lung cancer cells. Cell Oncol,2009.31(4):p.301-15.
79. Olopade, O.I., et al., Mapping of the shortest region of overlap of deletions of the short arm of chromosome 9 associated with human neoplasia. Genomics,1992.14(2):p.437-43.
80. Inglefield, J.R., et al., TLR7 agonist 852A inhibition of tumor cell proliferation is dependent on plasmacytoid dendritic cells and type Ⅰ IFN. J Interferon Cytokine Res,2008.28(4):p.253-63.
81. Imai, H., et al., Clinicopathological and therapeutic significance of CXCL12 expression in lung cancer. Int J Immunopathol Pharmacol,2010.23(1):p.153-64.
82. Salmaggi, A., et al., CXCL12, CXCR4 and CXCR7 expression in brain metastases. Cancer Biol Ther, 2009.8(17):p.1608-14.
83. Lonergan, K.M., et al., Identification of novel lung genes in bronchial epithelium by serial analysis of gene expression. Am J Respir Cell Mol Biol,2006.35(6):p.651-61.
84. Afjehi-Sadat, L., et al., Detection of hypothetical proteins in 10 individual human tumor cell lines. Biochim Biophys Acta,2005.1747(1):p.67-80.
85. Xiao, W., et al., Differentially expressed genes associated with human lung cancer. Oncol Rep,2005. 14(1):p.229-34.
86. Diesinger, I., et al., Toward a more complete recognition of immunoreactive antigens in squamous cell lung carcinoma. Int J Cancer,2002.102(4):p.372-8.
87.刘彦.中国协和医科大学中国医学科学院肿瘤医院博士研究生学位论文.2007.
88.蔡雄伟.中国协和医科大学中国医学科学院肿瘤医院博士研究生学位论文.2007.
89. Guang, W.; et al., MUC1 cell surface mucin attenuates epithelial inflammation in response to a common mucosal pathogen. J Biol Chem,2010.
90. Freeman, CM., et al., Cytotoxic Potential of Lung CD8+ T Cells Increases with Chronic Obstructive Pulmonary Disease Severity and with In Vitro Stimulation by IL-18 or IL-15. J Immunol,2010.
91. Engels, E.A., Inflammation in the development of lung cancer:epidemiological evidence. Expert Rev Anticancer Ther,2008.8(4):p.605-15.
92. AUERBACH, O., et al., Changes in bronchial epithelium in relation to cigarette smoking and in relation to lung cancer. N Engl J Med,1961.265:p.253-67.
93. Chari, R., et al., Effect of active smoking on the human bronchial epithelium transcriptome. BMC Genomics,2007.8:p.297.
94. Zochbauer-Muller, S., et al., Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers. Int J Cancer,2003.107(4):p.612-6.
95. Davies, J.J., I.M. Wilson and W.L. Lam, Array CGH technologies and their applications to cancer genomes. Chromosome Res,2005.13(3):p.237-48.
96. Shen, H., et al., Genomic alterations in lung adenocarcinomas detected by multicolor fluorescence in situ hybridization and comparative genomic hybridization. Cancer Genet Cytogenet,2008.181(2):p. 100-7.
97. Shen, H., et al., Multicolor fluorescence in situ hybridization and comparative genomic hybridization reveal molecular events in lung adenocarcinomas and squamous cell lung carcinomas. Biomed Pharmacother,2009.63(6):p.396-403.
98. Hung, J., et al., Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma. JAMA,1995.273(24):p.1908.
99. Hung, J., et al., Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma. JAMA,1995.273(7):p.558-63.
100. Kishimoto, Y., et al., Allele-specific loss in chromosome 9p loci in preneoplastic lesions accompanying non-small-cell lung cancers. J Natl Cancer Inst,1995.87(16):p.1224-9.
101. Spira, A., et al., Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat Med,2007.13(3):p.361-6.
(1)陈竺.全国第三次死因回顾抽样调查报告.中国协和医科大学出版
社.2008(10)：124-133
(2)Ahmedin Jemal, Rebecca Siegel, Elizabeth Ward, et al. Cancer Statistics, 2008. CA Cancer J Clin 2008(58):71-96
(3)Mountain CF. Revisions in the international system for staging lung cancer. [J] Chest,1997,111(6):1710-1717
(4)党国际99mTc-MIBI肺显像、多排螺旋CT和肿瘤标志物检测对肺癌的诊断价值.肿瘤研究与临床.2009,21(3)：172-173,177
(5)Woolner LB, Fontana RS, Cortese DA, et al. Roentgenographically occult lung cancer:pathologic findings and frequency of multicentricity during a 10-year period. [J] Mayo Clin Proc 1984,59:453-466
(6)Lam S, MacAulay C, Hung J, LeRiche J, Profio AE, Palcic B. Detection of dysplasia and carcinoma in situ with a lung imaging fluorescence endoscope device. [J] J Thoracic Cardiovasc Surg 1993,105:1035-1040
(7)Lam S, Kennedy T, Unger M, et al. Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy. [J] Chest 1998,113:696-702
(8)Kusunoki Y, Imamura F, Uda H, etal. Early detection of lung cancer with laser-induced fluorescence endoscopy and spectrofluorometry. [J] Chest 2000,118:1776-1782
(9)Hirsch FR, Prindiville SA, Miller YE, et al. Fluorescence versus white-light bronchoscopy for detection of preneoplastic lesions:a randomized study. [J] J Natl Cancer Inst 2001,93:1385-1391
(10)Hanibuchi M, Yano S, Nishioka Y, et al. Auto fluorescence bronchoscopy, a novel modality for the early detection of bronchial premalignant and malignant lesions. J Med Invest.2007 Aug;54(3-4):261-266
(11)Kurie JM, Lee JS, Morice RC, et al. Autofluorescence bronchoscopy in the detection of squamous metaplasia and dysplasia in current and former smokers. [J] J Natl Cancer Inst 1998,90:991-995.
(12)Norihiko Ikedaa, Toshimitsu Hiyoshia, Masatoshi Kakihana, et al. Histopathological evaluation of fluorescence bronchoscopy using
resected lungs in cases of lung cancer. Lung Cancer,2003,41 (3): 303-309
(13)Timothy C. Kennedy, Annette Mc Williams, etal. Bronchial Intraepithelial Neoplasia/Early Central Airways Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition). [J] Chest 2007; 132 (3_suppl):221-233.
(14)K Shibuya, H Hoshino, M Chiyo, etal. High magnification bronchovideoscopy combined with narrow band imaging could detect capillary loops of angiogenic squamous dysplasia in heavy smokers at high risk for lung cancer. [J] Thorax 2003,58:989-995.
(15)Vincent BD, Fraig M, Silvestri GA, et al. A pilot study of narrow-band imaging compared to white light bronchoscopy for evaluation of normal airways and premalignant and malignant airways disease. [J] Chest,2007, 131(6):1794-1799.
(16)Steiner RM, Liu JB, Goldberg BB, Cohn JR. The value of ultrasound guided fiberoptic bronchoscopy. [J] Clin Chest Med 1995,16:519-534.
(17)Hurter T, Hanrath P. Endobronchial sonography:feasibility and preliminary results. [J] Thorax 1992,47:565-567.
(18)Miyazu Y, Miyazawa T, Kurimoto N, etal. Endobronchial ultrasonography in the assessment of centrally located early-stage lung cancer before photodynamic therapy. [J] Am J Respir Crit Care Med 2002,165:832-837.
(19)N Kurimoto, M Murayama, S Yoshioka,etal. Analysis of the Internal Structure of Peripheral Pulmonary Lesions Using Endobronchial Ultrasonography [J] Chest 2002,122:1887-1894.
(20)N Kurimoto, T Miyazawa, S Okimasa,etal. Endobronchial Ultrasonography Using a Guide Sheath Increases the Ability To Diagnose Peripheral Pulmonary Lesions Endoscopically. [J] Chest 2004, 126;959-965.
(21)N Yamada, K Yamazaki, N Kurimoto, etal. Factors Related to Diagnostic
Yield of Transbronchial Biopsy Using Endobronchial Ultrasonography With a Guide Sheath in Small Peripheral Pulmonary Lesions [J] Chest 2007,132:603-608.
(22)Ralf Eberhardt, Devanand Anantham, Felix Herth, etal. Electromagnetic Navigation Diagnostic Bronchoscopy in Peripheral Lung Lesions. [J] Chest 2007,131:1800-1805.
(23)Todd S. Weiser, Kevin Hyman, Jaime Yun, etal. Electromagnetic Navigational Bronchoscopy:A Surgeon's Perspective. [J]Ann Thorac Surg 2008,85:797-801.
(24)Tanaka M, Satoh M, Kawanami O, Aihara K. A new bronchofiberscope for the study of diseases of very peripheral airways. [J] Chest 1984,85:590-594.
(25)S Yamamoto, K Ueno, F Imamura, etal. Usefulness of ultrathin bronchoscopy in diagnosis of lung cancer. [J] Lung Cancer 2004,46:43-48.
(26)Shinagawa N, Yamazaki K, Onodera Y, et al. CT-guided transbronchial biopsy using an ultrathin bronchoscope with virtual bronchoscopic navigation. [J] Chest 2004,125,1138-1143.
(27)N Shinagawa, K Yamazaki, Y Onodera,etal. Factors Related to Diagnostic Sensitivity Using an Ultrathin Bronchoscope Under CT Guidance. [J] Chest 2007,131:549-553.
(28)Sagawa M, Sugita M, Higashi K, Isobe T, Hirose T, Matsubara F, Ida M, Isse K, Sakuma T. Lung cancer with ground glass opacity diagnosed by transbronchial lung biopsy using an ultrathin bronchoscope and virtual bronchoscopy. [J] Kyobu Geka.2004,57(12):1121-1125.
2. Greengard, O. and A. Herzfeld, The undifferentiated enzymic composition of human fetal lung and pulmonary tumors. Cancer Res,1977.37(3):p.884-91.
3.陈竺,全国第三次死因回顾抽样调查报告.中国协和医科大学出版社,2008：p.124-133.
4. Jemal, A., et al., Cancer statistics,2008. CA Cancer J Clin,2008.58(2):p.71-96.
5. Jemal, A., et al., Annual report to the nation on the status of cancer,1975-2005, featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst,2008.100(23):p.1672-94.
6. Mountain, C.F., Revisions in the International System for Staging Lung Cancer. Chest,1997.111(6): p.1710-7.
7. Sone, S., et al., Characteristics of small lung cancers invisible on conventional chest radiography and detected by population based screening using spiral CT. Br J Radiol,2000.73(866):p.137-45.
8. Pastorino, U., Lung cancer screening. Br J Cancer,2010.
9. Warner, E., A. Jotkowitz and N. Maimon, Lung cancer screening-are we there yet?. Eur J Intern Med,2010.21(1):p.6-11.
10. Lam, S., et al., Detection of dysplasia and carcinoma in situ with a lung imaging fluorescence endoscope device. J Thorac Cardiovasc Surg,1993.105(6):p.1035-40.
11. Lam, S., et al., Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy. Chest,1998.113(3):p.696-702.
12. Ikeda, N., et al., Histopathological evaluation of fluorescence bronchoscopy using resected lungs in cases of lung cancer. Lung Cancer,2003.41(3):p.303-9.
13. Fearon, E.R. and B. Vogelstein, A genetic model for colorectal tumorigenesis. Cell,1990.61(5):p. 759-67.
14. Colby, T.V., I.I. Wistuba and A. Gazdar, Precursors to pulmonary neoplasia. Adv Anat Pathol,1998. 5(4):p.205-15.
15. Kerr, K.M., Pulmonary preinvasive neoplasia. J Clin Pathol,2001.54(4):p.257-71.
16. Hirsch, F.R., et al., Early detection of lung cancer:clinical perspectives of recent advances in biology and radiology. Clin Cancer Res,2001.7(1):p.5-22.
17. Belinsky, S.A., et al., Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. Cancer Res,2006.66(6):p.3338-44.
18. Prindiville, S.A. and T. Ried, Interphase cytogenetics of sputum cells for the early detection of lung carcinogenesis. Cancer Prev Res (Phila Pa),2010.3(4):p.416-9.
19. Varella-Garcia, M., et al., The detection of chromosomal aneusomy by fluorescence in situ hybridization in sputum predicts lung cancer incidence. Cancer Prev Res (Phila Pa),2010.3(4):p. 447-53.
20. Yu, L., et al., Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int J Cancer,2010.
21. Miyazu, Y.M., et al., Telomerase expression in noncancerous bronchial epithelia is a possible marker of early development of lung cancer. Cancer Res,2005.65(21):p.9623-7.
22. Tsou, J.A., et al., Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma. Mol Cancer,2007.6:p.70.
23. Rivera, M.P. and A.C. Mehta, Initial diagnosis of lung cancer:ACCP evidence-based clinical practice guidelines (2nd edition). Chest,2007.132(3 Suppl):p.131S-148S.
24. SLAUGHTER, D.P., H.W. SOUTHW1CK and W. SMEJKAL, Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer,1953.6(5):p.963-8.
25. Copper, M.P., et al., A panel of biomarkers of carcinogenesis of the upper aerodigestive tract as potential intermediate endpoints in chemoprevention trials. Cancer,1993.71(3):p.825-30.
26. Tabor, M.P., et al., Persistence of genetically altered fields in head and neck cancer patients: biological and clinical implications. Clin Cancer Res,2001.7(6):p.1523-32.
27. Nakajima, T., et al., Metachronous gastric cancers after endoscopic resection:how effective is annual endoscopic surveillance?. Gastric Cancer,2006.9(2):p.93-8.
28. Kammori, M., et al., Squamous cell carcinomas of the esophagus arise from a telomere-shortened epithelial field. Int J Mol Med,2007.20(6):p.793-9.
29. Heaphy, C.M., J.K. Griffith and M. Bisoffi, Mammary field cancerization:molecular evidence and clinical importance. Breast Cancer Res Treat,2009.118(2):p.229-39.
30. Lou, C., et al., Aberrant DNA methylation profile of hepatocellular carcinoma and surgically resected margin. Cancer Sci,2009.100(6):p.996-1004.
31. Knuchel, R., et al., [Precancerous lesions of the urothelium. From Feulgen staining to single cell CGH]. Pathologe,2008.29(5):p.364-70.
32. Lee, P., et al., Primary lung cancer after treatment of head and neck cancer without lymph node metastasis:is there a role for autofluorescence bronchoscopy?. Lung Cancer,2008.62(3):p.309-15.
33. Franklin, W.A., et al., Widely dispersed p53 mutation in respiratory epithelium. A novel mechanism for field carcinogenesis. J Clin Invest,1997.100(8):p.2133-7.
34. Guo, M., et al., Promoter hypermethylation of resected bronchial margins:a field defect of changes?. Clin Cancer Res,2004.10(15):p.5131-6.
35. Chu, T.Y., et al., Monoclonality and surface lesion-specific microsatellite alterations in premalignant and malignant neoplasia of uterine cervix:a local field effect ofgenomic instability and clonal evolution. Genes Chromosomes Cancer,1999.24(2):p.127-34.
36. Stern, R.S., et al., p53 mutation in nonmelanoma skin cancers occurring inpsoralen ultraviolet a-treated patients:evidence for heterogeneity and field cancerization. J Invest Dermatol,2002. 119(2):p.522-6.
37. Zochbauer-Muller, S., et al., Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers. Int J Cancer,2003.107(4):p.612-6.
38. BJ, B., et al., A genetic explanation of Slaughter's concept of field cancerization:evidence and clinical implications.2003. p.1727-30.
39. Nelson, M.A., J. Wymer and N.J. Clements, Detection of K-ras gene mutations in non-neoplastic lung tissue and lung cancers. Cancer Lett,1996.103(1):p.115-21.
40. Wistuba, I.I., et al., Molecular damage in the bronchial epithelium of current and former smokers. J Natl Cancer Inst,1997.89(18):p.1366-73.
41. Mao, L., et al., Clonal genetic alterations in the lungs of current and former smokers. J Natl Cancer Inst,1997.89(12):p.857-62.
42. Liu, Y., et al., Hypermethylation of p161NK4a in Chinese lung cancer patients:biological and clinical implications. Carcinogenesis,2003.24(12):p.1897-901.
43. Belinsky, S.A., et al., Predicting gene promoter methylation in non-small-cell lung cancer by evaluating sputum and serum. Br J Cancer,2007.96(8):p.1278-83.
44. Belinsky, S.A., et al., Gene promoter methylation in plasma and sputum increases with lung cancer risk. Clin Cancer Res,2005.11(18):p.6505-11.
45. Belinsky, S.A., et al., Aberrant methylation of p16(INK4a) is an early event in lung cancer and a potential biomarker for early diagnosis. Proc Natl Acad Sci USA,1998.95(20):p.11891-6.
46. Charles A. Powell, et al., Loss of Heterozygosity in epithelial Cells Obtained By Bronchial Brushing:Clinical Utility in Lung cancer, in Clinical Cancer Research.1999. p.2025-2034.
47. Spira, A., et al., Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat Med,2007.13(3):p.361-6.
48. Brock, M.V., et al., DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med,2008.358(11):p.1118-28.
49. Belinsky, S.A., J.H. Schiller and C.A. Stidley, DNA methylation biomarkers to assess therapy and chemoprevention for non-small cell lung cancer. Nutr Rev,2008.66 Suppl 1:p. S24-6.
50. von Zeidler, S.V., et al., Hypermethylation of the p16 gene in normal oral mucosa of smokers. Int J Mol Med,2004.14(5):p.807-11.
51. Ayan, N., et al., P53 overexpression in normal oral mucosa of heavy smokers. J Exp Clin Cancer Res, 2000.19(4):p.525-9.
52. Helland, A., et al., Mutations in the TP53 gene and protein expression of p53, MDM 2 and p21/WAF-1 in primary cervical carcinomas with no or low human papillomavirus load. Br J Cancer, 1998.78(1):p.69-72.
53. Colucci, S., et al., p53 mutations and protein expression in primary cultures of normal oral mucosa in smokers and non-smokers. Oral Oncol,1997.33(4):p.240-6.
54. Sridhar, S., et al., Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium. BMC Genomics,2008.9:p.259.
55. Tang, X., et al., EGFR tyrosine kinase domain mutations are detected in histologically normal respiratory epithelium in lung cancer patients. Cancer Res,2005.65(17):p.7568-72.
56. Stearman, R.S., et al., A macrophage gene expression signature defines a field effect in the lung tumor microenvironment. Cancer Res,2008.68(1):p.34-43.
57. Bhutani, M., et al., Oral epithelium as a surrogate tissue for assessing smoking-induced molecular alterations in the lungs. Cancer Prev Res (Phila Pa),2008.1(1):p.39-44.
58. Hackett, N.R., et al., Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers. Am J Respir Cell Mol Biol,2003.29(3 Pt 1):p.331-43.
59. Spira, A., et al., Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci USA,2004.101(27):p.10143-8.
60. Harvey, B.G., et al., Modification of gene expression of the small airway epithelium in response to cigarette smoking. J Mol Med,2007.85(1):p.39-53.
61. Steiling, K., et al., The field of tissue injury in the lung and airway. Cancer Prev Res (Phila Pa),2008. 1(6):p.396-403.
62. Belinsky, S.A., et al., Promoter hypermethylation of multiple genes in sputum precedes lung cancer incidence in a high-risk cohort. Cancer Res,2006.66(6):p.3338-44.
63.I,I., et al., Tumors of the Chest,2006:Springer Berlin Heidelberg.93-94.
64. Youlden, D.R., S.M. Cramb and P.D. Baade, The International Epidemiology of Lung Cancer: geographical distribution and secular trends. J Thorac Oncol,2008.3(8):p.819-31.
65. Proctor, R.N., Tobacco and the global lung cancer epidemic. Nat Rev Cancer,2001.1 (1):p.82-6.
66. Sanchez-Cespedes, M., et al., Chromosomal alterations in lung adenocarcinoma from smokers and nonsmokers. Cancer Res,2001.61(4):p.1309-13.
67. Bhattacharjee, A., et al., Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA,2001.98(24):p.13790-5.
68. MP, W., et al., Primary adenocarcinomas of the lung in nonsmokers show a distinct pattern of allelic imbalance, in Cancer Res.2002. p.4464-8.
69. Wilhelm, M., et al., Array-based comparative genomic hybridization for the differential diagnosis of renal cell cancer. Cancer Res,2002.62(4):p.957-60.
70. Schraml, P., et al., Combined array comparative genomic hybridization and tissue microarray analysis suggest PAK1 at 11q13.5-q14 as a critical oncogene target in ovarian carcinoma. Am J Pathol,2003.163(3):p.985-92.
71. Jain, A.N., et al., Quantitative analysis of chromosomal CGH in human breast tumors associates copy number abnormalities with p53 status and patient survival. Proc Natl Acad Sci USA,2001.98(14): p.7952-7.
72. Hui, A.B., et al., Genome wide detection of oncogene amplifications in nasopharyngeal carcinoma by array based comparative genomic hybridization. Int J Oncol,2002.20(3):p.467-73.
73. Bar-Shira, A., et al., Multiple genes in human 20q13 chromosomal region are involved in an advanced prostate cancer xenograft. Cancer Res,2002.62(23):p.6803-7.
74. Maciejewski, J.P., R.V. Tiu and C. O'Keefe, Application of array-based whole genome scanning technologies as a cytogenetic tool in haematological malignancies. Br J Haematol,2009.146(5):p. 479-88.
75. Shi, Q., et al., Polymorphisms of methionine synthase and methionine synthase reductase and risk of lung cancer:a case-control analysis. Pharmacogenet Genomics,2005.15(8):p.547-55.
76. Hung, R.J., et al., Folate-related genes and the risk of tobacco-related cancers in Central Europe. Carcinogenesis,2007.28(6):p.1334-40.
77. Wilson, B.S., et al., Calcium-dependent clustering of inositol 1,4,5-trisphosphate receptors. Mol Biol Cell,1998.9(6):p.1465-78.
78. Schrodl, K., et al., Altered Ca2+-homeostasis of cisplatin-treated and low level resistant non-small-cell and small-cell lung cancer cells. Cell Oncol,2009.31(4):p.301-15.
79. Olopade, O.I., et al., Mapping of the shortest region of overlap of deletions of the short arm of chromosome 9 associated with human neoplasia. Genomics,1992.14(2):p.437-43.
80. Inglefield, J.R., et al., TLR7 agonist 852A inhibition of tumor cell proliferation is dependent on plasmacytoid dendritic cells and type Ⅰ IFN. J Interferon Cytokine Res,2008.28(4):p.253-63.
81. Imai, H., et al., Clinicopathological and therapeutic significance of CXCL12 expression in lung cancer. Int J Immunopathol Pharmacol,2010.23(1):p.153-64.
82. Salmaggi, A., et al., CXCL12, CXCR4 and CXCR7 expression in brain metastases. Cancer Biol Ther, 2009.8(17):p.1608-14.
83. Lonergan, K.M., et al., Identification of novel lung genes in bronchial epithelium by serial analysis of gene expression. Am J Respir Cell Mol Biol,2006.35(6):p.651-61.
84. Afjehi-Sadat, L., et al., Detection of hypothetical proteins in 10 individual human tumor cell lines. Biochim Biophys Acta,2005.1747(1):p.67-80.
85. Xiao, W., et al., Differentially expressed genes associated with human lung cancer. Oncol Rep,2005. 14(1):p.229-34.
86. Diesinger, I., et al., Toward a more complete recognition of immunoreactive antigens in squamous cell lung carcinoma. Int J Cancer,2002.102(4):p.372-8.
87.刘彦.中国协和医科大学中国医学科学院肿瘤医院博士研究生学位论文.2007.
88.蔡雄伟.中国协和医科大学中国医学科学院肿瘤医院博士研究生学位论文.2007.
89. Guang, W.; et al., MUC1 cell surface mucin attenuates epithelial inflammation in response to a common mucosal pathogen. J Biol Chem,2010.
90. Freeman, CM., et al., Cytotoxic Potential of Lung CD8+ T Cells Increases with Chronic Obstructive Pulmonary Disease Severity and with In Vitro Stimulation by IL-18 or IL-15. J Immunol,2010.
91. Engels, E.A., Inflammation in the development of lung cancer:epidemiological evidence. Expert Rev Anticancer Ther,2008.8(4):p.605-15.
92. AUERBACH, O., et al., Changes in bronchial epithelium in relation to cigarette smoking and in relation to lung cancer. N Engl J Med,1961.265:p.253-67.
93. Chari, R., et al., Effect of active smoking on the human bronchial epithelium transcriptome. BMC Genomics,2007.8:p.297.
94. Zochbauer-Muller, S., et al., Aberrant methylation of multiple genes in the upper aerodigestive tract epithelium of heavy smokers. Int J Cancer,2003.107(4):p.612-6.
95. Davies, J.J., I.M. Wilson and W.L. Lam, Array CGH technologies and their applications to cancer genomes. Chromosome Res,2005.13(3):p.237-48.
96. Shen, H., et al., Genomic alterations in lung adenocarcinomas detected by multicolor fluorescence in situ hybridization and comparative genomic hybridization. Cancer Genet Cytogenet,2008.181(2):p. 100-7.
97. Shen, H., et al., Multicolor fluorescence in situ hybridization and comparative genomic hybridization reveal molecular events in lung adenocarcinomas and squamous cell lung carcinomas. Biomed Pharmacother,2009.63(6):p.396-403.
98. Hung, J., et al., Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma. JAMA,1995.273(24):p.1908.
99. Hung, J., et al., Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma. JAMA,1995.273(7):p.558-63.
100. Kishimoto, Y., et al., Allele-specific loss in chromosome 9p loci in preneoplastic lesions accompanying non-small-cell lung cancers. J Natl Cancer Inst,1995.87(16):p.1224-9.
101. Spira, A., et al., Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat Med,2007.13(3):p.361-6.
(1)陈竺.全国第三次死因回顾抽样调查报告.中国协和医科大学出版
社.2008(10)：124-133
(2)Ahmedin Jemal, Rebecca Siegel, Elizabeth Ward, et al. Cancer Statistics, 2008. CA Cancer J Clin 2008(58):71-96
(3)Mountain CF. Revisions in the international system for staging lung cancer. [J] Chest,1997,111(6):1710-1717
(4)党国际99mTc-MIBI肺显像、多排螺旋CT和肿瘤标志物检测对肺癌的诊断价值.肿瘤研究与临床.2009,21(3)：172-173,177
(5)Woolner LB, Fontana RS, Cortese DA, et al. Roentgenographically occult lung cancer:pathologic findings and frequency of multicentricity during a 10-year period. [J] Mayo Clin Proc 1984,59:453-466
(6)Lam S, MacAulay C, Hung J, LeRiche J, Profio AE, Palcic B. Detection of dysplasia and carcinoma in situ with a lung imaging fluorescence endoscope device. [J] J Thoracic Cardiovasc Surg 1993,105:1035-1040
(7)Lam S, Kennedy T, Unger M, et al. Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy. [J] Chest 1998,113:696-702
(8)Kusunoki Y, Imamura F, Uda H, etal. Early detection of lung cancer with laser-induced fluorescence endoscopy and spectrofluorometry. [J] Chest 2000,118:1776-1782
(9)Hirsch FR, Prindiville SA, Miller YE, et al. Fluorescence versus white-light bronchoscopy for detection of preneoplastic lesions:a randomized study. [J] J Natl Cancer Inst 2001,93:1385-1391
(10)Hanibuchi M, Yano S, Nishioka Y, et al. Auto fluorescence bronchoscopy, a novel modality for the early detection of bronchial premalignant and malignant lesions. J Med Invest.2007 Aug;54(3-4):261-266
(11)Kurie JM, Lee JS, Morice RC, et al. Autofluorescence bronchoscopy in the detection of squamous metaplasia and dysplasia in current and former smokers. [J] J Natl Cancer Inst 1998,90:991-995.
(12)Norihiko Ikedaa, Toshimitsu Hiyoshia, Masatoshi Kakihana, et al. Histopathological evaluation of fluorescence bronchoscopy using
resected lungs in cases of lung cancer. Lung Cancer,2003,41 (3): 303-309
(13)Timothy C. Kennedy, Annette Mc Williams, etal. Bronchial Intraepithelial Neoplasia/Early Central Airways Lung Cancer:ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition). [J] Chest 2007; 132 (3_suppl):221-233.
(14)K Shibuya, H Hoshino, M Chiyo, etal. High magnification bronchovideoscopy combined with narrow band imaging could detect capillary loops of angiogenic squamous dysplasia in heavy smokers at high risk for lung cancer. [J] Thorax 2003,58:989-995.
(15)Vincent BD, Fraig M, Silvestri GA, et al. A pilot study of narrow-band imaging compared to white light bronchoscopy for evaluation of normal airways and premalignant and malignant airways disease. [J] Chest,2007, 131(6):1794-1799.
(16)Steiner RM, Liu JB, Goldberg BB, Cohn JR. The value of ultrasound guided fiberoptic bronchoscopy. [J] Clin Chest Med 1995,16:519-534.
(17)Hurter T, Hanrath P. Endobronchial sonography:feasibility and preliminary results. [J] Thorax 1992,47:565-567.
(18)Miyazu Y, Miyazawa T, Kurimoto N, etal. Endobronchial ultrasonography in the assessment of centrally located early-stage lung cancer before photodynamic therapy. [J] Am J Respir Crit Care Med 2002,165:832-837.
(19)N Kurimoto, M Murayama, S Yoshioka,etal. Analysis of the Internal Structure of Peripheral Pulmonary Lesions Using Endobronchial Ultrasonography [J] Chest 2002,122:1887-1894.
(20)N Kurimoto, T Miyazawa, S Okimasa,etal. Endobronchial Ultrasonography Using a Guide Sheath Increases the Ability To Diagnose Peripheral Pulmonary Lesions Endoscopically. [J] Chest 2004, 126;959-965.
(21)N Yamada, K Yamazaki, N Kurimoto, etal. Factors Related to Diagnostic
Yield of Transbronchial Biopsy Using Endobronchial Ultrasonography With a Guide Sheath in Small Peripheral Pulmonary Lesions [J] Chest 2007,132:603-608.
(22)Ralf Eberhardt, Devanand Anantham, Felix Herth, etal. Electromagnetic Navigation Diagnostic Bronchoscopy in Peripheral Lung Lesions. [J] Chest 2007,131:1800-1805.
(23)Todd S. Weiser, Kevin Hyman, Jaime Yun, etal. Electromagnetic Navigational Bronchoscopy:A Surgeon's Perspective. [J]Ann Thorac Surg 2008,85:797-801.
(24)Tanaka M, Satoh M, Kawanami O, Aihara K. A new bronchofiberscope for the study of diseases of very peripheral airways. [J] Chest 1984,85:590-594.
(25)S Yamamoto, K Ueno, F Imamura, etal. Usefulness of ultrathin bronchoscopy in diagnosis of lung cancer. [J] Lung Cancer 2004,46:43-48.
(26)Shinagawa N, Yamazaki K, Onodera Y, et al. CT-guided transbronchial biopsy using an ultrathin bronchoscope with virtual bronchoscopic navigation. [J] Chest 2004,125,1138-1143.
(27)N Shinagawa, K Yamazaki, Y Onodera,etal. Factors Related to Diagnostic Sensitivity Using an Ultrathin Bronchoscope Under CT Guidance. [J] Chest 2007,131:549-553.
(28)Sagawa M, Sugita M, Higashi K, Isobe T, Hirose T, Matsubara F, Ida M, Isse K, Sakuma T. Lung cancer with ground glass opacity diagnosed by transbronchial lung biopsy using an ultrathin bronchoscope and virtual bronchoscopy. [J] Kyobu Geka.2004,57(12):1121-1125.
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