487 Vol. 36, pp. 487 493, 2008 : 20 10 21 PDT EBUS field cancerization 1 field cancerization dysplasia, metaplasia 2 1990 2, 3 1 PDT EBUS PDT PDT NCI PDT EBM B 4 PDT 58 PDT 101
488 1 2 EBUS high 1 -low 2 -high 3 -low 4 high 5 -low 6 -high 7 5 7 6, 7 3, 4 Am J Respir Crit Care Med 2002; 165: 832 837 1cm 4 PDT EBUS 5 EBUS 9 2 high 1 -low 2 -high 3 -low 4 -high 5 -low 6 -high 7 echo band 5 7 3, 4 4, 9 PDT PDT PDT PDT 3 CT EBUS PDT PDT CR 4 CT EBUS EBUS PDT PDT 4 RNA 10, 11 12 PDT 102
JK ±² ῌ 3 489 g e NO i CT ªFG: EBUS g Med 2002; 165: 832 837 ῌ 4 ῌ Am J Respir Crit Care T«Ve e NO EBUS G 9 T ªῌ Am J Respir Crit Care Med 2002; 165: 832 837 ῌ #$% - & ' ()./0123!" ~./01 3 ῌhTERT YZ ῌ *+, )9w ῌ 4 `a D ῌ H( I JK LM /0123 4 PQ. RS>TUV WX./0123YZ 4T[\ 16 ῌ ]^ JK T N 24 _ 27 `aῌ bs `a 9 `a LM r ] 3 `a A #$ % & ῌ LM r CR 9w e 19 `a O LM ) cde PDT 9f ghijlm klm LM nomptq r ῌCR #$% & ῌ klmlm nomptqw 12 13 15 ' NO) 9 NO ]' T q 17 ῌ ῌῌ 5 PDT LMTqw 15 `a 11 `a LM 4./05 67 89!:;< =>?@ABC' () EFG HG! NO stuvj xyz{[ T} e LM stuvtqw ῌ stuvj e W e htert YZ 4!G9 w ῌ 103
490 5 6 PDT CR Cancer Res. 2005; 65: 9623 9627 104
491 1 htert 7 PDT Cancer Res. 2005; 65: 9623 9627 7 htert htert n 26, P 0.0001 1 6 PDT 7 CR PDT HR metaplasia htert 7 CIS PDT 4 CR HE htert 3 field cancerization Field cancerization 1953 Slaughter 18 field cancerization 105
492 19 field cancerization field immortalization 19 PDT PDT PDT in vitro 20 21 in vivo field immortalization PDT PDT 1 Woolner LB, Fontana RS, Cortese DA, et al. Roentgenographically occult lung cancer: pathologic findings and frequency of multicentricity during a 10-year period. Mayo Clin Proc 1984; 59: 453 466. 2 Lam S, Kennedy T, Unger M, et al. Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy. Chest 1998; 113: 696 702. 3 Miyazu Y, Miyazawa T, Iwamoto Y, Kanoh K, Kurimoto N. The role of endoscopic techniques laser-induced fluorescence endoscopy, and endobronchial ultrasonography in choice of appropriate therapy for bronchial cancer. J Bronchol 2000; 8: 10 16. 4 EBM 2 2005: 5 Miyazu Y, Miyazawa T, Kurimoto N, Iwamoto Y, Kanoh K, Kohno N. Endobronchial ultrasonography in the assessment of centrally located early-stage lung cancer before photodynamic therapy. Am J Respir Crit Care Med 2002; 165: 832 837. 6 Moghissi K, Dixon K, Thorpe JA, Stringer M, Oxtoby C. Photodynamic therapy PDT in early central lung cancer: a treatment option for patients ineligible for surgical resection. Thorax 2007; 62: 391 395. 7 van Boxem AJ, Westerga J, Venmans BJ, Postmus PE, Sutedja G. Photodynamic therapy, Nd-YAG laser and electrocautery for treating early-stage intraluminal cancer: which to choose? Lung Cancer 2001 ; 31: 31 36. 8 Furuse K, Fukuoka M, Kato H, Horai T, Kubota K, Kodama N, Kusunoki Y, Takifuji N, Okunaka T, Konaka C, et al. A prospective phase II study on photodynamic therapy with photofrin II for centrally located earlystage lung cancer. The Japan Lung Cancer Photodynamic Therapy Study Group. J Clin Oncol 1993; 11: 1852 1857. 9 Kurimoto N, Miyazawa T. Endobronchial ultrasonography. Semin Respir Crit Care Med 2004; 25: 425 431. 10 Kim NW, Piatyszek MA, Prowse KR, et al. Specific association of human telomerase activity with immortal cells and cancer. Science 1994; 266: 2011 2015. 11 Hiyama E, Hiyama K. Clinical utility of telomerase in cancer. Oncogene 2002; 21: 643 9. 12 Bodnar AG, Ouellette M, Frolkis M, et al. Extension of life-span by introduction of te- 106
493 lomerase into normal human cells. Science 1998; 279: 349 352. 13 Soria JC, Moon C, Wang L, et al. E#ects of N- 4-hydroxyphenyl retinamide on htert expression in the bronchial epithelium of cigarette smokers. J Natl Cancer Inst 2001; 93: 1257 1263. 14 Shibuya K, Fujisawa T, Hoshino H, et al. Increased telomerase activity and elevated htert mrna expression during multistage carcinogenesis of squamous cell carcinoma of the lung. Cancer 2001; 92: 849 855. 15 Soria JC, Xu X, Liu DD, et al. Retinoic acid receptor beta and telomerase catalytic subunit expression in bronchial epithelium of heavy smokers. J Natl Cancer Inst 2003; 95: 165 168. 16 Miyazu YM, Miyazawa T, Hiyama K, Kurimoto N, Iwamoto Y, Matsuura H, Kanoh K, Kohno N, Nishiyama M, Hiyama E. Telomerase expression in noncancerous bronchial epithelia is a possible marker of early development of lung cancer. Cancer Res 2005; 65: 9623 9627. 17 Hiyama E, Hiyama K, Yokoyama T, Shay JW. Immunohistochemical detection of telomerase htert protein in human cancer tissues and a subset of cells in normal tissues. Neoplasia 2001; 3: 17 26. 18 Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified squamous epithelium; clinical implications of multicentric origin. Cancer 1953; 6: 963 968. 19 Hiyama K, Hiyama E, Ishioka S, et al. Telomerase activity in small-cell and non-smallcell lung cancers. J. Natl. Cancer Inst 1995; 87: 895 902. 20 Stewart SA, Hahn WC, O[Connor BF, et al. Telomerase contributes to tumorigenesis by a telomere length-independent mechanism. Proc Natl Acad Sci USA. 2002; 99: 12606 12611. 21 Ramirez RD, Sheridan S, Girard L, et al. Immortalization of human bronchial epithelial cells in the absence of viral oncoproteins. Cancer Res 2004; 64: 9027 9034. 107