7
腸腻腫腽腷膃膕膜臒臘 Vol. 36, pp. 487493, 2008 腖腓腏腘腍腆腔腕腄腑腛腀 腎腗腒腚腅腂腃腇腉腌腊腋腁腈腙腐 臰膎 腠腕腇腈 腄腏 腃腕 腩腛 腘腈腢腥 腍腐 腄腏腈腨 腝腡腖腉 腍腢腪 腇腇腏腋 膗臃 腠腍腜腧 腙腏 腜腧 膊臔 腛腞腣腠 腑腄腄腔 膄致 腄腛腅腆 腒腊 腡腚腏腒 腠腍腡腔 膇腐 腏腥腈腨 腒腆 腡腣腎腨 膧臻 腗腦腇腡 : 膕腅 20 10 21 腓腆腥腐 PDT膦膠臖臇腼腭膅腥腖膜EBUS膦膠膦膠臖field cancerization 腄腀腅腂 膦膠腡膦膠臖腙腘腛膦膠臖膭腖膓臗膦腸腼膈腈 腎腦膢腜臺膰膢腗腂腂膈腈腚腜膬腌腑腺腫 腇腁腦臺膰膢腛臶膰腜膢腖腁 臱腎腦膞臟腜臨膩膋臟腖腁腦腢腽臛膢 腜膈膢腩臱腌腡腎腂 1膩膋腙腘腛腮腏腱膈膮腩臤腊腡腎腂臁臇腡膇腚腠膢 腇臩腡腎腂膎膗腟腤腧腦腞腑膩膋臟腖腁腦腇膼腚膑腌腕腂腦膞 臟腇腆腤腛膺至腜 “field cancerization” 腗腂腃膚腗腌腕腪膡腋腧腕腂腦腎腙腨腓臨膩膋 腙腘腛膢膸臞腚腣腦膝膬腛腑腟腚膀腚膂臕膁臵腇腨腎膅腗腌腕膢膒腇臈腎腦腗腂腃 臆腄腖腁腦膦膠臖膭腛膨自腛腀膙腗腗腠腚臺膰膢腛臼腗臜膛腞腌腉腀膙腌腕腂腦腜腋腞腗腎腣腊腃腘腝腁腕腦 腏腑腌腉腔腍 臵腛膦臠腙臝膔膱膾腩膈腈腌腕腂 腌腆腌臺膰膢腡腐腛膎膗腖腁腦 dysplasia, metaplasia 腇膦膈腈腎腦腗膐膓腒腊膦腛臝膔膱膾腇膹臠腎腦腐腛膒腩腘膑腌腕膵臩腖腈腦腣腃腚腌腑腛腇膱膾膦膠臖 膭腖腁腦 21990 臌腣腥膱膾膦膠臖膭腇膘膺臑腖腜腃腠腛膱膾膦膠臖膭腇臮腚膍 腋腧腕腂腦 2,3膱膾膦膠臖膭腜臵腙膃膞臷腛臝膔膱膾腩膁臵腙膃膞腜臝膔膱膾腛膹 臠腇腸腳腽腴腚膶腄腦腣腃腚腯腽腵腺腲腵腇腬腆腧腕腂腦1膱膾膦膠臖膭腚腣腥臏腙膃膞 膒腩腄腦臙腇腖腈腣腥膤腛膙腖膢腩 膵臩腎腦臙腇腖腈腦腣腃腚腙腔腑腑腚腧腈腦腤 PDT腌腉腔腒腡腟腇腢腝腛腤 EBUS腣腥膤腛膙腖膢腩膵臩腎腦臙腇腖腈腧腝腒膩膧膜 PDT腙腘腛臗膭腇膓腁腦PDT 膾膟臤腄膒臞腗腼腀腰腀腚 腣腦臹臦腛臭腙腂臜膧膛膜腖腁腦臊腂膾膟臤腄膒臞腩腌腪腂臚膡膽腚膯腼腓腣 腚臧腋腧腑臐腇腼腀腰腀膾腚腣腥膾腒膩腱膉膍腩腮腏腱腚臣腇腴腹腀腱腋腧腑腥膲膠腇腴腹腀腱腋腏腑腥膍腛腙腘腚腣腥臅臣膿膖腇腤腧腦腗臆腄腤腧腕腂 膾膟臤腄膒臞腜腈膭腶臲腣腥膓腩臤腊膍腋腧腕腂腦NCI 腖腠臺膰腌腕 PDT 臬腋腧EBM 腛臡腚腣腦膢臼腭腬腶腺腬腽腚腅腂腕腠 膝腟腤腧腦臬腮腼腀腶 B 腛臜膧膜腖腁腦 4臨膩膋腚腣腥臺 膑腌腑膞臟腖腜腇腖腈腦 PDT 臡自腛 腠腟 腗腌腕膤 腋腧腕腂 5腁腏8PDT 膍腜腛膯腾腗膌腾腸腻腫腽腷膃膕膕膜 膻膪膣487 101

3605[103]igakukai.marianna-u.ac.jp/idaishi/www/365/05-36...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

Embed Size (px)

Citation preview

� � ����������Vol. 36, pp. 487�493, 2008

���������� ���������������

������

��

���

��

��

�����

������

������

��

��

����

������

������

��

��

���

��

������

������

� �� !

!"#

��

�"���"

#�����

��� ��

�"!

$���$�

%&%&��

�'� :�� 20� 10� 21��

����PDT' ()*+��,����' EBUS' ()�()*' field cancerization

��

()-()*./0()*1234(��5 !6789�:;"8<==' !59>#?@$%AB7( ���:;"80&C;9�� '82B7( �� D67EF9�GHF2B7( ��()I8-* 8J D?-6=1�( �GH./0+,-.KLJ'M-6=N+�-O.�P.' Q�5R8AS/-6=( �0812A3TUV7( W@' �GHF2B7AX5' ��:"Y405"?Z=7EFA*=( ��[U�0\]9 “field cancerization”<=^_6<?Z78`VZ=7( 6.ab�GH./08c9d5e7:;0@T5' �<f5g=�hiA>??' @j<?Z8kAAl67<=^mnB2B7( ()*10op0AC<<R5' �:;"80q�<�D98rW?sAC?Z=7(

�� ����������

������Ei0(� '9Ft.uvwxJ !?Z=

7( ?[?' �:;"8-y008122B7dysplasia, metaplasia A(� '5 !67<' y0GHzM(� '0uvwxA{t67( y02kJIJ?Z|S2}7e^5?@0Awx()*12B72�( 1990 �~e�wx()*1A� `

V' \�29' (�KL0wx()*1AM�5�N`VZ=72�, 3�( wx()*19' Ei.OP9Q�0uvwxJ ?' hi.OP9uvwx0{tA����5�n7e^5������ARS`VZ=7( �� 1�wx()*15e�' F�.OP02kJTn7�A2}' e�U�0V�2"8J|S67�A2}7e^5.�@(

�� !�" �PDT� ����#$%&'�(" �EBUS�

e�U�0V�2"8J|S67�A2}V�'xWX�D� �PDT� ./0�41-�DA342B7( PDT 9' x�'Y9d<5SX����5e7��0�.=�DB�2B7( �Z5$hY0�=x�'Y9dJ[7\���5' �Z�5]^-5�?`V@_ A' ����x5e�xWX�-`�J!�' +,-5�ZA�¡�¢`V@�'�Z£)A�¡�¢`¤@�' ¥)0a¦`�0bc./5e�§�Z¨©AdUV7<mnUVZ=7( x�'Y9d9' ª!ef«e�33J'M¬g�`VZ=7( h­ NCI 2R�:;U�"85i?Z PDT9j®`V' EBM0¯�5e7"8qD°±²�±�� 5³=ZR �´TUV7�'j®µ��² B0�D�2B74�( �GH5e�:"Y405"?@EF29' "Y4¶kA2}7PDT 9' ¯p0Ll�D<?Z�m`VZ=75��8�( PDT 0g�9' ���Z0·¸n<¹¸nA���������� ��� �º»¼��oD���

487

101

�������� ������� ���������� ������ 1 cm ����������4�� PDT � �������� !" #$� %� &'(�) *�+�,-./0��� 1�$� &'(2345�67� �EBUS� � �%� &'(�) *�+869:;0�<5��EBUS �$� &'(�$7=>�?�@�9���� 2�&'(�$32ABC high�1�-low�2�-high�3�-low�4�-high�5�-low�6�-high�7� echo band � � 57,/D$ 7 7=>9EF�� G 3, 4 7�&'(HI9�/0��4�, 9�� PDT JKLK$&'(HI94M�� �� &'(HI 32A�%�

�NO/0��PQ9 PDT RS�TM� PDT�U�/<� V<� &'(HI94M0%��WX/0��PQ$� PDT RS�$�D� YZ ��[\� ]^_`a� ,/D$b�cde fgU�� U�9:;<� � 3$������� h����� %�$� &'(i�$�j�kl�CT �?F������m� EBUS �$&'(HI 32A�NO/0�<� PDT RS�TM�PDT �n�/� o�pqrs �CR� 9t<� � 4$� &'(�94M0%��WX/0�<h����� �h�$� &'(i�$u+ �v� CT �$w'x�y�]� z?{|};<� EBUS �$%�3�~��V@� ��&'(HI9��� %�$&'(HI94M0���86/� ^_`a9:;<� ^_����� %�$&'(HI94M0WX/0����9��/<� EBUS� PDT ��*�+986/� R`���/0U�9:M�� PDT � ������������B;<4��

������

����K�$� �� RNA��9��0����� ������9�o��F��������� ����K�$����N ¡\9��/0�]� �¢£/<��e�����¤/0��10, 11�� ¥¦ §¦¨©�$����K�$�¤/0����� �¨©�$ª���¤F�<�� � �N ¡�$����K� �¤� «�TMC@0��12��

��� ��������

R`�RSh�9��/� PDT 9¬:/<��

� 1 ­®&'(i� �%� ?­®&'(i�$� §¦�&¯°!$"��� �����e��#$$±��²�?�@��

� 2 EBUS � �&'� ?&'32 ] high �1�-low �2� -high �3�-low �4�-high�5�-low�6�-high�7� 57,/D$ 77=>�?�@�� G 6, 7 7$³C@����,´�� HI$G 3, 47�=!�@0��� Am J Respir CritCare Med 2002; 165: 832�837 ]µ$

¶·%¸ ¹º»¼ C488

102

������� ���� ����� ����������� ����������� �!"�#$%���&���'�()���� *+,-���� ./0123��4�� ./05�67�89!:;<�=>?@ABC'�()�DEFG�13��15�� H(�I��� JK�����LM�� ��'�NO)�9�NO���� �� ./0123�4PQ���RS>TUV� ��� WX�./0123YZ��4T[\��16��]^�� JK���T�N�� 24_ 27`a� �bScde� PDT 9f�ghijLM� klmLM� noMpTq�� r�stuvTqw��

HG!�NO�stuvJ�xyz{[|T}�e~�./01�3����� �hTERT� YZ]'�����T�q��17�� �� 5� PDT �LMTqw� 15`a��� 11`a�� LM����� �CR�)9w�� �� 4`a������#$%���&��� ��� klmLM� noMpTqw� 12`a���� 9`a�LM�r�����9w��]�� 3`a���� A�������#$%���&��� LM�r� CR ����e�� 19`a�� �O�LM��������� )�LM��stuvJ������ ��eW�e� hTERT YZ��4���!G9�w�� ��

� 3 �������g ¡¢£�¤¥�e��NO���i��¦¦§¨� CT ��©ªFG:� EBUS ��¢£����g ¡¤¥� Am J Respir Crit CareMed 2002; 165: 832�837

� 4 ������T«Ve¢£�¬­�e��NOEBUS ��¢£®¯°�G���9�����T©ª� Am J Respir Crit Care Med 2002; 165: 832�837

JK����±² 489

103

� 5 ���������

� 6 PDT �� � CR �������Cancer Res. 2005; 65: 9623�9627

���� ���� �490

104

�� �������� 7���� ������ hTERT ������������ �����hTERT ������������������ !"#$%� �n�26, P�0.0001�� �� 1�� 6� PDT���� 7&'�� () CR �*+� ,-./#$-� PDT ��0��12��34�HR56#metaplasia� hTERT7856�9:#$%�� � 7 �./�� ;<=� CIS �>�% ?@� PDT �� 4AB�� CD CR �E%�� FG;<HI#�JKEL6FG�MN@�HE 56#�JKE;O���P�� ,�QR�ST��� hTERT ���U:#$%�� V./�

3WX��Y)�P����

�������� ��field cancerization

“Field cancerization” ��� 1953 & Slaughter��Q@Z[\]#^� _`a��bc#$-18�� �def�gha��\]�� iCjk��l#�Em� >,no�p�% ����q-�,Rrs��t��� Z[� uv� wv� xO� ;<H\]�� yz{|}�Q-~�# field canceriza-tion ���E@R-� �K� ������������#� �������:l�Q-������

� 1 �����?�- hTERT ������������

� 7 PDT ��Y)�P���./Cancer Res. 2005; 65: 9623�9627

�������� 491

105

���������� ���19�� �������� ����������� �!"#�$%&'�()*+,-.�/0�12345�� 6 �field cancerization 78��9�� ����������:;��/0#�$%&'<(+=> ? � “field immortalization” �12�@A>+�� �� ��,B#��3CD.�EF�GH�� I +J������K���$%&'�()*+L>���6MN� �J���OP$%&'<(Q>19��RST��6 ������,B#��� ��U�� PDT�VWXY>�Z[9\����5�$%&'�(L>����� PDT �MN]Z? ��� $%&'<(L>�^���� PDT ��1_#_`� ��,Babcd�@A>+��� ef in vitro �� $%&'�(+=> ? �ghEF�� #i.;620�� ghEF�� #�;cH��� $%&'�(�=> �jk #l�6+m�d�21�� $%&'�(+=> ? ������� in vivo �:;������12.�6�I#�I�/0� “field immortalization” �-n3Oo�� ��,Babc����c;��� ��

� � �

pqrs�3,B.�t��������N� �uvw�xyz{�|}��� MNJ��~��,�? �Ml�cd�� U��������+��qs�A+��#�:N� PDT c����w�Z[���>��cH������� #�#�9�� PDT ���,� ��;�RST��,B3��.�� I �������������� $%&'�(�,-+� �!"#�Bo�6+��? ��

����

1� Woolner LB, Fontana RS, Cortese DA, et al.Roentgenographically occult lung cancer:

pathologic findings and frequency of multicen-

tricity during a 10-year period. Mayo Clin

Proc 1984; 59: 453�466.2� Lam S, Kennedy T, Unger M, et al. Localiza-tion of bronchial intraepithelial neoplastic le-

sions by fluorescence bronchoscopy. Chest

1998; 113: 696�702.3� Miyazu Y, Miyazawa T, Iwamoto Y, KanohK, Kurimoto N. The role of endoscopic tech-

niques laser-induced fluorescence endoscopy,

and endobronchial ultrasonography in choice

of appropriate therapy for bronchial cancer. J

Bronchol 2000; 8: 10�16.4� ��s����� EBM ��\�M�s�x[����'��� R 2�� �� ¡� 2005:

5� Miyazu Y, Miyazawa T, Kurimoto N, Iwa-moto Y, Kanoh K, Kohno N. Endobronchial

ultrasonography in the assessment of centrally

located early-stage lung cancer before photody-

namic 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� inearly 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, Post-mus 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 prospec-

tive phase II study on photodynamic therapy

with photofrin II for centrally located early-

stage 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 activ-

ity with immortal cells and cancer. Science

1994; 266: 2011�2015.11� Hiyama E, Hiyama K. Clinical utility of te-lomerase in cancer. Oncogene 2002; 21: 643�9.

12� Bodnar AG, Ouellette M, Frolkis M, et al.Extension of life-span by introduction of te-

¢£¤¥ ¦§¨© �492

106

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 ex-pression in the bronchial epithelium of ciga-

rette 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 acidreceptor 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, Kuri-

moto N, Iwamoto Y, Matsuura H, Kanoh K,

Kohno N, Nishiyama M, Hiyama E. Te-

lomerase expression in noncancerous bronchial

epithelia is a possible marker of early develop-

ment of lung cancer. Cancer Res 2005; 65:

9623�9627.

17� Hiyama E, Hiyama K, Yokoyama T, ShayJW. Immunohistochemical detection of te-

lomerase �hTERT� protein in human cancertissues 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. Te-lomerase activity in small-cell and non-small-

cell 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. Im-mortalization of human bronchial epithelial

cells in the absence of viral oncoproteins.

Cancer Res 2004; 64: 9027�9034.

�������� 493

107