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1 ｧ8 BO06EIO08 6ﾑ8 A04 ﾌ6ｾ4, 19: , 2007 ﾒ ｦﾐ03ｦﾐ ﾒ ﾌ6ﾑ806 罍ﾞ6ｾ4ｦ ﾇ06ｦﾐ ﾞ ﾒ ﾇ 096ﾑ8 6ﾑ8ｦ ﾇ 閨 fi ｹ0 閨 ｹ ｸ7 09DR ｧ9080ｸ apple ｧ ｧ ｸ ｧ9 * M. K086ｦ ,2, 03. ｦﾌ , 03. 縺0800apple ｹ03, apple 09000ｷ303096ｧ9080ｸ71, ｦﾌ. 6ｾ46ｧ9 09 4, 04. ﾒ ｦ ｹ04, 02. ﾞ ｸ71 1 ｦﾌ ｧ8 ﾒ ｧ8 ﾞ ﾑ ｧ ｦﾌ ｧ80ｹ ｧ9 0ｹ0, ｦﾐ ｧ8 6ｾ ｧ8, ﾞ ﾞ ｧ8 ﾒ ｧ8, ﾞ ｧ8 ﾒ ｧ8, ｦﾐappleapple ｧ ｧ902090ｹ ｧ ｾ40208applefi0ｹ ｹ0 apple 03086ｦ004 0ｹ ｧ9 0ｹ0 006ｧ 閨 ｹ ｧ80ｹ0 閨 ｹ ｷ307 (mrna) 02080ｸ7 MDR ｧ9080ｸ apple ﾌ ｸ70404 閨 ｷ307 00apple06apple 陦0ｷ307 閨 ｧ80ｹ ｸ ｸ70ｹ ｷ300 閨07080ｸ70ｹ0 apple ｷ ｦ00ｹ0 apple ｹ0, applefi apple006ｧ9 6ｧ apple ｹ0 0ｸ7apple apple6ｧ80ｹ fi 閨 ｹ0: ｧ ｸ apple , ｧ fi0306, ｹ ｧ9 0ｹ0 5,5 閨0209 (006ｦ003080ｹ0: 閨0ｷ30ｹ0 12, ) 0000 ﾌ apple080ｸ7 閨 apple000ｸ fi apple030ｷ302fi BFM95. ｦ 閨 ｸ7 apple0802 閨 apple apple086ｧ9 0ｸ7apple ｧ ｷ ｧ ｸ ｧ ｧ9 apple080ｸ7 apple 閨 ｸ ｧ8. ﾇ 閨 ｸ7 mrna 02080ｸ7 09DR ｧ9080ｸ ｹ ｧ907090ｹ0 0ｷ30ｹ ｷ fi0ｹ ｸ703 0ｹ ｧ apple6ｦ ｦ ｸ7 000ｸ ｦ ｧ ｹ apple ｹ0 030ｸ ｷ3026ｧ ｧ apple08030ｸ ｹ0 (RT-PCR) ｸ70ｹ 閨0ｹ0. 030ｹ0 006ｧ ｹ0 閨 ｹ0 (046ﾑ8) 020ｷ307 MDR ｧ90ｷ ｧ apple09036ｧ ｹ0 閨 ｹ ｸ7 DNA 02080ｸ7 MDR ｧ9080ｸ7 apple03080ｹ0 0ｸ702fi 02090ｹ ｧ907090ｹ0. ﾞapple 閨 : fi0ｹ0 046ﾑ MDR ｧ 閨 (36,7%) ｧ90ｹ0. ﾇ 閨 ｸ7 MDR ｧ9080ｸ7 6ｧ ｹ ｸ fi ｸ70ｹ ｧ90ｹ ｹ 閨02090ｹ0 00 0ｹ 閨 閨 ｸ7. ﾌ ｧ90ｹ ｸ fi 046ﾑ MDR ｧ ｧ ｹ ｸ 閨 apple03fi09070ｷ 閨 ｸ702086ｦ00ｹ fi 046ﾑ8 [ fi ｦ ｹ0 07fi04080ｸ7 00apple066 56ｧ90ｷ304090ｹ0 86,67% ,56%, 07026ｧ (p log rank:0,03)]. 6ｾ ｸ fi ｹ0 046ﾑ 閨 ｸ7apple apple6ｧ ｹ0 07fi04080ｸ 閨 ﾑ ｷ ｨB006ｦ ｷ307 apple080ｸ ｧ fi ｷ30409 fi ｸ7apple apple6ｧ8. ﾇ 0ｸ ｧ8 閨 ｸ7 MDR ｧ9080ｸ ｨBfi fi 020ｷ ｸ ｧ90ｷ307, fi020ｸ7apple08, applefi ｧ apple ｨBfi07090ｹ ｹ ｦ007080ｸ NCI. 6ﾑ8apple06apple03 閨0807, ｧ90ｹ ｸ fi 046ﾑ MDR ｧ ｧ , 閨0ｹ0 0ｸ fi fi 026ｧ907 0ｸ ｧ904080ｸ707 0ｸ7apple apple6ｧ8 6ｧ apple6ｧ902000ｸ ｦ ｹ0. 6ｾ40ｸ700apple : ﾇ 閨 ｸ7 MDR ｧ9080ｸ7 apple ｧ9 閨 fi 006ｧ apple080ｸ ｧ ｸ ｦ007080ｸ apple000ｸ ｧ80ｹ0 apple08020ｸ7046ｧ9 0ｹ ｧ ｧ ｸ ｨB6ｧ ｸ70ｹ0 0ｸ7applefi030806apple080ｸ70ｹ0 apple ｷ ｦ00ｹ0 apple ｹ0. 閨 ｹ : ｧ ｧ ｸ ｧ9, apple08030ｸ ｸ ｧ ｧ8, apple ｷ ｧ9 apple ｹ0, apple ｧ ｧ9 Kourti 09, Vavatsi 03, Gombakis 03, Papageorgiou ｦ, Sidi V, Koliouskas D, Athanassiadou F. Study and evaluation of MDR1 gene expression in childhood acute lymphoblastic leukemia. 2nd Department of Pediatrics, Aristotle University of Thessaloniki, Biochemistry Department, Medical School, * ﾇ ｧ9 閨 ｸ703006ｧ ｦﾌ ｧ ｧ ｹ0 ﾒ 046ｧ900080ｹ ｹ ｧ80ｹ0 6ﾑ ｧ9 0ｹ0 ｦﾌ ｧ9080ｸ7 6ﾑ ｹ0, fi 6ｾ40ｸ700applefi040608, ｧ90209, ﾞapple036ｧ ｹ

2 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 19, 2 Aristotle University of Thessaloniki, 1st Department of Pediatrics, Aristotle University of Thessaloniki, Pediatric Oncology Department, Hippokrateion Hospital Greece. Paediatr N Gr 2007, 19: Aim of this prospective study was the analysis of expression of mrna of MDR1 gene which is implicated in the mechanism of multidrug resistance in relation with response to induction chemotherapy and relapse and the correlation with established prognostic factors. Material and methods: We studied prospectively 49 children with ALL (26 boys and 23 girls) with median age of 5.5 years (range: 15 months to 12.5 years), treated with the BFM95 chemotherapy protocol. As controls we used bone marrow (BM) mononuclear cells from 7 children who underwent a BM biopsy for diagnostic purposes which was negative for leukemia. Total RNA was isolated from BM samples at initial diagnosis with an excess of 90% leukemic blasts and at relapse. The expression of MDR1 gene and the housekeeping b-actin gene was detected by RT-PCR using the appropriate primers. The relative mrna expression of each MDR-gene was calculated using the following formula: Expression Index (EI): MDR1 gene product /b-actin PCR product. Results: Significantly higher expression of the MDR1 gene was found in patient samples compared with the control group. High EI for the MDR1 gene was found in 18 patients (36.7%) and their prognosis was significantly worse compared with those with low EI ((Event free survival (EFS): 55.56% vs 86.67%, p logrank=0.03). We found higher EI for MDR1 gene at relapse at four paired samples compared with that at diagnosis. High MDR1 gene expression was independent of initial white blood cell (wbc) count, immunophenotype, prednisone response and NCI risk classification. Patients with high MDR1 gene expression had 3.34 greater relative risk to experience early relapse or failure to achieve first complete remission. Conclusions: The expression of the MDR1 gene is a biologic marker helpful in predicting the risk of treatment failure and it is useful to be evaluated along with the other prognostic factors. Key words: acute lymphoblastic leukemia, multidrug resistance, prognostic factor, childhood. E ｷ3096ｧ8 ﾇ ｧ ｧ ｸ ｧ9 (O ) 006ｧ ｸ70407fi ｧ803090ｹ apple ｧ8 07fi04080ｹ ｹ0 apple ｧ80ｹ ｧ9 0ｹ ｷ303006ｧ apple03fi020ｸ7apple08 07fi ｧ80ｹ0 fi ｷ apple000ｸ apple ｷ307, 00 閨040ｷ3 000ｸ703 閨0ｷ ｸ apple 閨070ｷ , 0000 apple0802 閨 ｧ8 6ｦ ｹ0 00apple066 56ｧ90ｷ304090ｹ0 020ｷ apple03fi08 08 apple080ｸ7 閨 ｷ303006ｧ apple006ｧ9 020ｷ307 apple ｸ ｧ9, ｧ O, 閨 fi apple fi 0ｸ ｸ7apple apple0607ｨB ｧ ｷ3096ｧ ｦ ﾞ0ｸ702fi apple08 6ｧ ｸ7036ｧ90ｷ30ｹ ｧ80ｹ0 020ｷ ｧ8030ｷ ｸ ｷ ｸ70ｹ apple000ｸ ｦ00ｹ0 apple ｹ0, apple080ｸ7 apple ｧ apple08030ｸ ｸ ｧ ｧ8 (multidrug resistance, MDR) 1. O 020ｸ70306fi ｹ0 0002apple03fi040ｷ3apple080ｹ ｸ ｦ ｹ0 apple08030ｸ ｸ ｧ80ｹ ｧ80ｹ0 006ｧ ｸ7apple0003 閨 ｷ ｧ90ｷ307 apple080ｸ7 020ｷ apple ｦ ｹ ｷ 閨0ｹ ｸ 閨0ｹ0 apple030ｷ302000ｹ107000ｹ0 ( ﾞｦ 06binding cassette proteins, ﾞｦﾌC-proteins), apple086ｧ9000ｹ ｦ ｷ300 閨 ｸ ｸ70902 閨 ｷ ｧ8 apple apple086ｧ ｷ ｸ ｷ ｦ o ｧ9 06o ABCB1 (09DR1) 020ｷ apple ｧ ｸ70208apple030ｷ302000ｹ10709 (P-glycoprotein, P-gp) 09 08apple086ｧ9 006ｧ apple ｷ304026ｧ ｧ ｧ9 apple ｧ80ｹ fi030ｷ307 apple ｹ ｧ80ｹ apple000ｸ apple 03 09fi07020ｷ ｹ0 O, fiapple0ｷ30ｹ ｸ702036ｧ ｹ0 ( ｸ ｧ90709, 080ｸ ｸ ｧ90709), ｧ ｹ0 vinca ( ｧ90709), apple06apple ｸ ｧ907000ｹ0 (000208apple08046ｧ9 09), apple ｹ ｸ703086ｦ ｧ ｸ ﾇ fi ｹ0 076ｧ ｸ704090ｹ ｹ fi ｹ ｸ7 03fi03080ｸ ｸ7 MDR ｧ9080ｸ7 apple080ｸ 閨 fi 02090ｹ ｸ ｧ80ｹ ｧ80ｹ0 006ｧ 閨07 apple00 6ｧ ｧ9ｨB ｹ ｧ80ｹ ｧ9 0ｹ0. ﾇ 閨 , 09 apple ｦ ｹ0 閨 ｧ80ｹ ｸ ｸ70404 閨 ｧ ｹ applefi apple006ｧ9 006ｧ ｧ , ｷ3036ｧ9ｨB 閨 ｧ ｧ90ｹ0 apple080ｸ apple026ｦ001080ｸ ｧ apple006ｧ9. ﾒ ｸ707 鐶pple0006, 0ｸ702086ｧ9 006ｧ ｸ7036ｦ ｸ ｧ ｧ9 006ｧ apple08apple ｧ 閨 apple apple000ｸ fi apple030ｷ302fi apple080ｸ ｸ703086ｦ007. ﾇ apple 03086ｦ ｸ ｧ apple030808apple ｧ applefi 閨 ｹ ｧ80ｹ0 閨 ｹ ｷ307 (mrna) 02080ｸ7 MDR ｧ9080ｸ apple O ｸ70404 閨 ｷ307 00apple06apple 陦0ｷ307 閨 ｧ80ｹ ｸ70ｹ ｸ70ｹ ｷ300 閨07080ｸ70ｹ0 apple ｷ ｦ00ｹ0 apple ｹ0, applefi apple006ｧ9 6ｧ apple ｹ0 0ｸ7apple apple6ｧ80ｹ0.

3 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 19, A ｧ90ｹ 閨 ｦ 閨02090ｹ0 apple ｦ ｸ apple , ｧ fi O apple080ｸ7 閨 fi ｹ apple000ｸ fi 040ｸ fi apple030ｷ302fi ﾞLL-Berlin-Frankfurt- Mｨｹnstrer 95, (BFM95) apple086ｧ908 apple ｸ702036ｧ907000ｹ ｧ ｧ8 0ｸ7apple ｹ ｹ ｸ70208apple030ｷ302000ｹ107090ｹ0 apple080ｸ7 020ｷ apple ｧ MDR ｧ O ｧ90ｹ0 0ｸ702086ｧ apple ｷ3apple006ｦ0080ｸ apple fi apple ｸ70400fi 02090ｹ0 ｦﾌ ｧ9080ｸ7 6ﾑ ｹ O, apple086ｧ ｷ3apple6ｧ ｦﾌ ｧ8 ﾒ ｧ ｸ7 ﾞ ｧ9080ｸ apple ｧ9080ｸ ｧ902090ｹ fi ｦ 006ｧ ｸ7 ｦﾐappleapple ｸ ｧ9080ｸ ｧ902090ｹ0. O ｹ0 0403fi07080ｹ0 apple ｦ ｧ80ｹ ｸ70ｹ0 6ｧ ｧ807000ｹ0 (006ｦ003080ｹ0: ｧ ｹ0). 縺 apple 06 6ｧ9 040ｸ700apple ｷ307fi fi apple030ｷ3-02fi apple086ｧ908 0ｸ7apple6ｧ ｹ ｧ ｧ ｷ ｹ0 07fi04080ｸ7. ｦ ｧ9 6ｧ apple06070ｸ ｸ7 apple ｦ0, 08 02fiapple080ｹ ｧ80ｹ ｸ7, ｦ00308, ｧ9 09 閨 ｹ0, ｧ ｷ3096ｧ80ｹ ｧ8, ｧ ｷ304090ｹ ｹ0 07fi04080ｸ 閨 ｹ ｹ apple006ｧ9 0ｹ0, ｦ ｸ700apple ｷ3096ｧ80ｹ ｸ704fi07 6ｦ0apple apple ｧ9 0ｹ0, 04apple ｧ9 0ｹ0, apple ｹ0, ｸ ｧ8 6ｧ ｷ307 fi ｷ307 6ｧ ｸ ｦ ｸ ｦ0 040ｸ704026ｧ ｹ0 ( ﾒ.03.6ｾ4). ｦ ｸ7036ｧ ｧ fi0ｹ0 020ｷ ｸ ｧ90ｷ ｷ30409, ｧ ｹ ｧ907090ｹ0, fi0ｹ0 020ｷ apple ｧ90ｷ307, ｧ ｹ0 LDH. 6ﾑ8apple06apple03 閨0807, 040ｸ700apple ｷ307fi ｧ ｧ fi ｸ ｧ ｹ ｹ0 00apple6ｧ904090ｹ ｧ9 apple080ｸ ｦ apple ｧ ｹ0 07fi04080ｸ7 fiapple0ｷ30ｹ apple6ｧ902000ｸ ｧ ｦ ｹ 閨03, ｸ704fi07 0ｸ7apple apple6ｧ8, fi07080ｹ 閨 ｧ80ｹ ｹ0, ｹ0, fi07080ｹ ｧ ｸ7, fi07080ｹ apple6ｧ80ｹ ｹ apple006ｧ9 0ｹ ｸ702 6ｧ9 00apple6ｧ apple 07 閨 ﾞapplefi 02080ｸ70ｹ ｧ90ｹ ｹ 閨02090ｹ0 00 0ｹ0, ｧ90ｹ ｧ ｸ ｧ8 020ｷ307 fi ｷ307 6ｧ ｸ7 ﾒ.03.6ｾ ｷ ｹ0 07fi ｸ ｸ7applefi030806apple ｷ apple apple6ｧ ﾇ ｷ ｹ ｸ ｧ9 0ｹ0 02 閨 ｦ000080ｷ FAB ｧ ｸ7apple ｦ000080ｷ ｹ0 apple ｹ ｹ0 6ﾑ80ｸ7-030ｷ3apple 0ｸ8026ｧ80ｹ0 O0007 0ｹ ｧ fi ｷ ｸ (European Group for the Immunological Characterization of Leukemia, EGIL) 4,5. ｦ 閨 ｹ ｧ90ｹ ｧ ｧ ｷ ｹ0 apple ｹ0 000ｸ ｧ80ｹ0 0ｸ7apple apple6ｧ80ｹ0. ｦ 閨 ｸ7 apple0802 閨 apple ｧ ｹ ｧ9 0ｹ ｦ ｸ7, 02 08apple086ｧ9 0ｸ7apple ｧ ｷ ｧ ｸ ｧ ｧ9 apple080ｸ7 apple 閨 ｸ ｧ8. ﾇ apple036ｧ ｹ0 6ｦ ｧ ｦ000080ｷ ｹ0 apple ｹ ｹ ｹ0 BFM95, 0ｷ30ｹ0 09 apple 03080ｸ7046ｧ9 <5% ｸ ｷ ｸ70003fi 020ｷ 閨 閨 ｹ apple006ｧ9 0ｹ0. 090ｸ ｧ8 0ｸ7apple apple6ｧ ｧ apple6ｧ904090ｹ0 046ｦ000080ｷ BFM95, 0ｷ30ｹ0 09 apple 03080ｸ7046ｧ9 >25% ｸ ｷ ｸ70003fi 020ｷ ｹ0 apple03080ｹ fi ｧ80ｹ ｹ0, apple ｸ ｧ8 0ｸ7apple apple6ｧ ｧ ｧ ｹ fi ｷ applefi ｷ3046ｧ ｹ0 6ｧ8 apple fi applefi ｧ807000ｹ0 applefi ｷ fi applefi 6 006ｧ807000ｹ0 applefi ｧ8030ｷ ｹ apple006ｧ9 0ｹ06. ｦ 08 0ｸ fi 02090ｹ 閨02090ｹ0 apple ｦ ｧ ｸ ｦ0 applefi ｧ90ｹ ｷ ｹ0 07fi ｸ apple 閨 ｹ apple006ｧ9 0ｹ0, ｸ ｸ7 MDR ｧ9080ｸ ｧ apple6ｧ904090ｹ0 31 ｨB006ｦ ｷ ｸ ｦ0 apple080ｸ ｧ ｷ 閨 apple006ｧ9 0ｹ ｨB006ｦ ｷ ｷ ｸ7apple apple6ｧ ｹ0 07fi04080ｸ7, MDR ｧ ｧ ｸ7apple 閨040ｷ30ｹ0 6ｧ8 00 閨 ｹ fi ｧ ｷ ｦ0 020ｷ apple6ｦ ｷ ｸ ｷ ｸ 閨 ｧ9 0ｷ304090ｹ0 apple0ｸ70207fi ｹ ｸ700 Ficoll-Hypaque (Sigma Diagnostics) 7. ｦ 08 apple fi 020ｷ ｸ ｷ307 6ｧ >90% 0400 fi ｧ fiapple0ｷ30ｹ ｧ applefi 閨 ｸ ｸ apple ｷ applefi May-Grｨｹnwald-Giemsa. ﾞ ｸ703086ｦ ｷ30ｹ ｦ ｸ7 RNA. ﾞ07026ｧ RT-PCR ｦ ｸ fi 6ｧ9ｨB0900 0ｸ7apple apple 閨030ｷ ｧ ｦ ｹ ｸ7 RNA ｧ TRIzol 03 LS (ｦﾐnvitrogen, Life Technologies) ｸ ｹ ｹ ｧ9000ｹ ｸ ｸ ｧ8. ｦ ｧ ｸ702fi apple ｧ9 閨 fi ｸ ｸ ｧ80ｹ fi03090ｹ ｸ ｧ ｹ0 apple080ｸ7 apple ｧ9 036ｦ ｷ ｸ ｷ ｷ fi 020ｷ ｸ ｧ90ｷ307 applefi 0208 apple0ｸ fi 08016ｦ0, ｹ0 02 閨 RNA applefi apple fi apple fi ｷ ｸ7 RNA ｸ703086ｦ ｧ9 046ｦ ｹ ｸ7 c- DNA (040ｸ700apple ｷ ｦ0 apple03080ｹ 閨07 RNA) 9.

4 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 19, 2 096ｧ ｹ0 1. O ｹ 閨02090ｹ ﾞ fi0ｹ fi % 026ｦ00308 ﾞ09fi ﾒ08036ｧ ﾇ ｧ9 (0403fi0706 ) 1 閨0ｷ30ｹ0< ,6 ﾝ ,4 ﾞ fi0ｹ ｸ ｧ90ｷ307 (x10 9 /L) < ,7 ﾝ ,3 ﾞ fi0ｹ apple ｧ90ｷ307 (x10 9 /L) < ,4 ﾝ ,6 Hb(g/dl) ﾜ ,6 > ,4 LDH(IU/L) < ,1 ﾝ ,9 ﾇapple ｧ9 <3 cm 29 59,2 ﾝ3 cm 20 40,8 6ｾ4apple ｧ9 <3 cm 28 57,2 ﾝ3 cm 21 42, apple ｸ7046ｧ ,6 ﾞapple080ｸ7046ｧ ,4 ﾞ fi020ｸ7apple080ｹ apple0308 ｦﾌ 3 6,1 ﾒ ｧ8 O 31 63, ｦﾌ-O 9 18,4 T-O 6 12,2 NCI fi ｾ ｦ ｦ007080ｸ7 WBC<50x10 9 /L ｧ9 1-< , ｦ ｦ007080ｸ7 WBC ﾝ50x109/L 6ｧ ｧ9 ﾝ ,7 BFM fi ｾ ｦ ｦ007080ｸ7 ｦﾌ ｹ0 <1000/00L 閨 ｧ apple ｨBfi07090ｹ 閨03000ｹ WBC<20x10 9 /L ｧ9 ﾝ < apple036ｧ ｦ 閨03 (000ｸ70003fi0ｹ0: 091) apple080ｸ7046ｧ9 t(9;22) t(4;11) fi fi020ｸ7apple080ｹ0 ｦ -020ｸ ｧ80ｹ ｧ80ｹ ﾑ ｸ ｦ007080ｸ7 ｦﾌ ｹ0 <1000/00L 閨 ｧ apple ｨBfi07090ｹ 閨03000ｹ apple036ｧ ｦ 閨03 (000ｸ70003fi0ｹ0: 091) apple080ｸ7046ｧ9 t(9, 22) t(4;11) ｸ 閨07 applefi 02 02fi03080ｸ703 : WBC ﾝ20x10 9 /L 6ｧ ｧ9 <1 6ｧ8 ﾝ , ｦ ｦ007080ｸ7 Oapple0806o 6ｧ8apple applefi 02 apple ｷ applefi ｧ9 6ｧ8 WBC: ｦﾌ ｹ0 ﾝ1000/00L 閨 ｧ apple ｨBfi07090ｹ 閨03000ｹ0, 0009 apple036ｧ803090ｹ0 6ｦ 閨03, apple 03080ｸ7046ｧ9 t(9, 22)6ｧ8 t(4;11) 9 18,4

5 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 19, ﾑ ﾞ070206apple ｷ3apple000ｸ ｧ8 080ｷ ｧ apple00ｨB 0ｸ7apple ｸ70ｹ ｧ9 0ｹ0 020ｷ307 apple03080ｸ8fi07020ｷ ｹ0 PCR applefi fi ,5% apple ｧ fiｨB090ｹ ｷ ｦ ｧ O ｧ803000ｹ apple ｷ3apple006ｦ0080ｸ apple03080ｸ8fi ｹ0 PCR MDR ｧ ｧ90709, ｷ ｧ803000ｹ0 608, ｸ7apple apple6ｧ8, 07026ｧ L: 006ｧ ｹ ｦ 08 apple ｸ 閨07 c-dn ﾞ apple ｦ ｸ7applefi ｷ ｹ0 030ｸ ｷ3026ｧ80ｹ ｧ ｹ0 apple08030ｸ ｹ0 (Polymerase Chain Reaction, PCR) ｧ ｸ ｹ0 閨 ｹ ｸ7 MDR ｧ9080ｸ7. 縺 ｧ fi apple030ｷ302fi ｧ80ｹ ｹ0 PCR apple080ｸ7 apple apple ｦ 閨0ｹ0 040ｸ707036ｧ802000ｹ 閨 ｧ ｷ O 閨0ｹ0 00apple0603 閨 ｦ000080ｷ 閨 ﾇ 閨 ｷ ｧ90ｷ ｧ fi apple03fi ｰ ﾆero D-scan ｱ (Scananalytics Inc.) 閨 ｦ ｸ7apple ｧ applefi fi ｷ307 apple03080ｸ8fi07020ｷ307 PCR 0400 apple ｧ fiｨB090ｹ0 1,5% ｷ ｦ ｧ (6ﾑ ) 046ｦ000080ｷ ｹ ｧ9000ｹ ｸ ｸ ｧ8. 030ｹ0 006ｧ ｹ0 閨 ｹ0 (046ﾑ8) 020ｷ307 MDR ｧ9080ｸ ｧ apple09036ｧ ｹ0 閨 ｹ ｸ7 DNA 02080ｸ7 MDR ｧ9080ｸ7 apple03080ｹ0 0ｸ702fi 02090ｹ ｧ907090ｹ0. ｦ 08 apple fi 00 閨03080ｹ ｹ ｧ9 0ｹ0 0002apple08076ｧ ﾑ ｧ ｦﾌ ｧ80ｹ ｧ9 0ｹ ｸ7 ﾞ ｸ7applefi apple6ｧ ｹ ｧ ｹ0 02 0ｹ0 03. ｦﾌ ｾ ｧ ｸ70409 O ｧ90ｹ ｧ ｹ ｧ ｧ ｸ7 006ｧ 閨 ｹ 閨07 MDR ｧ9 0608, ｸ702086ｦ00ｹ ｸ ｧ8 閨 ｷ307 08apple086ｧ90ｷ ｧ ｹ0 閨 ｹ0 6ｧ ｦ ｹ0 6ｧ8 6ｧ904080ｹ ｹ ｹ ｧ80ｹ ｸ702086ｦ00ｹ ｧ8 閨 ｧ 閨 ｹ fi ｹ ｹ ｧ80ｹ014. 6ﾑ8apple06apple03 閨0807, ｸ70ｹ ｷ300 閨07080ｸ70ｹ0 apple ｷ ｦ00ｹ0 apple ｹ0 apple080ｸ ｨB ｧ ｹ ｷ304090ｹ0, ｧ ｹ ｹ0 fiapple0ｷ30ｹ0 08 6ｧ apple6ｧ O 閨0ｹ0 020ｷ apple 閨02030ｷ ｹ0 0ｸ7apple ｧ9000ｹ0 020ｷ ｧ ｧ9 x Mann Whitney U test ｸ ｹ0 040ｸ70404 閨 ｹ ｧ9 Spearman ｯs rank test. ﾇ ｧ ｹ ｦ ｹ0 07fi04080ｸ7 00apple066 56ｧ90ｷ304090ｹ0 (event-free survival, EFS) 閨 閨 ﾒaplan-Meier 11. ﾇ ｦ fi04080ｸ7 00apple066 56ｧ90ｷ ｸ7apple ｧ applefi ｧ ｹ ｷ304090ｹ0, ｧ ｹ ｸ702 6ｧ9 0ｹ0 00apple6ｧ ｹ 閨 ｧ8 00 閨 ｧ9 apple080ｸ7 0ｸ7apple6ｧ ｸ ｹ0 040ｸ ｧ apple08020ｸ7046ｧ apple6ｧ902000ｸ70109 apple036ｧ803080ｸ70ｹ0 6ｦ ｹ 閨 apple006ｧ9 0ｹ0 ( apple08020ｸ7-046ｧ apple006ｧ9 0ｹ0 0008fi 080ｸ7, ｧ ｸ ｧ9 ), ｸ7apple apple6ｧ8. O 閨0ｹ apple apple066 56ｧ90ｷ304090ｹ ｦ0 020ｷ fi030ｷ ｷ ｷ ｧ sided log-rank test. ﾇ apple ｷ ｧ8 016ｧ9 020ｷ ｷ 閨 ｸ70409 Cox-regression 12. O 閨0ｹ0 6ｧ fi0ｹ ｸ ｧ90ｷ307 ( ﾝ/<50x10 9 /L), fi020ｸ7apple080ｹ0 (ｦﾌ-O / ｦ - O ), fi NCI (0ｸ ｦ0/ ｦ ｦ007080ｸ7) ｸ fi0ｹ0 6ｧ fi0ｹ0 006ｧ ｹ0 閨 ｹ ｸ7 MDR ｧ9080ｸ7. H ｧ8 00apple ｧ9 020ｷ 閨070ｷ307 閨 apple 02 閨0208 ｰSPSS for windows ｱ, (Statistical Package for Social Sciences, version 10.0). ﾞapple 閨 ﾇ ｧ ｸ7 046ﾑ MDR ｧ ｧ ,35 (006ｦ003080ｹ0: 0,01-2,49) fi0ｹ0 046ﾑ MDR ｧ 閨 (36,7%) ｧ90ｹ0. 6ﾑ8apple06apple03 閨0807, 09 閨 ｸ7 MDR ｧ9080ｸ7 6ｧ ｹ ｸ fi ｸ70ｹ ｧ90ｹ ｹ 閨02090ｹ0 00 0ｹ 閨 閨 ｸ7.

6 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 19, 2 MD R1 3,0 2,5 2,0 1,5 1,0,5 0,0 -,5 A ｧ90ｹ0 Y fi0ｹ0 04E X fi0ｹ0 04E M ｸ703000ｹ0 6ﾑ ｾ fi ｹ apple ｹ0 020ｷ ｸ7 046ﾑ MDR ｸ70ｹ ｧ90ｹ ｹ 閨02090ｹ0 00 0ｹ 閨 ｸ7. ﾇ 040ｸ ｧ80ｹ ｧ8 0ｸ7apple ｦ ｧ ｸ7 046ﾑ8. ｦ apple ｹ ｹ ｧ80ｹ ｸ7 MDR ｧ9080ｸ ｦ0 020ｷ ｹ ｹ 閨 ｸ7 08 6ｧ fi07 2. ﾇ 040ｸ70407fi ｸ7 0ｸ ｦ0 6ｧ ｦ0 046ﾑ MDR ｧ 閨 ｦ0 020ｷ fi030ｷ ｷ ｷ ｸ70ｹ ｷ300 閨07080ｸ70ｹ0 apple ｷ ｦ00ｹ0 apple ｹ applefi07, ﾑ ｹ0 020ｷ fiapple0ｷ30ｹ fi0ｹ0 020ｷ ｸ ｧ90ｷ307 (</ ﾝ50x 10 3 /L), ｧ ｹ0 LDH (</ ﾝ1000IU/L), ｧ8 6ｧ ｧ applefi ｧ apple ｨBfi07090ｹ0 (< ｹ0/00L 6ｧ8 ﾝ ｹ0/00L 閨 apple006ｧ9 0ｹ0, 07026ｧ ), fi NCI ｸ ｦ0 6ｧ ｦ ｦ007080ｸ ｦﾌ- 6ｧ8 ｦ -020ｸ ｧ80ｹ ｧ80ｹ fi020ｸ7apple080ｹ0 (6ﾑ ). ﾇ 閨 ｸ7 MDR ｧ9080ｸ 閨 fi0206 閨 ｧ8 00apple6ｧ 閨 ｷ ｹ 閨02090ｹ0 00 0ｹ applefi07, 09 apple fi ｦ ｹ0 07fi04080ｸ7 00apple066 56ｧ90ｷ304090ｹ0 020ｷ ｸ fi 046ﾑ8 6ｧ ,56% ｧ ｹ ｸ 閨 閨 ｸ70ｹ ｧ90ｹ fi 046ﾑ apple fi EFS 86,7% (p log rank: 0,03) (E ) ｦ0 020ｷ ｸ fi 046ﾑ MDR ｧ9 0608, 4 (22,2%) apple ｸ ｧ8 0ｸ7apple apple6ｧ (22,2%) ｧ apple036ｧ80309 閨 閨 apple006ｧ9 0ｹ0. ﾇ ｸ ｹ0 閨 ｹ ｸ7 MDR ｧ9080ｸ ｦ0 020ｷ307 ｨB000ｸ ｷ ｷ ｷ apple080ｸ ｧ ｷ ｸ7apple apple6ｧ ｹ0 07fi04080ｸ7, 陦 fi ﾑ8 6ｧ ｸ fi ｹ ｸ7apple apple6ｧ ｹ0 07fi04080ｸ ｷ ｹ0 07fi04080ｸ7 (6ﾑ ). 6ﾑ8apple06apple03 閨0807, ｦ0 020ｷ ｨB000ｸ ｷ ｷ ｷ apple036ｧ ｦ ｹ0 07fi04080ｸ7, ﾑ ｸ7 MDR ｧ9080ｸ7 6ｧ ｹ fi ｹ ｦ ｹ0 07fi04080ｸ 閨 ｷ30409 (6ﾑ ). 縺 ｧ ｸ ｦ ｦ007080ｸ7 (relative risk) apple08066ｧ Cox regression ｸ fiapple0ｷ30ｹ0 apple0308 閨020ｸ ｧ90ｹ ｸ fi 046ﾑ MDR ｧ ｧ , 閨0ｹ0 0ｸ fi fi 026ｧ907 0ｸ ｧ904080ｸ707 0ｸ7apple apple6ｧ8 6ｧ apple6ｧ902000ｸ ｦ ｹ0 (096ｧ907. 2). 6ｾ40ｸ7ｨB6ｧ ｦ 060ｹ ｸ702 6ｧ9000ｹ ｧ9000ｹ0 閨 ｸ ｧ ｧ8 apple03fi08 080ｹ apple006ｧ ｹ0 O. ﾞ0ｸ702fi ｧ ｸ7036ｧ90ｷ30ｹ apple ｷ apple 03 09fi07020ｷ307, ｹ ｦ007080ｸ ｸ702086ｦ00ｹ0, apple020ｸ apple000ｸ ｧ applefi07 046ｦ ｷ307, apple 閨070ｷ307 apple08030ｸ apple000ｸ apple030ｷ fi03030ｷ apple apple ｧ90ｷ304090ｹ0 apple O 020ｸ700 6ｧ 閨0ｷ30ｹ0 80% ｯ fi03 0ｸ70207 apple00036ｧ9apple080ｸ % 020ｷ307 apple ｸ7apple apple ｸ ﾑ86ｧ 閨 fi ｸ ｷ ｸ ｷ ｧ fi0206 閨07 0ｹ fi0ｹ fi0ｹ0 0ｸ ｧ ｦ ｸ ｦ0-096ｧ ｹ ｷ ｧ9 apple ｹ fi0ｹ0 026ｧ907 0ｸ707080ｹ ｧ8 95% ｾ fi0ｹ0 ﾒ6ｧ907 0ｸ707080ｹ0 p ﾞ010608apple ｧ9 0ｹ0 (Relative Risk,RR) fi0ｹ ｧ ｹ0 閨 ｹ0 MDR1 1,02-11,34 3,34 0,04 WBC ﾝ50x10 9 /L 1,35-12,23 3,89 0, ｦ ｦ007080ｸ CI 0,39-6,63 1,61 0,5 T-O 0,35-2,46 0,93 0,8

7 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 19, WBC < 5000/L WBC ﾝ 5000/L ,8 85,2 80 p > 0, ,6 77,8 p > 0,05 B-O T-O ,2 14, ,4 22, A X fi0ｹ0 04E Y fi0ｹ0 04E 0 B X fi0ｹ0 04E Y fi0ｹ0 04E 100 NCI B ｦ ｦ007080ｸ7 NCI Y ｦ ｦ007080ｸ7 100 PGR(< ｹ0/00L) PPR( ﾝ ｹ0/00L) 80 63,3 p > 0,05 61, ,8 66, ,7 38, p > 0,05 33, ,2 0 ｦ 0 X fi0ｹ0 04E Y fi0ｹ0 04E X fi0ｹ0 04E Y fi0ｹ0 04E ｦ 6ﾑ ｧ9000ｹ ｧ9000ｹ0 % 020ｷ ｷ 閨 fi 020ｷ ｸ ｧ90ｷ307 ( ﾞ), fi020ｸ7apple08(ｦﾌ), fi ｹ ｦ007080ｸ NCI ( ), applefi apple ｨBfi0709 (04), ﾑ ｸ7 MDR ｧ9080ｸ7. pefs 1,0 0,8 0,6 0,4 0,2 0,0 MDR1 p log rank = 0,03 X ｧ8 閨 Y ｧ8 閨 M6ｧ807000ｹ0 6ﾑ ｹ0 Kaplan Meier ｸ704090ｹ ｹ0 apple fi ｹ ｦ ｹ0 07fi04080ｸ7 00apple066 56ｧ90ｷ304090ｹ0 (pefs) ｸ70ｹ ｧ90ｹ ｸ fi fi 046ﾑ MDR ｧ ｸ7 fiapple0ｷ30ｹ0 0ｸ7026ｧ8 apple ｦ0apple ｸ70ｹ ｷ3-00 閨07080ｸ70ｹ0 apple ｷ ｦ00ｹ0 apple ｹ ｸ 閨07, 046ｦ000080ｷ apple 閨 ｹ ｹ ｸ7 BFM 90, 50% 020ｷ307 0ｸ7apple apple0607 apple 03080ｸ ｸ70ｹ ｧ90ｹ ｧ8 O % ｧ ｹ0 閨 ｹ0 MDR1 1,4 1,2 1 0,8 0,6 0,4 0, ｷ ,29 1,14 0,93 0,59 Yapple apple6ｧ8 6ﾑ ｸ7 046ﾑ ｸ7 MDR ｧ9080ｸ ｨB006ｦ ｧ ｷ304090ｹ ｸ7apple apple6ｧ80ｹ0 020ｷ ｹ 閨02090ｹ0.

8 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 19, 2 MDR1mRNA/ ｧ ,0 2,5 2,0 1,5 1, ,0-0, ｷ30409 p < 0,05 6ｨ ﾑ Box plot ｸ7 046ﾑ ｸ7 MDR ｧ9080ｸ ｨB006ｦ ｧ ｷ304090ｹ apple036ｧ803080ｸ70ｹ0 6ｦ ｹ0 020ｷ ｹ 閨02090ｹ0 00 0ｹ ｸ70ｹ ｧ90ｹ ｧ applefi apple ｨBfi ｸ ｸ7apple ｸ707 fi ｧ ｷ ｷ300 閨070ｷ307 apple ｷ apple 03 09fi07020ｷ307 0ｸ ｧ9 07 apple 閨 apple036ｧ8030ｷ30ｹ ｧ907 0ｸ ｹ0 0ｸ7apple apple6ｧ80ｹ0. ﾞ016ｧ9ｨB ｸ70000 fi ｸ7apple apple6ｧ ｹ0 O ｧ9ｨB ｸ70407fi ｹ0 9, ｹ0 apple000306apple ｹ apple ｧ90ｷ30ｹ ｹ ｷ30ｹ 閨 ｸ70407fi ｧ fi ｹ0 apple ｧ80ｹ ｧ9 0ｹ022. ﾇ 040ｸ70407fi ｹ0 006ｧ apple 03fi ｸ7026ｧ8 020ｷ ｸ700apple fi09020ｷ ｸ fi applefi 0ｸ7026ｧ ｹ0 O apple ﾇ apple03fi ｷ3046ｧ ｹ0 fi000ｷ30ｹ0, 006ｧ ｸ ｧ80ｹ apple066 56ｧ90ｷ ｸ700 6ｧ applefi 8-65% 19. ﾞ0ｸ7026ｧ ｦ ｧ9ｨB ｦ0apple08 0ｸ7apple apple6ｧ80ｹ fi ｧ80ｹ ｹ applefi07, 0806 apple ｹ0 0ｸ7apple apple 閨0ｹ ｧ8 0ｸ702 閨0ｹ0 apple080ｸ ｧ9ｨB fi ｧ fi applefi ｧ807000ｹ0 applefi ｷ ｧ ｦ applefi ｧ807000ｹ0 applefi ｷ fi applefi 6 006ｧ807000ｹ0 applefi ｧ8030ｷ3046ｧ ｹ apple006ｧ9 0ｹ0 0008fi 080ｸ7, ｧ9ｨB080ｸ fi apple03fi09070ｷ apple apple080ｸ apple ｦ % 22. ﾞ07026ｧ apple ｹ0 0ｸ7apple apple 閨0ｹ apple apple066 56ｧ90ｷ304090ｹ0 閨0ｷ30ｹ0 65% ( fi >6 006ｧ807000ｹ0 applefi ｧ8-030ｷ ｹ apple006ｧ9 0ｹ0) 閨04080ｸ ｦ ｸ ｧ8 apple03fi09070ｷ 閨 ｹ0 apple ｹ0 0ｸ7apple apple 閨0ｹ0. ﾇ ｷ307 apple apple066 56ｧ90ｷ304090ｹ ｦ0 020ｷ307 apple ｷ apple ｷ307 0ｸ7apple apple 閨 ｦ ｸ7 026ｦ0apple080ｸ ｹ0 0ｸ7apple apple6ｧ80ｹ ｸ7 apple ｦ ｦ ｹ0. O06 apple ｹ0 0ｸ7apple apple 閨0ｹ ｷ303006ｧ fi0206 apple ｦ0apple02080ｸ707 applefi 03000ｸ ｦ apple080ｸ ｦ 閨 ｹ ｦ apple fi ｧ apple6ｧ ｹ apple006ｧ9 0ｹ021. ﾞ07026ｧ apple ｹ0 0ｸ7apple apple 閨0ｹ ｧ apple6ｧ ｸ7 000ｸ ｦ0 applefi 03000ｸ ｦ00ｹ ｸ70ｹ ｦ00ｹ apple006ｧ9 21. ﾇ apple08030ｸ ｸ ｧ ｧ8 (multidrug resistance, MDR) apple ｧ ｸ70306fi ｧ ｹ0 apple ｹ0 0ｸ7apple apple6ｧ80ｹ0. ﾇ apple ｸ ｧ ｧ8 閨 ｸ ｦ apple6ｧ9000ｸ70ｷ apple086ｧ ｧ ｸ703-apple ｸ fi 08016ｦ apple03 6ｧ90406 apple ｦ 閨03080ｸ723. ｦ , 0806 Dano ｸ ｹ ｸ apple ｸ ｹ0 080ｸ ｸ7026ｧ907090ｹ0 applefi ｦ apple080ｸ ｨB ｧ ｸ70ｹ apple000ｸ ｦ00ｹ0 apple ｹ0, fiapple0ｷ30ｹ ｧ ｹ0 vinca ｹ ｸ702036ｧ907000ｹ024. ｦ ｧ apple080ｸ7 020ｷ apple ｧ P-gp ｧ q ｷ3-00fi040ｷ ｸ70208apple08066ｧ ｷ30ｹ0 MDR ﾑ86ｧ kDa apple030ｷ302000ｹ10709 apple080ｸ7 apple ｧ applefi fi ｧ800 02, 閨07 020ｷ307 08apple086ｧ90ｷ307 apple 閨 閨0106 0ｸ7 03fi ｧ ｧ9 apple ｧ8 046ｦ ｹ ｸ7 ﾞｦ ﾑ86ｧ 閨03080ｹ ｹ0 000ｸ7036ｦ ｹ 閨 ｹ0 020ｷ307 ABC-apple030ｷ302000ｸ O fi0ｹ apple086ｧ ｸ ｸ70902 閨 ｷ ｷ ｸ , 02090ｹ fi07090ｹ0, 020ｷ , 020ｷ307 00apple06apple ｸ ｷ ｹ0 vinca, 0007 閨 apple036ｧ8030ｷ30ｹ ｸ ｧ9. ﾇ 020ｸ7036ｧ ｧ ｧ fi applefi apple000ｸ ｧ9 apple ｹ0 apple ｦ applefi ｸ fiapple 閨04080ｸ7 0007fi0ｹ ｦ0 apple080ｸ ｧ9ｨB applefi ｧ ｹ027,28. 6ﾑ ｨB ｸ70ｹ0 080ｸ ｦ00ｹ ｦ00ｹ ｸ703096ｧ9000ｹ ｦ0 6ｧ8 apple 閨 ｹ0, 040ｸ700apple 閨07080ｸ ｸ7 apple07006ｦ , 02080ｸ7 apple ｦ00702, 020ｷ307 fi ｷ307, 020ｷ , 02080ｸ7 6ｧ8apple 02080ｹ0, 02080ｸ7 apple 陦 02080ｹ ｸ ｸ ﾑ8apple06apple03 閨0807, ｨB apple apple ｦ ｦ ｸ ｸ7036ｧ ｸ ｦ007 fi gp apple 6ｧ9ｨB fi 03fi apple ｧ /6ｧ ｸ ﾞ 閨04080ｸ ｸ ｧ ｧ ｸ 閨0ｹ 閨0ｹ0, ｧ ｸ70ｹ ｧ 閨 apple036ｧ8030ｷ30ｹ ｸ ｧ9. 6ｾ apple 03086ｦ ｧ ｧ 閨 m-rna ｷ 閨

9 ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 19, ｧ8 apple ｸ70400fi 0000 apple fi ｦ ｸ7 80% ｹ ｷ ｹ0 07fi04080ｸ7, apple 閨 ｹ ｦ007 閨07 0ｸ7apple fi fi fi ﾇ 0ｸ7apple0003 閨 ｹ0 apple030ｷ302000ｹ107090ｹ0 apple080ｸ7 020ｷ apple ｧ MDR ｧ ｸ70ｹ ｧ ｹ ｧ ｸ ｧ9 006ｧ ｸ704076ｧ ｸ700 6ｧ applefi 22% 閨0ｷ30ｹ0 47% ｧ9ｨB apple08020ｸ7046ｧ9 00apple6ｧ902000ｸ701090ｹ0 apple036ｧ803080ｸ70ｹ0 6ｦ ｹ fi apple fi 00apple066 56ｧ90ｷ304090ｹ ｾ apple ｧ8 O ｸ700 閨07 apple 閨 ｹ0 020ｸ700 6ｧ applefi 14% 閨0ｷ30ｹ0 50% 020ｷ ｾ ｧ ｸ ｸ7036ｧ800 02, 0ｸ ｧ8 閨 ｸ7 MDR ｧ9080ｸ 閨 ｹ 閨 ｧ90ｹ0, apple fi apple080ｸ ｧ ,7% 020ｷ ｾ 閨0ｹ 閨02000ｹ0 apple O 02 0ｸ 閨07 00apple6ｧ9apple ｹ0 閨 ｹ ｹ0 P-gp 006ｧ apple6ｧ9- apple00 08 apple030ｷ302000ｹ107090ｹ0 006ｧ apple6ｧ9apple00 08 mrna ｷ307 fiapple0ｷ30ｹ0 00apple6ｧ904090ｹ ｸ 閨 ｸ fi ｹ0 P-gp ｧ9ｨB ｸ ｧ8 閨 , ｾ ｸ700080ｷ3076ｧ apple 閨 ｷ ｷ302 閨030ｷ ｸ , 閨 ｹ0 02 apple ｸ fi 006ｧ 閨 ｹ0 (046ﾑ8) MDR ｧ ｧ ｹ fi apple fi ｦ ｹ0 07fi04080ｸ7 00apple066 56ｧ90ｷ304090ｹ 閨 apple fi 046ﾑ8. ｦﾐ 06 6ｧ 閨 apple 03080ｸ ｨB fi0ｹ0 fi ｸ ｧ8 閨 ｸ7 MDR ｧ9080ｸ7 apple0308 閨020ｸ fi ｧ ｸ ｧ80ｹ0 apple ｷ fi0ｹ0 apple ｹ0, ｧ9ｨB 閨 ｷ ｷ300 閨070ｷ307 0ｸ apple ｷ apple 03 09fi07020ｷ307 fiapple0ｷ30ｹ0 08 0ｸ 閨07080ｹ fi0ｹ0 020ｷ ｸ ｧ90ｷ307, 09 0ｸ 閨 ｧ ｹ0 LDH, 08 ｦ -020ｸ ｧ80ｹ ｧ80ｹ fi020ｸ7apple080ｹ0, ｸ ｦ ｦ007080ｸ ｧ8 apple apple ｨBfi0709. ﾒ ｸ707 鐶pple0006, ｦ ｸ702fi ｦ apple ｷ ｧ ｦ ｹ0 0ｸ ｧ80ｹ0 閨 ｹ ｸ7 MDR ｧ9080ｸ ｸ ｧ9 fi apple ｷ ｧ ｸ7 016ｧ9 006ｧ applefi ｸ7036ｧ ﾑ8apple06apple03 閨0807, ｦ ｸ702fi 閨 apple ｷ303006ｧ ｹ 閨02000ｹ ｦﾐ 06 6ｧ ｧ9 閨 fi0ｹ0 fi ｸ7apple apple6ｧ ｹ0 07fi04080ｸ 閨 ｸ 閨 閨 ｸ7 MDR ｧ9080ｸ 閨 ｷ ｹ0 07fi04080ｸ7. ｦ 08 apple0802 閨 ｸ702fi 006ｧ ｸ700080ｷ3076ｧ apple 閨 ｷ307 Tafuri ｸ707., apple086ｧ ｸ7apple apple6ｧ ｹ0 07fi04080ｸ 閨03080ｸ707 0ｸ 閨0709 apple ｧ ｹ ｷ ｧ80ｹ0 Rhodamine, 09 08apple086ｧ apple ｧ 閨 ｸ ｸ ｹ0 MDR 38. 6ﾑ86ｧ ｧ9 00apple6ｧ904090ｹ apple 閨 ｷ ｷ307 Dhooge ｸ707., Wuchter ｸ707., 046ｦ000080ｷ apple086ｧ9 06 apple ｸ 閨07 00apple6ｧ9apple ｹ0 P-gp ｧ ｸ7apple apple6ｧ 閨 ｧ apple080ｸ ｧ ｸ ｨBfi apple036ｧ ｦ , fi03 0ｸ70207, 0ｸ7apple ｸ 閨02000ｹ apple086ｧ9000ｹ ｦ0080ｸ707 apple ｷ ｧ8 016ｧ ｸ7apple0003 閨 o0ｸ7 MDR ｧ9080ｸ736, ﾞ0ｸ ｸ7fi apple 閨 ｦ ｹ 閨0ｹ fi 080ｸ70ｹ0 apple080ｸ7 閨04080ｸ apple ｧ 閨 ｸ 閨07080ｸ ｹ0 apple08030ｸ ｸ ｧ80ｹ ｧ80ｹ apple6ｧ9apple00 08 apple030ｷ302000ｹ107090ｹ0, ｸ fi ｹ ｹ0 apple030ｷ ｹ107090ｹ0, 閨 ｹ0 mrna ｷ ｸ ｧ9080ｸ fi 080ｸ70ｹ0 fiapple0ｷ30ｹ ｸ ｧ9, ｸ ｧ ｧ80ｹ RT-PCR 07026ｧ ｧ ﾇ 04036ｧ ｷ ｷ ｷ ｸ ｧ ｸ ｧ ｧ80ｹ ｧ9ｨB ｧ fi fi apple ｧ ｦ ｦ00ｹ0 00apple0602fiapple080ｸ70ｹ ｹ0 apple030ｷ302000ｹ107090ｹ0, 6ｧ ｹ ｸ703086ｦ ｹ ｹ apple06apple03 閨 ｧ9ｨB fi apple fi 00apple fi ｹ0 020ｷ307 apple ｷ ｾ apple 03086ｦ 閨 apple08066ｧ ｧ ｹ0 PCR 07026ｧ ｹ apple086ｧ9 apple ｧ9 020ｷ307 0ｸ7apple ｧ9apple0ｷ ｸ ｧ fi fi ｹ0, 閨0ｹ0 00apple0603 閨 apple ｧ ｸ ｹ ｧ 閨 ｧ9 0608, ｸ ｧ ｹ0 020ｸ700 6ｧ fi ｧ ｸ704090ｹ0 0007fi0ｹ0 020ｸ ｸ7 apple080ｸ 閨0803 ｨB 閨 ｧ ｸ ｦ ｦ fi ｹ0 apple08030ｸ ｸ ｧ80ｹ ｧ80ｹ ｧ8 apple 閨 ｷ ｧ ｸ702 6ｧ9 0403fi fi apple ｸ704076ｧ ｸ ｧ80ｹ0 apple fi apple080ｸ ｷ3apple6ｧ9ｨB080ｸ ｧ90ｹ fi ｧ ｹ apple006ｧ9 0ｹ0 020ｷ O ｧ90ｹ0 00apple ｧ ｦ apple030ｷ30208apple 036ｧ ｧ ｧ ｷ ｹ0 07fi04080ｸ7 6ｧ apple026ｦ001080ｸ ｧ ｹ apple006ｧ9 0ｹ0 6ｧ ｸ7apple apple6ｧ ｹ0 07fi04080ｸ7 (00apple6ｧ ｧ8) apple ｸ ｹ0 apple030800apple0803 閨 ｹ0 apple080ｸ7 03 apple03 鐶pple apple ｦ apple 閨07080ｸ ｷ303006ｧ ｧ ｧ ｹ0 apple08030ｸ ｸ ｧ80ｹ ｧ80ｹ apple ｸ ｹ0 閨 ｹ0 0007fi0ｹ0 040ｸ 閨07080ｸ ｦ ｧ applefi ｧ ｦ ｷ ｸ ｸ7fi07020ｷ30ｹ0 09 閨 ｸ702086ｦ ｸ ｦ ｧ9ｨB ｧ8 閨 ｸ ｷ ｾ apple 03086ｦ 閨 ｦ ｸ702 閨0ｹ apple030800apple0803 閨 ｹ ｹ 閨0209 閨 ｧ8 apple ｸ70400fi ｸ ｷ ｧ ｹ0 PCR 07026ｧ ｹ ｷ3036ｧ fi ｸ7apple0003 閨 ｸ7