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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 000309 046ｧ9 閨040006 6 503 6 5000ｸ703006ｧ9 0000 0208 ｦﾌ03 6 5006ｧ908 0001036ｧ90402080ｹ0 ﾒ 046ｧ900080ｹ003 02090ｹ0 09 06 06 020306026ｧ80ｹ0 6ﾑ802 0603006ｧ9 0ｹ0 ｦﾌ0803006ｧ9080ｸ7 6ﾑ8030307 080ｹ0, 040208 3608 09 06 06 02030602fi 6ｾ40ｸ700applefi040608, 05000404 0308076ｧ90209, ﾞapple036ｧ90306080ｹ0 2006.
13134 09 06 06 020306026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: 133-144. 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. 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apple006ｧ9 0ｹ0 02 06 4 ｨB006ｦ00909 0006090007020ｷ307 02 0207 0209 060709070ｷ30409 02 06 020907 0ｸ7apple08020308apple6ｧ8 02090ｹ0 07fi04080ｸ7, 0906 0208 MDR1 0908076ｧ9 0608. 0003 02 006ｧ90900 02 0ｸ7apple086 5070303080702 07 00 閨040ｷ30ｹ0 6ｧ8 00 閨04 0400 3 0603000ｹ0 0208 0309fi02000308 0400 06 0602 046ｧ9 06 040ｷ303060400086ｦ0 020ｷ307 00080708apple6ｦ00309070ｷ307 020ｸ7020207030ｷ307 0000 080ｸ7090802 閨070203090409 6 5 03006ｧ9 0ｷ304090ｹ0 apple0ｸ70207fi020902 0ｹ0 0000 0208 0607030ｸ700 Ficoll-Hypaque (Sigma Diagnostics) 7. ｦ 08 apple0804080402fi 020ｷ307 6 503-040206020607 020ｸ7020207030ｷ307 6ｧ802 07 >90% 0400 fi03 02 006ｧ90900 02 040300070607 fiapple0ｷ30ｹ0 02 0308036ｧ90402090200 applefi 0209 000003 閨0209 020ｸ70202-0306020607 000ｸ7000306020607 00apple06040306040007020ｷ307 00000207 applefi 0403060409 02 0207 May-Grｨｹnwald-Giemsa. ﾞ020803080ｸ703086ｦ00400 00-040ｷ30ｹ0 09 0002046ｦ003060409 02080ｸ7 RNA. ﾞ07026ｧ9 03 0409 RT-PCR ｦ 08 020ｸ70202 030602fi 6ｧ9ｨB0900 0ｸ7apple086 5070303080702 07 apple0003 0602 閨030ｷ3 0400 06 0602 046ｧ9 0002046ｦ0030604090ｹ0 02080ｸ7 RNA 8 0000 0208 070206 03-04026ｧ8030608 TRIzol 03 LS (ｦﾐnvitrogen, Life Technologies) 020803080ｸ703060702 0ｹ0 02060ｹ0 08 09096ｧ9000ｹ0 02080ｸ7 02 02 0402000ｸ7 04026ｧ8. ｦ 08 070206 03 04026ｧ8030608 0ｸ702fi apple08020003006ｧ9 閨07 0008070808 040602fi 0607030ｸ700 06040803000608020ｸ7 0706026ｧ80ｹ0 08 0607fi03090ｹ0 02 06 09080ｸ7 0706 6ｧ9-07090ｹ0 apple080ｸ7 apple030802 03006ｧ9 036ｦ00409 020ｷ307 020ｸ7020207030ｷ307 02 06 06 040ｷ30306-0400fi 020ｷ307 020ｸ70202 0306020607 0402080604006ｧ90ｷ307 applefi 0208 apple0ｸ70309070602fi 08016ｦ0, 06 020903060702 0ｹ0 02 閨03 0608 0208 RNA. 09000207 applefi apple08-0408020602fi apple030804 060803060400fi 08 0400 0208080ｷ3020800000203060207 02080ｸ7 RNA 020803080ｸ703086ｦ00400 09 06 0602 046ｧ9 046ｦ007030004090ｹ0 02080ｸ7 c- DNA (040ｸ700apple0309030ｷ300 020602086ｦ0 apple03080ｹ0 0208 0001 0403 閨07 RNA) 9.
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O06 0002-0206070902 閨0ｹ0 00apple0603 閨04030902 07 046ｦ000080ｷ307 0000 02 6 5066 50306080903 0806-0207 00 0800 閨07 10. ﾇ 閨020803 0409 020ｷ307 09080706 6ｧ90ｷ307 00000300026ｧ803090200 0000 090300-02020308070602fi apple03fi0903 0000 ｰ ﾆero D-scan ｱ (Scananalytics Inc.) 0000 6 5070409 020907 閨0702 0409 08030803060400086ｦ0 0400 0ｸ7apple00-030606 09 02020607086 508036ｧ9 00000207 applefi 0903000202030808fi03090409 020ｷ307 apple03080ｸ8fi07020ｷ307 PCR 0400 apple0902026ｧ8 09 03fiｨB090ｹ0 1,5% 0000 6 5030ｷ3-0006086ｦ00408 06036ｧ9 0608 (6ﾑ80602. 1) 046ｦ000080ｷ307 0000 02060ｹ0 08 09096ｧ9000ｹ0 02080ｸ7 02 02 0402000ｸ7 04026ｧ8. 030ｹ0 006ｧ90202090ｹ0 閨020803 04090ｹ0 (046ﾑ8) 020ｷ307 MDR1-09080706 6ｧ9080ｸ7 08036ｧ90402090200 0208 apple09036ｧ90208 02090ｹ0 閨0702 04090ｹ0 02080ｸ7 DNA 02080ｸ7 MDR1 09080706 6ｧ9080ｸ7 apple03080ｹ0 0ｸ702fi 02090ｹ0 6 5-02026ｧ907090ｹ0. ｦ 08 apple000603 00 020602fi 00 閨03080ｹ0 02090ｹ0 000309 046ｧ9 0ｹ0 0002apple08076ｧ8-03090200 040208 6ﾑ80309 04026ｧ8030608 ｦﾌ060803080906026ｧ80ｹ0 010900006ｧ9 0ｹ0 02080ｸ7 ﾞ.09.05. 02 06 0ｸ7applefi 020907 00apple6ｧ96 503006 709 02090ｹ0 02 0309096ｧ8020306 0ｹ0 02 0ｹ0 03. ｦﾌ 6 507020409-0103060402070209. 6ｾ402 0206040206026ｧ8 0707030ｸ70409 O06 04030007006ｧ90ｹ0 02 01060708006ｧ8030902 07 0400 2 080007 000ｹ0 0000 020306026ｧ8030608 0209 060700000409 0206006ｧ8 02080ｸ7 006ｧ9020209 閨020803 04090ｹ0 0906 02 03 閨07 MDR-0908076ｧ9 0608, 0400 0ｸ702086ｦ00ｹ0 0000 0ｸ76 709036ｧ8 閨020803-0409 020ｷ307 08apple086ｧ90ｷ307 08 006ｧ90202090ｹ0 閨020803 04090ｹ0 6ｧ802 07 000009 036ｦ00200-03080ｹ0 6ｧ8 6ｧ904080ｹ0 02090ｹ0 0607000004090ｹ0 0206006ｧ80ｹ0 02 06 0400 0ｸ702086ｦ00ｹ0 0000 04-0009036ｧ8 閨020803 0409 0000 006ｧ9020209 閨020803 04090ｹ0 00060203fi02000308 02090ｹ0 0607000004090ｹ0 0206006ｧ80ｹ014. 6ﾑ8apple06apple03 閨0807, 0707030809 0000 02080ｸ70ｹ0 02-030600030ｷ300 閨07080ｸ70ｹ0 apple030809070ｷ304020602086ｦ00ｹ0 apple 030709080702000ｹ0 apple080ｸ7 0001-0803 ｨB 07 02 0207 020907 09000003080009076ｧ9 02090ｹ0 060709070ｷ304090ｹ0, 02 0106-0708006ｧ8030902 07 0400 0607080803000ｹ0 080007 000ｹ0 fiapple0ｷ30ｹ0 08 6ｧ9070002 06 04020807 apple6ｧ907 02 1. O06 06 080803 閨0ｹ0 020ｷ307 0203060706020607 02 06 0003-09 0402090306 020607 apple 03 00 閨02030ｷ307 0707000004 0402060ｹ0 0ｸ7apple0802 0209-0908036ｧ9000ｹ0 020ｷ307 040300070607 00000300026ｧ8030902 07 0000 0209 08020600 046ｧ9 x 2 02 06 0208 Mann Whitney U test 02 06 09 0707030ｸ70409 02090ｹ0 040ｸ70404 閨020604090ｹ0 0000 0209 08020600 046ｧ9 Spearman ｯs rank test. ﾇ 0002026ｧ900090409 02090ｹ0 0003006ｦ0030003090ｹ0 07fi04080ｸ7 00apple066 56ｧ90ｷ304090ｹ0 (event-free survival, EFS) 閨09060700 0000 020907 00 閨0308 08 ﾒaplan-Meier 11. ﾇ 0003006ｦ003000309 07fi04080ｸ7 00apple066 56ｧ90ｷ30409 0ｸ7apple08-0308096ｧ90402090200 applefi 020907 09000003080009076ｧ9 02090ｹ0 060709070ｷ304090ｹ0, 00-040306 020907 09000003080009076ｧ9 02090ｹ0 020003000ｸ702 6ｧ9 0ｹ0 00apple6ｧ90402006 7090ｹ0 0906 閨0300090408 6ｧ8 00 閨040306 020907 09000003080009076ｧ9 apple080ｸ7 0ｸ7apple6ｧ8030400 040ｸ700-6 50707. 030ｹ0 040ｸ7006 50707 08036ｧ90402090200 09 apple08020ｸ7046ｧ9 0906 00apple6ｧ902000ｸ70109 apple036ｧ803080ｸ70ｹ0 6ｦ0080004090ｹ0 020907 33 09 0900 閨03 030003 apple006ｧ9 0ｹ0 ( apple08020ｸ7-046ｧ9 030003 apple006ｧ9 0ｹ0 0008fi 080ｸ7, 070300020206026ｧ8 03000ｸ704 06006ｧ9 ), 02 06 09 0ｸ7apple08020308apple6ｧ8. O06 06 080803 閨0ｹ0 0402 apple080408040207 00apple066 56ｧ90ｷ304090ｹ0 0000-02 016ｦ0 020ｷ307 06 08fi030ｷ307 080007 0ｷ307 020ｷ307 040300070607 00020206006ｧ80309-02 07 0000 0208 2-sided log-rank test. ﾇ apple030809070ｷ3040206026ｧ8 016ｧ9 020ｷ307 0203060706020607 02 06 000309 0402090306 020607 000002 6 50309020607 020ｷ307 040300070607 閨09060700 0000 020907 0707030ｸ70409 Cox-regression 12. O06 000002 6 5030902 閨0ｹ0 6ｧ802 07 08 03060300fi0ｹ0 03000ｸ7020607 0600080408 06036ｧ90ｷ307 ( ﾝ/<50x10 9 /L), 08 0708040808 0607fi020ｸ7apple080ｹ0 (ｦﾌ-O / ｦ - O ), 09 02 010607fi00090409 02 0207 NCI (0ｸ76 70903086ｦ0/04 000903086ｦ0 020607 6ｦ007080ｸ7) 02 06 08 0ｸ76 70903fi0ｹ0 6ｧ8 04 000903fi0ｹ0 006ｧ90202090ｹ0 閨020803-04090ｹ0 02080ｸ7 MDR1 09080706 6ｧ9080ｸ7. H 0402 0206040206026ｧ8 00apple0001000309-046ｧ9 020ｷ307 00 0800 閨070ｷ307 閨09060700 0000 0208 apple 02 閨0208 ｰSPSS for windows ｱ, (Statistical Package for Social Sciences, version 10.0). ﾞapple08020003 閨0400 02 ﾇ 060700000409 0206006ｧ8 02080ｸ7 046ﾑ8 0906 0208 MDR1 0908076ｧ9 0608 6ｧ802 07 0,35 (006ｦ003080ｹ0: 0,01-2,49). 086 70903fi0ｹ0 046ﾑ8 0906 0208 MDR1 0908076ｧ9 0608 6 503 閨03090200 0400 18 (36,7%) 04030007006ｧ90ｹ0. 6ﾑ8apple06apple03 閨0807, 09 閨020803 0409 02080ｸ7 MDR1 09080706 6ｧ9080ｸ7 6ｧ802 07 0402 020604020602060ｹ0 040900 0702060207 0ｸ76 70903fi02000309 0402080ｸ70ｹ0 04030007006ｧ90ｹ0 02090ｹ0 000003 閨02090ｹ0 00 0ｹ0 0400 0404 閨0409 0000 020907 080007 0003 閨0904080ｸ7.
13138 09 06 06 020306026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 A04030007006ｧ90ｹ0 Y6 70903fi0ｹ0 04E X 000903fi0ｹ0 04E M0703020ｸ703000ｹ0 6ﾑ80602. 2. 6ｾ402060202fi 06070903 0000 02090ｹ0 06 04apple0803070ｹ0 020ｷ307 0206000607 02080ｸ7 046ﾑ8 0906 0208 MDR1 0402080ｸ70ｹ0 04030007006ｧ90ｹ0 02090ｹ0 000003 閨02090ｹ0 00 0ｹ0 02 06 04020907 080007 0003 閨0904080ｸ7. ﾇ 040ｸ70700046ｧ80ｹ0 0903 00006ｧ8 0ｸ7apple08 000602076ｦ00006 0209 06070000-0409 0206006ｧ8 02080ｸ7 046ﾑ8. ｦ 08 06070903 0000 06 04apple0803070ｹ0 02090ｹ0 0206006ｧ80ｹ0 02080ｸ7 MDR1-09080706 6ｧ9080ｸ7 000002 016ｦ0 020ｷ307 040300070607 02 06 02090ｹ0 080007 0ｹ0 0003 閨0904080ｸ7 08 6ｧ9070002 06 04020907 000602fi07 2. ﾇ 040ｸ70407fi020902 02080ｸ7 0ｸ76 70903086ｦ0 6ｧ8 04 000903086ｦ0 046ﾑ8 0906 0208 MDR1 0908076ｧ9 0608 00 06 閨08000300 040900 0702060207 000002 016ｦ0 020ｷ307 06 08fi030ｷ307 080007 0ｷ307 020ｷ307 040300070607 0000 6 5070409 02080ｸ70ｹ0 02-030600030ｷ300 閨07080ｸ70ｹ0 apple030809070ｷ304020602086ｦ00ｹ0 apple 030709080702000ｹ0. 7002 07 030806applefi07, 08 046ﾑ8 0700010703020902080ｹ0 020ｷ307 0203060706020607 02 06 000309-0402090306 020607 04 03 0202090306040206020607 fiapple0ｷ30ｹ0 08 03060300fi0ｹ0 020ｷ307 03000ｸ7020607 0600080408 06036ｧ90ｷ307 (</ ﾝ50x 10 3 /L), 09 0206006ｧ8 02090ｹ0 LDH (</ ﾝ1000IU/L), 09 02 036ｧ8 6ｧ8 02 026ｧ8 0702 applefi0203060409 040209 0408036ｧ809090409 apple0300 0706ｨBfi07090ｹ0 (<1000 6 503070402000ｹ0/00L 6ｧ8 ﾝ1000 6 503070402000ｹ0/00L 020907 7 09 0900 閨03 030003 apple006ｧ9 0ｹ0, 07026ｧ9-0402080604 ), 09 02 010607fi00090409 02 0207 NCI 0400 080007 0ｸ76 70903086ｦ0 6ｧ8 0402 030003086ｦ0 020607 6ｦ007080ｸ7 02 06 08 ｦﾌ- 6ｧ8 ｦ -020ｸ70202 0306026ｧ80ｹ0 03-046ｧ80ｹ0 0708040808 0607fi020ｸ7apple080ｹ0 (6ﾑ80602. 3). ﾇ 閨020803 0409 02080ｸ7 MDR1 09080706 6ｧ9080ｸ7 6 503 閨03090200 fi0206 閨040006 040900 070206026ｧ8 00apple6ｧ9 03 0409 04020907 閨026 5 0409 020ｷ307 040300-070607 02090ｹ0 000003 閨02090ｹ0 00 0ｹ0. 03020406 030806applefi07, 09 apple0603 07fi020902 0003006ｦ0030003090ｹ0 07fi04080ｸ7 00apple066 56ｧ90ｷ304090ｹ0 020ｷ307 040300070607 0000 0ｸ76 709-03fi 046ﾑ8 6ｧ802 07 55,56% 0903 6ｧ8 0402 020604020602060ｹ0 040900 0702060207 0ｸ704000007 閨0402000309 0400 0404 閨0409 0000 02080ｸ70ｹ0 04030007006ｧ90ｹ0 0000 04 0009-03fi 046ﾑ8 02 06 apple0603 07fi020902 EFS 86,7% (p log rank: 0,03) (E0602. 4). 090002 016ｦ0 020ｷ307 18 040300070607 0000 0ｸ76 70903fi 046ﾑ8 0906 0208 MDR1 0908076ｧ9 0608, 4 (22,2%) 00000807070604 07 apple0306060009 000ｸ7000306026ｧ8 0ｸ7apple08020308apple6ｧ8 000706 0703030806 4 (22,2%) 0007 006ｧ904 07 apple036ｧ80309 閨08000409 020907 33 09 0900 閨03 030003 apple006ｧ9 0ｹ0. ﾇ 0707030ｸ70409 02090ｹ0 閨020803 04090ｹ0 02080ｸ7 MDR1 09080706 6ｧ9080ｸ7 000002 016ｦ0 020ｷ307 ｨB000ｸ7090607 020ｷ307 0006090007020ｷ307 020ｷ307 040300070607 apple080ｸ7 00036ｧ808030904 07 02 0207 0209 060709070ｷ30409 02 06 020907 0ｸ7apple08020308apple6ｧ8 02090ｹ0 07fi04080ｸ7, 陦00060100 fi0206 08 046ﾑ8 6ｧ802 07 040900 0702060207 0ｸ76 70903fi020003080ｹ0 02 0207 020907 0ｸ7apple08020308apple6ｧ8 02090ｹ0 07fi04080ｸ7 0400 0404-0409 0000 0209 060709070ｷ30409 02090ｹ0 07fi04080ｸ7 (6ﾑ80602. 5). 6ﾑ8apple06apple03 閨0807, 000002 016ｦ0 020ｷ307 31 ｨB000ｸ7090607 020ｷ307 0006090007020ｷ307 02 0207 0209 0607-09070ｷ30409 02 06 02 0207 020907 apple036ｧ80309 6ｦ008000409 02090ｹ0 07fi04080ｸ7, 08 046ﾑ8 02080ｸ7 MDR1 09080706 6ｧ9080ｸ7 6ｧ802 07 0402 020604020602060ｹ0 040900 0702060207 04 000903fi020003080ｹ0 02 0207 020907 6ｦ008000409 02090ｹ0 07fi04080ｸ7 0400 0404 閨0409 0000 0209 060709070ｷ30409 (6ﾑ80602. 6). 縺06 020907 0002026ｧ900090409 02080ｸ7 040400020602086ｦ0 020607 6ｦ007080ｸ7 (relative risk) 04030904060008apple08066ｧ803090200 09 Cox regression 0707-030ｸ70409 02 06 fiapple0ｷ30ｹ0 apple0308 閨020ｸ76 700 0806 04030007006ｧ90ｹ0 0000 0ｸ76 70903fi 046ﾑ8 0906 0208 MDR1 0908076ｧ9 0608 006ｧ904 07 3,34 080803 閨0ｹ0 0ｸ76 70903fi02000308 040400020602fi 026ｧ907 0ｸ70708 07 000008 076ｧ904080ｸ707 0ｸ7apple08020308apple6ｧ8 6ｧ8 0009 00apple6ｧ902000ｸ70109 6ｦ0080004090ｹ0 (096ｧ907. 2). 6ｾ40ｸ7ｨB6ｧ802090409 ｦ 060ｹ0 020003000ｸ702 6ｧ9000ｹ0 0002 00026ｧ9000ｹ0 閨040006 040ｸ707020003000402006ｧ9 0409-00 070206026ｧ8 apple03fi08 080ｹ0 040209 030003 apple006ｧ9 02090ｹ0 O. ﾞ0ｸ702fi 0808006ｧ9030002 06 020ｸ7036ｧ90ｷ30ｹ0 04020907 07 09070603060409 apple030809070ｷ3040206020607 apple 03 09fi07020ｷ307, 04020907 02 020702 0109 040300070607 0400 080007 000ｹ0 020607 6ｦ007080ｸ7 0000 6 5070409 0ｸ702086ｦ00ｹ0, 02 06 020907 070703080909 0707- apple020ｸ70109 030003 apple000ｸ70206020607 040203 02090906020607. 0900 0209 04036ｧ80409 030806applefi07 046ｦ009040308070ｷ307, 000702 02060208apple08060900 閨070ｷ307 apple08030ｸ7-0409- 00000608030003 apple000ｸ70206020607 apple030ｷ3020802fi03030ｷ307 02 apple080408040207 00apple06-6 56ｧ90ｷ304090ｹ0 apple 06 060607 0000 O 020ｸ700 6ｧ907080702 06 閨0ｷ30ｹ0 80% 13-20. 09 03 ｯ fi03 0ｸ70207 apple00036ｧ9apple080ｸ7 25-30% 020ｷ307 apple 06 060607 03 0ｸ7apple08020308apple060704080ｸ707 20-21. 6ﾑ86ｧ907 06 0302000207 0007 06 08 閨030807 fi0206 09 0707030ｸ70409 020ｷ307 04 03 0202090306040206020607 0ｸ7020607 020ｷ307 040300-070607 006ｧ904070006 fi0206 閨07 0ｹ0 040900 07020602fi0ｹ0 03060300fi0ｹ0 0ｸ7020607 076ｧ8020006 04020907 080007 6 5 040602086ｦ0 02 06 0007 0607000004080ｸ7 020607 6ｦ0-096ｧ907 02 0ｹ0 2. 09030809070ｷ304020602086ｧ9 apple 030709080702000ｹ0 02 06 040400020602fi0ｹ0 026ｧ907 0ｸ707080ｹ0 090002 6 50309026ｧ8 95% 04060704020900 6ｾ40400020602fi0ｹ0 ﾒ6ｧ907 0ｸ707080ｹ0 p ﾞ010608apple0604026ｧ9 0ｹ0 (Relative Risk,RR) 086 70903fi0ｹ0 04006ｧ90202090ｹ0 閨020803 04090ｹ0 MDR1 1,02-11,34 3,34 0,04 WBC ﾝ50x10 9 /L 1,35-12,23 3,89 0,03 086 70903086ｦ0 020607 6ｦ007080ｸ7 02 0207 03CI 0,39-6,63 1,61 0,5 T-O 0,35-2,46 0,93 0,8
1309 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 19, 2 139 100 WBC < 5000/L WBC ﾝ 5000/L 100 90 77,8 85,2 80 p > 0,05 80 70 80,6 77,8 p > 0,05 B-O T-O 60 60 50 40 40 30 20 22,2 14,8 20 19,4 22,2 10 0 A X 000903fi0ｹ0 04E Y6 70903fi0ｹ0 04E 0 B X 000903fi0ｹ0 04E Y6 70903fi0ｹ0 04E 100 NCI B 040602086ｦ0 020607 6ｦ007080ｸ7 NCI Y6 70903086ｦ0 020607 6ｦ007080ｸ7 100 PGR(<10006 503070402000ｹ0/00L) PPR( ﾝ10006 503070402000ｹ0/00L) 80 63,3 p > 0,05 61,1 80 81,8 66,7 60 40 36,7 38,9 60 40 p > 0,05 33,3 20 20 18,2 0 ｦ 0 X 000903fi0ｹ0 04E Y6 70903fi0ｹ0 04E X 000903fi0ｹ0 04E Y6 70903fi0ｹ0 04E ｦ 6ﾑ80602. 3. 09080408040206 6ｧ9000ｹ0 07 0308096ｧ9000ｹ0 % 020ｷ307 040300070607 02 0207 0209 060709070ｷ30409 0400 0404 閨0409 0000 020807 03060300fi 020ｷ307 03000ｸ7020607 0600080408 06036ｧ90ｷ307 ( ﾞ), 020807 0708040808 0607fi020ｸ7apple08(ｦﾌ), 020907 02 010607fi00090409 0400 080007 000ｹ0 020607 6ｦ007080ｸ7 02 0207 NCI ( ), 020907 0702 applefi0203060409 04020907 apple0300 0706ｨBfi0709 (04), 02 06 0208 046ﾑ8 02080ｸ7 MDR1 09080706 6ｧ9080ｸ7. pefs 1,0 0,8 0,6 0,4 0,2 0,0 MDR1 p log rank = 0,03 X 0009036ｧ8 閨020803 0409 Y6 709036ｧ8 閨020803 0409 0 10 20 30 40 M6ｧ807000ｹ0 6ﾑ80602. 4. 0406070903 0000 02090ｹ0 Kaplan Meier 0707030ｸ704090ｹ0 02090ｹ0 apple0603 07fi- 020902 0ｹ0 0003006ｦ0030003090ｹ0 07fi04080ｸ7 00apple066 56ｧ90ｷ304090ｹ0 (pefs) 0707000004 0402080ｸ70ｹ0 04030007006ｧ90ｹ0 0000 0ｸ76 70903fi 02 06 04 000903fi 046ﾑ8 0906 0208 MDR1 0908076ｧ9 0608. 07080ｸ7 fiapple0ｷ30ｹ0 0ｸ7026ｧ8 apple0308026ｦ0apple020006 0000 6 5070409 02080ｸ70ｹ0 02 030600030ｷ3-00 閨07080ｸ70ｹ0 apple030809070ｷ304020602086ｦ00ｹ0 apple 030709080702000ｹ0. 090608 040ｸ7090200020306-00 閨07, 046ｦ000080ｷ307 0000 02 apple08020003 閨0400 02 02090ｹ0 080007 0ｹ0 02080ｸ7 BFM 90, 50% 020ｷ307 0ｸ7apple08020308apple0607 apple 03080ｸ7040607040209-02 07 0402080ｸ70ｹ0 04030007006ｧ90ｹ0 0000 020806076ｧ8 O 02 06 70% 0707-04006ｧ90202090ｹ0 閨020803 04090ｹ0 MDR1 1,4 1,2 1 0,8 0,6 0,4 0,2 0 04060709070ｷ30409 1,29 1,14 0,93 0,59 Yapple08020308apple6ｧ8 6ﾑ80602. 5. 0406070903 0000 0206000607 02080ｸ7 046ﾑ8 02080ｸ7 MDR1 09080706 6ｧ9080ｸ7 0402 4 02 0207 ｨB006ｦ00909 006ｧ90900 02 060709070ｷ304090ｹ0 02 06 0ｸ7apple08020308apple6ｧ80ｹ0 020ｷ307 040300070607 02090ｹ0 000003 閨02090ｹ0.
13140 09 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 19, 2 MDR1mRNA/6 5-02026ｧ90709 3,0 2,5 2,0 1,5 1,0 0.5 0,0-0,5 04060709070ｷ30409 p < 0,05 6ｨ808000409 6ﾑ80602. 6. Box plot 06070903 0000 02080ｸ7 046ﾑ8 02080ｸ7 MDR1 09080706 6ｧ9080ｸ7 0402 31 02 0207 ｨB006ｦ00909 006ｧ90900 02 060709070ｷ304090ｹ0 02 06 apple036ｧ803080ｸ70ｹ0 6ｦ00800-04090ｹ0 020ｷ307 040300070607 02090ｹ0 000003 閨02090ｹ0 00 0ｹ0. 000004 0402080ｸ70ｹ0 04030007006ｧ90ｹ0 0000 02 036ｧ8 0702 applefi0203060409 040209 apple0300 0706ｨBfi0709 20. 0003 0ｸ70207 0ｸ7apple08 09030607080ｸ707 fi0206 09 04036ｧ80409 020ｷ307 02 030600030ｷ300 閨070ｷ307 apple030809070ｷ3040206020607 apple 03 09fi07020ｷ307 0ｸ707 02006ｧ9 07 apple03086 503 閨6 70006 apple036ｧ8030ｷ30ｹ0 020807 026ｧ907 0ｸ70708 00000807-070604090ｹ0 0ｸ7apple08020308apple6ｧ80ｹ0. ﾞ016ｧ9ｨB0006 07 04090000060604080ｸ70000 fi0206 09 0ｸ7apple08020308apple6ｧ8 02090ｹ0 O 000008 076ｧ9ｨB0002 06 0000 040ｸ70407fi020902 00000807070604090ｹ0 9,3 07-000ｹ0 apple000306apple02060400060ｹ0 0707 10 6 apple 06 0607 000209046ｧ90ｷ30ｹ0 02 02 020704-04080702 0ｹ0 020907 0ｷ30ｹ0 020907 02 閨02 030209 040ｸ70407fi02000309 02 02086ｧ80309 07fi- 0408 02090ｹ0 apple 06 06026ｧ80ｹ0 090306026ｧ9 0ｹ022. ﾇ 040ｸ70407fi02090207 02090ｹ0 006ｧ907 06 apple 03fi000806 0000 0ｸ7026ｧ8 020ｷ307 040ｸ700apple 090607 fi09020ｷ307 02 06 0ｸ76 709-03fi02000309 applefi 0ｸ7026ｧ8 02090ｹ0 O09 0402 apple 06 0607 21. ﾇ apple03fi- 09070ｷ3046ｧ8 02090ｹ0 fi000ｷ30ｹ0, 006ｧ907 06 0001 06030002060207 0ｸ7040000076ｧ80ｹ0 02 06 09 00apple066 56ｧ90ｷ30409 020ｸ700 6ｧ9070002 06 applefi 8-65% 19. ﾞ0ｸ7026ｧ8 09 06 026ｦ0-00 070409 040400026ｧ9ｨB0002 06 0000 020807 026ｦ0apple08 0ｸ7apple08020308apple6ｧ80ｹ0 0000 6 5070409 0208 0403fi0708 000008070706046ｧ80ｹ0 02090ｹ0. 03020406 030806applefi07, 0806 apple03060600000ｹ0 0ｸ7apple08020308apple 閨0ｹ0 0903 6ｧ8 0ｸ702 閨0ｹ0 apple080ｸ7 000008 076ｧ9ｨB080702 06 0400 040308070602fi 060704020900 006ｧ90200 00060203fi02000308 applefi 18 006ｧ807000ｹ0 applefi 0209 060709070ｷ30409 006ｧ90200 0400 060704020900 000009 036ｦ002000308 applefi 18 006ｧ807000ｹ0 applefi 0209 060709070ｷ30409 030307 00060203fi02000308 applefi 6 006ｧ807000ｹ0 applefi 020907 08030802036ｧ8030ｷ3046ｧ8 02090ｹ0 030003 apple006ｧ9 0ｹ0 0008fi 080ｸ7, 000008 076ｧ9ｨB080ｸ707 0209 04000603fi02000309 apple03fi09070ｷ30409 0000 apple080408040207 apple080ｸ7 0007 0100apple000307086ｦ007 0208 10% 22. ﾞ07026ｧ9030002 0806 apple06020003000ｹ0 0ｸ7apple08020308apple 閨0ｹ0 0000 apple080408040207 00apple066 56ｧ90ｷ304090ｹ0 閨0ｷ30ｹ0 65% (040308070602fi 060704020900 >6 006ｧ807000ｹ0 applefi 020907 08030802036ｧ8-030ｷ30409 02090ｹ0 030003 apple006ｧ9 0ｹ0) 閨04080ｸ707 02 036ｦ002000309 000007 030307 070206020006000007060207 0ｸ7040000076ｧ8 apple03fi09070ｷ30409 0400 0404 閨0409 0000 02060ｹ0 apple03060600000ｹ0 0ｸ7apple08020308apple 閨0ｹ0. ﾇ 06 08080307 020ｷ307 apple08040804020607 00apple066 56ｧ90ｷ304090ｹ0 000002 016ｦ0 020ｷ307 apple030606000ｷ307 02 06 apple060200030ｷ307 0ｸ7apple08020308apple0607 0702 07-020307 0209 0404 閨0409 000002 016ｦ0 02080ｸ7 026ｦ0apple080ｸ7 02090ｹ0 0ｸ7apple08020308apple6ｧ80ｹ0 02 06 02080ｸ7 apple 030809000700020602086ｦ0 000904 07060400086ｦ0 02090ｹ0. O06 apple06020003000ｹ0 0ｸ7apple08020308apple 閨0ｹ0 03000ｷ303006ｧ902 06 fi0206 apple0308026ｦ0apple02080ｸ707 applefi 03000ｸ704 06-00060207 026ｦ00202 03 apple080ｸ7 03 0303086 506086ｦ007 0400 03 閨0400060ｹ0 02 02 086ｦ0-0906 02 06 0001 apple030607080702 06 01 0707 fi02 07 0402 00 026ｧ8040006 09 apple6ｧ900-0409 02090ｹ0 040900000608030003 apple006ｧ9 0ｹ021. ﾞ07026ｧ9030002 0806 apple03060600000ｹ0 0ｸ7apple08020308apple 閨0ｹ0 0808006ｧ903080702 06 0400 00030306apple6ｧ8 020703 030409 02080ｸ7 000ｸ700-03086ｦ0 applefi 03000ｸ704 06000602086ｦ00ｹ0 02030607080ｸ70ｹ0 07030002020602086ｦ00ｹ0 040209 030003 apple006ｧ9 21. ﾇ apple08030ｸ708 0300 02000ｸ70206026ｧ8 070208046ｧ8 (multidrug resistance, MDR) apple08020003006ｧ9 020907 020ｸ70306fi02000309 06026ｧ9 0000-0807070604090ｹ0 apple03060600090ｹ0 0ｸ7apple08020308apple6ｧ80ｹ0. ﾇ apple03060209 07 08080307 040209 08 0300 02000ｸ70206026ｧ8 070208046ｧ8 閨09060700 0208 1950 0400 03000ｸ704 06-00060207 026ｦ00202 03 00apple6ｧ9000ｸ70ｷ307 02 08apple086ｧ9 00000807070604 07 070208046ｧ8 040208 4-00060708-0310-0000030ｸ703-apple020003080903080ｸ702 000602fi 08016ｦ0 0402 apple03 6ｧ90406 apple000603 00 020602086ｦ0 00080702 閨03080ｸ723. ｦ 08 1973, 0806 Dano 02 06 040ｸ7070003090702000ｹ0 07 0207030ｸ76 7 07 020907 apple08000702030ｸ7070409 02090ｹ0 080ｸ70708000ｸ7026ｧ907090ｹ0 applefi 0703000202060207 026ｦ00202 03 apple080ｸ7 000008070706ｨB 07 070208046ｧ8 02 06 0400 070303080ｸ70ｹ0 040900000608030003 apple000ｸ7-020602086ｦ00ｹ0 apple 030709080702000ｹ0, fiapple0ｷ30ｹ0 02 0302 03080006 6ｧ8 02090ｹ0 vinca 02 06 070303000ｹ0 070303 020ｸ702036ｧ907000ｹ024. ｦ 08 0908076ｧ9 0608 apple080ｸ7 020ｷ3 06-0208apple0806006ｧ9 020907 P-gp 04 0302080903 086ｧ803090200 040208 7q21.1 04030ｷ3-00fi040ｷ300 02 06 02 0ｸ70208apple08066ｧ803090200 0ｷ30ｹ0 MDR1 25. 6ﾑ86ｧ907 06 0006 170kDa apple030ｷ302000ｹ10709 apple080ｸ7 apple08020003006ｧ902 06 applefi 2 0800fi030809 02006ｧ800 02, 0208 02 03 閨07 020ｷ307 08apple086ｧ90ｷ307 apple000306 閨040006 閨0106 0ｸ7 03fi- 08086 5 06 0000006 503 07060207 02006ｧ800 02 02 06 006ｧ9 apple00030608046ｧ8 046ｦ007 0004090ｹ0 02080ｸ7 ﾞｦ 06 26. 6ﾑ86ｧ907 06 00 閨03080ｹ0 02090ｹ0 000ｸ7036ｦ0020003090ｹ0 0806020809 閨070006 0ｹ0 020ｷ307 ABC-apple030ｷ302000ｸ8070607. O 000904 07060400fi0ｹ0 0000 020807 08apple086ｧ908 0003 020206070006 020907 0007-08020ｸ70202070306 040ｸ70902 閨0702030ｷ30409 020ｷ307 070303 020ｸ7020306070607, 02090ｹ0 0006020801 070203fi07090ｹ0, 020ｷ307 02 01 070607, 020ｷ307 00apple06apple08 08080ｸ703080208-0106070607 02 06 020ｷ307 0302 03080006 0607 02090ｹ0 vinca, 0007 閨040006 apple036ｧ8030ｷ30ｹ0 06000ｸ702030607060402006ｧ9. ﾇ 020ｸ7036ｧ9 030409 07026ｧ903096 709 006ｧ907 06 fi0206 0806 0306applefi0806030806 040900000608030003 apple000ｸ7020602086ｧ9 apple 030709080702000ｹ0 apple0800 02036ｦ007080702 06 applefi 0208 020ｸ70202 03fiapple03 0400 06 00 閨04080ｸ7 0007fi0ｹ0 02 07 0306086ｦ0 apple080ｸ7 04040900 026ｧ9ｨB0002 06 applefi 02 06 000000-6 503 07060207 02006ｧ800 0207 02090ｹ027,28. 6ﾑ802080307ｨB0002 06 0400 06070808-03080ｸ70ｹ0 080ｸ70406080308090602086ｦ00ｹ0 060402086ｦ00ｹ0 0000 03000602080ｸ703096ｧ9000ｹ0 0803 09-00086ｦ0 6ｧ8 apple 閨0202030604090ｹ0, 040ｸ700apple00030603 006 5 070800 閨07080ｸ7 02080ｸ7 apple07006ｦ0000807, 02080ｸ7 apple03 02086ｦ00702, 020ｷ307 fi0304000ｷ307, 020ｷ307 0700-08030607, 02080ｸ7 6ｧ8apple 02080ｹ0, 02080ｸ7 apple 090203 陦 02080ｹ0 02 06 02080ｸ7 00090200-080703080ｸ729-30. 6ﾑ8apple06apple03 閨0807, 0002080307ｨB0002 06 0402 060008apple0806090206-0207 apple0308090807060207 026ｦ00202 03 02 06 0402 0300000808026ｦ00202 03 31-32. 0003 0ｸ70207 02 000ｸ7036ｧ800 02 040ｸ70709090803086ｦ007 fi0206 09 06-gp apple 6ｧ9ｨB0006 040900 07020602fi 03fi0308 04020907 apple086 508036ｧ8 02 06/6ｧ8 000002-08080307 020ｸ70202 030802080106020607 010007086 506080206020607. ﾞ07 02 06 閨04080ｸ707 060003000ｸ7070903006ｧ9 06070808030806 000904 07060400086ｧ9 0400 020ｸ70202 030602 閨0ｹ0 04000603 閨0ｹ0, 09 0203060706026ｧ8 02080ｸ70ｹ0 040900 046ｧ9 0007 閨040006 apple036ｧ8030ｷ30ｹ0 06-000ｸ702030607060402006ｧ9. 6ｾ4020907 apple 03086ｦ004 000309 046ｧ9 00000300026ｧ803090200 09 閨020803 0409 m-rna 000002 0903 08090007020ｷ307 0400 閨07 07 08000806-
1309 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 19, 2 141 080900076ｧ8 apple0309030ｸ70400fi 0000 apple0804080402fi 000009 036ｦ002000308 02080ｸ7 80% 0400 6 503070402000ｹ0 02 0207 0209 060709070ｷ30409 02090ｹ0 07fi04080ｸ7, 06040200 02 apple08020003 閨0400 0207 00 0ｹ0 07 0702 07 0203086ｦ007 閨07 0ｸ7apple 030202fi 6 506080308090602fi 08 0607fi00000708. ﾇ 0ｸ7apple0003 閨020803 0409 02090ｹ0 apple030ｷ302000ｹ107090ｹ0 apple080ｸ7 020ｷ3 060208apple0806006ｧ9 0208 MDR1 0908076ｧ9 0608 0402080ｸ70ｹ0 00076ｧ8030602000ｹ0 0000 0801006ｧ9 03000ｸ704 06006ｧ9 006ｧ907 06 040ｸ704076ｧ8 02 06 020ｸ700 6ｧ9070002 06 applefi 22% 閨0ｷ30ｹ0 47% 02 06 040400026ｧ9ｨB0002 06 0000 020907 apple08020ｸ7046ｧ9 00apple6ｧ902000ｸ701090ｹ0 apple036ｧ803080ｸ70ｹ0 6ｦ0080004090ｹ0 02 06 04 000903fi apple0804080402fi 00apple066 56ｧ90ｷ304090ｹ033-34. 6ｾ4020907 apple 06 06026ｧ8 O 02 0900080406000ｸ700 閨07 apple080408040207 閨020803 04090ｹ0 020ｸ700 6ｧ907080702 06 applefi 14% 閨0ｷ30ｹ0 50% 020ｷ307 040300070607 35-36. 6ｾ400 07020604020806046ｧ9 0000 0ｸ70207 02 000ｸ7036ｧ800 02, 0ｸ76 709036ｧ8 閨020803 0409 02080ｸ7 MDR1 09080706 6ｧ9080ｸ7 040209 000003 閨0209 00 0ｹ0 6 503 閨03090200 0400 18 04030007006ｧ90ｹ0, apple0804080402fi apple080ｸ7 070206-0402080604006ｧ9 0400 36,7% 020ｷ307 040300070607. 6ｾ400 03020002 閨0ｹ0 000003 閨02000ｹ0 apple 06 060607 0000 O 02 0ｸ70109-00 閨07 00apple6ｧ9apple00 02090ｹ0 閨020803 04090ｹ0 02090ｹ0 P-gp 006ｧ90200 0400 00apple6ｧ9- apple00 08 apple030ｷ302000ｹ107090ｹ0 006ｧ90200 0400 00apple6ｧ9apple00 08 mrna 000002 0903-08090007020ｷ307 fiapple0ｷ30ｹ0 00apple6ｧ904090ｹ0 02 06 09 0ｸ7010900 閨0709 03000602080ｸ7030906-02fi020902 02090ｹ0 P-gp 040400026ｧ9ｨB080702 06 0000 040900 0702060207 0ｸ7040000-076ｧ8 閨026 5 0409 35,37-39. 6ｾ400 040ｸ700080ｷ3076ｧ9 0000 02 apple08020003 閨0400-02 020ｷ307 070ｷ302 閨030ｷ3 0003000ｸ7070607, 040209 000003 閨0209 00 0ｹ0 02 apple 06-0607 0000 0ｸ76 70903fi 006ｧ9020209 閨020803 04090ｹ0 (046ﾑ8) 0906 0208 MDR1 0908076ｧ9 0608 006ｧ904 07 0402 020604020602060ｹ0 040900 0702060207 04 000903fi02000308 apple0804080402fi 0003006ｦ0030003090ｹ0 07fi04080ｸ7 00apple066 56ｧ90ｷ304090ｹ0 0400 0404 閨0409 0000 02 apple 06 0607 0000 04 000903fi 046ﾑ8. ｦﾐ 06 6ｧ902000308 0007 06 08 閨030807 apple 03080ｸ7040607ｨB0006 0208 0900090807fi0ｹ0 fi0206 07 02 06 09 0ｸ76 709036ｧ8 閨02-0803 0409 02080ｸ7 MDR1 09080706 6ｧ9080ｸ7 apple0308 閨020ｸ76 700 fi0206 006ｧ907 06 0ｸ7-040000076ｧ80ｹ0 apple030809070ｷ304020602fi0ｹ0 apple 030709080702 0ｹ0, 00 040400026ｧ9ｨB080702 07 0000 020907 閨020803 0409 0703030ｷ307 02 030600030ｷ300 閨070ｷ307 0ｸ7040000070607 apple030809070ｷ3040206020607 apple 03 09fi07020ｷ307 fiapple0ｷ30ｹ0 08 0ｸ7010900 閨07080ｹ0 03060300fi0ｹ0 020ｷ307 03000ｸ7020607 0600080408 06036ｧ90ｷ307, 09 0ｸ7010900 閨0709 0206-006ｧ8 02090ｹ0 LDH, 08 ｦ -020ｸ70202 0306026ｧ80ｹ0 03046ｧ80ｹ0 0708040808 0607fi020ｸ7apple080ｹ0, 09 02 020702 0109 0400 080007 0ｸ76 70903086ｦ0 020607 6ｦ007080ｸ7 02 06 09 02 026ｧ8 apple070702090409 040209 apple0300 0706ｨBfi0709. ﾒ 0207 040ｸ707 鐶pple0006, 0208 006ｦ0030900 0ｸ702fi 00070604046ｦ00006 020907 apple030809070ｷ3040206026ｧ8 0604046ｦ0 02090ｹ0 0ｸ76 709036ｧ80ｹ0 閨020803 04090ｹ0 02080ｸ7 MDR1 09080706 6ｧ9080ｸ7 02 06 040ｸ70709-090803006ｧ9 fi0206 09 apple030809070ｷ3040206026ｧ8 02080ｸ7 016ｧ9 006ｧ907 06 07000107030209-0209 applefi 070303 02030607060207 02 06 000309 0402090306 0207 000ｸ7036ｧ800 02. 6ﾑ8apple06apple03 閨0807, 0208 006ｦ0030900 0ｸ702fi 閨040006 00apple066 5006 5 060ｷ303006ｧ9 02 06 0400 070303000ｹ0 000003 閨02000ｹ039-40. ｦﾐ 06 6ｧ902000309 040900 046ｧ9 閨040006 0208 0900090807fi0ｹ0 fi0206 02 0207 020907 0ｸ7apple08020308apple6ｧ8 02090ｹ0 07fi04080ｸ7 6 503 閨03090200 0ｸ7010900 閨0709 09 閨02-0803 0409 02080ｸ7 MDR1 09080706 6ｧ9080ｸ7 0400 0404 閨0409 0000 0209 0607-09070ｷ30409 02090ｹ0 07fi04080ｸ7. ｦ 08 apple0802 閨03000400 0ｸ702fi 006ｧ907 06 0400 040ｸ700080ｷ3076ｧ9 0000 02 apple08020003 閨0400 02 020ｷ307 Tafuri 02 06 040ｸ707., 0806 08apple086ｧ90806 02 0207 020907 0ｸ7apple08020308apple6ｧ8 02090ｹ0 07fi04080ｸ7 07 08 閨03080ｸ707 0ｸ7010900 閨0709 apple086 508036ｧ8 02090ｹ0 04030ｷ3040206026ｧ80ｹ0 Rhodamine, 09 08apple086ｧ9 04030904060008apple0806006ｧ902 06 0906 0209 000003 閨0209 02080ｸ7 08 06070800-07080ｸ7 02090ｹ0 MDR 38. 6ﾑ86ｧ907 06 0400 07020604020806046ｧ9 00apple6ｧ904090ｹ0 0000 02 apple08020003 閨0400 02 020ｷ307 00000300020607 020ｷ307 Dhooge 02 06 040ｸ707., 02 06 Wuchter 02 06 040ｸ707., 046ｦ000080ｷ307 0000 02 08apple086ｧ9 06 apple06-040206030902 07 0ｸ7010900 閨07 00apple6ｧ9apple00 02090ｹ0 P-gp 0400 006ｧ90900 02 02 0207 020907 0ｸ7apple08020308apple6ｧ8 0400 0404 閨0409 0000 006ｧ90900 02 040300070607 apple080ｸ7 6 5036ｧ90402080702 07 0400 040ｸ707000406ｨBfi00000709 apple036ｧ80309 6ｦ008000409 35,39. 09 03fi03 0ｸ70207, 0ｸ7apple070304080ｸ707 000003 閨02000ｹ0 0806 08apple086ｧ9000ｹ0 0007 02-02 000602076ｦ0080ｸ707 apple030809070ｷ3040206026ｧ8 016ｧ9 04020907 0ｸ7apple0003 閨020803-0409 02o0ｸ7 MDR1 09080706 6ｧ9080ｸ736,42-43. ﾞ0ｸ70207 02 0702060203080ｸ7fi- 000007 apple08020003 閨0400 02 0702 07 0203086ｦ007 02060ｹ0 06 08080300020602 閨0ｹ0 000003fi 080ｸ70ｹ0 apple080ｸ7 閨04080ｸ707 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O06 04030007006ｧ90ｹ0 00apple0803006ｧ9 07 000008 07060402086ｦ007 0000 apple030ｷ30208apple 036ｧ8 070208046ｧ8 02 0207 020907 030406-026ｧ8 060709070ｷ30409 02090ｹ0 07fi04080ｸ7 6ｧ8 07 07 apple026ｦ001080ｸ707 070208046ｧ8 040209 060703020006 02090ｹ0 030003 apple006ｧ9 0ｹ0 6ｧ8 02 0207 020907 0ｸ7apple08020308apple6ｧ8 02090ｹ0 07fi04080ｸ7 (00apple6ｧ90202090209 070208046ｧ8) 46. 08apple070304080ｸ707 0803060400-07000ｹ0 apple030800apple0803 閨0400060ｹ0 apple080ｸ7 03 apple03 鐶pple0006 07 apple030903086ｦ00702 06 apple030802000600 閨07080ｸ7 07 00 03 060ｷ303006ｧ9 09 0203060706026ｧ8 040900 046ｧ9 02090ｹ0 apple08030ｸ708 0300 02000ｸ70206026ｧ80ｹ0 070208046ｧ80ｹ0 02 06 apple00030603 006 50707080ｸ707 0304060207 020907 07 09070603060409 02090ｹ0 閨020803 04090ｹ0 0007fi0ｹ0 040ｸ7090200-02030600 閨07080ｸ7 000904 07060400086ｦ0 0400 006ｧ90900 02 applefi 02 02086ｧ80309 026ｦ00202 03 020ｷ307 040300070607 02 06 000ｸ7020003000ｸ7fi07020ｷ30ｹ0 09 閨02-0803 0409 0ｸ702086ｦ0 02080ｸ7 000904 07060400086ｦ0 07 040400026ｧ9ｨB0002 06 0000 020907 0203060706026ｧ8 閨026 5 0409 0ｸ7020607 020ｷ307 040300070607. 6ｾ4020907 apple 03086ｦ0-04 000003 閨0209 02 036ｦ008030902 07 0ｸ702 閨0ｹ0 0806 apple030800apple0803 閨0400060ｹ0 02-03060ｹ0 09 000003 閨0209 閨09060700 0400 08000806080900076ｧ8 apple0309030ｸ70400fi 6 503-040206020607 020ｸ7020207030ｷ307 02 06 0000 0209 04036ｧ80409 02090ｹ0 PCR 07026ｧ9-03 04090ｹ0 07 09070ｷ3036ｧ90402090200 fi0206 09 0ｸ7apple0003 閨020803 0409 02080ｸ7
13142 09 06 06 020306026ｧ8 B ﾌ066ﾑ8I ﾌ08 6ﾑ8 ﾞ04 ﾌ6ｾ4, 19, 2 MDR1 09080706 6ｧ9080ｸ7 00apple0803006ｧ9 07 02 0308036ｧ9040006 020907 閨026 5 0409 020ｷ307 040300070607. 6ﾑ8apple06apple03 閨0807, 046ｦ000080ｷ307 0000 02 000ｸ7036ｧ800 0207 00 0ｹ0 09 0ｸ7-010900 閨0709 閨020803 0409 02080ｸ7 09080706 6ｧ9080ｸ7 MDR1 02 0207 0209 0607-09070ｷ30409, apple080ｸ7 090306070006 apple030ｷ30208apple 036ｧ8 070208046ｧ8, 006ｧ907 06 閨07 0ｹ0 0ｸ7040000076ｧ80ｹ0 apple030809070ｷ304020602fi0ｹ0 apple 030709080702 0ｹ0 02 06 040400-026ｧ9ｨB0002 06 07000004 0000 020907 0009 00apple6ｧ902000ｸ70109 apple036ｧ803080ｸ70ｹ0 6ｦ0080004090ｹ0 6ｧ8 020907 0000080707060409 0ｸ7apple08020308apple6ｧ80ｹ0. 6ﾑ80202fi0ｹ0 fi000ｷ30ｹ0 0ｸ702086ｦ0 02 06 02 0207 0209 08070409 02090ｹ0 0ｸ7apple08020308apple6ｧ80ｹ0 02090ｹ0 07fi04080ｸ7 ( 000ｸ702000308apple 036ｧ80ｹ0 070208046ｧ8) 09 閨020803 0409 02080ｸ7 09080706 6ｧ9080ｸ7 MDR1 6ｧ802 07 0ｸ7010900 閨0709 0400 0404 閨0409 0000 0209 060709070ｷ30409 02090ｹ0 07fi- 04080ｸ7. 03020406 030806applefi07, 09 apple08030ｸ708 0300 02000ｸ70206026ｧ8 070208046ｧ8 04020907 apple 06 06026ｧ8 O 006ｧ907 06 閨07 0ｸ7apple 030202fi 02 06 07 09070ｷ3-036ｧ904060008 6 506080308090602fi 08 0607fi00000708, apple080ｸ7 apple08020003006ｧ9 0006 applefi 02060ｹ0 apple030ｷ302 03040602 閨0ｹ0 06026ｧ9000ｹ0 02090ｹ0 030003 apple000ｸ70206026ｧ80ｹ0 apple08-020ｸ7046ｧ9 0ｹ0. 6ﾑ8apple06apple03 閨0807, 046ｦ000080ｷ307 0000 0208 040308070602fi 0607040209-00 apple 03 020803086ｦ0030904090ｹ0 020ｷ307 040300070607 02 036ｦ06 7 0000 0208 08 0607fi00000708 020ｷ307 apple030606000ｷ307 0ｸ7apple08020308apple0607, 0806 08apple086ｧ9000ｹ0 fiapple0ｷ30ｹ0 6ｧ8 09 07 08 閨03 0000 閨04080ｸ707 0209 0ｸ704000007 閨0402000309 apple03fi- 09070ｷ30409 02 06 006ｧ907 06 0ｸ702 閨0ｹ0 apple080ｸ7 02 02000108046ｧ807 040400026ｧ9ｨB080702 06 0000 0208 08 0607fi00000708 02090ｹ0 apple08030ｸ708 0300 02000ｸ70206026ｧ80ｹ0 070208046ｧ80ｹ0. ﾇ 07 09070603060409 02 06 020ｸ7036ｧ90ｷ30ｹ0 09 07 04020308086ｧ8 0ｸ702086ｦ0 02080ｸ7 08 06070800 閨07080ｸ7 apple08020003006ｧ9 閨07 07 applefi 02080ｸ70ｹ0 020ｸ70306fi020003080ｸ70ｹ0 0402fi04080ｸ70ｹ0 02080ｸ7 040400 06 0400086ｦ0 020ｷ307 0000030308070206020607 030003 - 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