ROLE OF STROMAL FIBROBLASTS INTERACTION WITH PROSTATIC CANCER CELLS IN ACHIEVEMENT OF METASTATIC PHENOTYPE.

Eur Urol Suppl 2010;9(2):114

YRLGLQJORZHVWYDOXHDQGUHWXUQHGWR!ZLWKLQVHFRQGV(LJKWZHHNV DIWHUREVWUXFWLRQVDWXUDWLRQZDVVLJQLᚏFDQWO\SXQSDLUHGVWXGHQWWWHVWORZHU FRPSDUHG WR WKH VKDP JURXS ERWK GXULQJ ᚏOOLQJ ORZHVW YDOXH  DQG YRLGLQJ ORZHVWYDOXH7KHGHFUHDVHZDVSRVLWLYHO\UHODWHGWREODGGHUSUHVVXUHERWK GXULQJᚏOOLQJDQGYRLGLQJDQGZDVVWURQJHVWZKHQRYHUDFWLYLW\ZDVSUHVHQW7KLV SDWWHUQRIFKDQJHVZDVDOVRIRXQGDIWHUZHHNV,QWKHVHFRQGVEHIRUHYRLGLQJ EORRGYROXPHZDVIRXQGWRLQFUHDVHVLJQLᚏFDQWO\7KLVRFFXUUHGEHIRUH!RI WKHUHFRUGHGYRLGLQJV

Conclusions: $ QRUPDO IXQFWLRQLQJ EODGGHU PDLQWDLQV D KLJK R[\JHQ VDWXUDWLRQ OHYHO %ODGGHU REVWUXFWLRQ FRPSURPLVHV WKLV DELOLW\ HVSHFLDOO\ ZKHQ LW LQYROYHV RYHUDFWLYLW\0RQLWRULQJEODGGHUR[\JHQVDWXUDWLRQZLOOEHRIFOLQLFDOYDOXH,WFDQ EH SHUIRUPHG ZLWK WKH '36 WHFKQLTXH XVLQJ JODVV ᚏEHUV WKDW ᚏW LQ WKH ZRUNLQJ FKDQQHO RI D F\VWRVFRSH 7KH TXHVWLRQ LV UDLVHG KRZ WKH R[\JHQ VDWXUDWLRQ UHVSRQGVWRWUHDWPHQWVDLPLQJVSHFLᚏFDOO\DWEODGGHUIXQFWLRQRUWKRVHDLPLQJWR LPSURYH EODGGHU EORRG FLUFXODWLRQ 7KH FKDQJHV LQ EORRG YROXPH WKDW RFFXUUHG EHIRUHYRLGLQJFDQKDYHWZRH[SODQDWLRQV)LUVWEODGGHUFRQWUDFWLRQVWDUWVDWWKH EDVHDQGEORRGLVSURSHOOHGWRWKHWRSRXUPHDVXUHPHQWVLWHEHIRUHWRWDOEODGGHU FRQWUDFWLRQLVREWDLQHGDQGSUHVVXUHULVHVRUEORRGVXSSO\DQGEODGGHUYRLGLQJDUH UHJXODWHGVLPXOWDQHRXVO\

277

THE INHIBITORY ROLE OF MELATONIN ON ISOLATED

_{RAT URINARY BLADDER CONTRACTION: THE}

NOVEL PATHWAY FOR THE PHARMACOLOGICAL

MANAGEMENT OF NOCTURIA

.LP7+_&KDQJ,+_+D06_.ZRQ<:_/HH0<_.LP:<_.LP-6_

+\XQ-6_0\XQJ6&

1_{College of Medicine, Chung-Ang University, Dept. of Urology, Seoul, South}

Korea, 2_{Chung-Ang University Hospital, Dept. of Urology, Seoul, South Korea,} 3_{Gyeongsang National University College of Medicine, Dept. of Urology, Jinju,}

South Korea

Introduction & Objectives: 1RFWXUQDOPHODWRQLQOHYHOVPD\DᚎHFWEODGGHUDFWLYLW\ +HUHZHWHVWHGWKHHᚎHFWVRIPHODWRQLQRQGHWUXVRUPXVFOHFRQWUDFWLRQRILVRODWHG UDWEODGGHU

Material & Methods: :HHYDOXDWHGWKHHᚎHFWVRIPHODWRQLQRQWKHFRQWUDFWLRQV LQGXFHGE\SKHQ\OHSKULQH3(DFHW\OFKROLQH$&KEHWDQHFKRO%&K.&ODQG HOHFWULFDOᚏHOGVWLPXODWLRQ()6LQGHWUXVRUVPRRWKPXVFOHVRI6SUDJXH'DZOH\ UDWV 7R GHWHUPLQH WKH PHFKDQLVPV RI WKH LQKLELWRU\ UHVSRQVHV DIWHU PHODWRQLQ PHODWRQLQ SUHWUHDWHG PXVFOH VWULSV ZHUH UHDFWHG ZLWK WKH FDOFLXP FKDQQHO DQWDJRQLVW YHUDSDPLO WKH SRWDVVLXP FKDQQHO EORFNHUV >WHWUDHWK\O DPPRQLXP 7($ DPLQRS\ULGLQH $3 DQG JOLEHQFODPLGH@ GLUHFW YROWDJH GHSHQGHQW FDOFLXPFKDQQHORSHQHU%D\.DQG.1>VSHFLᚏFFDOFLXPFDOPRGXOLQ GHSHQGHQWNLQDVH,,&D0.,,LQKLELWRU@

Results: 0HODWRQLQ SUHWUHDWPHQW _a_{ 0 GRVHGHSHQGHQWO\ GHFUHDVHG WKH}

FRQWUDFWLOHUHVSRQVHVRI3(_a_{0DQG$FK}_a_{00HODWRQLQ} _{ 0 DOVR EORFNHG FRQWUDFWLRQ LQGXFHG E\ KLJK .&O >.&O@(&)   P0  P0}

 P0 DQG  P0 DQG ()6 9HUDSDPLO SRWHQWLDWHG WKH UHOD[DWLRQ UHVSRQVH RIPHODWRQLQWUHDWHGVWULSV_{0EXWRWKHUSRWDVVLXPFKDQQHOEORFNHUVGLGQRW}

0HODWRQLQSUHWUHDWPHQWVLJQLᚏFDQWO\GHFUHDVHGWKHFRQWUDFWLOHUHVSRQVHVRI%D\. _a_{0.1HQKDQFHGPHODWRQLQLQGXFHGUHOD[DWLRQ}

Conclusions: 7KH SUHVHQW UHVXOWV VXJJHVW WKDW PHODWRQLQ FDQ LQKLELW EODGGHU VPRRWKPXVFOHVDVDYROWDJHGHSHQGHQWFDOFLXPDQWDJRQLVWLFHᚎHFWDQGFDOPRGXOLQ &D0.,,V\VWHPLQKLELWLRQ&OLQLFDOVLJQLᚏFDQFHZLOOEHVWXGLHGLQWKHIXWXUH

Oral Session 5

PROSTATE CANCER STEM/INITIATING CELLS AND

THE MICROENVIRONMENT

Sunday, 18 April, 12.15-13.45, Amsterdam Room

278

ROLE OF STROMAL FIBROBLASTS INTERACTION WITH

_{PROSTATIC CANCER CELLS IN ACHIEVEMENT OF}

METASTATIC PHENOTYPE

6HUQL6_{*LDQQRQL(}_0DVLHUL/_{&DORULQL/}_{/DQFLRWWL0}_,HUDUGL$_

0LQHUYLQL$_/DSLQL$_&DULQL0_{&KLDUXJL3}

1_{University of Florence, Dept. of Urology, Florence, Italy,} 2_{University of Florence,}

Dept. of Biochemistry, Florence, Italy

Introduction & Objectives: 7XPRUDO PLFURHQYLURQPHQW DOVR FDOOHG ಯUHDFWLYH VWURPDರ SOD\V DQ LPSRUWDQW UROH LQ SURVWDWH FDQFHU SURJUHVVLRQ DQG LQ WKH DFKLHYHPHQWRIDPHWDVWDWLFSKHQRW\SH3DUWLFXODUO\DFWLYDWHGᚏEUREODVWV$)ZLWK DQH[QRYRH[SUHVVLRQRI˞60$SURWHLQVPRRWKPXVFOHDFWLQDUHVXSSRVHGWR HQKDQFH WXPRUDO FHOO DJJUHVVLYH FKDUDFWHUV DQG PHWDVWDWLF FDSDFLW\ $LP RI RXU VWXG\ZDVWRDQDO\]HWKHELXQLYRFDOLQWHUDFWLRQEHWZHHQᚏEUREODVWVDQGSURVWDWLF FDQFHU FHOOV DQG WR HVWDEOLVK KRZ WXPRUDO FHOOV DFKLHYH WKH DJJUHVVLYH DQG PHWDVWDWLFSKHQRW\SH

Material & Methods: :HSHUIRUPHGFXOWXUHVRIᚏEUREODVWVXQWUDQVIRUPHGSURVWDWLF HSLWKHOLDO FHOOV 317 ZHUH FXOWLYDWHG LQ 530, PHGLXP DQG SURVWDWLF FDQFHU 7DEOH+073.)ROORZLQJ$GPLQLVWUDWLRQRI)HVRWHURGLQH$ORQHRU &RDGPLQLVWUDWLRQRI)HVRWHURGLQHDQG)OXFRQD]ROH )HVRWHURGLQH PJ)OXFRQD]ROH PJ%,'7HVW )HVRWHURGLQH PJ $ORQH5HIHUHQFH 7HVW5HIHUHQFH 5DWLR &, $8&෱QJKP/     &PD[QJP/     7PD[K ದ ದ 1' WK   1'

&, FRQᚏGHQFHLQWHUYDO%,' WZLFHGDLO\1' QRWGHWHUPLQHG$8&෱DQG &PD[SUHVHQWHGDVDGMXVWHGJHRPHWULFPHDQV7PD[SUHVHQWHGDVPHGLDQ UDQJHDQGWSUHVHQWHGDVDULWKPHWLFPHDQFRHᚑFLHQWRIYDULDWLRQ 5DWLR RIDGMXVWHGJHRPHWULFPHDQV

275

ALTERED DETRUSOR FUNCTION IN FEMALE CAVEOLIN-

_{1-DEFICIENT MICE}

1_{Lund University, Dept. of Experimental Medical Science, Lund, Sweden,} 2_Lund

University, Dept. of Urology, Clinical Sciences, Lund, Sweden

Introduction & Objectives: &DYHRODHDUHRPHJDVKDSHGPHPEUDQHRUJDQHOOHV WKDWKDYHEHHQVKRZQWRVHTXHVWHUDQGUHJXODWHLPSRUWDQWVLJQDOOLQJLQWHUPHGLDULHV &DYHRODELRJHQHVLVGHSHQGVRQSURWHLQVIURPWKHFDYHROLQDQGFDYLQIDPLOLHVDQG RQ PHPEUDQH FKROHVWHURO &DYHROLQGHᚏFLHQF\ LV DVVRFLDWHG ZLWK VXEVWDQWLDO XURJHQLWDODOWHUDWLRQVLQPDOHPLFH7KHVHFKDQJHVLQFOXGHSURVWDWHK\SHUWURSK\ GLVWHQVLRQ RI WKH VHPLQDO YHVLFOHV GLVWXUEHG HUHFWLOH IXQFWLRQ DQG LPSDLUHG PXVFDULQLFFRQWUDFWLOLW\RILVRODWHGGHWUXVRUVWULSVLQYLWUR:KHWKHUWKHFRQWUDFWLOH FKDQJHV LQ WKH EODGGHU DUH VHFRQGDU\ WR RXWᚐRZ REVWUXFWLRQ FDXVHG E\ WKH K\SHUWURSKLFSURVWDWHRUUHᚐHFWDSULPDU\UROHRIFDYHRODHLQGHWUXVRUVLJQDOOLQJLV QRWNQRZQ7KLVZDVDGGUHVVHGE\PDNLQJDGHWDLOHGIXQFWLRQDOFKDUDFWHUL]DWLRQRI GHWUXVRUFRQWUDFWLOLW\LQZLOGW\SH:7DQGFDYHROLQGHᚏFLHQW.2IHPDOHPLFH Material & Methods: 'HWUXVRUVIURPZHHNROG.2DQGFRQJHQLF:7IHPDOH PLFHZHUHH[DPLQHGLQYLWURXVLQJP\RJUDSK\'LXUHVLVZDVHVWLPDWHGE\ZDWHU FRQVXPSWLRQ /HQJWKWHQVLRQ UHODWLRQVKLSV ZHUH JHQHUDWHG DQG FRQWUDFWLOLW\ LQ UHVSRQVH WR WKH PXVFDULQLF DJRQLVW FDUEDFKRO ZDV GHWHUPLQHG DW WKH RSWLPXP OHQJWK / IRU DFWLYH IRUFH :HVWHUQ EORWWLQJ ZDV XVHG WR DVVHVV FRQWHQWV RI FDYHROLQFDYLQDQGPXVFDULQLF0UHFHSWRUV Results: .2PLFHFRQVXPHGVLJQLᚏFDQWO\OHVVZDWHUSHUGD\VXJJHVWLQJUHGXFHG GLXUHVLV7KHEODGGHUWRERG\ZHLJKWUDWLRZDVQRWFKDQJHGLQ.2PLFH7KHSDVVLYH OHQJWKWHQVLRQUHODWLRQVKLSRIWKH.2EODGGHUVZDVOHIWVKLIWHGLQFRPSDULVRQZLWK :7EODGGHUV0D[LPDOFDUEDFKROLQGXFHGIRUFHDW/ZDVLQFUHDVHGLQ.2EODGGHU ZKHQQRUPDOL]HGWRKLJK._{FRQWUDFWLRQ} Conclusions: *HQHWLFDEODWLRQRIFDYHRODHLQWKHIHPDOHPRXVHOHDGVWRVXEVWDQWLDO IXQFWLRQDOFKDQJHVLQWKHEODGGHUUXOLQJRXWREVWUXFWLRQUHODWHGK\SHUWURSK\DVD FRQWULEXWLQJ IDFWRU 7KH OHIWVKLIW RI WKH SDVVLYH OHQJWKWHQVLRQ UHODWLRQVKLS LQ WKH .2EODGGHUPD\UHᚐHFWDGDSWDWLRQWRUHGXFHGGLXUHVLVRULQFUHDVHGWLVVXHVWLᚎQHVV &DUEDFKRO FRQWUDFWLRQ LV LQFUHDVHG LQ WKH FDYHRODHGHᚏFLHQW IHPDOH GHWUXVRU VXJJHVWLQJWKDWWKHSUHVHQFHRIFDYHRODHVXSSUHVVHVPXVFDULQLFVLJQDOOLQJLQWKH IHPDOHPRXVHEODGGHU

276

CHANGES IN BLADDER WALL PERFUSION IN THE

_{OVERACTIVE OBSTRUCTED BLADDER}

1_{Erasmus Medical Center, Dept. of Urology, Paediatric Urology, Rotterdam, The}

Netherlands, 2_{Erasmus Medical Center, Dept. of Radiotherapy, Rotterdam, The}

Netherlands, 3_{Erasmus Medical Center, Dept. of Pathology, Rotterdam, The}

Netherlands

Introduction & Objectives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

Material & Methods: 2[\JHQDWLRQ DQG EORRG YROXPH RI WKH EODGGHU ZDOO ZDV PHDVXUHG LQ YLYR E\ GLᚎHUHQWLDO SDWKOHQJWK VSHFWURVFRS\ '36 XVLQJ JODVV ᚏEHUV LQ JXLQHD SLJV VKDP RSHUDWHG Q  DQG XUHWKUDOO\ REVWUXFWHG Q  0HDVXUHPHQWVZHUHSHUIRUPHGPDLQO\RQWKHEODGGHUWRSGXULQJPXOWLSOHYRLGLQJ ᚏOOLQJF\FOHVEHIRUHVXUJHU\ZHHNVDIWHU6+$0DQGREVWUXFWHGDQGHLJKW ZHHNVDIWHU8URG\QDPLFLQYHVWLJDWLRQVGXULQJWKHZHHNSHULRGSURYLGHG GDWD RQ EODGGHUSUHVVXUH FRPSOLDQFH FRQWUDFWLOLW\ DQG ದRYHUDFWLYLW\ DQG XULQH ᚐRZUDWH

Results: %HIRUHVXUJHU\LQERWKJURXSVDQGZHHNVDIWHU6+$0VXUJHU\R[\JHQ VDWXUDWLRQ LQ WKH EODGGHU ZDOO ZDV DERYH  GXULQJ ᚏOOLQJ ,W GURSSHG GXULQJ

Eur Urol Suppl 2010;9(2):115

NHS Foundation Trust, Dept. of Urology, Manchester, United Kingdom

Introduction & Objectives: 3URVWDWHFDQFHUSUHIHUHQWLDOO\PHWDVWDVL]HVWRWKHERQH DQGZHKDYHSUHYLRXVO\VKRZQWKDWWKHSRO\XQVDWXUDWHGIDWW\DFLGDUDFKLGRQLFDFLG LVDSRWHQWVWLPXODWRURI&D3LQYDVLRQ+HUHZHSUHVHQWWKDWDUDFKLGRQLFDFLGDOVR SURPRWHVSURVWDWHFDQFHULQYDVLRQE\LQGXFLQJERQHPDUURZDGLSRF\WHIRUPDWLRQ Material & Methods: %R\GHQLQYDVLRQFKDPEHUVZHUHXVHGWRDVVHVVWKHDELOLW\ RI GLHWDU\ RLOV DQG WKHLU SRO\XQVDWXUDWHG IDWW\ DFLG FRPSRQHQWV WR LQGXFH 3& LQYDVLRQ $GLSRF\WHV ORDGHG ZLWK VSHFLᚏF SRO\XQVDWXUDWHG IDWW\ DFLG JHQHUDWHG IURPSULPDU\KXPDQERQHPDUURZPHVHQFK\PDOVWHPFHOOVZHUHXVHGDVLQYDVLRQ VWLPXODQWV LQ %R\GHQ FKDPEHU DVVD\V DQG LQ FRFXOWXUH H[SHULPHQWV ZLWK WKH KXPDQ ERQH PHWDVWDWLF SURVWDWH 3& FHOO OLQH /LSLG WUDQVIHU DQG PHWDEROLVP ZDVIROORZHGXVLQJGHXWHUDWHGSRO\XQVDWXUDWHGIDWW\DFLGDQGWLPHODSVH)RXULHU 7UDQVIRUPHG,QIUDUHG6SHFWURVFRS\

Results: 'LHWDU\ RLOV XQOLNH WKHLU SRO\XQVDWXUDWHG IDWW\ DFLG FRPSRQHQWV GR QRW LQGXFH 3& LQYDVLRQ VXJJHVWLQJ WKDW LW LV WKH FRPSRVLWLRQ RI WKH RLOV WKDW LV RI LPSRUWDQFH 3RO\XQVDWXUDWHG IDWW\ DFLGV LQGXFH ERQH PDUURZ DGLSRF\WH GLᚎHUHQWLDWLRQZLWKDUDFKLGRQLFDFLGLQGXFLQJKLJKHUOHYHOVRIERQHPDUURZDGLSRF\WH GLᚎHUHQWLDWLRQDVFRPSDUHGZLWKRWKHUSRO\XQVDWXUDWHGIDWW\DFLGVYV  S  $UDFKLGRQLF DFLG SXOVHG DGLSRF\WHV VWLPXODWHG JUHDWHU SURVWDWH HSLWKHOLDO FHOO LQYDVLRQ WKDQ IUHH DUDFKLGRQLF DFLG  YV S RUDGLSRF\WHVJHQHUDWHGLQWKHSUHVHQFHRIRWKHUSRO\ XQVDWXUDWHGIDWW\DFLGV,QWKHFRFXOWXUHPRGHORIERQHPHWDVWDVLV3&DQGERQH PDUURZDGLSRF\WHLQWHUDFWLRQVUHVXOWLQGLUHFWXSWDNHDQGPHWDEROLVPRIDUDFKLGRQLF DFLG E\ 3& FHOOV GHVWUXFWLRQ RI WKH DGLSRF\WH DQG VXEVHTXHQW IRUPDWLRQ RI D ERQHPHWDVWDVLV

Conclusions: 7KH GDWD VXSSRUWV WKH K\SRWKHVLV WKDW DUDFKLGRQLF DFLG QRW RQO\ SURPRWHV&D3LQYDVLRQLWDOVRSUHSDUHVWKHಯVRLOರPDNLQJLWPRUHVXSSRUWLYHIRU LPSODQWDWLRQDQGSURSDJDWLRQRIWKHPLJUDWLQJPHWDVWDWLFFHOO

281

NOGGIN CONTRIBUTES TO THE OSTEOLYTIC

_{RESPONSE IN BONE METASTASIS OF PROSTATE}

CANCER (CAP)

6HFRQGLQL&_{:HWWHUZDOG$}_{6FKZDQLQJHU5}_{7KDOPDQQ*1}_{&HFFKLQL0*}

1_{University Hospital of Berne, Dept. of Clinical Research, Berne, Switzerland,} 2_{University Hospital of Berne, Dept. of Urology, Berne, Switzerland}

Introduction & Objectives: 0HPEHUVRIWKHERQHPRUSKRJHQHWLFSURWHLQ%03DQG RIWKHZLQJOHVV:QWSURWHLQIDPLO\SOD\DUHOHYDQWUROHLQWKHRVWHREODVWUHVSRQVH WR&D3ERQHPHWDVWDVLV([WUDFHOOXODUDQWDJRQLVWVDUHFUXFLDOIRUWKHPRGXODWLRQ RI WKHLU ELRORJLFDO DFWLYLW\ :H KDYH UHSRUWHG WKDW WKH ODFN RI H[SUHVVLRQ RI WKH %03DQWDJRQLVWQRJJLQE\FDQFHUFHOOOLQHVLVDGHWHUPLQDQWRIWKHLURVWHRLQGXFWLYH DFWLYLW\LQYLYR,QFRQWUDVWRVWHRO\WLFFHOOOLQHVH[SUHVVQRJJLQFRQVWLWXWLYHO\7KH :QWDQWDJRQLVWGLFNNRSI'..KDVEHHQVKRZQWRSDUWLFLSDWHLQWKHRVWHRO\WLF SURFHVV RI PXOWLSOH P\HORPD 00 E\ UHSUHVVLQJ ERQH IRUPDWLRQ WKXV DGGLQJ DQRVWHRSHQLFFRPSRQHQWWRWKHOHVLRQ1RJJLQPD\FRQWULEXWHE\DQHTXLYDOHQW PHFKDQLVPWRRVWHRO\VLVLQERQHPHWDVWDVLVRI&D37KHUHIRUHZHXWLOL]HGD51$ VLOHQFLQJVWUDWHJ\WRLQYHVWLJDWHZKHWKHUWKHFRQVWLWXWLYHQRJJLQH[SUHVVLRQE\DQ RVWHRO\WLF&D3FHOOOLQHSOD\VDUROHLQWKHRVWHRO\WLFUHVSRQVHLQGXFHGE\LWVERQH PHWDVWDVLV

Material & Methods: 6WDEOH QRJJLQNQRFN GRZQ 1RJ.' ZDV DFKLHYHG E\ WUDQVIHFWLRQRIPXOWLSOHVK51$YHFWRUVLQWRDOXFLIHUDVHH[SUHVVLQJ3&FHOOFORQH 3&OXF$YHFWRUHQFRGLQJDQRQWDUJHWLQJVK51$PRFNZDVXVHGDVQHJDWLYH FRQWURO6LOHQFLQJHᚑFLHQF\ZDVPRQLWRUHGDWWKHP51$DQGSURWHLQOHYHOE\UHDO WLPH 3&5 DQG LPPXQREORWWLQJ UHVSHFWLYHO\ 6HYHUDO 1RJ.' DQG PRFN FORQHV ZHUH[HQRJUDIWHGLQWRWKHWLELDRILPPXQRFRPSURPLVHGPLFH7KHLULQWUDRVVHRXV JURZWKDQGRVWHRO\WLFHᚎHFWZHUHPRQLWRUHGE\ELROXPLQHVFHQWLPDJLQJ%/,DQG UDGLRJUDSK\UHVSHFWLYHO\'LPDJHVRIWKH[HQRJUDIWHGWLELDHZHUHJHQHUDWHGE\ PLFURWRPRJUDSK\˩&7%RQHVWUXFWXUDOSDUDPHWHUVZHUHDQDO\]HGE\SHULSKHUDO TXDQWLWDWLYHFRPSXWHUL]HGWRPRJUDSK\S4&7DQGKLVWRPRUSKRPHWU\

Results: 6LJQLᚏFDQW UHGXFWLRQ RI QRJJLQ P51$ DQG SURWHLQ H[SUHVVLRQ ZDV DFKLHYHGLQVHYHUDO1RJ.'FORQHV7KHLUJURZWKUDWHRUH[SUHVVLRQLQYLWURRIWKH RVWHRO\WLFF\WRNLQHVSDUDWK\URLGKRUPRQHUHODWHGSURWHLQDQGLQWHUOHXNLQDQGRI '..ZHUHQRWPDUNHGO\DᚎHFWHG7XPRXUJURZWKLQERQH[HQRJUDIWVRIGLᚎHUHQW PRFNDQG1RJ.'FORQHVZDVRQO\PDUJLQDOO\RUQRWDᚎHFWHG5DGLRJUDSKLFDQG P&7DQDO\VLVVKRZHGWKDWWKHERQHV[HQRJUDIWHGZLWKWKH1RJ.'FORQHVKDYH VWUXFWXUDOPRGLᚏFDWLRQVLQGLFDWLYHRIERQHIRUPDWLRQUHSDLUDFWLYLW\ZKLFKFRXOGQRW EHREVHUYHGLQSDUHQWDO3&FHOOVDQGPRFNFORQHV%RQHKLVWRPRUSKRPHWU\DQG S4&7KDYHIXUWKHUFRUURERUDWHGWKHVHᚏQGLQJV

Conclusions: 7KH VK51$PHGLDWHG VXSSUHVVLRQ RI QRJJLQ H[SUHVVLRQ LQ WKH RVWHRO\WLF FHOO OLQH 3& PD\ KDYH UHVWRUHG WKH ERQH IRUPDWLRQ WKDW QRUPDOO\ IROORZVERQHUHVRUSWLRQDVDQHᚎHFWRIWKHಯFRXSOLQJSKHQRPHQRQರ&RQYHUVHO\ QRJJLQH[SUHVVLRQE\&D3PD\FRQWULEXWHWRWKHLQGXFWLRQRIDQRVWHRO\WLFOHVLRQE\ DGGLQJDQRVWHRSHQLFFRPSRQHQWVLPLODUO\WRWKHPHFKDQLVPVKRZQWRRSHUDWHLQ 001RJJLQVXSSUHVVLRQPD\EHDQDGGLWLRQDOWKHUDSHXWLFRSWLRQIRUWKHWUHDWPHQW RIRVWHRO\WLFERQHPHWDVWDVHVE\VROLGFDQFHUV

FHOOV 3& ZHUH FXOWLYDWHG LQ '0(0 PHGLXP WR REVHUYH FHOO WR FHOO LQWHUDFWLRQ EHWZHHQWKRVHFHOOVSODFHGLQFRQWDFWDPRQJWKHP$IWHUKRXUVZHVHSDUDWHG WKHFHOOXODUOLQHVRQWKHEDVLVRIWKHLUGLᚎHUHQWWLPHVRISODWHDGKHVLRQ:HXVHG %R\GHQ FKDPEHU IRU WKH WULGLPHQVLRQDO WHVW RI FHOOV PLJUDWLRQ LQ '0(0  PHGLXPFKHPRDWWUDFWLYH0LJUDWHGFHOOVWKDWZHUHIRXQGLQᚏOWHUSRUHVᚏ[HGDQG LQNHG ZHUH FRXQWHG DW PLFURVFRSH &HOOXODU LQYDVLRQ ZDV HYDOXDWHG E\ %R\GHQ FKDPEHUZLWKDᚏOWHUFRQWDLQLQJPDWULJHOWRFRS\H[WUDFHOOXODUPDWUL[

Results: :HLVRODWHGDPRQJFDQFHUDFWLYDWHGᚏEUREODVWV&$)WKHP\RᚏEUREODVWV LQ DGGLWLRQ WR ˞60$ QHJDWLYH ᚏEUREODVWV 3&$) ZLWK D UHPDUNDEOH DELOLW\ WR HQKDQFH PLJUDWLRQ DQG LQYDVLYHQHVV RI 3& (ᚎHFWV LQGXFHG E\ 0) DQG 3&$) RQLQYDVLYHFDSDFLWLHVRI3&UHVXOWHGGLᚎHUHQW0)LQGXFHVDX3$X3$UV\VWHP PHGLDWHG LQYDVLYHQHVV ZKLOH 3&$) SURPRWHV D PHWDOORSURWHDVH GHSHQGHQW LQYDVLYHQHVV,/UHVXOWHGWREHDEOHWRLQGXFHWUDQVGLᚎHUHQWLDWLRQRIᚏEUREODVWV LQ 3&$) 2XU UHVXOWV VKRZ WKDW DFWLYDWHG ᚏEUREODVWV GHWHUPLQH DQ LQFUHDVH RI LQYDVLYHQHVV RI 3& ZKLOH GRQಬW DᚎHFW WXPRULJHQHVLV ,Q SULPDU\ FXOWXUHV RI SURVWDWLFᚏEUREODVWVWKHVHFDQEHDFWLYDWHGHLWKHUE\7*)˟LQ0)DQGPXFKPRUH E\ ,/ LQ 3&$) $QDO\VLV RI FDQFHU DVVRFLDWHG ᚏEUREODVWV &$) DOORZHG XV WR FRQᚏUPWKHLUIDFLOLWDWRUUROHLQWXPRXUFHOOLQYDVLYHQHVV

Conclusions: ,QRXUUHVXOWVZHKLJKOLJKWVWKHH[LVWHQFHRIDELXQLYRFDOFRRSHUDWLRQ EHWZHHQᚏEUREODVWVDQGSURVWDWHFDQFHUFHOOVZKLFKZDVLPSOHPHQWHGE\,/RU 7*)˟GHSHQGHQW PDQQHULQSURPRWLQJDPHWDVWDWLFDQGDJJUHVVLYHSKHQRW\SH ,QGHHG3&LQGXFHᚏEUREODVWVDFWLYDWLRQZLWKRUZLWKRXWH[SUHVVLRQRI˞E60$ WKURXJK WKH SURGXFWLRQ RI 7*)˟ RU ,/ 7KHVH DFWLYDWHG ᚏEUREODVWV LQFUHDVH WKH DJJUHVVLYHQHVV RI 3& LQGXFLQJ D SURLQYDVLYH SKHQRW\SH WKURXJK WKH V\VWHP GHSHQGHQWRQX3$X3$URU003

279

STROMA REACTION IN MOUSE XENOGRAFT MODELS

_{OF PROSTATE CANCER BONE METASTASIS}

&HFFKLQL0*_{7KDOPDQQ*1}

1_{University Hospital of Berne, Urology Research Laboratory, Berne, Switzerland,} 2_{Swiss Institute of Bioinformatics, Lausanne, Switzerland,} 3_{University Hospital of}

Berne, Dept. of Urology, Berne, Switzerland

Introduction & Objectives: $QDO\VLVRIWKHVWURPDOHSLWKHOLDOLQWHUDFWLRQLQFDQFHU LV SUREOHPDWLF :H SUHVHQW DQ H[SHULPHQWDO PHWKRG RI JOREDO JHQH H[SUHVVLRQ DQDO\VLVLQEXONWLVVXHVSHFLPHQVRIERQHPHWDVWDVLVDEOHWRGLVVHFWWKHFDQFHU FHOOVSHFLᚏF IURP WKH VWURPDO FHOOVSHFLᚏF WUDQVFULSWRPH LQGXFHG E\ WKH VWURPDO HSLWKHOLDOLQWHUDFWLRQZLWKRXWSULRUFHOOVHSDUDWLRQ7KLVPHWKRGLVEDVHGRQVSHFLHV VSHFLᚏFPRXVHDQGKXPDQUHVSHFWLYHO\F'1$JHQHDUUD\VZKHUHWKHVWURPD LQGXFHGUHVSRQVHLQWKHPRXVHWLELDERQHPDUURZWR[HQRJUDIWHGSURVWDWHFDQFHU 3&FHOOOLQHVLVFRPSDUHGWRQRUPDOERQH

Material & Methods: 7KH KXPDQ RVWHRLQGXFWLYH 3& FHOO OLQH &% ZDV [HQRJUDIWHGLQWRWKHWLELDRI6&,'PLFH0LFHZHUHVDFULᚏFHGZKHQWKHRVWHREODVW UHVSRQVH ZDV HYLGHQW DW UDGLRJUDSK\ DQG 51$ ZDV H[WUDFWHG IURP WKH WXPRXU EHDULQJ ERQH VKDIW 51$ H[WUDFWHG IURP DQ HTXLYDOHQW SRUWLRQ RI LQWDFW WLELDH RI DJHPDWFKHG PLFH VHUYHG DV D ಯPRXVHRQO\ರ FRQWURO DQG IURP FXOWXUHG &% FHOOVDVDಯKXPDQRQO\ರFRQWURO(DFKSUREHZDVK\EULGL]HGRQWRWKHZKROHKXPDQ 8$  $ᚎ\PHWUL[ DQG PRXVH $  $ᚎ\PHWUL[ JHQRPH DUUD\ 7KH F'1$ SUREH VHTXHQFHV ZHUH FRPSDUHG E\ ELRLQIRUPDWLFV DQDO\VLV DQG FURVV K\EULGL]LQJSUREHVZHUHH[FOXGHGIURPDQDO\VLVE\FRPSXWDWLRQDOPDVN Results: $OLPLWHGQXPEHURIJHQHVZHUHH[FOXGHGEHFDXVHRIFURVVK\EULGL]DWLRQ EHWZHHQ KXPDQ DQG PRXVH  DQG  UHVSHFWLYHO\ ,Q WKH ERQH VWURPDO FRPSDUWPHQWJHQHVZHUHXSUHJXODWHGDWOHDVWIROGLQSUHVHQFHRI3&FHOOV$ OLWHUDWXUHDQDO\VLVFRQᚏUPHGWKDWWKHLUH[SUHVVLRQLVFRQᚏQHGWRWKHVWURPDDQGQRW WRWKHFDQFHUFHOOFRPSRQHQWRIYDULRXVFDQFHUV$VJHQHVHQFRGLQJH[WUDFHOOXODU PDWUL[(&0SURWHLQVRYHUH[SUHVVHGE\WKHVWURPDUHDFWLYHWRFDQFHUFHOOVPD\ UHSUHVHQW SXWDWLYH ELRPDUNHUV RI SURVWDWH FDQFHU ERQH PHWDVWDVLV  RI WKHVH KLJKO\ XSUHJXODWHG (&0 SURWHLQV QDPHO\ SHULRVWLQ 32671 DVSRULQ $631 KHYLQ63$5&/ZHUHIXUWKHUDQDO\]HG5HDOWLPH573&5DVVD\VZLWKPRXVH VWURPD VSHFLᚏF SUREHV YDOLGDWHG WKH VWURPDO H[SUHVVLRQ RI WKH  JHQHV RI LQWHUHVW *R, DQG WKHLU RYHUH[SUHVVLRQ LQ SUHVHQFH RI RVWHRLQGXFWLYH 3& FHOOV ,PPXQRKLVWRFKHPLVWU\SHUIRUPHGRQWXPRXU[HQRJUDIWHGPRXVHERQHSULPDU\3& EHQLJQSURVWDWHK\SHUSODVLD%3+DQGERQHPHWDVWDVLVVDPSOHVIXUWKHUFRQᚏUPHG WKDW WKH SURWHLQ SURGXFWV RI WKHVH  *R, DUH H[FOXVLYHO\ ORFDOL]HG LQ WKH VWURPD P51$ H[SUHVVLRQ OHYHOV RI 32671 $631 DQG 63$5&/ LQ PXULQH SULPDU\ FDOYDULD RVWHREODVWV LQ FRFXOWXUHV ZLWK &% FHOOV DUH VLJQLᚏFDQWO\ LQFUHDVHG DIWHUKFRPSDUHGWRWKHH[SUHVVLRQOHYHOVLQDEVHQFHRI&% Conclusions: 6SHFLHVVSHFLᚏFPLFURDUUD\VDUHDEOHWRGLVVHFWUHOLDEO\WKHVWURPD GHULYHGJHQHH[SUHVVLRQIURPWKHFDQFHUGHULYHGJHQHH[SUHVVLRQ&DQFHUFHOOV LQGXFHH[SUHVVLRQRI(&0SURWHLQVLQERQHPDUURZVWURPD*HQHVXSUHJXODWHGDV WKHUHVXOWRIWKHFURVVWDONEHWZHHQWKHFDQFHUFHOOVDQGERQHPDUURZVWURPDPD\ UHSUHVHQWSRWHQWLDOPDUNHUVIRUERQHPLFURPDFURPHWDVWDVLV

280

ARACHIDONIC ACID PRIMES HUMAN BONE MARROW

_{STROMA FOR PROSTATE CANCER METASTASIS}

1_{Paterson Institute for Cancer Research, Genito Urinary Cancer Research,}

Manchester, United Kingdom, 2_{University of Manchester, School of Chemical}