Reference : Study  of  breast  cancer  adaptation  to  anti-­angiogenic  therapies  by   molecula...
Scientific congresses and symposiums : Unpublished conference
Human health sciences : Multidisciplinary, general & others
http://hdl.handle.net/2268/131796
Study  of  breast  cancer  adaptation  to  anti-­angiogenic  therapies  by   molecular  imaging  on  tissue  slides
English
[en]  Study  of  breast  cancer  adaptation  to  anti-­angiogenic  therapies  by   molecular  imaging  on  tissue  slides
Cimino, Jonathan mailto [Université de Liège - ULg > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.) >]
Calligaris, David [Université de Liège - ULg > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.) >]
Debois, Delphine mailto [Université de Liège - ULg > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.) >]
Sounni, Nor Eddine mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
Noël, Agnès mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme >]
De Pauw, Edwin mailto [Université de Liège - ULg > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.) >]
4-Sep-2012
1
1Bombonati,  A.  and  Sgroi,  D.C.,  2010.The  molecular  pathology  of  breast  cancer  progression.  J  Pathol.   2Burstein,  H.J.,  and  Miller,  K.D.,  2008.  Phase  II  study  of  sunitinib  malate,  an  oral  multitargeted  tyrosine  kinase  inhibitor,   in   patients   with   metastatic   breast   cancer   previously   treated   with   an   anthracycline   and   a   taxane.   J   ClinOncol,   26(11):   1810-­‐1816.   3Bergers,  G.  and  Hanahan,  D.,  2008.Modes  of  resistance  to  anti-­‐angiogenic  therapy.  Nat  Rev  Cancer,  8(8):  592-­‐603.   4Ebos,   J.M.   and   Kerbel,   R.S.,   2009.Tumor   and   host-­‐mediated   pathways   of   resistance   and   disease   progression   in   response  to  antiangiogenic  therapy.Clin  Cancer  Res,  15(16):  5020-­‐5025.   5Schwamborn  K.  and  Caprioli  R.M.,  2010.  Molecular  imaging  by  mass  spectrometry-­‐-­‐looking  beyond  classical  histology.   Nature  Review  Cancer  10(9):  639-­‐646.  
Yes
No
International
OurCon 2012 Ourense Conference on Imaging Mass Spectrometry
du 02 septembre au 06 septembre
3rd - 5th September 2012 Co-organized in cooperation with COST action BM 1104 Co-organized in cooperation with ProteoRed
OurCon Spain
Spain
[en] Angiogenesis ; MALDI Imaging ; Cancer
[en] Breast   carcinoma   is   the   most   common   and   second   leading   cause   of   cancer   mortality   in   women1.   The   ␣␣␣␣␣␣␣␣␣␣␣␣ ␣␣␣ ␣␣␣␣ ␣␣␣␣␣␣␣␣␣␣␣␣ ␣␣␣␣␣␣␣␣ ␣␣␣ ␣␣ ␣␣␣␣-­‐limiting   secondary   step   in   tumorigenesis   led   to   extensive   pre-­‐clinical   researches   on   angiogenesis   and   finally   the   approval   of   VEGF-­‐neutralizing   antibodies   (bevacizumab)  and  VEGF  receptor  tyrosine  kinase  inhibitors  (RTKs:sunitinib).  The  Sunitinib  has  been  used   clinically   in   patients   with   breast   cancer   refractory   to   other   therapeutic   agents2.   Unfortunately,   like   the   cytotoxic   therapies,   these   drugs   do   not   produce   lasting   effects   and   resistance   to   treatment   appeared   clinically3.   Recently,   independent   laboratories   have   reported   experimental   data   demonstrating   that   anti-­‐ angiogenic   treatments   inhibit   tumor   growth,   but   also   stimulate   the   formation   of   lung   metastases   after   treatment   discontinuation4.   The   field   of   imaging   mass   spectrometry   provides   new   tools   to   visualize   and   study  the  profiles  of  proteins  and  small  molecules  associated  with  biomedical  problems5.  
To  this  aim,  we  conducted  a  series  of  experiments  to  setup  a  reproductible  model  of  resistance  to  sunitinib.   The   cells   MDA-­‐MB-­‐231   triple   negative,   from   human   breast   cancer   and   expressing   luciferase   are   injected   subcutaneously  into  mice  RAG1-­‐/-­‐.  The  mice  were  divided  into  four  experimental  groups  including,  on  the   one  hand,  control  mice  treated  with  placebo  (Carboxymethyl  cellulose,  CMC)  sacrificed  on  day  30  (group  1)   or  when  the  tumor  reached  a  volume  of  300  mm3  (group  2).    On  the  other  hand,  Sunitinib-­‐treated  mice  (LC   Laboratories,   40mg/kg/day),   sacrificed   at   day   30   (group   3),   or   when   the   tumor   reached   a   volume   of   300   mm3  (group  4).  MALDI  mass  spectrometry  imaging  was  performed  on  tissue  sections  of  tumors  and  organs   subsequently   colonized   by   metastases.   Matrix   sublimation   was   used   to   coat   tumor   sections   (14   μm-­‐tick)   with   1.5   Diaminonaphthalene   (1.5   DAN)   for   lipids   analysis   and   Sinapinic   acid   (SA)   for   entire   proteins   analysis.   Ion   cartographies   were   recorded   with   a   Solarix9.4T   FTMS   instrument   for   lipids   and   with   an   Ultraflex   II   TOF-­‐TOF   instrument   for   entire   proteins   (BrukerDaltonics,   Bremen,   Germany)   with   a   spatial   resolution  of  100  μm.    
The  analysis  of  differential  protein/lipid  profiles  with  high  mass  accuracy  and  broadband  resolution  allows   detection   of   intense   signals   from   lipid   families   such   as   Phosphatidylcholine   (PC),   Triglyceride   (TAG),   Sphingomyelin   (SM)   and   precise   lipid   droplets   or   tumor   cells   differentiated   location   in   the   Sunitinib   resistant   tumor   cells   compared   to   control   cells.The   protein   profiles   of   the   4   groups   of   mice   show   differences   in   intensity   and   location,   enabling   a   correlation   to   inflammatory   (highlighted   by   histological   staining)  and  angiogenic  phenomenon.  
Université de Liege
Researchers ; Professionals ; Students ; General public ; Others
http://hdl.handle.net/2268/131796

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