Stearic acid and carcinogenesis

Stearic acid and carcinogenesis

s Meeting Abstracts 1748 highertremdtodevelopsecm%rychanges. AUmPHx PEmYLATICNAND RE&ATICNSRIP~ KINASKAcmVlXY OF P56LCK - controlmicediedwithin 35...

123KB Sizes 1 Downloads 68 Views

s

Meeting Abstracts

1748

highertremdtodevelopsecm%rychanges. AUmPHx PEmYLATICNAND RE&ATICNSRIP~ KINASKAcmVlXY OF P56LCK -

controlmicediedwithin 35days. Therefore this study has slmwn a beueficial anti-cancer effectof radiolabelled C215 in improvingsurvivalinthetreatedmic+

R.Fagard,I-Bail& arxlS.Fis&er

mRARIcACIDANDc!ARQxGEmS1s

INSKRM u 15, Institut de Pathologie Molkularie, 24 rue du FQ St. Jacques, 75014-Paris, Frame

B.Ranmr(l),N.A.Wabib(l), C.R.Wocd(Z), K.Apo&mlm(3), W.Razbez(3), M.J.Eershmn(2) M.Aslam(3), D.H&mann(2), W.E.Jeokins(4), J.R.W.Wasters(4) ard M.J.=(5)

A novel putative oncogene has been described: lck isamf&eroftheQmsine Kinase(TPK)xnily, it shares70% hanology with=. We have described the TPK (P56) forby_inISTPA, a murine coded lympham induced by M&uLV. P56 is highly expressed inmlm, in several human lymphams, in oue case of acutemyeloblastic leukamia,ithas been detected innormal ardmitogenstimulatedTlymphoqtes. Itis expres=d at a very low level in B [email protected] and is thoughtto be l-tic specific. We have studiedP56 both in cm% menbrane preparations ax-d with immxqurified P56 using a specificantibody prepared by inmnizing rabbits againsta peptidefran the N-terminalregiccof P56, a regionsharingnohamlcgywith other known TPKs (in particular P60~). Inthetwo systems, wa observed that P56 autophosphoxylation leads to anincreased TPK activity tmards exogenms substrates. cknicals that change the autophosphorylation of P56 have identical effects cc the TPK activity. EYan these data, it appears thatautophosphorylaticmis ~61portant step of the activation of -. TmTmmEmrIcuSKCFRAD1CACTIVS RURINSlmNSPLANrm~

C215 IN

B.Dsrmer(l), N.A.Sabib(l), L.LkRmlm(2), F.C.EIOCZae(3), B.Iarssax (2),ELpalmer(4), C.B.Wmd(5) d R.C.N.Willkmm(l) Departmentsof (1)Surgery and (3)Wsdicine, Bristol Royal Infirmazy, Bristol, U.K.; (2)Departmsntof Microbiology,Gothenbsq University,Gothenberg,Sweden;Department of (4)Radiologyaud (5)Surgery, Royal Postgraduate MedicalSchool,kndon, U.K. The therapeuticrole of mmoclonal antibcdy C215 labelled with 13lI was investigatedintransplantdmurine mamary IOnq carcinanas. Fragments (approximately ofmmarytmxr fran (P xPc) Fl hybrid mice) were implanted subcutaneous ly in 15 miceofthesame strain. Right micewere injectedwith 13lI-C215 startingfran day 12 implantationat-d these following tmxr survived subsequently. In contrast,all 7

(1)-t of Surgery, Bristol Royal Infirmay, Bristol, U.K.; Deparbnmts of (3)Virology, Royal (2)surgery and Postgraduate Medical School, Imdon, U.K.; (4)DepMment of Pathology, Institute of Urology, Iordon, U.K.; (5)Cancer Research Laboratories, University of Qmpaign Nottinghsm, Nottingham,U.K. Decreased memtxane rigidityis one of the characteristicsof malignant cells, resultinginpart fran thedesatuxatiouof stearic acid into oleic acid. In this study, we investigatedthe influencesof stearic acid in tuzuurcell inhibition in vitro and tumour developnent-in vi= stearicacid inhibited the colony-forming ability of faur cut of five rat and two humn tulTour continucus cell lines &l In contrast, the colony-forming m. abilitv of rat filxoblasts was not inhibikd. Using a model of rat mamary ildued by nitrosanethylurea CarCincrna (Euu),the subcutaneous injectionofstearic acid at weekly intervalspreventedtummr development in 5 of IO rats. using icdostearic acid twiceweekly,11 of 19 rats were aliveand tumcurfree at week 22 whilst all of 14 animals injected with NMU alcme had died oftmourbythesixteeeuthweek. The ratio of stearic to oleic acids in erythrocytenmbranes was significantly reducedin thetumur-bearing rats,lcutwas nomalintumur-free animals treat&with These stearic icdostearic acid. preliminaryordata indicatethatstearicacid kills human tumxr cells & vitro and inhibitsturncur developmnt in rats. -INHIsm

-OFHuMANcoLL)NIC!

ADE%XY%CZl04AC!ELLLINESINVITRC A.G.T.W.Fienms ,A.G.Graut, D.A.Wint&mme,andJ.Dszfsn-Taylor Dqmkmeut of Surgery,St. George'sRospital l&dicalSchool,CramerTe.rrace,IondcmSWl7 ORE, U.K. Under canpetitiveculture corditious with grmth-inhibitory activity cells sbxld, if themselvesrefractory, be amng