%PDF-1.7
%
57 0 obj
<>/OCGs[60 0 R]>>/PageLabels 48 0 R/Pages 50 0 R/Type/Catalog>>
endobj
58 0 obj
<>/Font<>>>/Fields 43 0 R>>
endobj
54 0 obj
<>stream
application/pdf
untitled
2016-07-06T07:23:06-07:00
2016-10-05T00:29:14+02:00
'Certified by IEEE PDFeXpress at 07/06/2016 7:23:10 AM'
2016-10-05T00:29:14+02:00
Acrobat Distiller 9.0.0 (Windows)
uuid:1a8c5999-7b1e-4371-b9e6-c4a6f6a37477
uuid:312efb80-2ce5-4f79-87e7-47d5a4bec57b
'Certified by IEEE PDFeXpress at 07/06/2016 7:23:10 AM'
endstream
endobj
59 0 obj
<>
endobj
48 0 obj
<>
endobj
50 0 obj
<>
endobj
61 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/TrimBox[121.89 172.913 717.276 1015.25]/Type/Page>>
endobj
1 0 obj
<>/Font<>/ProcSet[/PDF/Text]/XObject<>>>/Rotate 0/TrimBox[121.89 172.913 717.276 1015.25]/Type/Page>>
endobj
3 0 obj
<>/ExtGState<>/Font<>/ProcSet[/PDF/Text/ImageC/ImageI]/XObject<>>>/Rotate 0/TrimBox[121.89 172.913 717.276 1015.25]/Type/Page>>
endobj
7 0 obj
<>/ExtGState<>/Font<>/ProcSet[/PDF/Text/ImageC/ImageI]/XObject<>>>/Rotate 0/TrimBox[121.89 172.913 717.276 1015.25]/Type/Page>>
endobj
18 0 obj
<>/ExtGState<>/Font<>/ProcSet[/PDF/Text/ImageC/ImageI]/XObject<>>>/Rotate 0/TrimBox[121.89 172.913 717.276 1015.25]/Type/Page>>
endobj
22 0 obj
<>/ExtGState<>/Font<>/ProcSet[/PDF/Text/ImageC/ImageI]/XObject<>>>/Rotate 0/TrimBox[121.89 172.913 717.276 1015.25]/Type/Page>>
endobj
164 0 obj
<>stream
BT
/GS0 gs
/TT0 1 Tf
10.016 0 0 10.02 179.7 936.6203 Tm
( )Tj
ET
q
232.6799927 0 0 166.3800049 179.6999969 768.9199982 cm
/Im0 Do
Q
BT
/TT0 1 Tf
7.9767 0 0 7.98 412.38 768.9203 Tm
( )Tj
-0.0049 Tc 0.289 Tw -29.17 -1.158 Td
[(Fig.)4( 4.)4( )-7(Co)-9(m)13(p)-1(ar)5(is)-7(on of the ther)5(apies as a function of total inhibitor)-10( )]TJ
-0.0064 Tc 0.1325 Tw 0 -1.06 TD
[(concentr)-4(ation and stead)-10(y stat)-7(e tu)-10(m)12(o)-10(r)-4( )]TJ
-0.0049 Tc 0.131 Tw [(volu)-9(m)13(e.)4( Pr)5(otocol )-7(based ther)5(apies: )]TJ
0.0182 Tw 0 -1.068 TD
[(bolus doses with )-15(m)6(a)3(xim)13(u)-16(m)13( tolerate)]TJ
-0.0039 Tc 0.0172 Tw 14.126 0 Td
[(d )-7(dose \()6(B)1(D MT)5(D\),)5( b)-8(olus doses \()6(B)-6(D\), )]TJ
-0.0042 Tc 0.3936 Tw -14.126 -1.06 Td
[(low-)5(dose )-15(m)14(e)-4(tr)5(ono)-8(m)14(i)-5(c regim)14(e)-4(n \(L)5(DM)5(\),)5( continuous infusion ther)5(apy)-8( )]TJ
-0.005 Tc 0.1085 Tw 0 -1.06 TD
[(\()5(c)3(ont\).)4( Dis)-7(c)3(rete co)-9(ntr)5(o)-1(ller)5( based ther)4(apies: satu)-9(r)5(a)3(tion: 100 )-8(m)21(g)-1(/kg \()5(s)-7(at = )]TJ
-0.0036 Tc -0.0057 Tw 0 -1.053 TD
[(100\))6(,)6( satur)6(a)-3(tion: 2)-8(0 )-7(m)15(g/kg )-7(\()6(s)2(at = 20\), )9(saturation: 2.)6(5 )-15(m)15(g/kg \()6(s)2(at = 2.)6(5\). )]TJ
0 Tc 0 Tw 10.016 0 0 10.02 179.7 704.6003 Tm
( )Tj
-0.0069 Tc 0.1882 Tw 0 -1.305 TD
[(au)-4(to)-4(mated)-4( trea)-6(t)-5(m)10(en)-4(ts)-7( ach)-4(iev)-4(e)-6( co)-4(n)-4(s)-1(id)-4(erab)-4(ly lo)-4(wer stead)-4(y)-4( )]TJ
0.3678 Tw 0 -1.06 TD
[(state)-6( tu)-10(m)10(o)-4(r v)-10(o)-4(lu)-4(m)10(es)-7( wh)-4(ile)-6( u)-4(s)-1(in)-4(g)-4( less t)-4(h)-4(an)-4( h)-4(alf to)-4(tal)-4( )]TJ
-0.0045 Tc 0.0001 Tw 0 -1.054 TD
[(i)4(nhi)4(bi)4(t)4(o)-2(r conce)8(n)-2(t)4(r)-1(at)4(i)4(on. The choi)4(ce bet)4(w)-1(een t)4(h)-2(e aut)4(o)-8(m)13(a)2(ted )]TJ
-0.0056 Tc 0.0911 Tw 0 -1.06 TD
(treatments depends on the cu)Tj
-0.0049 Tc 0.0904 Tw 11.819 0 Td
[(rrent therapeut)9(i)3(c goal. If the)-4( )]TJ
-0.0047 Tc 0.0243 Tw -11.819 -1.054 Td
[(goal)4( i)4(s)1( t)4(o)-2( reduc)8(e t)4(h)-2(e t)4(u)-8(m)12(o)-2(r vol)4(um)12(e )-6(as fast)4( as )-6(possi)4(bl)4(e, an)4(d)4( )]TJ
-0.0041 Tc 0.5209 Tw T*
[(t)4(h)-1(e pat)4(i)4(e)2(nt)4( tol)4(e)2(rat)4(e)2(s M)5(T)2(D bol)4(uses, t)4(h)-1(e)8( 10)5(0 m)13(g)-1(/)4(k)-1(g)-7( )]TJ
-0.0067 Tc 1.0267 Tw 0 -1.054 TD
[(satu)-4(ratio)-4(n)-4( is th)-4(e )-6(m)10(o)-4(st)-4( ap)-4(p)-4(r)3(o)-4(p)-4(r)-3(iate way. Th)-4(e )1024( )]TJ
-0.0045 Tc 0.4194 Tw 0 -1.06 TD
[(20 m)13(g)-2(/)4(kg sat)4(u)-2(rat)4(i)4(on l)4(e)2(vel)4( )6(i)4(s)1( a t)4(r)-1(ade-of)5(f)5( choi)4(ce:)4( t)4(h)-2(e )]TJ
-0.004 Tc 0.2812 Tw 0 -1.054 TD
[(phy)5(si)4(ol)4(ogi)4(cal)4( load of t)4(h)-1(e pa)9(t)4(i)4(e)3(nt)4( )-6(i)4(s)2( )-6(l)4(e)3(ss; )-6(howe)9(v)-1(er, t)4(h)-1(e)9( )]TJ
-0.0063 Tc 0.1457 Tw T*
[(gained steady )6(state tu)-9(m)11(o)-3(r volu)]TJ
-0.0056 Tc 0.145 Tw 12.622 0 Td
[(m)12(e)1( is higher com)12(p)-3(ared to )]TJ
-0.0073 Tc 0.2904 Tw -12.622 -1.06 Td
[(th)-4(e BD MTD th)-4(erap)-4(y. Tak)-4(i)1(n)-4(g)-4( in)-4(to)-4( accoun)-4(t th)-4(e ab)-4(ov)-4(e )]TJ
-0.0043 Tc 0.551 Tw T*
[(m)7(e)2(nt)4(i)4(oned va)8(scul)4(at)4(ure no)5(r)5(m)7(ali)4(z)2(at)4(i)4(on aspect)4( and t)4(h)-1(e )]TJ
-0.0041 Tc 0.0297 Tw 0 -1.06 TD
[(m)7(i)4(nim)7(a)-3(l)4( si)4(de effect)4(s;)4( 2.5 m)13(g)-1(/kg sat)4(u)-1(rat)4(i)4(o)-1(n)5( s)8(e)2(em)13(s t)4(o)-1( be t)4(h)-1(e )]TJ
-0.0057 Tc 0.0013 Tw 0 -1.054 TD
[(best therapeutic choice in m)11(o)-9(st cases.)-7( )]TJ
0.0026 Tc 0 Tw 6.284 -2.18 Td
(VI.)Tj
/TT1 1 Tf
0 Tc 1.306 0 Td
( )Tj
/TT0 1 Tf
1.144 0 Td
(A)Tj
-0.0006 Tc 7.9767 0 0 7.98 274.44 532.0403 Tm
[(CKNOWL)-7(E)1(DG)-8(EME)-7(NT)]TJ
0 Tc 10.016 0 0 10.02 353.46 532.0403 Tm
( )Tj
-0.0052 Tc 0.4261 Tw -16.342 -1.473 Td
(The research was supported by the Research and )Tj
-0.004 Tc 0.4788 Tw -1.006 -1.06 Td
[(Inn)5(ovat)4(i)4(o)-1(n)5( C)4(e)3(nt)4(er of)6( \323)5(b)-1(u)5(d)5(a)3( Uni)4(v)-1(ersi)4(t)4(y)5( and )6(by)5( t)4(h)-1(e )]TJ
-0.006 Tc 0.4629 Tw T*
[(European Research Council Starting Gra)7(n)-3(t ERC-StG )]TJ
-0.0028 Tc 0 Tw 0 -1.06 TD
[(67)6(96)6(81.)8( )]TJ
0 Tc 9.034 -2.174 Td
(R)Tj
-0.0006 Tc 7.9767 0 0 7.98 276.84 463.7003 Tm
[(EFER)-11(ENCES)]TJ
0 Tc 10.016 0 0 10.02 321.72 463.7003 Tm
( )Tj
0.0048 Tc 7.9767 0 0 7.98 179.7 450.2003 Tm
([1])Tj
/TT1 1 Tf
0 Tc 1.166 0 Td
( )Tj
/TT0 1 Tf
0.0008 Tc 0.3209 Tw 1.091 0 Td
[(DE. Ge)-7(rber, \223)-7(T)2(ar)-5(geted therapies: a new generation )8(of)-5( cancer )]TJ
0.0001 Tc 0 Tw 0 -1.128 TD
[(treat)-15(m)11(ents\224, )]TJ
/TT2 1 Tf
-0.0002 Tc 0.0059 Tw 5.122 0 Td
[(Am F)-6(a)-4(m )8(Ph)-4(ysicia)-4(n)]TJ
/TT0 1 Tf
0.0039 Tc -0.0057 Tw 7.635 0 Td
[(,)6( vol.)6( 77\()6(3\))6(,)6( pp.)6( 311-)6(31)8(9,)6( 2008.)13( )]TJ
0.0048 Tc 0 Tw -15.014 -1.383 Td
([2])Tj
/TT1 1 Tf
0 Tc 1.166 0 Td
( )Tj
/TT0 1 Tf
0.0023 Tc 0.0486 Tw 1.091 0 Td
[(T)4(A)2(.)4( Baudino,)4( \223T)4(ar)4(geted Cancer)4( T)4(h)]TJ
0.0008 Tc 0.0501 Tw 14.397 0 Td
(erapy: The Next Generation of )Tj
0.0651 Tw -14.397 -1.128 Td
[(Cancer T)-5(r)3(eat)-15(m)11(e)1(nt)-7(\224, )]TJ
/TT2 1 Tf
0.0021 Tc 0.0638 Tw 8.289 0 Td
(Curr Drug Discov Technol)Tj
/TT0 1 Tf
0.0037 Tc 0.0622 Tw 11.042 0 Td
[(,)6( vol.)6( 12\()6(1\))6(,)6( pp.)6( 3-)]TJ
0.004 Tc -0.0058 Tw -19.331 -1.128 Td
[(20,)6( 2015.)13( )]TJ
0.0048 Tc 0 Tw -2.257 -1.376 Td
([3])Tj
/TT1 1 Tf
0 Tc 1.166 0 Td
( )Tj
/TT0 1 Tf
0.0022 Tc 0.2442 Tw 1.091 0 Td
[(Y.)4( Kubota,)4( \223T)4(u)-9(m)13(or)4( angiogenesis)8( a)10(nd anti-)4(angio)6(g)-2(eni)9(c)2( ther)4(apy)6(\224)2(,)-11( )]TJ
/TT2 1 Tf
0.0007 Tc -0.0025 Tw T*
(Keio J Med)Tj
/TT0 1 Tf
0.0038 Tc -0.0056 Tw 4.618 0 Td
[(.)6(,)-2( vol.)6( 61\()6(2\))6(,)6( pp.)6( 47-)6(56,)6( 2012.)6( )]TJ
0.0048 Tc 0 Tw -6.875 -1.376 Td
([4])Tj
/TT1 1 Tf
0 Tc 1.166 0 Td
( )Tj
/TT0 1 Tf
0.0037 Tc 0.0923 Tw 1.091 0 Td
[(L)5(.)6( )-7(Am)14(it,)6( I.)6( Ben-Ahar)6(on,)6( L)5(.)-2( Vida)]TJ
0.0032 Tc 0.0928 Tw 13.524 0 Td
[(l, L.)5( L)5(e)3(ibovici,)5( )-7(and S. Ste)-12(m)6(m)14(er)5(, )]TJ
0.0023 Tc 0.1238 Tw -13.524 -1.128 Td
[(\223T)4(he im)20(pact of Bevacizu)-9(m)13(a)2(b \()4(A)2(vas)-7(tin\))4( on sur)4(v)-2(i)9(v)-2(al in)6( )-7(m)13(e)2(tastatic )]TJ
0.0009 Tc 0.0801 Tw T*
[(solid tu)-11(m)19(o)-3(rs-)-5(-)3(a )-15(meta-anal)-7(y)5(sis and syste)-7(m)12(a)-7(tic r)-5(e)1(view\224,)-5( )]TJ
/TT2 1 Tf
0.0016 Tc 0.0794 Tw 22.46 0 Td
[(PLoS One,)-4( )]TJ
/TT0 1 Tf
0.0032 Tc -0.005 Tw -22.46 -1.128 Td
[(8\()5(1\))5(:e51780.)5( doi: )8(10.)5(137)7(1/jour)5(nal.)5(po)7(ne.)5(0051)7(780.)5( 20)7(13.)13( )]TJ
0.0048 Tc 0 Tw -2.257 -1.383 Td
([5])Tj
/TT1 1 Tf
0 Tc 1.166 0 Td
( )Tj
/TT0 1 Tf
0.0022 Tc 0.1389 Tw 1.091 0 Td
[(Y.)4( Cao,)4( and L)4(.)4( Xue,)4( \223Angiostatin\224,)12( )]TJ
/TT2 1 Tf
0.002 Tc 0.1391 Tw 15.239 0 Td
[(Semin Thromb H)10(emost)]TJ
/TT0 1 Tf
0.004 Tc 0.1371 Tw 9.47 0 Td
[(,)6( vol. )]TJ
-0.0058 Tw -24.709 -1.128 Td
[(30\()6(1\))6(,)6( pp.)6( 83-)6(93,)6( 2004.)13( )]TJ
0.0048 Tc 0 Tw -2.257 -1.376 Td
([6])Tj
/TT1 1 Tf
0 Tc 1.166 0 Td
( )Tj
/TT0 1 Tf
0.0004 Tc 0.231 Tw 1.091 0 Td
[(MS. O'Reill)-8(y, T)-6(.)2( Boeh)-11(m)19(,)2( Y)-7(.)2( Shing, N. Fukai, G. Vasios, WS.)-5( )]TJ
0.0025 Tc 0.4019 Tw T*
[(L)4(a)3(ne,)4( E)4(.)4( Fly)6(nn,)4( JR.)4( Bir)5(khead,)4( B)8(R.)4( Olsen,)4( and J.)12( Folk)-9(m)21(a)3(n, )]TJ
0.0028 Tc 0.1534 Tw T*
[(\223E)4(ndo)6(statin: an e)10(ndoge)10(nous)8( inhi)10(bitor)5( of)5( angio)6(g)-1(enesis)8( and tum)21(o)-1(r )]TJ
0.002 Tc 0 Tw T*
[(gr)4(owth\224,)4( )]TJ
/TT2 1 Tf
0.0008 Tc 3.784 0 Td
(Cell,)Tj
/TT0 1 Tf
0.004 Tc -0.0058 Tw 1.918 0 Td
[( vol. 88\()6(2\))6(,)6( pp.)6( 277-)6(28)8(5,)6( 1997.)13( )]TJ
0.0048 Tc 0 Tw 23.318 80.414 Td
([7])Tj
/TT1 1 Tf
0 Tc 1.166 0 Td
( )Tj
/TT0 1 Tf
0.0004 Tc 0.0129 Tw 1.091 0 Td
[(J. S\341pi, DA. Drexl)-8(e)1(r, and L. Kov\341cs, \223)-7(D)1(iscrete ti)-8(m)11(e)1( stat)-8(e f)-5(eedback )]TJ
0.0013 Tc 0.0421 Tw T*
[(with setpoint contr)11(o)-3(l,)3( actual stat)]TJ
0.0023 Tc 0.0411 Tw 13.005 0 Td
[(e obser)4(ver)4( and load estim)13(ation for)12( )]TJ
0.001 Tc 0.2379 Tw -13.005 -1.128 Td
[(a tu)-10(m)19(o)-3(r growth m)12(odel\224)-6(, sub)-10(m)19(itt)-7(ed to )]TJ
/TT2 1 Tf
0.0034 Tc 0.2355 Tw 16.541 0 Td
[(SA)5(CI)5(20)7(16 -)5( )8(1)7(1)-1(th I)5(E)5(E)5(E)-3( )]TJ
0.0019 Tc 0.1768 Tw -16.541 -1.128 Td
[(International Sym)10(posium on Applie)10(d Computatio)6(nal )8(Intelligence)-6( )]TJ
0.0023 Tc -0.0041 Tw T*
[(and I)4(n)-2(formatics)]TJ
/TT0 1 Tf
0.004 Tc -0.0058 Tw 6.386 0 Td
[(,)6( 0)8(7.)6(03.)6(201)8(6)8( )]TJ
0.0048 Tc 0 Tw -8.643 -1.376 Td
([8])Tj
/TT1 1 Tf
0 Tc 1.166 0 Td
( )Tj
/TT0 1 Tf
0.0005 Tc 0.0052 Tw 1.091 0 Td
[(DA. Drexle)-7(r, J. S\341pi, and L. Kov\341cs, \223)-7(O)1(n t)8(h)-3(e opti)-7(m)19(a)1(l di)-7(screte ti)-7(m)11(e)-7( )]TJ
0.0016 Tc 0.0041 Tw T*
[(control of antiangi)9(ogenic tu)-10(m)20(o)-2(r thera)-6(p)-2(y\224, sub)-10(m)12(itt)-6(ed to )]TJ
/TT2 1 Tf
0.0031 Tc 0.0026 Tw 22.227 0 Td
[(CDC2016 -)5( )]TJ
0.002 Tc -0.0038 Tw -22.227 -1.128 Td
[(55th IEEE Confere)-5(n)-2(ce on Decision and Control)]TJ
/TT0 1 Tf
0.004 Tc -0.0058 Tw 19.286 0 Td
[(,)6( 14.)6(0)8(3.)6(2016)8( )]TJ
0.0048 Tc 0 Tw -21.543 -1.376 Td
([9])Tj
/TT1 1 Tf
0 Tc 1.166 0 Td
( )Tj
/TT0 1 Tf
0.0031 Tc 0.4013 Tw 1.091 0 Td
[(F.)5( Xu,)5( Q.)5( Ma,)5( )-7(and H.)5( Sha,)5( \223Optim)21(izing dr)5(ug d)7(e)3(liver)5(y)7( fo)-8(r )]TJ
0.0016 Tc 0.1471 Tw T*
[(enhancing t)9(h)-2(erapeutic efficacy)5( of re)9(co)-10(m)20(b)-2(inant hu)-10(m)12(a)2(n)-10( endostatin)5( )]TJ
0.0004 Tc 0.0505 Tw T*
[(in cancer treat)-15(m)11(e)1(nt\224, )]TJ
/TT2 1 Tf
0.0013 Tc 0.0496 Tw [(Crit Rev Ther Drug Carrier )8(Syst, )]TJ
/TT0 1 Tf
0.0028 Tc 0 Tw 22.634 0 Td
(vol.)Tj
/TT2 1 Tf
0 Tc 1.534 0 Td
( )Tj
/TT0 1 Tf
0.004 Tc 0.301 0 Td
[(24\()6(5\))6(,)6( )]TJ
-0.0058 Tw -24.469 -1.128 Td
[(pp.)6( 445-)6(49)8(2,)6( 2007.)13( )]TJ
0.0044 Tc 0 Tw -2.257 -1.383 Td
([10])Tj
/TT1 1 Tf
0 Tc 1.67 0 Td
( )Tj
/TT0 1 Tf
0.0028 Tc 0.2361 Tw 0.587 0 Td
[(O.)5( Kisker,)5( CM)4(. )-7(Becker)5(,)5( D.)5( Pr)5(ox,)5( )-7(M)4(.)5( Fannon,)5( R.)5( D'Am)13(ato,)5( )-7(E)4(.)-3( )]TJ
-0.001 Tc 0.0293 Tw T*
[(Flyn)-5(n)-5(,)1( )-7(WE. )-7(Fo)-5(g)-5(l)-1(er)-6(, BK. Si)-16(m)10(,)-7( EN)-8(. )]TJ
0.0002 Tc 0.0281 Tw 14.043 0 Td
[(Al)-8(lred, SR. )-7(Pirie)-7(-She)-7(pherd, and )]TJ
0.0027 Tc 0.68 Tw -14.043 -1.128 Td
[(J.)5( Folk)-9(m)13(a)3(n,)5( \223Continu)6(ous ad)-9(m)21(i)2(nistr)5(a)3(tion of endo)6(statin by)6( )]TJ
0.0015 Tc 0.1848 Tw T*
[(intraperitoneally i)-6(m)12(pl)-6(anted os)-8(m)20(o)]TJ
0.0011 Tc 0.1852 Tw 13.675 0 Td
[(tic)-6( pu)-10(m)19(p)-3( i)-7(m)12(proves the ef)-4(f)-4(i)1(cacy )]TJ
0.0022 Tc 0.3195 Tw -13.675 -1.128 Td
[(and potency)6( o)6(f)-3( t)9(h)-2(er)4(apy)6( in a )-7(m)13(ouse xenogr)4(aft t)9(u)-9(m)13(o)-2(r)4( )-7(m)20(odel\224)-13(, )]TJ
/TT2 1 Tf
0.001 Tc -0.0028 Tw T*
(Cancer Res)Tj
/TT0 1 Tf
0.0039 Tc -0.0057 Tw 4.649 0 Td
[(,)6( vol.)6( 6)-8(1\()6(20\))6(,)6( pp.)6( 7669-)6(76)8(74,)6( 2001.)13( )]TJ
0.0044 Tc 0 Tw -6.905 -1.376 Td
([11])Tj
/TT1 1 Tf
0 Tc 1.67 0 Td
( )Tj
/TT0 1 Tf
0.0027 Tc 0.146 Tw 0.587 0 Td
[(P.)5( Hahnfeldt,)5( D.)5( )-7(Panigr)5(ahy)6(,)5( J. Folkm)13(a)-5(n,)5( and L.)5( Hlatky)6(,)5( \223T)4(u)-9(m)13(o)-9(r)-3( )]TJ
0.0023 Tc 0.1464 Tw T*
[(develop)-9(m)20(ent unde)10(r)4( angiogenic si)9(gna)]TJ
0.003 Tc 0.1457 Tw 15.164 0 Td
[(ling: A dy)7(nam)21(i)3(cal theor)5(y)7( of )]TJ
0.0025 Tc 0.1988 Tw -15.164 -1.128 Td
[(tu)-9(m)21(o)-1(r)5( gr)5(owth,)4( tr)5(eatm)13(ent r)5(e)3(sponse,)5( and p)6(o)-1(stvascular)5( )8(dorm)13(a)3(ncy)6(\224)-5(, )]TJ
/TT2 1 Tf
0.0013 Tc -0.0031 Tw T*
(Cancer research)Tj
/TT0 1 Tf
0.0038 Tc -0.0056 Tw 6.717 0 Td
[(,)6( vol.)6( 59,)6( pp.)6( 4770)7(\226)7(4775,)6( 19)7(99.)13( )]TJ
0.0044 Tc 0 Tw -8.974 -1.376 Td
([12])Tj
/TT1 1 Tf
0 Tc 1.67 0 Td
( )Tj
/TT0 1 Tf
0.0017 Tc 0.1244 Tw 0.587 0 Td
[(U.)4( L)3(e)2(dzewicz,)4( an)-10(d H.)4( Sch\344tler)4(,)4( \223A )-7(sy)5(nthesis of o)5(p)-2(tim)12(a)2(l contr)4(o)-2(ls )]TJ
0.0026 Tc 0.1235 Tw T*
[(for)5( a )-7(m)13(odel of tum)13(o)-9(r)5( gr)5(owth )]TJ
0.0024 Tc 0.1237 Tw 12.456 0 Td
[(under angiogenic inhibi)9(tor)4(s\224,)4( )]TJ
/TT2 1 Tf
0.0012 Tc 0 Tw 12.366 0 Td
[(CDC)-9( )]TJ
0.0022 Tc 0.1088 Tw -24.822 -1.128 Td
[(2005 \226 4)6(4)-2(th IEEE Conference on Decision and Co)6(ntr)8(o)-2(l, and the )]TJ
0.0023 Tc 0.3419 Tw T*
[(E)4(u)-2(ropean)6( Contr)8(o)-2(l)9( Conference)]TJ
/TT0 1 Tf
0.0018 Tc 0.3424 Tw 12.885 0 Td
[(, pp.)11( 934)5(\22693)5(9, Decem)12(b)-10(e)2(r 2005, )]TJ
0.001 Tc -0.0028 Tw -12.885 -1.128 Td
[(Sevilla, Spain.)-5( )]TJ
0.0044 Tc 0 Tw -2.257 -1.383 Td
([13])Tj
/TT1 1 Tf
0 Tc 1.67 0 Td
( )Tj
/T1_0 1 Tf
0.003 Tc 0.1231 Tw 0.587 0 Td
[(O.)5(G.)5( Sch)7(a)-4(r)5(o)-1(v)7(s)-7(k)7(y)-1(,)5( L)5(.)5(E.)5( M)4(a)3(in)7(etti,)5( and V.)5(R.)5( Ro)7(zado)7(s.)5( )-7(Metr)5(ono)7(m)6(i)-5(c )]TJ
-0.0017 Tc 0.0451 Tw T*
[(che)-9(m)2(o)-6(t)-2(he)-9(ra)-9(py: ch)-6(a)-9(ngi)-9(n)-6(g)2( )8(t)-9(h)2(e para)-9(di)-9(g)-6(m)2( )8(t)-9(h)2(at mo)-6(re )8(is)-4( bett)-9(er. )]TJ
/T1_1 1 Tf
0.0013 Tc 0 Tw 23.709 0 Td
[(C)-9(u)5(rren)5(t)-6( )]TJ
-0.0029 Tc -23.709 -1.128 Td
[(Onc)-10(o)1(l)-11(ogy)]TJ
/T1_0 1 Tf
-0.0024 Tc 0.0081 Tw 3.896 0 Td
[(, 16)-6(\(2)-6(\):)-10(7)-6(-)113(-)]TJ
0.004 Tc -0.0058 Tw 3.626 0 Td
[(-)6(15)8(,)-2( 200)8(9.)]TJ
/TT0 1 Tf
0 Tc 0 Tw 4.099 0 Td
( )Tj
0.0044 Tc -13.878 -1.376 Td
([14])Tj
/TT1 1 Tf
0 Tc 1.67 0 Td
( )Tj
/T1_0 1 Tf
-0.0004 Tc 0.0362 Tw 0.586 -0.001 Td
[(T. B)-10(r)2(owde)-8(r,)-6( C. )-8(E.)-6( )-8(Butter)-6(f)2(iel)-8(d)3(,)-6( B. )-8(M.)-6( )-8(Kr\250ali)-8(ng,)-6( B S)-8(h)3(i,)-6( B.)-6( Ma)-8(rshall)-8(, )]TJ
-0.0017 Tc 0.2406 Tw T*
(M. S. O)Tj
3.645 0.005 Td
(\222R)Tj
7.9767 0 0 7.98 447.18 653.9003 Tm
4.647 -1.128 Td
[(e)-1(ill)-9(y, a)-9(nd J)-4(. )-7(Fol)-9(k)-6(ma)-9(n. A)-9(n)2(tia)-9(ngi)-9(o)-6(ge)-9(nic s)-4(c)-1(h)-6(e)-1(d)-6(u)2(lin)-6(g )-7(o)-6(f)-7( )]TJ
0.5491 Tw -4.647 -1.128 Td
[(che)-9(m)1(o)-6(t)-2(he)-9(ra)-9(py)-6( im)-6(pr)-7(ov)-6(es)-4( ef)-7(ficac)-9(y )-7(agai)-10(ns)-4(t e)-9(x)-6(peri)-10(me)-9(ntal )-7(dr)-7(u)-6(g)2(-)]TJ
-0.0002 Tc -0.0016 Tw T*
[(resistan)3(t)-8( ca)-7(n)3(ce)-7(r)2(. )]TJ
/T1_1 1 Tf
0.0005 Tc -0.0023 Tw 6.702 0 Td
[(C)-9(a)4(ncer R)-5(e)1(searc)-7(h)]TJ
/T1_0 1 Tf
0.0046 Tc -0.0064 Tw 6.935 0 Td
[(, 60)8(\(7)8(\))7(:)-3(18)8(78-)120(-)]TJ
-0.0029 Tc 0.0011 Tw 5.13 0 Td
[(-1)-7(88)-7(6,)-9( 2)-7(0)1(0)-7(0)1(.)]TJ
/TT0 1 Tf
0 Tc 0 Tw 5.092 0 Td
( )Tj
0.0044 Tc -26.116 -1.376 Td
([15])Tj
/TT1 1 Tf
0 Tc 1.67 0 Td
( )Tj
/T1_0 1 Tf
-0.0017 Tc 0.2181 Tw 0.587 0 Td
[(R)-4(. S. K)-9(e)-1(r)-7(b)2(el. )-7(I)-7(m)-6(pr)-7(ovi)-9(n)-6(g)2( c)-9(o)-6(nve)-9(nti)-9(o)-6(nal )-7(or l)-9(o)2(w)-9( d)-6(o)2(s)-4(e)-1( )-7(metr)-7(o)-6(n)2(o)-6(m)2(ic)-9( )]TJ
0.7221 Tw T*
[(che)-9(m)1(o)-6(t)-2(he)-9(ra)-9(py )-7(wi)-10(th ta)-9(rge)-9(t)-2(ed)-6( ant)-10(i)-10(a)-2(n)-6(g)2(io)-6(ge)-9(nic )-7(dr)-7(u)-6(g)2(s)-4(. )]TJ
/T1_1 1 Tf
0.0004 Tc 0 Tw 23.935 0 Td
[(Cancer)-9( )]TJ
0.0031 Tc 0.0026 Tw -23.935 -1.128 Td
[(R)5(e)3(sea)7(r)1(ch)7( an)7(d )8(Treatmen)7(t)]TJ
/T1_0 1 Tf
-0.0021 Tc 0.0078 Tw 9.861 0 Td
[(, 39)-6(\(4)-6(\):1)-6(5)-6(0)2(-)113(-)]TJ
-0.0029 Tc 0.0086 Tw 4.618 0 Td
[(-)-8(1)-7(59)-7(, 20)-7(0)-7(7)1(.)]TJ
/TT0 1 Tf
0 Tc 0 Tw 4.603 0 Td
( )Tj
0.0044 Tc -21.34 -1.383 Td
([16])Tj
/TT1 1 Tf
0 Tc 1.67 0 Td
( )Tj
/TT0 1 Tf
0.0003 Tc 0.201 Tw 0.587 0 Td
[(J. S\341pi, )-7(L.)-5( Kov\341c)-7(s)-2(, D.)-5(A. )-7(Drexler)-5(,)2( )-7(P. Kocsis,)-5( D.)-5( Gaj)-8(\341ri, )-7(and Z.)-5( )]TJ
0.0015 Tc 0.8166 Tw T*
[(S\341pi, \223)-6(T)3(u)-10(m)20(o)-10(r)4( )-7(Volu)-10(m)12(e)2( Esti)-14(m)12(a)2(ti)-6(on and Quasi-Continuous )]TJ
0.0005 Tc 0.1707 Tw T*
[(Ad)-11(m)11(inistration f)-5(o)-3(r Most Ef)-5(f)-5(ective Bevacizu)-11(m)11(a)1(b Thera)-7(p)-3(y\224, )]TJ
/TT2 1 Tf
-0.0006 Tc 0 Tw 24.988 0 Td
[(Plo)-5(S)-12( )]TJ
0.002 Tc -24.988 -1.128 Td
(One)Tj
/TT0 1 Tf
0.0032 Tc -0.005 Tw 1.67 0 Td
[(,)5( vol.)5( 10:\()5(11\))5(,)5( )-7(Paper)5( e0142190.)5( 2)7(0)-1( p,)5( 2015.)13( )]TJ
0.0044 Tc 0 Tw -3.926 -1.376 Td
([17])Tj
/TT1 1 Tf
0 Tc 1.67 0 Td
( )Tj
/TT0 1 Tf
0.0003 Tc 0.1258 Tw 0.587 0 Td
[(T. N)-7(ing, M.)-5( Jiang, Q.)-5( Peng, X)-7(.)2( )-7(Yan, Z)-6(.)2(-J.)-5( Lu, )-7(Y.-)-5(L)2(.P)-8(eng, et al.)-13(,)-5( )]TJ
0.0024 Tc 0.2516 Tw T*
[(\223L)4(ow-)4(dose endost)9(a)3(tin norm)13(a)3(lizes)-7( the str)4(u)-2(ctur)4(e and )-7(functio)6(n of)4( )]TJ
0.0022 Tc 0.4022 Tw T*
[(tu)-9(m)20(o)-2(r)4( vasculatur)4(e and im)20(pr)4(oves the deliver)4(y)6( and )8(anti-)4(tu)-9(m)20(o)-9(r )]TJ
0.0019 Tc 0.2521 Tw T*
[(efficacy)6( of cy)6(totoxic drugs in )]TJ
0.0017 Tc 0.2523 Tw 13.336 0 Td
[(a lung cancer xenograft )-7(m)20(u)-10(rine)-6( )]TJ
0.0032 Tc 0 Tw -13.336 -1.128 Td
[(m)14(odel\224,)5( )]TJ
/TT2 1 Tf
0.002 Tc -0.0038 Tw 3.445 0 Td
[(Thorac.)4( C)-8(ancer)]TJ
/TT0 1 Tf
0.0039 Tc -0.0057 Tw 6.363 0 Td
[(,)6( vol.)6( 3\()6(2012)8(\))6(,)6( pp.)6( 229\226238,)6( 20)8(12.)6( )]TJ
0.0044 Tc 0 Tw -12.065 -1.376 Td
([18])Tj
/TT1 1 Tf
0 Tc 1.67 0 Td
( )Tj
/TT0 1 Tf
0.0012 Tc 0.3656 Tw 0.587 0 Td
[(RK. Jain, \223)-6(N)1(ormalization of tu)]TJ
0.0029 Tc 0.3639 Tw 13.848 0 Td
[(m)21(o)-9(r)5( vasculatur)5(e: an)-9( em)14(er)5(ging )]TJ
0.001 Tc 0.1552 Tw -13.848 -1.128 Td
(concept in antiangiogenic therapy\224, )Tj
/TT2 1 Tf
0.0014 Tc 0 Tw 15.134 0 Td
(Science)Tj
/TT0 1 Tf
0.0038 Tc 0.1524 Tw 3.061 0 Td
[(,)6( vol.)6( 307\()6(5706\))6(,)6( pp.)6( )]TJ
0.004 Tc -0.0058 Tw -18.195 -1.128 Td
[(58-)6(62,)6( 200)8(5.)6( )]TJ
0.0044 Tc 0 Tw -2.257 -1.383 Td
([19])Tj
/TT1 1 Tf
0 Tc 1.67 0 Td
( )Tj
/TT0 1 Tf
0.0025 Tc 0.0559 Tw 0.587 0 Td
[(DR.)4( Sor)5(e)3(nsen, T)4(A)-5(.)4( Read,)4( \223Delivery )]TJ
0.0023 Tc 0.0561 Tw 14.984 0 Td
[(of endostatin in ex)6(per)4(i)-6(m)13(e)2(ntal )]TJ
0.0003 Tc -0.0021 Tw -14.984 -1.128 Td
[(cancer ther)-5(apy\224,)-5( )]TJ
/TT2 1 Tf
0.0023 Tc -0.0041 Tw 6.815 0 Td
[(I)4(n)-9(t J Exp P)4(a)-2(thol)]TJ
/TT0 1 Tf
0.0039 Tc -0.0057 Tw 6.552 0 Td
[(,)6( vol.)6( 83\()6(6\))6(,)6( pp.)6( 265\22627)8(4,)6( 2002.)13( )]TJ
0.0044 Tc 0 Tw -15.623 -1.376 Td
([20])Tj
/TT1 1 Tf
0 Tc 1.67 0 Td
( )Tj
/TT0 1 Tf
0.0008 Tc 0.2908 Tw 0.587 0 Td
[(J. Wu, D)-7(.)3( Ding,)-5( G. Ren, X. )-7(Xu,)-5( X. Yin, Y)-7(.)3( Hu,)-5( \223)-7(Sustaine)8(d)4( )]TJ
0.002 Tc 0.1241 Tw T*
[(delivery)6( of endost)9(a)2(tin i)-6(m)20(p)-9(r)4(oves th)]TJ
0.0011 Tc 0.125 Tw 14.262 0 Td
[(e efficacy)5( of therap)5(y)5( in Lewis)-16( )]TJ
0.0022 Tc 0.2518 Tw -14.262 -1.128 Td
[(lung cancer)4( )-7(m)13(odel\224,)4( )]TJ
/TT2 1 Tf
0.002 Tc 0.252 Tw [(J Control R)4(e)2(lease,)]TJ
/TT0 1 Tf
0.0038 Tc 0.2502 Tw [( vol.)6( 134\()6(2\))6(,)6( pp.)6( 91-)6(7,)6( )]TJ
0.004 Tc 0 Tw T*
[(2009.)13( )]TJ
0.0044 Tc -2.257 -1.376 Td
([21])Tj
/TT1 1 Tf
0 Tc 1.67 0 Td
( )Tj
/TT0 1 Tf
0.0006 Tc 0.0728 Tw 0.587 0 Td
[(M. Capillo, P. )-8(Ma)-7(ncuso, A. Gobbi, )]TJ
0.0008 Tc 0.0726 Tw 14.758 0 Td
[(S. Monestiroli, G)-7(.)3( )-8(Pruneri, C. )]TJ
0.0017 Tc 0.1996 Tw -14.758 -1.128 Td
[(Dell'Agnola,)4( G.)4( )-7(M)3(a)2(r)4(tinelli,)4( L.)4( S)]TJ
0.0024 Tc 0.1989 Tw [(hultz,)4( F. Ber)4(t)2(olini,)4( \223Continu)6(ous )]TJ
0.0022 Tc 0.2292 Tw T*
[(infusi)9(on of endos)8(tatin inhibits )8(di)]TJ
0.0016 Tc 0.2373 Tw 13.961 0 Td
[(ffe)9(r)4(entiation, m)20(obiliz)-6(ation, )8(and )]TJ
0.0019 Tc 0.0791 Tw -13.961 -1.128 Td
[(clonogenic )8(potenti)9(al of e)10(ndot)9(helial cell pr)4(ogenitor)4(s\224,)4( )]TJ
/TT2 1 Tf
0.0017 Tc 0.0793 Tw 21.889 0 Td
[(C)7(lin Cancer)7( )]TJ
-0.0009 Tc 0 Tw -21.889 -1.128 Td
(Res)Tj
/TT0 1 Tf
0.004 Tc -0.0058 Tw 1.444 0 Td
[(.)6( vol.)6( 9\()6(1\),)6( pp.)6( )-7(377-)6(38)8(2,)6( 2003.)13( )]TJ
0 Tc 0 Tw -1.444 -1.383 Td
( )Tj
0 -1.376 TD
( )Tj
-2.257 -1.376 Td
( )Tj
0 -1.383 TD
( )Tj
0 -1.376 TD
( )Tj
10.016 0 0 10.02 439.26 311.6603 Tm
( )Tj
0 -1.305 TD
( )Tj
7.9767 0 0 7.98 420.72 286.5203 Tm
( )Tj
0 -1.376 TD
( )Tj
-32.72 -1.383 Td
( )Tj
0 -1.053 TD
( )Tj
ET
/Artifact <>BDC
q
1 0 0 1 261.8588257 990.5175781 cm
/GS1 gs
/Fm0 Do
Q
EMC
/Artifact <>BDC
q
1 0 0 1 607.8358154 206.0288086 cm
/GS1 gs
/Fm1 Do
Q
EMC
endstream
endobj
91 0 obj
<>>>/Resources 95 0 R/Subtype/Form>>stream
0 g 0 G 0 i 0 J []0 d 0 j 1 w 10 M 0 Tc 0 Tw 100 Tz 0 TL 0 Tr 0 Ts
BT
/ArialNarrow 9 Tf
0 g
0 -7.106 Td
(2016 ) Tj
18.47 0 Td
(IEEE ) Tj
18.87 0 Td
(International ) Tj
42.676 0 Td
(Conference ) Tj
40.205 0 Td
(on ) Tj
10.261 0 Td
(Systems, ) Tj
32.406 0 Td
(Man, ) Tj
18.461 0 Td
(and ) Tj
14.366 0 Td
(Cybernetics ) Tj
41.018 0 Td
(\225 ) Tj
4.637 0 Td
(SMC ) Tj
18.448 0 Td
(2016 ) Tj
18.47 0 Td
(| ) Tj
3.968 0 Td
(October ) Tj
28.31 0 Td
(9-12, ) Tj
18.874 0 Td
(2016 ) Tj
18.471 0 Td
(\225 ) Tj
4.636 0 Td
(Budapest, ) Tj
35.292 0 Td
(Hungary) Tj
ET
endstream
endobj
159 0 obj
<>>>/Resources 160 0 R/Subtype/Form>>stream
0 g 0 G 0 i 0 J []0 d 0 j 1 w 10 M 0 Tc 0 Tw 100 Tz 0 TL 0 Tr 0 Ts
BT
/ArialNarrow 9 Tf
0 g
0 -7.106 Td
(SMC_2016 ) Tj
45.127 0 Td
(003835) Tj
ET
endstream
endobj
27 0 obj
<>stream
hK۸ӝLq6xxx=#EUEǖtp%
oT" H@"$ H$@D$ H$@H$ H@HWA!97YW)ޭGi~@QH["仐bhg}n&GFx!px ȷ M/FNA
q_8ɯ_m]AvQ"?97Hv7˗_۷oyE}B%Hd H!gtȳ6D$@
})r H@~2^H^>!dڻt
h.>ztr7stlFs I3HٹB/]BZrhr
W$
mN@2 %'L_.0 .;Ҷ]N!9bKUyg$'cJ!yv):&Ŏv%n{%2@n
ax{_/GH퉞6sdFl~@ن25[Fz\f 5<
Bo<