ࡱ> ad` bjbjVV M"<<D 3;; I I=P=P=PQPQPQP8PP$QPcJPPPPPRRR(c*c*c*c*c*c*c$ hjNc-=PRRRRRNc I IPPX{csYsYsYR I2P=PPbZsYR(csYsYVR`@;NaP`QPT` bc0c`xkVkaa@k=PVbdRRsYRRRRRNcNcsYRRRcRRRRkRRRRRRRRR; G: SUPPLEMENTARY MATERIALS AND METHODS Primer sequences and probes used for Taqman PCR: mmu HIF-1( upper, 5-gcactagacaaagttcacctgaga-3 mmu HIF-1( lower, 5-cgctatccacatcaaagcaa-3, Probe: #95 mmu PDK-1 upper, 5-gttgaaacgtcccgtgct-3 mmu PDK-1 lower, 5-gcgtgatatgggcaatcc-3, Probe: #20 mmu GLUT-1 upper, 5-atggatcccagcagcaag-3 mmu GLUT-1 lower, 5-ccagtgttatagccgaactgc-3, Probe: #52 mmu PFK-L upper, 5-ccatggacgaggagaggtt-3 mmu PFK-L lower, 5-tccagttgttctcaaagctcct-3, Probe: #42 mmu ENO-1 upper, 5-gaggcgcttagtgctgct-3 mmu ENO-1 lower, 5-agaatagacatggcgaatttctg-3, Probe: #91 mmu OSM-R upper, 5- ccaaaaagagttcagcacacc -3 mmu OSM-R lower, 5- ccgaccacacttgtctccat -3, Probe: #32 mmu PDGFRa upper, 5-gtcgttgacctgcagtgga-3 mmu PDGFRa lower, 5-ccagcatggtgatacctttgt-3, Probe: #80 mmu SOCS-3 upper, 5-atttcgcttcgggactagc-3 mmu SOCS-3 lower, 5-aacttgctgtgggtgaccat-3, Probe: #83 mmu ATP-5L upper, 5-aaggaagctgtgctgaatgg-3 mmu ATP-5L lower, 5-atgccacgtttgcctatga-3, Probe: #42 mmu FH-1 upper, 5-gcaccccaatgatcatgtta-3 mmu FH-1 lower, 5-cattgctgtgggaaaggtg -3, Probe: #106 mmu NDUFB4 upper, 5-agggtggtgaagtggaagag-3 mmu NDUFB4 lower, 5-tggccacttccactggtta-3, Probe: #31 mmu NDUFA6 upper, 5-cccactcccaagaactcact-3 mmu NDUFA6 lower, 5-tggataagtctttcctttctgtcc-3, Probe: #17 hsa HIF-1( upper, 5-ggttcactttttcaagcagtagg-3 hsa HIF-1( lower, 5-tggtaatccactttcatccattg-3, Probe: #3 hsa PDK-1 upper, 5-gctgggtaatgaggatttgact-3 hsa PDK-1 lower, 5-aagtctgtcaattttcctcaaagg-3, Probe: #10 hsa ENO-1 upper, 5-gctccgggacaatgataaga-3 hsa ENO-1 lower, 5-tgatgtgctcaacagccttt-3, Probe: #60 Antibodies. Rabbit polyclonal against p-Stat3, p-Akt and Caspase-3 (Cell Signaling Technology, Danvers MA, USA), Stat3 and Actin (Santa Cruz Biotechnology, Santa Cruz CA, USA), Vdac-1 (Abcam, Cambridge, UK). Mouse monoclonal against Hif-1( (Novus Biologicals, Littleton CO, USA), Sod2 (Abcam) and (-Tubulin (Santa Cruz Biotechnology). Mouse monoclonal against Akt was generated in house by immunization with a MBP-Akt fusion protein and purified against the recombinant protein. The MitoProfile total OXPHOS rodent WB Antibody Cocktail (Mitosciences, Eugene OR, USA) was used for mitochondrial complexes. In vivo model. 8 Female mice 5 to 7 weeks of age were s.c. implanted in CD-1 mice (Charles River Laboratories, Inc.) with MDA-MB468. Cells were harvested using trypsin and washed with PBS. 107 Cells were resuspended in 200 L PBS and injected s.c. into the left flank of mice. 14 days after the inoculation of tumour cells, mice were randomly divided in two groups and the first PET acquisition was performed. Subsequently the first group (n=5) rec$%V_`  ) @ $ % 0 G T U ` w 0DSTUaCD~϶϶ϟϟ϶϶϶϶ώ϶{϶ h>/GCJh#ph>/GCJmHsH!h#ph>/GB*CJmHphsH-h#ph>/G0JBB*CJOJQJ^JaJphh#ph>/GB*CJph jah#ph>/GCJh#ph>/GCJh#ph>/G>*CJh>/G5CJOJQJ$h h>/G5B*CJOJQJph+$%V! L  P   K  L %$ & 0` P@d1$7$8$H$a$gd>/G $da$gd>/Gdgd>/GL y  K TU $da$gd>/G%$ & 0` P@d1$7$8$H$a$gd>/G~r ǵhp hh4h>/GhFTjhFTU(hi!h>/G5B*CJOJQJaJph33"h>/G5B*CJOJQJaJph33h<2Xh>/G5CJOJQJUh#ph>/GCJH*h#ph>/G>*CJh#ph>/GCJ jbh#ph>/GCJeived in the tail vein a 5 mg/kg of S3I three time per week for 2 consecutive weeks; the second group (n=3) was not treated. All mice were monitored two times weekly for body weight and tumour measurement.           $da$gd>/GK01h:p>/G/ =!"#$% P0 f 7777777777777777777777777777777777777777777777777777777777H77777777777777777777777777777777777777777777777777777777777772 0@P`p2( 0@P`p 0@P`p 0@P`p 0@P`p 0@P`p 0@P`p8XV~OJQJ_HmH nH sH tH H`H ZjNormal CJOJQJ_HaJmH sH tH PP Zj Heading 1$d@&a$5OJQJ\^J:: Zj0 Heading 2$@&6]ZZ Zj0 Heading 3$<@&5CJOJPJQJ\^JaJVV Zj0 Heading 4$<@&5CJPJ\aJmH sH LL Zj0 Heading 5$@&>*CJPJaJmH sH bbb Zj0 Heading 6@&/5B*CJOJPJQJ\^JaJmH ph333sH NN Zj0 Heading 7$@&5CJPJ\aJmH sH TT Zj0 Heading 8$@& 56CJPJ\]aJmH sH DA`D Default Paragraph FontRiR 0 Table Normal4 l4a (k ( 0No List VV C0Heading 1 Char"5CJ KH OJQJ\^JaJ tH NN Zj0Heading 2 Char6CJOJQJ]^JaJNN Zj0Heading 3 Char5CJOJQJ\^JaJV!V Zj0Heading 4 Char"5CJOJQJ\^JaJmH sH T1T Zj0Heading 5 Char>*CJOJQJ^JaJmH sH `A` Zj0Heading 6 Char+5B*CJOJQJ\^JaJmH ph333sH VQV Zj0Heading 7 Char"5CJOJQJ\^JaJmH sH \a\ Zj0Heading 8 Char(56CJOJQJ\]^JaJmH sH >Br> Zj Body Texta$ OJQJ^JLL C0Body Text CharCJOJQJ^JaJtH << Zjmeth1hd dmH sH 44 ZjHeader !FF C0 Header CharCJOJQJ^JaJtH 4 4 Zj0Footer !FF C0 Footer CharCJOJQJ^JaJtH :): Zj Page Number OJQJ^JFF ZjLEGEND dOJQJ^JmH sH << Zj0CM12 1$7$8$H$ OJQJ^J\/\ Zj0Default!1$7$8$H$%B*CJ^J_HaJmH phsH tH .. Zj0CM13" B*phBU1B Zj Hyperlink>*B*OJQJ^Jph:: Zj0CM10$B*OJQJ^Jph>> Zj0CM1%dB*OJQJ^Jph:: Zj0CM11&B*OJQJ^Jph@@ Zj0CM2'd1$7$8$H$ OJQJ^Jbb Zj0Data Field 11pt-Single(7$8$CJOJQJ^JaJFCF ?Zj0Body Text Indent )dxZZ )C0Body Text Indent CharCJOJQJ^JaJtH N'N ZjComment ReferenceCJOJQJ^JaJHH -Zj Comment Text,CJaJmHsHtHRR ,CComment Text CharCJOJQJ^JaJtH @j@ /ZjComment Subject.5\FF .CComment Subject Char5\TT 1Zj Balloon Text0 CJOJ QJ ^J aJmHsHtHNN 0CBalloon Text CharCJOJQJ^JtH P"P Zj0Thesis2d*$1$`ha$OJQJ^JmHsHVT2V Zj0 Block Text3dh7$8$H$]^a$ OJQJ^J,A, Zj0bold OJQJ^J:XQ: Zj@Emphasis6OJQJ]^J0a0 Zj0italic OJQJ^J8q8 Zj0 yshortcuts OJQJ^JZZ Zj0reference-journal-title26OJQJ]^J66 Zjp-ni 9dmH sH (( Zjabs:5\** Zjmeth1;`7  ZjBX<PRP >Zj0Body Text Indent 2 =d`6]`` =Zj0Body Text Indent 2 Char6CJOJQJ]^JaJXX )Zj0Body Text Indent Char1CJOJQJ^JaJ(( Zj0ti OJQJ^JB^B Zj0 Normal (Web)Add[$\$Jg@!J ZjHTML TypewriterCJOJ QJ ^J aJ212 Zj0ti2CJOJQJ^JaJ@A@ Zj0 journalname6OJQJ]^JBRB FZj0 Footnote TextE CJaJtHLaL EZj0Footnote Text CharOJPJ^JtHL&qL Zj0Footnote ReferenceH*OJQJ^JN/N Zj0!B8;L1H7$8$ CJOJQJ_HaJmH sH tH44 Zj0textbold OJQJ^JBQB KZj0 Body Text 3Jx CJaJtHPP JZj0Body Text 3 CharCJOJQJ^JaJtHxx Zj0Colorful List - Accent 11Ld^CJOJQJ^JaJmH sH 6W6 Zj0Strong5OJQJ\^J^^ Zj0Data Field 11ptNd7$8$CJOJPJQJ^JaJTT Zj0Data Field 11pt CharCJOJQJ^JaJjj Zj0 contentparaPdd[$\$)B*CJOJPJQJ^JaJmH phsH @@ Zj0TxBr_p4 Qd1$ PJmH sH H"H Zj0TxBr_p2Rd1$ PJmH sH P2P Zj0TxBr_p3Sd1$^1` PJmH sH RAR Zj0 xpapertitle1!@B*CJOJ QJ ^J aJphFQF Zj0xauthor15@CJOJ QJ \^J aJZaZ Zj0Body Text Indent 3 CharOJ QJ ^J mH sH lSrl XZj0Body Text Indent 3 W1$^7` CJOJ PJQJ ^J aJmH sH `` WC0Body Text Indent 3 Char1CJOJQJ^JaJtH && Zj0w OJQJ^J&& Zj0a OJQJ^J** Zj0doi OJQJ^JBB Zj0fm-vol-iss-date OJQJ^JLL Zj0 fm-author]dd[$\$PJmH sH tH ** Zj0atl OJQJ^J>> Zj0 journalnumber OJQJ^JBB Zj0cite-month-year OJQJ^J<"< Zj0Caption axx 5PJ\J"J Zj0abstractbdd[$\$PJmH sH tH H>2H dZj0Title ca$5>*CJPJ\aJJAJ cZj0 Title Char5>*CJOJQJ\^JaJ<aQ< Zj0 HTML Cite6OJQJ]^J.a. Zj0z3988 OJQJ^J0q0 Zj0volume OJQJ^J.. Zj0issue OJQJ^J.. Zj0pages OJQJ^JFF Zj0featured_linkouts OJQJ^J22 Zj0linkbar OJQJ^J44 Zj0bodytext OJQJ^JNN Zj0citation-abbreviation OJQJ^JVV Zj0citation-publication-date OJQJ^JBB Zj0citation-volume OJQJ^J@@ Zj0citation-issue OJQJ^JDD Zj0citation-flpages OJQJ^J8!8 Zj0 css_author OJQJ^J:1: Zj0 ref-journal OJQJ^J2A2 Zj0ref-vol OJQJ^JeR vZj0HTML Preformatted7u2( Px 4 #\'*.25@9CJOJ PJQJ ^J aJPaP uZj0HTML Preformatted Char OJ QJ ^J 2q2 Zj0authors OJQJ^J,, Zj0icon OJQJ^J22 Zj0dblinks OJQJ^J:: Zj0 moz-txt-tag OJQJ^JBB Zj0 articleref{dd[$\$PJLL Zj0articlecitation|dd[$\$PJ,, Zj0name OJQJ^J66 Zj0 forenames OJQJ^J22 Zj0surname OJQJ^J88 Zj0titledd[$\$PJ:: Zj0sourcedd[$\$PJ<!< Zj0 nlm_xref-aff OJQJ^JRV1R Zj0FollowedHyperlink>*B* OJQJ^JphB t0/Char1 Char Char   Char   Char Char Char dCJOJ QJ aJ\Q\ t0fm-vol-iss-date1$CJOJQJ^J_HaJmH sH tH rar t0maintextbldleft195>*B*CJOJQJY(\^J_HaJmH phsH tH fqf t0 maintextleft13>*B*CJOJQJY(^J_HaJmH phsH tH >> t0heading2dd[$\$_H LL t0 smallcaps1:OJQJ^J_HmH sH tH JJ t0normal1$CJOJQJ^J_HaJmH sH tH >> t0times new roman_H dd t0 seriestitle135B* CJOJ QJ \^J_HaJmH phfsH tH XX t0 black9pt1-B*CJOJ QJ ^J_HaJmH phsH tH PP t0title21*5CJOJ QJ \^J_HaJmH sH tH RR At0Normal (Web) CharCJOJQJ^JaJtH  t0HTML Preformatted172( Px 4 #\'*.25@9 CJOJ QJ ^J _H aJmH sH : : t0Style 21$7$8$`ha$P! P t0body1-B*CJOJQJ^J_HaJmH phsH tH 2 t0HTML Preformatted272( Px 4 #\'*.25@9CJOJ QJ ^J aJjB j t0Char Char1 Char1 Char Char dCJOJ QJ aJZQ Z t0 refpreview1,<OJ QJ ^J_HmH q sH tH Da D t0xref-sepOJ QJ ^J_HmH sH tH Dq D t0slug-volOJ QJ ^J_HmH sH tH H H t0 slug-issueOJ QJ ^J_HmH sH tH @ @ t0Char1 dCJOJ QJ aJ> > t0citationdd[$\$_H b b t0 auth_list!ddM [$\$]CJOJ QJ _H aJ~ ~ t0$Char Char1 Char1 Char Char Char Char dCJOJ QJ aJ t0?Char1 Char Char   Char   Char Char Char   Char Char dCJOJ QJ aJ t0JChar1 Char Char   Char   Char Char Char   Char Char   Char dCJOJ QJ aJR R o0title2M CJOJ QJ aJmH$sH$tH$< < oaffdd[$\$ mH$sH$tH$" " H0src^J$! $ H0jrnl^J`2 ` H0 rprtbody2""M CJOJ QJ aJmH$sH$tH$:/A : H0src2CJOJ QJ q NQ N 2 0 articletext1B*CJOJ QJ ^JaJphHZb H I Plain TextOJ QJ ^JaJmH sH Rq R IPlain Text CharCJOJ QJ ^JaJmH sH z z *r@0 Table Grid7:V0CJOJQJaJP P 0Colorful List - Accent 1^$ $ 0src1^J> > 0 rprtbody1 ""CJaJ0 0 0title1CJaJ@+ @ 8#0 Endnote Text CJaJtHJ J 8#0Endnote Text CharOJQJ^JtHB* B 8#0Endnote ReferenceH*^JL L 8#0 Char Char dCJOJ QJ ^J aJ,/ , B[0List ^h`@" @ (arttitle5CJ OJQJaJ&2 & (augaJL/B L (p7dh`7CJOJQJ_HmH sH tH 0R 0 (bibcitxaJ*b * (ackCJaJ4r 4 (meth1ttl5aJ4 4 (receivedCJaJ,q , (corr5CJ0 0 (TBLTTL5CJ> > (TBLROWdhCJOJQJaJ& & (TBLFN4 4 (footnoteCJaJ2 2 (sec1ttl\aJ, , (fd 9!aJ$a  $ (supp8 8 (apple-style-spanB! B (apple-converted-space8/1 8 (0A55B*CJ \^JaJ ph"<< (0Pa5d1$7$8$H$OJQJPK![Content_Types].xmlj0Eжr(΢Iw},-j4 wP-t#bΙ{UTU^hd}㨫)*1P' ^W0)T9<l#$yi};~@(Hu* Dנz/0ǰ $ X3aZ,D0j~3߶b~i>3\`?/[G\!-Rk.sԻ..a濭?PK!֧6 _rels/.relsj0 }Q%v/C/}(h"O = C?hv=Ʌ%[xp{۵_Pѣ<1H0ORBdJE4b$q_6LR7`0̞O,En7Lib/SeеPK!kytheme/theme/themeManager.xml M @}w7c(EbˮCAǠҟ7՛K Y, e.|,H,lxɴIsQ}#Ր ֵ+!,^$j=GW)E+& 8PK!Ptheme/theme/theme1.xmlYOo6w toc'vuر-MniP@I}úama[إ4:lЯGRX^6؊>$ !)O^rC$y@/yH*񄴽)޵߻UDb`}"qۋJחX^)I`nEp)liV[]1M<OP6r=zgbIguSebORD۫qu gZo~ٺlAplxpT0+[}`jzAV2Fi@qv֬5\|ʜ̭NleXdsjcs7f W+Ն7`g ȘJj|h(KD- dXiJ؇(x$( :;˹! I_TS 1?E??ZBΪmU/?~xY'y5g&΋/ɋ>GMGeD3Vq%'#q$8K)fw9:ĵ x}rxwr:\TZaG*y8IjbRc|XŻǿI u3KGnD1NIBs RuK>V.EL+M2#'fi ~V vl{u8zH *:(W☕ ~JTe\O*tHGHY}KNP*ݾ˦TѼ9/#A7qZ$*c?qUnwN%Oi4 =3ڗP 1Pm \\9Mؓ2aD];Yt\[x]}Wr|]g- eW )6-rCSj id DЇAΜIqbJ#x꺃 6k#ASh&ʌt(Q%p%m&]caSl=X\P1Mh9MVdDAaVB[݈fJíP|8 քAV^f Hn- "d>znNJ ة>b&2vKyϼD:,AGm\nziÙ.uχYC6OMf3or$5NHT[XF64T,ќM0E)`#5XY`פ;%1U٥m;R>QD DcpU'&LE/pm%]8firS4d 7y\`JnίI R3U~7+׸#m qBiDi*L69mY&iHE=(K&N!V.KeLDĕ{D vEꦚdeNƟe(MN9ߜR6&3(a/DUz<{ˊYȳV)9Z[4^n5!J?Q3eBoCM m<.vpIYfZY_p[=al-Y}Nc͙ŋ4vfavl'SA8|*u{-ߟ0%M07%<ҍPK! ѐ'theme/theme/_rels/themeManager.xml.relsM 0wooӺ&݈Э5 6?$Q ,.aic21h:qm@RN;d`o7gK(M&$R(.1r'JЊT8V"AȻHu}|$b{P8g/]QAsم(#L[PK-![Content_Types].xmlPK-!֧6 +_rels/.relsPK-!kytheme/theme/themeManager.xmlPK-!Ptheme/theme/theme1.xmlPK-! ѐ' theme/theme/_rels/themeManager.xml.relsPK]   !"#$%&'()*+,-./012 %           ! "!#"$#%$&&''(())**++,11,-..//00-2P  !"#$%&'()*+,-./0125  !"#$%&'()*+,-./01 " ~ L  d07`# AA@ _0(  B S  ?H0( @@  JPVY!$LOPSez"KNLOy|KNLWsx8CnzS Z  - 3 D F G I J L M O Q VY!$LOPS"KNLOy|KNU`a$% D F G I J L M O Q 3333333333333333333333333333333333333UUD F G I J L M O Q Q R R S S T T U U V V W W X X Y Y Z Z [ [ \ \ ] ] ^ ^ _ _ ` ` a a b b c c d d e e f f g g h h i i j j k k l l m m n n o o p p q q r r s s t t u u v v w w x x y y z z { { | | } } ~ ~   f2UXKxQڻjg-tt< hh^h`5\^J.88^8`^J.L^`L^J.  ^ `^J.  ^ `^J.xLx^x`L^J.HH^H`^J.^`^J.L^`L^J.^`^J.^`^J.pLp^p`L^J.@ @ ^@ `^J.^`^J.L^`L^J.^`^J.^`^J.PLP^P`L^J.^`OJPJQJ^Jo(-^`OJ QJ ^Jo(o p^p`OJQJo( @ ^@ `OJQJo(^`OJ QJ ^Jo(o ^`OJQJo( ^`OJQJo(^`OJ QJ ^Jo(o P^P`OJQJo(f2KxQg-t؃J         j[m<[m<[m<[m<[m<[m< [m<[m<[m<[m<dd[m<[m<:dd[m<[m<[m<[m<[m<[m<[m<[m<[m<[m<[m<[m<[m<[m<[m<:dd[m<[m<[m<[m<[m<[m<7#V-;%9>/GLO'O9LRlU"g'`4Np FTr-.bD F  EN.Layoutp6 EN.Libraries6?????????????@(s s @8@UnknownG* Times New Roman5Symbol3. * ArialQTimes New Roman Bold7.{ @Calibri3Times7K@CambriaG5  hMS Mincho-3 fg5"M Geneva5. *aTahoma?= * Courier New7.  Verdana;" Helvetica9=  K @Consolas?MTradeGothic={PMinion Pro;WingdingsA BCambria Math"A#&@F  24d? ? 3HX ?C2!xxTdSir2 and Dmp53 interact to mediate aspects of CR-dependent life span extension in DOffice 2004 Test Drive User r.saravanan   Oh+'0(4H \h    XdSir2 and Dmp53 interact to mediate aspects of CR-dependent life span extension in DOffice 2004 Test Drive User Normal.dotm r.saravanan27Microsoft Office Word@F#@!@@h# ՜.+,D՜.+,X hp  9 Cold Spring Harbor Laboratory?  UdSir2 and Dmp53 interact to mediate aspects of CR-dependent life span extension in D Title<@0_AdHocReviewCycleID_EmailSubject _AuthorEmail_AuthorEmailDisplayName_ReviewingToolsShownOnceAging Submissiongpani@rm.unicatt.itGiovambattista Pani  !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOQRSTUVWYZ[\]^_bcfRoot Entry FvneData 1TablekWordDocument M"SummaryInformation(PDocumentSummaryInformation8XMsoDataStore M`3TY2BIVSZX5X==2 M`Item  PropertiesUCompObj y   F'Microsoft Office Word 97-2003 Document MSWordDocWord.Document.89q