1i1b.~p'i'''1 tiw.J C:1 i1t.1t1" thl~l"hpl(i~ 8(~J'"jI6 '1',1)
Revisiting the AL,A/N (a-Lipoic Acid/LowDose Naltrexone) Protocol for People With Metastatic and Nonmetastatic Pancreatic Cancer: A Report of 3 New Cases
1,9)1'110 Autll\.II'I.J 2009 R!:rJrll'\t:: n1lrj 1}~'I'HII~:!I'~11: 11~I:p:l/www, e,i'\!1l:lPli G, ;;;1.111111 ') 1,1 nVII~I\'I'I1' I'i Iii 01 '~.IItI"
0(')1: 10, I I 7711 S34/:~S'109'l,~2d01 h,~p:lllt::unl;(qJlIbt:glll
($JSAGE
Burton M. Berl(son, MD, 1"15, PhD,I,. Daniel M. Rubin, NO, FABNO,3 and Arthur J. Berkson, M[)i
Abstract The authors, 'Ill ~ pl'eviOUI al'tl~le, d.,cl'lbed the long-term $ul'vival of a mal1 with panu'e8tlc cancel' and l11etasta~lll W the liver, treated with Intravel10us a1phll-lipolc acid and ol'al low-dos. l1altrexone (ALAIN) wit:hout any adv.'-'. effact', ~I. Is alive ;:Inc! well 78 months (lftCf Initial t?t'J~scntation, TI1I-(;c additioM31 pancreatic C,'lrlC(:t' case 111'\E1 pna..slZ!rlccd 11"1 thL~ ~"'ticle,At th¢ timc of this wl'ltll1g, the fll',t p!lticnt, GB, is .livc and well 39 l110nths aftel' 1,,'e'.l1tlng wi~h ndel10Cal-clllol11a of thft1 f:lnncl'c;J,S with ji141tastnsas to th~ Iivcl'.The second patl'ent,Jl<., who presentGd to the cli'tllc with the satnti; dim,gllosls W("lS t,.eoted with the ALAIN pl"ocoeol and aftel' 5 l110nths of therapy, PET scan demonstrated 110 evid""~~ of third pntiGI"lt, RC, In udditiol1 to his panCI'Ci1tic: l.;;om;i:1!" with liver ~nd l'ctl"Operitone.aJ 111cta5t~$lt)$, has a histol7 of B~celllYl'rqdhornrl and p!'(J!';tntc ndenocar(;lnorna,After -4 l1'1onths of the ALAIN protocol his PET sClln d~~IllQllstrat~c:1 no signs of ~::II'ICCr. In tbls ",.ticlo, the (lllthOI" dl,cuss thG poly activity of ALA: as all agel1t that I'educe' oxldativelt;!'CSS, It, ability to stabilize NF".B, its ability ro stimLllate pro-oxidant ap~ll~tOSic activity, and It' discl'lmin.tlve ability to dl,cou,'oge I:he p,.olifel'''I;IOl1 of l11allgl",nl: cells, In additlol1, the ability or lowclose ,',altl'exon. to modul.te an endogenollS In1mUl1C re,ponse Is discusse~,Thls is th~ second f,rtlcle published 011 the ALAIN "rotocol and the a"th~I-' bollcv. the I""tocol w"mlnts clil1ic,,1 LI'iaL l(eywol"ds pl:Il"lt;;nZl;:ltlC canCEW, gcnlcltabine
mtltt"t;':xone.
low~do~c naltl"eXOhtSl,
111 Mllt'l:h ",' 11llJ6, till' ""Ihol's l'.1ubli,hod II c""0
LDN, ALAIN;
,Iudy
dcserjhin~ [11(: 1t111g~tcl'm NUI"vlvull1fu 1'1'Vll\ (,11\) WIth ~l dli1Q."
with I1H~I'n~l,[ISCb\ ll) hi\.i !'IVl::L I Thl: dingnn~ls wo,s l11LH:1e flllluwing binpsy nl: tl v,'cll·rl'~I1I,)L;lcd UC:UCk~ll'li(: I1lcdicuJ conk!', '1'h(;,; gOIit:1CI11Ul1 W{iii ril'i~i!1(111y (l'cl.1lcd I,..vH!1 0 single dl1~:t;,~ ole::! NtLlI1dllrd k:hCl11o" Ihr::rupy PI'ult1Vt)I, which ruik:d, and Iw wU:J t.old to go home nu~~i,'i ill" P;U1I,,~!'~Ul'ic ::'l~ll)I1Oi':Un.;ih(1llH1
hwcatl~1,! h(~: f11'u!:!,11n~l~ WUt'l Ilupdi,;~!~. Ojvl'!l IhiN ~l:eI1UrilJ.
JA pn::ll:l1lull
In Ihe Inl'ca,rntivl.;:
Mod",nl ('ellie,' ,,"New Mexico (IIVICNMI Hnd w"" ,,,en ,n """lIlllIlilm hy lhe ulIllw,' (liMB), An inlc:gl"lIlive medical f1lllg":I111 Ihell dcyclnpetl lIl1d PI"l1SCI'ipcd IIlI' the pUlletl!. 'fhe pllrp(l~l~ ul'lhe pmgnltll WU~ J.. jhld: (lll111trlliol'lal support c:!IWvlllliy Ihroll~h spcellh: 1llllil1xitlnnlllgL'I1IS, (2) clIl1lfOl'1 ,\11<.1 p:i111:'li~H1, tlnd ~J) il11111Ul18 ~y~,lcl1' l11odul11tiun VIn biD" lug, Il~:11 1'I::spon,I'K~ Ilh'll.:1 i rklll illll, The I11qiOl' lhc('upculic ag,cn I'~: WVI'" iI1lI'''V0I101l, (IV) ",.Iip"io ",itl (ALA), 30010 /lOO 1111" 2 LlHY\-( lJt,;r \vctd-:.< l1nd luw~dnt4i,.;: llultroxclI1c (LDN), ik5 mg hy 111ll11lh Cll b~~clli1'l1l.:, Inlldditioll, ~1 tt"Jplc i.1l1lloxidunl: r~gi .. IlIUI ':UI1Ni"lil1g or Ul'lIl I\I,A (600 mu PCI' d(ly), ,r;;l cl1iul11
w",
c1~lipoic cH;;id,
Nr
l·d3, nuclear factt)I' I..:B, l'llltloxld<ll1t,
Don
(200 l11cg twkc dailyl. ;,Ind Nilylnol'in 11'ILl ii, l.iI11L~t; rI (h'IY) WM ~ltlrIGd, ,I;\, vVil::; al.so plt1l.,:~~d UI1 U g~IlLmllly· acccplc'd-fls h"'liihy db! I1l1d lir"slylc l'I"ugl'''''1. AflCl' Ihe 11M IV trlil11illlSir::rt;ol1 uf the :\l.iI, 11>" pntiolll ImpnwGd ~1,lbjl;;ctiv~ly. pi:l)l11p1111g his v\~ILlntlHY C\~111Ill(J111, "I hnvC' il1cn..;a~t,;d energy ul'ld a Sl:'n~(: ul" '\,'(,~IJ'·bt,:iljg," 'l'll\,,' PI"Ogl'illl1 W(;l~ (,;ontlnul:'LL UIIL! Jt\ Wl!::> iJ:'dl'L,~llldy COlllpl;mtL Ancl' j mDt1th:~ 1.')'1" ('.'I,~I;I'~"\: HL'id (Iml Inw.. duNl' lP'111J\,','HlIH: V\[,A/N) Il1el'llpy, .Iii ,01 ul'l1cli III wI'l'k PI'l'SCll11y, 78 111~)111'l1.1" n)lluwing initinl dlllgll(lSis. ,1/\ ,ppCIII', Lind fecl~ IlOl'Il ,LlI, 'lIId Ills CT ;;Clln displuys IIllelll"'lion orthc pal1c!"t.:atlc "lIl1'1~lI"S HlltllhL; hL'P::ltil: md"l!-:lHSCS, IThl:l Illtegl''atlvn Medical
'Ni2w MQxl.:o Stntel
Cl'I'I\'UI" Q(
l)hi\lw'~,l,Y;
Las
l\Jew Ml7lxic;:Cl, L:is Ci·lJ(8~,
Cnlt;tlh, t"~i1,
USA
NM, USA
JSol.llhwlll~t College tlr N;J,t'JI"0pllllllc I'hysiciiln:~1 $t,(msd"It:l,AZ, USA COt'I'espot'1~litig Authl;1r; Dml11fJI M, Rubin, SO~jI:hwll:tt CollcJje of Nntlln:;pild'dc I'hysit;inllli., 7331 E Osborn DI', SLlIt:~ 330, Scrll',~~';d,,,I(;!,AZ, BS15 I, USA
El11nll;I·Llbll'I@I1;]t~II"O!'Ulhl(~;ptlt:!~llsl!';;C::Qm
417 111~\'plvlldH'I' III ,"!l1!7,lhl:' ~;111'1'11"~ :Iu!hrq'!~ I1Ubliy!wt! i1 C:,l.':C ',1111,1-; lIl'll {1! :iVlli"idd 1111\11 wilh W!I'l-III.ldgklllb 1;.'ll'Iphnl11u,:
Illl'nllll' 1l1l" rl."li~;il111'~ I\HIS,ill!:\,
II\' I\'I'II:-:\'d !.. j"1I1,1:lnl
Un pre.,
1111l! l'i1~;(,;,'I':III,sl/,t:lII,\'l11ph 11Ixk;::; ill hi~ l:,l:I'"k:l1
Iq:
'1'llll\li(lll.
11'1'1111'1 iilHI Ivl'l Wllill il,'~ Ih'I'IHII1~~ll'iil...'d
hy
1'1.::'1'
[I
:-It:i'lI'I; llI'lt:;
IIIIIIL' t.'lllll:lllh"d lill'11:..;y"pl'I'\l'll liliill,t!,lHlI1l'y, /\lh:'I' (I 1'III,1I1111!~
di,'IIHIII'~II';ill:d \\!I'11111,1'" Ill'
rmlildll!,'.lcul
i',:
~U1l1
I"F,T
'IV /\1,/\, :,\
1,1' I I'll\,) 1l1uI':1I 1,\' :1111,1 ('llll,v :: ,vL'cb:
l'l:II'II~,'<;1i'1I1: :'11 Ihe lil1'lC (d' Ihis
:·;Iill l'l't:v I'd Ili!"C:I,';I,', ~'/ IllUl'1(h~ nlh:r
his
di\lf~'"
Iii I'..; i'~ II: II v 1'11(,,' lill)~:lL'1 (Irl1111' Il1ili;lI ptlhlil:nll\\I1IH1\(
1IIIIl'I
Illlli('liI:.;
)'1:ll11'I'C . ,,(il~
\','111'1
cnu:-;cd
;~l:vGrul
l::'lllc~r 1(,1 PI'~:"'Lilll. III Ih~
11\'Il 'Nrvll\·\PI\,,';.,ltll,'" :ll~Cl'S:'; lnlhc ,'\I,,/\IN pl'nl,l1cl,1l, Ihi" illlil\' 1\\'I,:l'It 1.:I1:"',~ :':lwli("s ill\' pl\>;cnt12l1
,Some l,I'
hen::,
Patient I: OS lVII"; ( Til j~, II 7, I "'>'(':lI'''lll d ~'11) i !ilrtlir,II'IWI,iI'l1:l11
1'1'1 1 111
,vhu i\iUS d i nb;M willi 1:,:111,,,:,;111111: 1'1illh:,I'~:rl!ili:, III l!.)l)(l, ~hl~ l\:t~(lvL'l'cd Ilei' :·:VII'1I11(111Ii,; :11'Il1 wm; p!;h'l'd ll11 l1'I'linli.'lll111(\' Ihl,:I'"
1111,\'
'",Ill' 11:111 11(\ 1'111'111\"'1
IIIII,('d
1'~'11111111111\.\
ul11il 1~1\',,,;cl1ll1liull in
1: 1 ,111'11:1['," (II' 111flrl, wlwil liming I1hysil':i1I:XI'llll,;'I I11m:s 111 IH'I t:I'lll'ih!l'k 1\'~,~k\l1,
I\:dll:llvtl
1111111 i1 I:I!',I~\"
III
1I1ih"
i\ C'T :.. 1.:1.111
hl:,II,:1 (11· hl.'I"
IIIL:
WI:1S
d('11'1\1IlNll'1I1'!;:d
11tll\l'l'C:1J.' U~ \'v'r'll n~
;';Iilll,' hk:P:lli\~ 1~:li'\\II\'ll,VIl1:lI ;l1'1I'II)I'Il1:dilit\~" IlwU9,hl II) I'('pl'(,;"
',vllIIIU'!II:"lnlll' IkI111i~II~~, ~;illlil 111l.'IL':II'kl, ,I r'illL>Ill:l'I,lh,) :1!.[I,il""lll' Ill" I ilL' pU!I~:rCi1N 111'111l111"ll'dll.'\lllllll'illi'I\IS Ild""1'1\10:'11\'iIH'1I11~\' Dl;,\':>1,1irc
,'i:III~;' 111')1,1111' III qll id, Iy
h\.'!;i 11
hcr
pl1Y~ii~
ili'l illh,:m;IVc ~:hCI1lI,1lhl~I';'II'\.;lIlit'
Il'!',iIIIVI1. :~11l.' l!n'lim'd hl'I.'lltlhl' 11\'1' rcligicl\I.'I hl:li,:l1~ PI'C~ l'llldvd "'\Ilh ,I
1'1j(\i'I,II\l~,I!;
I'd" ,\
~l.Ih:-:l'~llI\'l1lly,
111;11, 1\1 11
i
l'd' Ii rio:
i'll'illl
II' ~J\;,;
sll"'~ wm; givl:;l1 II
did
l1(1t IlllL.1cl",i?\ lilt:
1':ldl\~lobicrll n:I1lI.';,-:;i\ll1 h)1
11 1","1' ,'~\lrvl'il\III'Il;L; {l:ILlllrc:,: ~1 ,Ind 11,,';' ('1'.;,';\ i\nd ("\ ll)~q hlllh IH'il'il'litii/\','d 1"1'l\111 6.7 1(1 D,l) Ullt! fl'Pl11 JIJ II) I~, Il';;j'1t~l:(ivt:ly, 1\[ Illl' Illlle llflhl.'1 wdli111,~, .1':'1 111UI11'I1." lllh::I' Iwr \li(l.l:U'tn~i.~, til,' I.~(~IIIII'III~;: ~J. 8(~!\11~\t;.k:dly,
wilh IlL'I' li'I;~;'\lI11\.,'t1t 1,1:'111 lInd Iln~ 11L\ ~::it~,I1:,';
(\1"
j'iillinculll'
di~:l,:n:~c,
P!'!11111.'.;vd dll'II'(lllH.'I':lp~/ II'l~~dI'lW1'1IS,
1\.'11',"; {IP.·,'~ Irk:IHI II:,HI l'I.:'Uti ilbl)lll lhc ;llil! "II!,!,,\.l(::.:I('d
kl'l
/\1../\/1\1 pl'nll.l~'nl 111:11 ~:IIl: 11')1 11'11.' :1I~PI'l'lI'ICIl hCL':Hl"C' sh~~ Wl'L"i
\\'1111 lill 1'lllll'I' Il'nS\1!1:I11il': II'C'11111'..'111 nl'11',11'ILlllilic::;,
(.'in
\'ill'IIL' itl IIIL: H'v1( hll'.'l 11'1 NI')1Il:lnl'1\,:1' ~(ln6 wII), l:(lllipll1ll'l,~:
1,1 1'1'lly iltl'('kl,IIIII'!'!, 11111,\ pnll"i\llild
L'l1l'i'lillt: I"nl1)].\I'; nl1d
ilhlliilllllllil Pilill t.lli I~hy:'i('ili C~Ulll (il.) wns i'~I\ht;rl,hitl rliid
Patient 2: JK Jl( j:~ :111 ~I}'yc:lr,t\ld W0ll1iH1 \\,1ill1 101,\..;I'H•.'I':l1i'l.l,,;(\ ;lIhL,'I'l1:;clc:~ I'l'llll' \':I.,:,\l:ultlI' (iI",Vili';l;', dli.'lt:'J10,':"i.,:ll 'I\'il'h ill!l,'lll'ICI1I'l:inllil'lll
I'hc: l'i:l11l'1'k.'I'IS will1l'lll,o.;sihlc 111('l:1.... lnllc diNC',l~l' ~)rlhc I I \'l': I· 111 Scp1l.:!11hl,'t'
ul'
.~D('I.,z;,
I"ilk, nlll!:1 lili),i,l' II ill.'":'''; W:P';
I'eel Vt.'I'Y lil"L~tL
IIL'I'
WCI,!bht,
(';IIVIII\IVI'l1hl\'I,ll'liv
11idl1i1kd 11111u lilli'll'!' lI1'1dl\I1'Il'l1 i\i111.!.;l,,'j'1 {C'I:,,\i \\'111' (1,7 (11'1d 11t..:1'
C','ll'l lI dl;.,(!nlll' ,I\IIII!'VII I()·"q (('/\ II),.\)) \!"'i"".i~),
I
'\ III
111111I11:111!
Illl~ rii".I1IIIPPl;1"
1,1' ilH' 1111(1I111'CI1 \\ilh 1111111l.'l'lHi\' l1yj:Wt'111C\'.lhl)lk
:111,';1,'; ill 1111,' li\'!.'I' {l'I,ilIII"
m'
I), I:HvlH
Her
I
Ilvv\,;ILi]'1~:d
did :Iddl"l",':';;' Ih(' Hl'llIhlUl'd~
Ihc pll\1cnt lI~(1ill AL"r\/N, ('(l11~CI1I('d lo
pl,,'rl\';ITlwd Oil 1'11(' 11:H\L'I'cn\!\,' 1111\'11,"1' III
:1:, 111111:'lkd, i\:\ llll,' li\'il!l'iIVl'1t rV!,:inlL:n l'lllliHIl\(:d, Mrs, Ci13 \V:t~ fLll~ Illll'L'tI 1.':IIT!lilly willi l"1l~rill(lk· Llhi,~I',:iI(lIY ~11,d pl1'y,,:Ii.:nl '11v1L ill\<,1 111\,' (Iv:IIIIII,'T'lt \\
,\ll~J'1 ill1l,II1,;''::lII: ill
(1,\
111'111
1\ 1;11'\;'11
liI'11I'1)\',,: in
:'''1
p~lr,1I1'1l:lt1n< ::;l,,'I't)~
:~'I,.'nll~\uI1Wlk:i'\I\y,
IJy
Fchl'll:'lry
,~{)I,):-\. (iB \o\:~'I:, (lccl;,ll'criln ht'
111
n(,,,~t.,'lTlhl.'r ,WII';.
11111.1
t11(' lil,lthnlt.1~Y Iilh 1\'j1t'll"lcd lhn1 il llml mi;;~;l~d Il'tt: l'I;111L:I.'I',
rvll':-I,11< h:lll "I
:-~I,l.' vl'n!illll\:d
Insi,:
111\)U!~111 [(I he 11IL'llISf:'llk n'lll'!'l j'lw pnl'll'n,'ns. /\ 1.1111p(:,\1 \\-,,'11'
,qlll' Iv:\." lold 111:,11 111 ~pil(~
111!,'ivplly, 1'1hYl'-killl~',
~I'I\: hl.'U,'II'1 1\,
11(::(1(\ ~,I' Iht:: 11nl1l'I'~l\~~ "'111'1 (1(l1l,'I' k:~':\l'l1h in 11'il' 11','(:1'
1111.'
jll'(lIt11111\' tll.'I'lil'll'I,1
1,''\:1111""
u<lrliN,
gl:llVi';l! iI1101'1'li:41' Si,.'lll l'in l'l\ :.'1 !~ilsll'(,ll,:l'1ll'I'tlll,l~
ill' \::II'\' :111PI'I\ill'h 1111' lit:\' di:·:',::t!.. l.'. \vlli\'h -...;11(.: \\'d-: lll'it:I\"d
il'Il~lllll;;
Ili'l \I i..:l': I. illHI ,'"Inrll'd 1('1
~:i;-;I' \\'1'1\' (11'1:I('I'(:d,n CT SC(ll1 ;Inti diil,!.l,11(1,1.l('d n IUI'IJ,C b..;il,lli III
:~I::lll \"':1'., 111l'll l'vrl'pl'lrli:d d'~'1l'tUIl:':II'(llilljJ n Ih~du~
1;11 IriVII'4 (11'J.'IJ1liliH'vl! ,\1,IiICI1;';t:: I11L'Iiil1ldhill in
ur
1"\\1'1111.'1' Wlwkllj' ;11 ,111 ('C'lt!l.;11liL'
ul'
11(1:-.11111;11, lind
lhl' l'II.'t~~:ll(iv,; hillp~:Y1 ~;ht 11:1d
!'l\lllL'i\'(lIit", t:tl111..~l;I' i'111d W:I~~ ,!J,iVl'l1 :1 ,uyim j1n:lI;,!H',;i~~, Nil I'l.Ir~
(1·(~;lhnCll( \,V;,I!.[ ~\Iggl'::';lc~d bC\l:11U ... 1' 1"1' hCI" {ldVi1Ill'\",d ,'1!J,l', I"nl11ilv (h)l' I 1.'11", whn wns li1Il1ili:It' \:vilh Ih~;: i111IPvtlttvC' UIH":(ll('I~Y iiICI'i1I\II\~, 111i.1l ~l1G ti')' n l1t'll'lsli1I1(I:,II'l!
l'hcr
.11<:::>
IljJpH'Q,ICh I(il'
111'y
1'11.'2001'1,
hel'
il\I1C~;~,
Silt:.,
\,.'(11111.:' IL~ tlw IIV\CNI'v! In .1:111\1·
Flgul'o 4, MI's 11<J~III,I.tI'y
),OOt,
1m.! Iil'llil'lIl! Ilild I li.l rl1 III I ~i1\llld'路, :1I1l! 1'11)111 11 1.:\
W';'I'I,'
IdI'l\'~ 111;1~::; wns ,';Isil\' p:dpIIIL'd III In'l' ,hII1Ullr)~!llHl
1.'I'I)!,;hll'l.;
IlIb\'I,II"I')' n:'itill~ ',IH1\\
n:p.ll,Hl.
,路tI
!I'L'IIII:'
il!lilndll, ,I bl1\l I'll 1111 lil'\,'I' 1'1111\;111111., !lYI'i'I}'lyl'L'1i1iu, :lI1d II 1 \
1',1 q!lf :\S:;, i\ l'Ji'j
',I
,11'1 \\;l~ 11I.Tl'ul'11I,',1 ill1\.1 ~:II\I\\l'd illill
Hill:;;': il\ Ib\,' IIL'ild ,d'III,' Pill!\'I\:a~1 \liill' pi 111,:I:I'il;ili,; di>:(::I'l~ ill 1111.' Ih'I;'I' I. 11\; .I L Tlw \ :tlll1lh ~,IlIII\I.II(1 Ilvill 1111:111
l,iplillll~
WI,I",'
In ddily ~tIl:h
nJ1lillll,~li; hU\l'~'\'\'I, .II\. ,(,ltlll.'d Iwl'
iHld
ill
111,:11
P!'l.lli'I:(~1 (\1'1
H'~
l1w 11''::,1\111,'111
"':,\:.11111:11
Illlt!L:l'h',\l IIIV
\\'U~" il\lll,II,',]
\1',1" 1't,11111\',:d \,1':11\:1'1.111: wllh
1'1:
.'\1.1\ N
:llld ':I>lllillll>.;,!.
.di\,' luh\l!',illiry ,\1'\1.1
pli~,~it::ll \.';';i,llll:i, Sill: ,'I"llllIlll~'1i 1111'\11 1,111 \\vjl~liI 111111 1t11\I:
I iI11PIWd~IIWIlI 111 Lill.' .I'II'iI: ~11111(,
dl:ll10lHilnlbk,
r~ I1H1llth~ Iil'll:r 1t\.'1' il~iti;t1 visil L:I I'l.TI::iI j'\.I' ;i"ilil ',v:h l\ilTI1(:tl,
lid"
lilll(' dI.'IIHlIl:o<tl'inill.\!
~ih:lIs
IH\
(11'
jllllll:IViillc
:ldl.:l1il~:;ll"dmlllld(I:I!~I1I'1.' :'ii, 1\'11',~ II-:. t'11l1111lUvd hl'III'l'I,lllh'lli PI'\llll'i'1I11. ,1111'1 11\.'1' IiVil:1 Ii Willi
Iii July ,II' llltd :;luP!1,:d
1~IH'll\ ,II... I'dllllh:d 1",,'1 :\\ .\, I~
1t'1
."'/11 q~I,III I 1''1.'1: lIvl' Ilnn'I\,' 11'1 ('111I1'11'lli:1
In:llt I 1l1.'1i1
11:):1.1111,'11.
1\~'
,\
Ill! 11"; II I iT ~l'JlII WII" IWl f'\['ilNd, wltkh !'lll.,i\I,vd iIlili Illl: 1"1111\"IVlili,: ~ldl.'IIllt';lll'IIiPlll:1 llild irllkL"d 1"'1111'11\".1. ,";il.;; ';'\1111\.11 ill r'~ 211111,. 1,1
.11\
hlld 1\1 h~'
lldl'vd hy lwr I'ri"'IH.I
bt'r:IIN' ,;Ilk' WII,; Ita! 111,'(lk It 1 \\'1111.: 11I1d
111\\) Ill" ,'.":.1111 I"H."m
"land
by
r. On
1111)I'h'illl:~!lln, ;;1 H.' II;P; 1I'llIH,II" 1"1: ,':,1:11.;1:'.: und 1"'1' ~~:II lI'iI', lilld l1i.,'1' 1~\'I,'j'lI(: \H'I'I: klc;I'i,'. 1'1,'1' ILlI1';~'
~li\)(i, ~111.' h:I~,,111 h'l 1':1,'1
ill
1'111':11111:, f.ilk'willg,
li,1I
t11;1;.;,II',''''''' .
Patient 3: RC Rt.', II 117.~i~'ill'-cild
111,'lk \\',1;; L:nm\:llllill'llilly [n'llIe'I,1
1,11 11:'1;'
j11'n:<tlIIL: ('mll'l~I' willi hllll'hyllH:IU\iY in
1111)/1.
111
I'ul
1\}I1N, I{j,'
419 , I
,
d\\'\'llIlwd ilhdilllll!\:l1 pull! 1111<1
\\,1,'
dllll;.llll~cd with ;1
dir-
Iii: Wk\.~ ln~nkd will, I, 1:\Tk" I'd' Illi W (lydpI11'1l""phiI111Id,~, L1t 1;1;1,11'l,Ibidt1. \ JIlI'I'I,,1 i!1('" :lIlt! prvtll1l,';I'IlI')llt1d l'iIIll:!l Ihl:nJpv, 'i'vil
111;;,'
IU' dVll'l1
111111'1111\
1\,t':I,'1I
II.
1":i!II1I'!'il,jl1lill,lin' 111 Mil\'
III :1 (Ii~:l:il. ",'1111111\11
.11'\'
"I'
fIr
I~r ~,111litlll,'d lll~: ALAiN \\11111 1"'dml:1I'Y :~OCI7 WII(:I\ 1.\111)1'11(;1' 1"1':.'1' t:(i,\n W:L~ 1'\':I'f(1I'I'i1I,'I,1. II :dll,I\V~~tl n 1'(:sidlllii.ll1 t"!' lhl" PI\:vi.:,m;ly (k~I1'\(lIl:;1 mll;'d pil 11'.'1',',: 11 it: and rdl'I"IH.:rili1-
k:.lnm; (Figlll'i.' ) RC
hill: tlll'.:l I ,h:,ITI.l\'IIt'll 1:\\11t'11'nlt 1ry
l,nl'I'IIII~'d I'l" l;ulilq,'. :1 11l111I'I~:":L'lllblt; Pill1l:l'C111i, \'ill',:illi.'111i1, t 1l: \I11ik'nlvlll :1 t,'III\h:d(ldllldlll.!tkl1i1~:tllIl1Y willi l'ili,I';,'il'jllllll"hlllly Till) P'Ii'II1I'VI'/III\l' nll1f,';0 bl""IIIT1~ 1111111'11\;111,'.1
:lild
1I1!.!111
111'1
'lhd"IIIIII(l1 il1'1'-:\.'II"II
t,'I1\I\",':-'I"I':llltibkilk'!,,,
dl'lIil!i1£,C
Hi:.; \;'\I'l'nutl
DCI'I~IlI:IIH>
drilill \\'111, Ill'\ 1.'1 l'nll,;, l'IIIW[\(lII:'II, n:~lIl1il1g 111 11',lllli'1i1 Vpl\:llih", .. 1'\'111 I,;, 1,;1' \\'I,'II! III :1 iq flli.:dl\:iill.\'f1Iv,' 11'1 S(111 l)k~l;ll !"Ol' :1 ',c'I-I'lhl \ll'illilll1.'\ t T H:ill'l \'I'm; 1'(1'1\'1'111\.:11. Illld II d~I1WI1' ',!ml",1 IWlll'IVillll' !';Im'v,!". li\','1' !llvl:l~I!,l~l'~, and pl:l'il\)n ztd ' \,:11\·1111,111111<,1:,,1::, In', 111<", '-':11,; Ii Ill.! \11:,11 11\'l1\I1h.'n! \lilnlld 1'11l:'~1 111,1,1\ vivid lilllt: I 11l.'lllk h,.'m:l'il 1I11I11lrai 111,1 11'C'i1l111l:n! 111:I,V Iw II1\' l'I\'!'I,:\hl,· dji,il:C Ihl' him ,',wmll "II:.. l'lliill \'
HI,'
:l111\l'd:iI 1111:
IMl'Nf'.'1 ill
'Nu
;;(11lh, HiZWll;4
ill ,;,';'l1l'rilll~ I1lH11' 11(\:11111, IIi:, CF'/\ "\!I~: 'U; IllId Iii:,; ('1\ II) q \III~ :i,\j\, '" 1'1,:''1' ~1.:;\11 \>\'i1:; pt.:I'I <il'l 1I,'r1 , WIIII:11 :,II I ,'\IVII 11\1'<..'I'llIvlllhldk n:ln']Jl'l'il\llH:,i1 1,,·;i'111';. 111'1111" 1111' Iv I'! il111II'ig!1I, ill\lindivl' ,)rtll,il'l,'\\:' I~:\il· ,'II':111L' 111111\11 \\'llh 111 I !'!l,'I\HI''; 111(:I:I:,ln'lI~~ 1(1 iln: Ih'tl' il'II'.llll' 1;1. I it' 11'<1', Il\IIIIIi:11 hi,; dl~:,':H;C WU~ \\lei I
,'III'l<'iilll:,1 :111,,1 :q11"':ll'vd
IltI\'illll'l'\1 :\lld Il1nl :111 1\1 ,'\:'N fill \\,i,1Lih:1 he til;vd1'I'l'li 1j,:11 ,'I'Ilid 1\ll,-,:-lhl)' PI'pli'lI~ III:: li]\' Opl I'llI' 1;(' 1\'111' :,,1111'1 liI\ I 11N ,k:' m,i', heftl"l.' bed
,IIUlII: \\ill1 IV /\1,\
Wili,
111,\,1 ~II gnn,j 111111
Il\ h~I\L.:' 1111 i!1lt\I'11alirOlil 111
"dllp.l:IY \\,1;';
\11'
W;I~
111l; lK'i;'l.:lIll1l'1l'lllIS
l,IililllY dli'lill 1\1 I\Lirvh l11' :::007, i'lL' WI:li,> G\l1I'n i 1'1 cd by II !m;d· 11.:(11 oI'IL:ull1,",i~1 who 1:\\1111'11!.il1kd II1I11 (II (ldH pl,lll\!. IH" hnd rdllll\\'ly Utili: 111 111I,~ t'l I~ lilI1 (lllilllt::, Tlli' Inll:I'" Ilill17Lllil'l1l <:d'lhi:; hil drHI11 WII~ p".1'1\1I"l1Wd. lind lIll hii'
me'dk'il \111CI',II\t~i~1
'" I'CI.,'0l'1lll1';l1d,11
Ill}
hl,.'II,(l11 ;'I CI'III i\~' ,11
"",,,,,,,,,,,1,:,,,,',, J\I~1 hvllil'~ ~l:lltil1tJ, l.'11L'lnnllll:l;II'~'. hi:.; l,'IA 11111'1 I'nl kll 1'1\1111 ~1,{i 1\1 ,:.<', lind h I,: V i\ I I,J, ',J dn,ppl'I,1 I'nJll'I \.1.('11'1 II :\, Hi~ ,';,'\'(:1'(,' klbdnll1il1t:ll"nll1 I"l'I\il'lwd IS,: lJl' Ih(~ 11i:i~d l\.lr 111.11\'111 I~(' WlI': 1;lk":l1 (1!'1lw: !.I'll\l, 1[,,' "\1\,111 dcvl:,IOI1,~d :-1''1'1111'1:1111(1, hI: l' ': I 1'1'11: II 11 1\';:P"'I1;-,1 "", lilid (;:\]111""11 ill Mny :;;1111'7, 1:: 1110111'1'1;..; nlh'l' inili,r! d,lii<\ilnhlh,
Di5CU~sio" wilh (1(i1"\11\:,"'d ":ll'lilll'lIl1ll l,d'lh.: p;IIi\'r~a~ 11.1\1' i1 Vl'I',V p!'lIy,lli,1;,k Till' II~U{d l<.:m~1I1 Ill' ,':III'Ii\ol rlllll1Wllllf, ll1ll1ul rLll1.\lL':' 1'1\)\'11 ,~ Il,l 1\ 111\11\111'" 111 Ci.:l'I'n111 1;i1:iCli. I Inl~'rlll'I'11 il1l1 i~ 111,11 :111 \ll1ti"I1. ,1 1111 Pl1ll~IIIS with IIdl':\II('vll dis('ll,"", r:l1\,I,\' live 111\\1',.' Ih0l1l1 I\~\\ wcck,s,T'hc 1:U1'I'('l1i \IL'\\' i, lhu! 1:rcoili\Cnl ~h\'l!ld 1;,\1111:,'1,11':111:
111111'111.:'1',11.
pnlHn1hl(' l111,lil;ll',I~I'1H:I'I!, i JA wns 11)'i'lll1.'l1l wlll1 hlopsY'I,11'''VCI1 I hI.: pnI1~:I'C'n~ IV il \1 111(~ltl;'\ l\~,(,~'\ \t.1 1111:: Ii VI,,'I' ! lin I
I,ltl
11111111(1 ',\il'
III'
,"llHl\'d
420 Iht! IMCNf\1 \\'1111 \'11\:1'1":';11, ,111\llHJk'c" 1111(\ Ilhduliii!\l!l pili", 11IUil,I\'ul I'llI' hi;, 1"\;,,";111 Hllll I il"
Ill: ill,::lirCL,I,·\I.i\!N qui,:kly
1111.'1'121'",1",. .
\\'L"lli\,,1 hil1'I~..::11" L111' Lt!'
Ih.: LPN IhC:i\LAlN
hi:.;
llill'!;\;III' 1111<,1
\,;(iI1!l',i]1,'lIl, ,"i,1I111 ~\
pn,ll\.\l\'L I{(
,;;I~II'IIII~;,
III:' l,d';;\1
1III,11'UI,.;1 hulll:I'
Ihal he \\ICI11 I'D MII'yel')' III iI1IL~rnn"~!,1: his IWI"t.'III:lIWi,lI!:'; hil
dn,Jln, Fnlhn\lil\J:!
i1l:!.I;"Y, ilL' d~'\'('ltll'\'ll :'i01" Il:,\..' II 11,1 iilHI
ditd ill MlIY l,lfltlll7,
I~ IIHlI'1lh::; I'qllll\villi," Ilw ;Jiilt",lll,.,:i'i \II'
III')'
j111Ilcn:',Il!1,: .:a11..:(: I,
IIll1hL1n, h,'liI.'\!~' 11'1;11 till'
,'Uol,' i~ Jill BI\'Ill, "l"1l\!; 1':;
lily '..II' (IlL: 1~l\\1\:1I1 \; \",~ t.!l,'\'l.:lupi.:d
I\l/.\/N
lil lilt:
:·i\Ib;·ltul1Iintvd
l'UI'
pl'lIlm'I'd
Illil'i(lII\:j1lll'1
\Iii
til
Pllli~~111 ,1;\,,1
"I'ht::iL:
cU~~:'i
:1 111,1;h LlU~11
1.111
r~'pl\:~iL.:lIl, al !IlL;
\11'
iii'\,;'
rill' ilil
plllll:n:Cltk t.:ll\1l:!.:'1', ~u\'1i ;III
kin·;!
iI n.:III:;lrlklllt'l1l ul
11lili"I1I~ whu
II'llh 111I: .'\1/\11\1
<l\'l1k\lI.:III\.'111
pl'i1lm.:ul n,~ i1 prI..,lIHi"in", IWW (l'cIIlllll"'1I 1l.11 ilL't\pll' with Ihl', di~L'IINt:.
et,-UpOic ACid AL;\ is Ihl) nl'~1 ~ump.\ll"i\1 il1111('I"II'\\I\I\'III. II I~ ;111<11\11'1111, !hul i..~ Ill.: II V,) ill illl :t:''i,.I'lli''';111 11[\)ll"/yIlIL \'0111 pll::xc;, I hlll ~:l",n Il'cd 111du hrd 1~1I1. i Ill: IlIdlll].! 1111: n lJ1\ \,,.. "ILlll 01' pyruvale II) \::Ih'I'~,V in 1'llii"L'IIIHldl'il.ll1, AI,i\ ii, lI!:m LI Ih.),,: nl(I·!.\11 :;~'II\'L'I1If.I:I'lh>lllla~ ,k'nllll'I,·;II:oI!.'.! Il(;~'l.Il'l·ing ":t.lj)lt:!tll"
11'<.',11 III!', wilh Iltv AI.A:i"J 1"1'1.1("('1)1 h NI"I','l11hcl I Jusl 1111t1 ,Ii 'Ie I' I 1'\1111'1(11,\ IHlli!\'I;q,1~" .1,,\ wu:; hv II l'I'pllllll111: il~':llkl'l1ll 1lll:'dil~nl t'l'lIle,i'IiE'11 1111'1l' Viii:; Iiltl.:: I'll"!,,,! 1'1\1' III,; ,111','11',11. Iii,; pl'''!:!,t""" Ii' 11('11 I,!,!. C1' l'llilll' 1;\ I
~1:illl:; !!IILl 1'\,'1 l'I,:tll"" IIlHl Ii" !WS lhllW VV\'Y wl'\1 1\11 111~ ,'\1.VN l'nd(I~'111. 111\',7)\ l'I'1lil'i1II.'i !Irkl' IllS lllilil1l 111\;,~l.'11Iiil lilli, I,v ii; hill' k :,11 wl1rk, 1'1',:1.' I'1'1,11'1'1 ~VI 1'11111.1111"" :lnd 1\!111I11I11 prnl:n,'~;silill 111'111:';
.Ii ",::1 I' l' , t. ill Willi dlll)J,IIi'I','d willi I'HlI1l'I'C:.llk l."ill1\,\'I' in h:hl'lIury 01 .'1111(1, sil\;, I'VI'IINl'd IllI.' :.;lilllll"II'd II1L'ITlpk:, ht:,'ul,I;;C nr I'L~li 1,:11111', l'I.:iI~,)jh Shu \\I:I~ :.;I:!II,,:d pll 1111.' /\1 ..\ PI',',Il.'il'lllllnd I;'; :iI i Vl' iliid Ih'I,' ,iI III Id sYll1pll lillS" q I l'iPiHh" illl,~1' iIIi I ia 1
Ihe ilbilily 1\1
l'I.:d1.l""
. . 11\.:';;:-
III d IIUlllhi.:J' rd' 11i~I1I"
111.~llIdilli!,
dlnl1cl,':'" li\~:1' dis'~\I:"I.:" alld l:illl~I;1. Thnc; llil',': b'~('11 n 111111'11'>,'1' lll' a1'1IL;It,;:, NlI,~,L!,t:'i1 il1/\ IIw tI~,'.' \If /\1,./\ in Ihl:: In,'~lln'11.:11I. 0[' \ Ul'il II IS t'illi\'VI'S. (WI" ill'lld .... l'I.:[1ll1'llH.I i'hlil 1\1. . \ 11'11 1:11 it'll 111' hil'l\III~~', Ili~I(1111"S 01\: prulcil1s 111:11 :11'\;' \ll~li\e III
IIIl' pl'lfliil'1 :i11\'11
l'ill1\:~'1
,'1.;11:-;, Il1l1ihitil.\I1l,lI',,"\'h tnwl:lI'd 111" l~pI,qllotiLI III this l11lHlY lyp"s
cell
L,'I..!I1
hUI'l1l111 1.':1111.;~n
I~' nth:! bl:'ill,Y.
1111.'); hC;\'ill11,'
III
dri", ill.'l'll li,1
.'\1 i\
Wlll!'r,:(I~ Ih~'1.;n11H: Ircnllll,'l'il \1I'I1("I'I1HII,:"1I11IW,, did Ill'Illlldllt;\:
np\lphH,i" I
,If..: 11':1"
Iwilll
1111I1l'IVllli,,'l'ill'('ilm1li:'1 wilh lnc'I"I~"
i\IH'III1i:I'111I:l(lhnl1l~I'I'I
IIiWi. h. IiiI' li\~'i' ill S\'I'i\"lllh~;r ,,1':'1 Hi.'i, \\'lll~11 ~:Ii" :\ITIH'd :11 Illl
III ,liillll;II)'
\11 :'(1\1("
111.'1'
SII\,' \\';I~"PIIIIHIIVl:d IiIHI
qlllliily
Ill'
IiI'"
\VHf; P(I\,'1I',
1.I\I\:lic\'Iit.', ~Iw, \\1(1/1
ph,y:,i-
I'IIII\' lind ;:1111 II 111111.11 Iv \~,\ hil\lNII..;d, ami ,,:umplilllll,t! \)I\~rll\~llllli ilhd!llllllliil p:1111 illld IlillN';I,
A 11,'1' :: 'I~~w 'Nl,,~b
\11'
i\IJ\/N
1111'1':111:'.11111 "Yil1plll!1\S 1(,/ 1111\1\",\V\", Ilnd \l1'l1t)l'Ilhi' :ilk.\' "''''''.(ll'',,~ and (I I1HIllths n,IIOI,VII1,/, 111,' irllli:lIiOI1 i,ll" I hI.:n IllY, 111'1 1'1 i I'·UIII 1:11 Ivtllil dL'l11ul H·d,I'IlI,; ,I \ '<I;a",1 1'1.'\:111'1'(;1'11':':, r,lll!'Il'I!~
Illi.\\
'1.1.11 (,
f;l1l' I(dl
l'lli
~:o,:;l,'IlIil'lllv
wil'hmll
pailll'I' 11i11N'il, i\ 1'l-:I'l'l'Illl'Illlig III ill,'I' la,lIm' sl:Jl':,IH,;n:hL:IIWS 1\'I'I!:i\'t1 lil ;;1'11111.111' Ih: ,1\1
llilt! II hlil'l.;
,AIN
11I'LlI1..1\,;"!. ~hc :';ilhl';":~luvI1i1y
n'\.'lli'l\.'J1l~l,.· l\nd ~i1,i\'I;III'11b\',d III ~lIdl ill
NI,I"':ll'Ih\,'l' :~11Ij(1, 1,1 1\1'..111
1,{' L:lIril,'l! IIIL' d
li,lh,l\\'il1hi, illilk,1 djU':;11,)~;jK \';1' ,I priJ11illy IlH1Hgl1l:l11L'k~,:
IldL'II!!i:ill\'II1lJI'I'III, 1H111,,1'1\ldgkill
pi\lIl'll:JlI!l' (il.,kIHlL'lll'i;il1l11lltl.
IYlllplll"ll1W, ami
lie illilinlly pr,~NL:nlCd I'q
ol'l.~lIm·l:1
1l1l.11:lclll' 111\:[I,lI' KB
c'l'I1:',
,\1..;\ 111:1~' di""lIll"Ul~~' III"; Ilbilily 1,1 ,;1:1I,i11/1; NI' 1,1,\ 11111'111,11"11\11111"111111.'1';';, NIi 1,'11
11' 1[:,.
V Ii
dil'l1t:n: l'I..:side il1 Ihe '~Jltll'd"'I\I,
II\,WL:".'I'. 11'11"11\'<111.'11. Iii\,,' pl',lldn \,'\,llllp"::'> willl,I':III,!t','llll' il1llll'h,' IIlli"1ll.l;, ll:'1 i\L:li" \':\IIIHl, it will 1"'11 1'Ii': h Illl: IlIdul",ti\'111IJr 1'11111\' 111t111,;O\l lllll<:Ci dLll1'llll1i:<lrnlcd 1'1.1 Sl'PI1t'''S~ 111,1,111(('1;;(;; (\:,<:;111,,; IIHI ,':II,\"d ,III'
viva!)
lind II1dul.'~ 1.'~IIIIlul' IITIII,;!l,lI'lllill"'II, pl'\llil~,t"llli!l!l,
i!lVilSi!.111, 111l:'I.n~I:l,is, \,hl'I1WI't:;;islnlH'I,', 1':ldill Iv:<i,l:ln,'I.'-
tlod
infl:III'II'IUltion,"
NI'" 1,;1,\
ii':t l.'tII'l't..' lll '111L.! rllllll'" lill'/,.'1 ill
(,l\l~'I)lny.y 11'':·:1111'1('1'11, tvludl'Tll pl1<'II'1 11',11'111,,),(1.'11 1 11'1.'1,1111('111
11t'll:i puil1h.:l! l\lWnl'd NF 1,'11. il1 11",,( I,JI"(i!emHII1'II) 111I1ihll\1I'.
inldbilH NI" 1,:13
:1 11\1\'~'1 (>I' it,.; \:lIl1i.~d
bpl'Il.'/Plillh, :I', 111l\"
d~~I11(1 II" Il'a l i tlli'",
/\iJdilinl1l111,.. '1'1\ I· :.111d Th2,!1tl'diall'd imllll1tll; i.lI:II:; rl~ll\:l hi P,tlllUL!,Clli,' in~i\lls wilh Vl1Iiill,l:, l'~'IIIIH:lllhl':1 I1ml', I'I:.:\;Cpll'!'S, MmlY 1,01' III¢~~' 1\:(;cpll,Jl" ~'Iilll n
III'
421 VVl'l1l~ thnl :lL'li\':lIc I.ral'l:-:(TlptiOl'l I"Flctnr NI~ 10::13," Becilllse
nf'll1is, NI 1..:I'll11uys n signilicnili. role 1l1lhc 1'Cl~1IIntli)n (If iilf1i1ll'1llwlnry illdll,,~t1 !iCIH; lill1diol1, HIlih drl,lcs "f Al.A, Whl~11 lIdded I~l (.'ell l'ullUrc have l'ccil ~llCWI'11 to inhihil thl,:~ dL,tivullll1llirNF I<ltl I\IlJ\I1i",~I' nnil:k: slH1wi,:d l,witll~l1t:v nf t\ 11'H.::chLI\11sm by wlll('h AL.A 1I',;ghl he hc'lpl'ul in CIl11Cel' therapy bc,",I."" of Ihe 1',,"llh'" it "lin sliIIIUI"i(', prl1(!,xidllnH(l'iven ~11,,'pl()',S 111 1111111:11'1 cnlnl1 1.:\1111.,'1;:1" cl'lh'" This l1ml~css is tlctivutl.'Jd by lIll II'll.,,'n;:lsl,:d tlll(nkc: (11' I.'l;,dl'1i~,<'lblc ~l.Ih~[rnl,i;i'1 Into th(~ 111ilo~ l'h\1IHld\ln,~~ 111 UIH'1111l:1" I"ludy, ALA was showl1 to jll~rl!:rti'H: \1(111'\l~~y:-:l\;lll(,' ~lml'Clllmli01IF wilhin CnnCl:l" c¢\ls in ccrlflil1 l'slilhli~hL~d L'UIICln' L~l~11 Illles,l) Tile lllcrctisod htnnocyslL':i11c ri,lt1t;l:l1lr:lli()n~~ \'VL;I'C (I)xil: 1~)1' (he 111ldi!~l1nl1l cc\L~, All
Liddiffl
others Wt~l'e rCplJI'IN! to clos0 lt1 1\'lrds~il)n" 1:1
hHV!ll Llchil.rvcd n:Il1i."s(O!l N W(,,1t'L:
ZnBon and M,I.,ilughlin lJ rcpol'leclthal LDN slowed Ihe gl'(,1w(.h ofl1(~uJt)I)ltl;;tllllHl cellK II, ('ultun: ulid I"tlggl;)~IL~d
II' l11uy
h(\v~ i\
ruh: in "he
l.l'cu11118111
ol\:Ql'lnin
lhut
l.;t1l1i,iL:TS,
MallgnHllt nS[I'(lc)J1'OI1UIt: tll'~ nul bclh:)vcd (tl h",~ ~urUl"'Jh.1,
,111(1 t1"1:" In1"111 i, II Il110d al' pall in t I" n, Li "so 11 I C1,,1 " 1', ported 011 the 11\\:r(mel11 \11' Ih,s l11nlignill1cy with IHlllrcXi.1I1(' pillS !"Hc!iolhernpy (In), '1"110 tum"r regressiol1 nile in j1"lictil~ IMlted wilh Rt' pil" I'InIIT8X1.J1IC WI1,' ""lllcwhlli higher Ihnll Iho,e tl'l~lIt,1d witll RT "I(mc, 11l1d Ille pCI'CCl1ta!:l" (!I' Ilm,e SLlI'vivlllg 1.11' [ yeti I' was slgnif1c~llll1y higlwl' in pntk~nls
l,"e"led with [{T pi", 11,i1ITO",lI'," Ihlln il1 111o," Il'enled with RT "h'11e,
II'."" II'I ill Ikul iUlI ,'ol1""lc,d l'h"l A L/\ I1dl'cd Iho 111"0111'01'1111,," 1l\1I'lllill hl\l11;lll lytll11[,(lcytCb: lIl,1t:1 ~1l)\'Vl;d down the: pro'" lil'-:l'il 1il,111 I'll':: k~1IIwI11lt: 'r~~cll lill~~l-l,11I Thl1 discrl111innlillg lo:d\,'ily llr /\1./\ W:IS hC'L;(ll\,L.;I,: of Ihe inductioll of L1PlJplo~iN
Ill'
",,'k
il1 Illc k,d'''I"lu ALA "I,,) "()Ii,,eubly il1c\"l;uscd Ihe IlId""I;',,, I!I' 1"'''I'(''L1klll-2 (I ) I11RNA nnd I 11\"l1lclrl ,('(:I','lillll ill ,'11110"1" l'C' II." The 111111101', ,ll1lcd Lhnt Ille diflcrL'llli:i\ cITI..:L'I~ (11' 1\1 l11ity
Nlll~l~il'y
\1
.1\ ~1I1 Ilf,lI" I11nI ,Ind ll:llklt.:1l11c lyl1'!1'll1oeylcs I"tllhwny Imvnrd thl~ develol"'Jll'lcllt of
IIV"\'
tlll'nq1i,;\III't: ilgL'11\~ I~,'ll' L'nl1l'l'I', M:ll1lnvill,i :md Mt'H:l'io " dClTll'll'l~lTi.'l(l::t1lhQ l'.1hHHy of ;\LA ((I \"\l1'1'lJC( 1'1I111:11l'11'11:'1I dcfl':\.,:1:.; in Ill;l'ipl1crnI hlood 111(,,1n(111U~
"kill' ('c'lI, i:;,.IIlrc'(1
n'()111
(l(lv'1I1c,,'<I
cancer l'aLielll",
T\\'\"I\\)' pnllen!.': ''''ilh mIV:llll:cd Ct'lllL:Cl'1-; of l'he lung. (,vary,
HIHlll01\t! n\ld 1'\eck \Vcl"t~ C;,\(1111\11C(], The ~Cl'UI11 11,-", IIA" TNI'-iJ" "'1(\ sIL-2R were ,ig. t'lll'i~"01l1lly hi~h(.'r in t:Lllll',l~r rHlt1cI1IN l'h~lt'l in paliclIt8 with 110 kl1!!\\11 "illll.'"r', '1'1,(: "ddili,1!'1 "I' ALA inlll ti,e cell eullures ,'i 1j~ll I Ih:llllil Y I lll~I\";(:.:;(,d Ihl:: rcsp()j)sl.' Ofl,;'ill1CDr P~ll'it~111I1H.nw~ lilleklll' L'ell" I'hl, I'cporl dCI'I1l111SII'IIl"d Ihnl ALA h", :r hL'tH::rit.'inl (,;1'1\:(:1 elll i1l'11'1l1l1l(~ cell 1\I11dlnn In nrlval'l(;~d~~tt'\gc l'lldll1111:1ntll'll,
11\
bc'ls ,ii' II
Conc;lusion Wl.~ nrc not ~~~rtt:lill jl'l'I'lI.'::rc is \'l syllcrgist.ic: nr mklilivc rdill'iol1sl1i'l bcl.weel1 ALA ond LDN, As the lil11e of Ihis Wrtlil'lg" Ihl.lrc dl,'1L:~ nOl ~,com III be (Illy dil'ljt;tly CCll'lll11l'l1 biochcmicallnllbwny, 'It i~ n.:::a:-;lll1ClblL; lo (hil1k tllnt there illdc~d IN ;,It lt~I:1SI' (,111(; (ll'thl:~(" (:ffcds 1lI'I'hnl' their l;mltlinil'liR1Julion illiHtlt~8 :1 lHWt.:! ~11NCndt~ 01' bl't11t\lji(:nI cnb;ht (( i::< i'C1.\!4(lI1ub!i;! t(,"l bl::lil~V8 ilS w!,';!! that on~; CUl11POllClll or 1:l1c AL.AiN pl"\)lOl.::ol bears gl'l-~illcr l'lICl';:lpCuliL' \,:fl'icacy thnn l'h~ nl'llcl', It is I'cusl)m:lblc 1'11,1( l,:cnuin 111::';1\')1 (1g1C<\1 1)'pl,;S lif P<1l1Cl\~IHic ClII'Icor will 1'~'p(111d 10 ALAIN, Thi, is the "ccol1lllll'ticlo pub(i$l1~~d 011 this slIbjcd, nnd Wl' bcllcv!; tlHl!' thlr: t1(1l,~~ Wtll'~ n1111. deepcr elil1ien( invoslig,'li<1I1 vil1 11 clil11clIi Il'i:1l, especially givel'l the PO(ll' clil1ielll cour,e ol'lel1 experienced
or
by
tho!:lc dingnol)ct!
will1
1l1t:mstol'ic rHll'lCl'l;':i1lic ('lmeel',
In SlImn111l"y, tllc inlcgr(llivc rhcntpy tk,,,:ribcd Il1ll1i, 1I1'licit: 1'I1(1y ht1v(~ the j10sSibilHy ol'cxtending the lil~ tll'u !~l1liC1l1
ill \hl~ therapy or thl;;
wh,\) I;:; ClIstCJl'I1i:ll'ily cOl1sidcl"cd h~I'1l1ilml, 1~hl.s wns lH:C(1Il1~ plir;h~d wIlh l\ pl'ngnt11'1 (If::tl1 an1'il)xidnI'H' lhnl ht:.,!.lt''i KnOwn l'111li!lIl11Ul' ~l(,~tivily (nIl11H:ly, }\LAl llnd nl1 llpi::llc bll)cknd~ ngcnt 1'\'0(: ('[II] 8j'iI11UI:;\(~ 1.111 undogl:ll0l\S il11111UIh.,~ l'e~pl'\nSQ, AB w~~ ,S[lltC('\ in Oltl' ~n.rlkl' I1I'fil~lc, W~' hi.;']ll'V1-1 th~ll bin1'1lcc1ical Bckncc \vill om:: d~)y (,'h::vcll;J):1 1'1 Cl1l"C !:l)1' Il1l'lnsl:nti(,; ptl\1cn.::r:dk Ct111('t)l" perlHI])S \'iu g\'~n(: thern!:'!)! (11' 11llOll'ir,:1' bl(l~
pilliCllI:i. Ntil'IUl'l1i'lIly dus('d I J)N hlockr; C!1(1(l~;l!:lln118 OpiLlIt:: n,'I,,'I,,'plOI'~~ l\\!' U \\:1)' ~~horlliilK', Dl1l'il11~ this 1"1::(,;(,'1'1'01' bll1tJl,;udc, Ihl: h(1\ly PI'\')dllt:l.:~ lill'~,~l.:: 1l1ll(1l111tS ufopii'llcK 1111'CSj1tl118C to 11lL' 110,"ilhiL: l\.'l'lIIHIl.::k, 'fIll' GlltlUgl'110l.1S upinllt.," bl::\,~(1I1H':
Il'InrkGt, ITI(lI\~OY{,;I' QVl1lv~ unci nrc l't;l1ll?:cd, Ihe ALAIN thcr~ tq,y ~hol1ld be c(ln~i(kl'ed, given il0lth:;k l)l"tuxicily i1\ k,vds I'CPI1l"lcli 11~I'c 111, Its l'c,,,ly 'I \'11 i I:II'i lily, (lml ii,' elTceL (111 1110 ,1
(I VLlIl:lhk' Hild !:'l'\1 \ (j'~dl' I"l~l..~(J'I:'! IU1'$ (111 ,":'\I;ioUN celLs in lhc 1!11f1rUnC
patients
\.'i\11L'1:1' p:ll1Vl'1lf.;.
Naltrexone L11t\1
\\'i\!4 Ih~ s(,~v(lll(l kl.:~Y illgrcdi~~I'd
logklil-iype plllllbrm, Blil L1111il silch pl'J.1I"eol,
di~c.\l;it.(l;d ill thi~~ ~1l1TC1,l
(:"l11e
I"
iI1'tielc,
!"1ybl '..:111.
II! 19 ', Illl1:I1"': !"irsl l.I"cd LDN 111 Ireul penl,k With " tl!licd l,DN for
P"d",",ltiQn of Conflicting Il1t".",.t.
1\11)~: 1;,h:i.~11 hlN )11\'In;sil1t~ \'Ct4Ii\\,,,, hI.; Inl'CI"
Tlw lHithors dl,)clnl'~~d
Ih\,~ tl\.'i\\111l'll1 ('ii' 1:'1I:\l!lIC'
ml j:hnl"",I1\p lInd/ur IJlIblil.:l.\liul'\ l\Hhl:i l1rtklc,
!1\,l1l\ini!411,'I'l~d
wilh \,:lIllccl", (Jvl;;r (he ycnl'~, h~ 1,I)N 10 ;;1,50 11liticnlhi with Ctlll!.~el', 111t1~l of
\\1\1(1111 1l:l1l ndk'~\ 11lL: ,"lIW'l(lnl'tl ll'l:t'ltinc:nls, A~~4nrdit1g 1'0 I~ill:lt'i, ql' 3,"1,4 ]lnli(:lils who [HId rl;.~gl,llur flllkl\v-l1IJS, 86
s!luw\\1 ill
llJ!l:~t n 7~Hi;) 1\;dllClj(111 in tumor
bulle tllld I
I1U 1:l)llflil~lS
nf inl'l:h::"l with rCbpecl tu \Iw
Funding Tht: uuthort< t'c0L:h'l~d
n(1
nlllhr.11'i'111'P ol'll1b' :lI1'kll,.,',
l"inl1nchl1 SUPI'l(11'1 I"l)l' IIle 1'(;SC,ll't~h l.\Ild/(lr
,';
U,
WVI~:~\,~I
1'1
Nld;I'1 /\. 1:,hll'ill,,.1
/\II"llld,11I1(lk ,iVI,1 ill(IIII~'"
lIr'\11'11,1:;": in!IIIIIIi'II'II'(llul'i 1,:;11'1\,'\,'1' L',\"II:.; h,\' II\L'I'I:'I:·:\I\:.:.llllli1\,II"I' I(Vl'k'iilli, HI\"1, I,: ilhi'll I)
dI'lLlII'!":;'I'ill';lli\111 \\ 1111:1 ~'111\I.'UI1Iil(1111 (,j.~",il_.:':\,'lll,'lilli\lll,
IhTblli'II\J '111l" 1i~111;'~hI'l11 ~\lr\'i\':,11
willi
111'111'1;111"111 \1,'111, 1":\111,',1'1.'1111,' L':II1\.'\:1
11\'~'1' :111,'1' 11\':IIIIIVill l\illl, ii'lL' 11'llrIl\.'l'I\llli~; :ill,llil-1i11tIlL ;1';'I'I!; 1I'li',d,,\V Il"IIIIV~('il1l.' pIUI'IVI"L
q
I [11!llwl',S H, l\ill,I\,llilIIII!1I1I,ll\':\!t;I\",~'IILlLII' l)o\lll(\~',v>,H'II1k: ~"IIIU'II" 11':IIII,il1 jlllnI11,,'II' n'111111L',:-;, ('lill ('funi II 'Iii, ,~(ltl,l",', 'Ill: 1:- I I ~iJ,
('~rJll'~'I' 'I'IiVI' :',\)(Hl;:~:
1(1, 1":II:k RA. l\i.li\ly I"';, ~lndlU.l111 1:',:lk~;!1i1. \l1\'!, l{III'lli
I),
Ih'I'k',1111
!\,I
\';'<.'\(.;'I';':ill ill'
\,\'I\I]'lIiilli'" liI"1 li",11 1-;'1'I1pll1.'11'1111 III :1 l'llll'le?I'1 i,l;',il1!~
'lilly
k'\lI~(\t.:111it.' II, t\'1Utllt'1l,,'Ulll
;
I\I;il'l. ~:,
lillllli:[':,
11."/1<, ii'
('llvll ,Ll..l, ,''';ivllliU 1<" ,:i d'11I,:III.!v111 l'L,11
\,:yL'k·
,'lln'~1 11'1 11i'i1HI';II'I~l'l1rllwd
,'\".',!!,'II\\"ill
11,1\-'lIl,'11
t'd:-l,
(,:1'11 1'1'\ \.'1'11:"'·'III,III~:i,;\1
I{\l"
.'1'1'(1."/1('/',
:--:111:,:IIUdl:1
>:11111'1
J II,
~ llli~~h :~,
[\'\',11-'1111,11' 1i.'II'~(:I:;
ill,!, ',II. li11111; / I I yl 'I. I ,,1" i\I',}'.:il\1.I1
11111.1 L',llli:n,llilll, "\VI'1,'1oi:,l.'d
,j,(lIl:;~
Lhi'I'li1i P,
I:t
l.'lillwr
S,
'llIl'~
1'11\1 :lllIlilid 1,1\\
Y'dl,
\;::hlvlli\ 1,1'
V(ll'k, )\IY
.'\lplli\~III'IlIL' ,'11:1.1 i~':1
:1\'11'.,1111,111 ill IHlll1:,II~
11'1"1/)1'111 lilll/,/li'S /\'1', r. '"IIi!!/I!!!. I(lil,~ l:iilI711t),,17I,S,
I'
~:I:lh;,
Iii S,'\',.: ::i 1',iI ':; II' i 'il
111,-':'. 1,,'n'<:\;,lli V, ~'I ,ii, l't:ldiil~'llIlllt:llli\: Illn'i]\I' 1
111111.'1111111111111111' 1,1 ,1\11 "bllp:1
Ni:\\,
ill 111I!.'L' willi I'IL'I II'p1'd, I ~" 1(1111: I. S/ 11'1 In'
1:1,
I1lbl'llillllll1llll~, \\'111 IIIL' 11tll:kl.:r
Ii 1\\\.i.II'I\I'I!II-,\,'lliIIIIVWliV
I h\
1)I'\~'';L'III,·~I;lI
l'l1!liIn 11, kL'.Ylll'li'..' ilddl'l.'i,S,
~(',ii:II('~'~': .lUI",.' II
',il' dk'I:II',\'
I,
Hit,
~(H1U:r:(1'N,J,: ;"; ..17
I, I ZII,i,~\111 Is" ~,k I ,IItIL:,IIIIII] '.I, N;dll\'MIIIL' 11iL'1,!I IIIIIV" 11111\\ ii' 1\'~I"! 'II.~,'
,.'llil":;~.ill:\ II,·I·IIN
:~,
(',IIJI ','I'
11, I,\)N :11\d l;:IIII.l.'I' lilll''",
1)(1:';,' Nl.lltl'~','\(,IIl\.' l "lIli~'i'L'lil'L' ,'il llw Ni,.'\\)
!lr!l":' I
L'!''i1111!i..'\ I'UI' t'~I'
:1:'."111'" lill Iln:\'l'llli,ill illHI IIWI;IP)' ld \"I1I~'!,,'i, /ill'I('I/I"1I1 /iIILII''''
,";11 J,III"I 1'1
il1'11/klll 1.1
h: Y, I ) ',"nlil hll' L
1>,11111;;11 :11'111":llllill I,
12, 1'11l1i11'1
(Hi Ilill'SiI"I,
I 1,1, I', \," ,;, ':'1 (I I'
L'~::;ll'iI'H.', Inl ,I
:iI, 1\II,h"j·lq1ull: :il'id
\1,11 liln,::,; ,ll'Id IIIH11)lil~;b ill 111111\11' ~:vll 11111.:;;, ./
1 i'i,'
U, 1\,11\,'1,'11' :,\, l\L':-;I\\I'lllilll'1 Iii' I'JI111'11\l11;11 (1,'kl'l~
l'iilk'11b hv 1i'l1('1 :,111Ii(I,\ltliil1l:e: :dl'!I:I"lqHIIL' :I~'itl ,,111,1 '\"'iI'\'I\'I
".'1,';" 1,1111 tli:
liiil'll';IIl':,
,1111,1
Imillillll'!, ;~\)1I:;JN:7.\,;,."!,!
I' i:vlb, :'flii
iii pL'I'iI111t:1'<I1 hl',ll'I,,1 illl:II1!\III.lI,'I\:~11' ('viI:< hlil,lh'd Il'liI\i i',llll'''l
i 1":1:-, :1I1'! hili:li'> ">",Iul'i: 11;II'I<:il.':IIIL'IIIII'1I1\.11''', I~,\/.I, ~(I()I;,l~:1:
"11(1,1:
1)llft'Il'IIII,iI
IluIL'1.! pVi'i['11IL'1(11 hlill;d !~'i
tiOI1 ql"
l(iW_
I ).111'1'11;1:111 I .. I i,V\'!; ildiiilli l.I, i\ nl"" 1\1' 111,,(','1"(,"": Ill' 11\\'1', 111\11-
I\'IL', Ilulll N\!
c,ITI,Tl:; id' till: IlIlIill\ldt1l11 :ilph:\-lllll!ll' ;1\'1\1 (lll llw Ili1l1Ih:i',I'
Iliid
Fh ," : I \117 ,I, ", ::IJ~,,';\,q{\
Iii 1;;1.' 11:'11111.'\1 illL', r'/II '.',,'1' [fliin '!'
Irili/'III"
\'is, ~1'11,1:;: 111:'i:'()· lli~,
I11vl\lI'IIIW:, lllii'!\:
iI,:IIIII": \'111\~ltI
111'11.: .111 d!.i,~it',~'i:lllllil \\ 11111';,ldl\l\ll~:I'\IP~", liilillil!, I 'JiJ
11'1111'0';\
,:'7')'
I \),~
~ill.