`
`

`

`Publishing
`
`Information
`
`Cancer
`Research
`
`Print ISSN: 0008-5472 0 Online iSSN: 1538-7445
`
`AACR Officers
`judy Ii. Garlicr. President
`Frank McCormie . President-Elect
`Elizabeth ll. Blackburn. Past I‘msidelll
`William N. llait. 'I‘rL’asurer
`Margaret l-'oti. Chief tiara-alive Officer
`
`Publications Committee
`Michael A. Caliginri. Chairperson
`Christine it. Amhmsone
`Andrew ]. Barker
`Puwel IL Brown
`Richard M. Caprioli
`Ami M. Chinuaiynli
`Chi Van Hang
`Yves ill. IJl' Lilert‘k
`Jessica t‘lugne Dellarl
`Lisa Dilier
`Levi A. [tarraway
`]-'. Peter (inengerirli
`l-eriesl 'i'. Hawk
`Sandra J. Morning
`Nancy E. llynes
`Paisi A. timer
`Kenneth W. Kin-cler
`(itsillt'rmiiia I Imam:
`
`David H.
`I
`: kmsnn
`
`David l'iwnit Worms
`Christoph I’lass
`Leona I). Samson
`llolicrl ll. Vonderhuiilc
`George I). ‘i‘aiirowuios
`
`Publishing Staff
`Publisher
`Diane Hmtt-liehlcr
`Hireelor. lidilnrial
`liclen liarsky Atkins
`Asst. Director. Editorial Syulems a:
`Managing Editor
`KellyI A. Iladsull
`Senior Axum-Into Editor
`'I‘ruet-y Pulsky
`I'Zdilorial Stuff
`Morgan ISIIrns
`{'rystal t‘heirpialoni
`i‘uuir Klinlili
`Naima t}. Stone
`‘I’iluollnr liiueiiarl
`l’illrit'iii Ilussli
`Assoeiule Director. l'rodut-llou
`Charlene .‘iqiiilih
`Produeiton Stall
`Iirendu ltolierslni
`Jeremy ItusI-nlmg
`Hue Itussell
`
`Director. Electronic Publishing:
`Mielnu-l lterei'idiu-
`Electronic Publishing Stuff
`Sliira Carroll
`Mary Itirtli ('unney
`I}iime M. Mariiielli
`Mani-tale Director.
`Sales and Marketing
`Nicola |.. ilill
`Assistant Director.
`Circulation and Fulfillment
`Karol“ Itat'
`
`Marketing and
`Creative Services
`Ilireclnr
`Paul l‘lriseoll
`Design Stall
`Susan Moore
`
`
`L'um'r'r Hesr'i’trr'lr is published [wine a Illtllllli.
`one volume per year. by the Ana-ric- n Assut'ial ion
`l'or {'alit'er lit-sirzirrii.
`lTIt'. l'oriodit-als postage paid
`
`:il Philadelphia. |’i\. and additional mailing amt-rs.
`l’US‘i'MAS’l'lall: Send address eilanges to [‘aiit'er
`llesearrli. Meniher Sirl'rires. Anti“. (1| 5 ('liesl nut
`Street. l'flh Floor. [’liilzulelphia. PA l‘lillli-‘l'lll'l or
`
`I‘Z-niail: ineiiihe '
`'Iiip(nI.-iaer.urg. ('opyright Zlilit liy
`the Aliii‘riean Assot‘ialion I'or (‘nueer lit'fil'tlrt'll. ll'tt‘.
`Printed on acid tree paper in the United Slates
`at America.
`
`Scope
`
`'l-s. reviews.
`t‘mieer Iii-semen puhli. 'll
`
`
`
`t.
`'igintieziiit-i mil hrnad
`and opinion pieces olle
`.
`impact to a diverse audience. The main snipe ol
`
`
`the journal is captured in ils priii . ry tillllh't’t‘lill
`Iwhieh linens on moteeular and eeilillar paliiuliio]
`ngy. tumor and stem t'ell biology. llierapeulirs and
`targets. iiiicroenvlrounienl and inlnilnlolnmv.
`ll'l'-
`venlion and epidemiology. and integrated systems.
`and technology.
`firm-er Research is :ihslral'ted amlfor indexed in
`
`
`MlfillLINI’
`index Medic Wei) ul'h‘eient'e.
`Seiem-e (' ation Index. ( urreiil ('onleiilsi'lill-
`
`
`Sell-tires. {'urrelil (’onlenlsfl’linital Miriiii-ine.
`
`BIUSIS l'reviews. ('lieniieal Mist arts. and
`St‘uplls.
`
`Submission of Manuscripts
`llnline iiizuiust'ripl submission is welcomed all
`
`litlp:f.-"ran.i siihniilJii-l. Please note that a
`lltllll‘t'llllli .ihlir suhniission I'ee at $75 per
`
`Iiiuiiuseript niusl be paid v'
`credit card at Illt'
`lane of sulmiis
`_'t'liis tee is levied (III all
`nianusi'ripts r1 landless oi the (lee 'on on lln-
`
`
`
`paper.
`ItL-l'oi'e slillllllllltlf}, a iii-.nius
`'ipt. pli
`mat the Inslrin-Iioiis for Authors. \vliirli is available
`from the Ioia'iial‘s home page al
`liltpzfi’t'aiit-erres.
`aarriinu'nalsurg.
`
`Page. Charges
`iii-repled Illiinusi'ripls li'lll l)l' pulllisliell with llll'
`Inalerstaniling Iiial
`iln- aulliorlsl will pay a l'iiarge
`ol 5'13 per printed page lor arlieles one to six pages
`in length; 'iil'zll per iiildilional page. lJisenunIi-il
`i'lialgtls are ll\'illlill)ll’ llll Ineirllii-I's.
`
`Subscription lntormation
`.-\r\t'lt Member-v. ‘w'nlI-‘er'rplimi options are prinl
`l\'llll lllllllll‘ in I In." Ill" lllllllil' iu'i't'ss (Ilily. {‘Iillliu'l
`Ilri'mlierslupmnor-Lore, or we lIIIput.I'wwn'aaernrg
`llllll Hit In lllt' llll’llllll'l'hillp page iiil' llll'lliei'
`Iilllniuarinn.
`Instilntions mid Nolilnelnliers. l unlal'ts listed
`lii'lnu- are to: single site lilllllli' :a-i'rss only [limited
`In one lilir'ury only] illlll tlllllllllill III'IIII
`sillisi'rtplmw.
`“‘1“. t 'aiiadii. tltlll Mtlxll'li
`l'iIrpIIi Iiistiiliutiml.
`i'lit' llll'at'llel'i'. llli Weill kili'I-I-I. New Milllml. l'i
`llli'."'r'h: plunlv Hlill-Il'ill Illl-Ii, lax Hlill Ill)“ llllii'l. I’ lIIiIIl
`IlII'piImamIurpiii lllslrllltllltill.t'tiltl.
`Japan
`|'il'rltl III'llel's .‘itltl lliltiliries in Ullt' Ill Ii|(' lililliirlllp.
`t'tililai'ls: tI-sltppurl[rtrltliirlizviLl'II.i|I:
`
`
`ililtli’uip.
`\'l'l‘t.('{llll: i
`)illlfrr-Ulml'll.l'lllll:
`innrnaha-lurinkniiiyi :-n.jp: iisaeiuni-lism-oi'uip.
`Rest ul' I|World leiu'luding alum-I
`
`Turpin llistrilnition. Pegasus lirive. .‘itrallou
`I’ai
`iii-ss- l'ark. Itiggii-swade. lirtll'nrdsliire .‘il'rlt'l
`311}. l'iiited Kingdom: plume t'l‘l- l)
`ITI‘IT-HI-l ‘1":‘1".
`lax i-i-l- [l-l7li?-hlI-l-‘}$?.
`lam +-l-|
`ll-thn'f-I‘ilIl-h-lll.
`e-rilail ('Ilfilh‘i’l‘t‘fit'lIlt‘l'llll-tlit-i|rillllllllilJ'ltill.
`liill-rnalional subscriptions lllt'lltllt’ rust of sill-lau-
`inail. I'predited inailingis available. tioiital-t 'I'Iirpill
`llistrihiilinn for rali-s.
`
`Silt:
`or us ‘iend site licensi- lonline arress open
`
`to niallipli- h lilings. locations. remote and proxy]
`inquiries to .‘illl'llt‘l'J'lSl'fin-tlilt'l'.tll'g.
`
`Helul I‘llallgl' lil' address
`('Iitulge of Address.
`
`nnlilir'atimi till ila'
`ll iltlwll'll't’ 'Illll
`llit'llitlt’ lmlli
`
`
`old and new iltltll't’hi
`Mitriillel
`llh't‘l'lllt’rt-i silliillll
`
`(‘lilllilt'l AAI'" Nit’llllfl'l' Hm't'it'l's. lilS (‘lIl-sllllll 5L.
`ITlli t-loor. I'llil'ldeiplzia. I'r’l
`lliIlKi--l-ltI-i: e-Inail
`
`liltrlllllt'
`‘ 1mm tenure. Nonmeiilhersillisi'riliers
`should euntaei 'I'Itrpin liislrilnllioii. 'I'he llll'lll'llt'l‘)"
`I-lit West Street. New Mi hnd. ("l‘ Illi'iI'Ttn; e-niail
`
`Iln'piiiuniu-lurpiii-dislriliulin mm. or 'l'urpin
`
`iiislrihuliun. Pegasus lJrivr. Slralttni Business Park.
`itiggleswadi- Iteiil'nriislnre StilH H'I‘Q. linilt'd
`
`Kingdom
`uail t'lltiitil'fvtrelllrIlttl-tllfllrlltlllllll1.(’tiltl.
`
`Claims. t‘lamis i'ur l'ill.‘ 'iiig issues made \villiin
`‘itl days of Iiio issue's pnhlit-alion date will he
`
`honored while supplies Lst. Menihei
`lmerihers
`should t'aiital't nieIiiliershipro-aaerurg, phone
`215-440-930”. lax 2h") -|-lll-‘}-ll2. lristiltllitilin‘ and
`noiuiieiuher suhst'rihers should iiii'ei'l t'laiuis lo
`‘l'urp'ni llislriliuliuu al the appropriate address
`above or by e-mail IIll‘|iillllilfu‘lllrlllli-
`ilislrihuliinwoin.
`
`Single Issue ‘inles. Single issues and hark stoek of
`the journals may he ordered ironi the. AMT“ main
`
`other by railing Hfiii--12.'t-Zl‘)l‘i5 llull-l'reel or Elfi-l-ltt
`‘litlltl. Priee ol'a single.
`ssue is will and ineludes LLS.
`suri'arl- puslugo. Orders milside ol' the llfi. are 5-765
`and ini'iilde postage.
`
`Advertising Information
`Inquiries about advertising should lie dil'ta-iui to:
`M. .l- M rvii‘a ilssm'iales. Int-u Wesl ’l'aunloii
`Avenue. lierlin. N] tIHlJlF-J Il‘lione: [85(1) Tex-Ham:
`I-‘ax: {8:16) i'l‘iit-lltlh-I: li-nuiil: timatlierrmlnrvieaunul.
`Copyright and Permissions
`As a not-I'or-pruiil organizalion im-urpm'aled in the
`
`lliiilud Slates. .n‘ii‘il’ll adheres to US ('npyriglil
`IaW(|’|.'J-l-551t], wliirli Iii-value rill
`live _Ian|iar\- I,
`I‘JTH. The law stipulates llial enpyrighl for works
`is vesled in the author l'mni the moment ul'
`creation and remains the proper! y ill' the aullinr
`
`Iltllii
`legally lrai
`Ii rred. Authors who wish to
`publish arlil'les and other material in rlr'it‘ll
`inur-
`
`nals must formally II
`‘i'er ropyriglil to ANGEL
`"the mpvriyjil transfer l'urm must In» signed hy all
`aulliurs lie ore :‘iAt‘ll ran pron-rd with |‘ltlllllt‘:l|lntl.
`.-\I'ler a iiiaiinsr'ripl has ill-en deemed potentiallyr
`
`
`tl('l'l.‘|)l.‘ll)ll.'. all aulli
`on the iiianu
`';II will he
`
`requested In i'oIinIt-le an online eopyi gilt Ii'allsli-I'
`agreement through llitr Snlal'l
`iihniil system. The
`AAt'll ioiimals will not ‘
`ihlisli :I paper unless
`Iin'ins Inn-r hero proper y enliipleled itlltl I'('llll'l|l'(l
`l)_\’ .-\|.|. authors.
`
`.I\.-\{‘|l'.~ ['opyi'iglit
`To read the t'oiiiplele \‘e'silni ul'
`itllii i'ei'llilssluns l'tilil'y'. please visit l|It|J:.I"i'
`
`r:iim-rrn--...-r.i
`'jlllll'll nirgisiieflnisi'iilhra.
`
`Alllinlfii'npyiigliipi-rniisslnus. 1 his pi
`t'y iiii-Iusles
`
`lm'lliei' iill'iirlllillllltl III! ulllluil's' I'Igllls Ill Ilsngl'.
`perlliiwiun requests. lroni liliril purlie.,
`ll'l'l' :a'i'I-s‘. In .I‘iill'll Inltl'lliil-i, Illlillillg agent-y-
`l'l’l lure merits, illlll Ilie anional iIisIIIIIIi-s ul'llenllii
`l'u Ill(' Arm-ss- Pulley.
`No responsibility is m'eepled lay the Editors or
`by i‘lM'll. hie. l'nr Ilie opinions es iressed hi.-
`emilrililllurh' or I'm ”In t'unll'lll [I "w
`I
`
`
`mlvertis nenls
`lion for ('iuu‘l'r Ileseurt'li
`Ann-r5:
`silo
`
`tutti t'lirstnul Hln-et
`I'liiladelpliia. |'.I\
`ItJJtII‘p -l-ItIl
`l’liuil
`HIT—n
`llll 'liill’il
`Fax
`-
`2 Fri
`
`
` . III 'Vffl'lll'll'lflll'g
`
`“-i-Ii-alI-r wwaIarrJn-g
`
`
`
`IKQ. .iuieiimn ,-l~\rrnilmn for Cattet’rRPmrdt
`
`Cancer Research
`
`Thisrnaterial wascopied
`at the N'LM and maybe
`Subject US Copyright Laws
`
`

`

`
`
`Cancer
`Research
`
`February 15, 2012 I Volume 72 0 Number 4
`
`BREAKING ADVANCES
`
`MICROENVIRONMENT AND IMMUNOLOGY
`
`829
`
`Highlights from Iii-cent Cancer
`Literature
`
`865
`
`REVIEWS
`
`831
`
`335
`
`The Ilark Side of Mast (Yell—'l'argelcd
`Therapy in Prostate Cancer
`Paula l-'illuui and Mario Paulo Colombo
`
`Regulation of Cancer Progression
`by B-I-lndorphin Neuron
`Dipak K. Hurliar. Sengnltlwelarl Murllgan.
`Chongqing Zhang. and Natlka Iloymliim’rl
`
`MEETING REPORT
`
`341
`
`'l'wenly-Third Annual I'ezcollcr
`Symposium: Engineering Influences
`in Cancer Research
`I’eler Frit'tll..II'I'I'IIIIIIIJL’II. ”in-"HI Livingrilun. :ImI
`I'lllrieo Miliitili
`
`CLINICAL STUDIES
`
`845
`
`N-Mye Regulates Expression of the
`Detoxifying l-Inzynie (ilntathione
`'I'ransl'erasae GS’l'lI’l', a Marker of Poor
`Outcome in Neurohlusloina
`Iamie l. l-‘letellcr. Sauna-Io Iiherarili. ,Iayuv Marl“):
`(‘ulht-rinv A. linrkharl. Anaemia Russell.
`l-llrlanuele Valli. Janice Smilli. Andre (Jherllmer.
`Lesley J. {\shlun. “-‘cntly ll. London.
`(ilenrl M. Marshall. Murray I). Norris.
`(iinvunni I’crini. and Michelle llahcr
`
`Prefix: Islprcssirm (ff-{he gluirrfirimre rlermffierm'rm
`system may lie prrrri'rm’arir r'nqmrmar in an-rlinh'ug
`r‘lrrmrm'r'x'r'srrrmre effluents that Imr‘brir' M:lei {fuel-{1'
`gene rml'pl'r'fir'ul'r'rms.
`r35 srrggefled here in .s'i‘ma’ies of
`Herrr'nhlusp‘rmm. r: rrnrrrmrm pedr'uir‘re tumor.
`
`INTEGRATED SYSTEMS AND
`TECHNOLOGIES
`
`854
`
`llylierpolurizcd ”C Spectroscopy Detects
`liarly Changes in Turner Vasculaturc and
`Metabolism alter VF.(£I~‘ Neutralization
`Sarah |-'.. liuhlltliek. Mikku I. Kellum'n. lJe-eli “IL
`and Kevin M. Brindle
`
`Prceiw Hl'l'x shun dryer-inns m: .lflil nudging ”Minx!
`Hm! run he “.er m mmr'rrlrrixil'elr ”minim I'rtsr‘rrl'rrr
`rl'l'krupffurr rrrrra’ rrrarrrl'rdrl‘rm'uuIfiiflrill'fug l'I-L‘F
`Malinda: (“likening H eh'm'em’ New! in rrrpr'rigfl'
`el'rrhml'e rile Men rrrrpuef allrrrfirrrrgr'ugem'e ”It'l'flfll m
`pain-Hts.
`
`876
`
`387
`
`89?
`
`Metastatic Cells Can Escape lhc
`l'ronpopiolic Effects of TNF-u through
`Increased Autocrine Il.-6;’S'I‘;\'I'3
`Signaling
`Slllln I.I. Ni \\'ang. anll [’nina IImLII
`
`Pun-is: Hrr's' s'rrrr{1- defines: rm RIF-l" driver:
`meekml'ixrrr rift-(mew em"! .urrr'w'wrl' Him is r‘r'ii‘reaifiir
`rmrrrrsimr'r eul'nm'cuir'mr rgffl're fiver. Hogan-mire Hm!
`INF-u" r'reepim' mmrgom'srs errrrerrri'v in irfiuierr.’ {Hulk
`may have prrr'riem’rrr merry in Hearing mfrm ermr‘ers
`um! (Hirer r‘rrrreers {first metro-1'ruin:{it 'ql'reu'ilr in liver.
`
`Monocytic CCR2' Myeloid-Ilerived
`Suppressor Cells Promote Immune
`Escape by Limiting Activated (IDS
`'l‘-ccll Infiltration into the 'I‘urnor
`M ieroenvironlncnt
`Alexander M. Lestlkhin. 'I'nhirls M. iIuIII.
`Sliigehisa Ritalin. (‘zrina L'urlez.
`Daniel IIirsel11mI'n-(‘yIm-rmzln.
`Frauleesea Avugadl‘i. ilahrielle r\. lilzzulo.
`John]. Lazarus. I".rie ti. I‘aaier. Alan N. llnuglilon.
`'I'aha Merglmtlll. and ledd I). Wolelmk
`
`Prim-ix: The el-iukr'rre (Lil-(1W1 which is med m
`errrrrrrree Iekr'h' eel! enmity in marry (mm-r pollen-‘51
`also rttprmrb' rr paprri’rrrirm ofiommm'-.\‘upprr-sxr've
`worming-fie eelh: that run Nani Hie em’rr rgf'm'ffl'rrfrrl
`uufmmrrir'
`'i' evils mm Hie immir mi:'r'm-rrenviron-m.
`perhaps umeffliugfl- r'rmfrr'hrrfiug m r'rrmrrme “wipe.
`
`(3)8 ‘ 1‘ Cells Specific for Turner Antigens
`(‘an Be Rendered Dysfunctional by the
`Turner Microcnviromnent through
`IJpregulation of the Inhibitory
`Receptors 811.11 and I'll-I
`Julie” Poureadu Khaniun Sun. Urnellu Paglianu.
`Philippe Guillaume. Immanuel I". inc-seller.
`(‘indy Sander._ln|1n M. Kirkwund. Daniel Ulire.
`\'iii|)' Klu‘llruu. nnil Ilasmne M. Xalmur
`I’réeia‘: Hrirsl'rrri'y :'_I. feuds krroll'ierlge ruriem'niug Imn'
`rm impurfrmf inhibitor} elrrss rgfr‘o-r'eeqiirir moleerriex
`rm '1" evils are; m Mori- their ammflie (:l-‘IIJHM fr arrivin-
`«game rmrmr relic therein-- deepening insights in!"
`Emir in reverse this ‘ITII' meelrrirrfiwr rgf‘rmnume urea!»
`in furrmrsjbr Hn’rripr’l'rffe herrefff.
`
`Hedgehog Signaling Inhibition Blocks
`Growth of Resistant Tunion's through
`Effects on Tumor Mierocnvironment
`Emanuele Heller. Michelle .v'\. illn'eliln._lingyu Mane...
`Xinnling Sn. Sara Chen. Joeln-n Schneider.
`Kyu-Sangjneng Mareus Vidal, Leah (inlillacrg.
`llougju Ilt'llg. Mary C. llorniek. Julie |.. Prior.
`David |’iwniea-I‘i’orms. i‘anxin Long. Ross (‘agauL
`and Katherine N. Ill-'eilhaecher
`
`
`A Journal 01 the American Association for Cancer Research
`wwweacrjournalscrg
`
`

`

`
`
`908
`
`9‘1?
`
`928
`
`Prefix: Libraries rhwmm‘h’uh' :i ”Heel mi'efiu'
`hedgehog signaling in uan'm'hnfflim'h'rm rmn’
`rfemrun'rmfe Hm! hedging i'nhr'hi'mrx rm’uer' mmnr
`burden Himngh ri'h'ei'lf (fleets m: mmm' rem:
`ras'n'm'fiisix. mm’ .un'rmm! veils with!“ me imam-
`mi:'m:'m’irmmreuf.
`
`mill—20a Encoded by the iniII—I7—‘J2
`Cluster Increases Ille Metastatic
`
`Potential of (lstensareoma Cells by
`Regulating Fas Expression
`(inngxinng Iliumg. Kaxninasa Nisliimutn.
`Khit'liuu Zilnll. lit-unis llilglll'h. and
`Eugenie S. Klriln-rman
`
`I’rfieis; I-‘fmfiugx pmw'de insight-i mm {he menus In-
`Iiriu'r'h brme r'imrei'c gm); Her-e55 In the June. by
`mrxra’ufrm'ng germ-33in“ {if}: mi'r'thxI pmgi'mu Hm:
`"N’I'HI'HK' murm' re” survive! in the hing
`HIIi‘i'm‘flI’ti'tiiimt'fli.
`
`Immune Inhibitory Molecules LAG-II
`
`and I'll-I Synerg
`ieally Regulate 'l‘—eeil
`Funelion In I'rnnmle ’l'umeral Immune
`Escape
`'J'm-niu.
`Sr-ng-Iiynnp, \-\'nn. I-li'glian I-J.
`Mnniea \'. (iolilhei‘g._ ulshrez- lianknli. Mark Selby.
`(‘hr'islnphm' 1. Nina-h]. MaHheu' l..
`|Ie1tini.
`Iluvid M. [irax-anu. l'l-Ier \"I-gvl. ('liih lung Lin.
`.‘ilephanie 'lanesuinlialvisil, luwph |-'. (irmm.
`George Nelle, Mallhew l'.l’il1}i'l1?.{'l‘. Alcitlt-s ['huux.
`Paul _I.
`l'ly._ I'l‘t'IL" _I. \\'nrkn1iln. IJI'eu' M, I'zII'tIuIL
`.-\|an _I. Kurinan. {'lmi'les ti, Drake. illld
`Darin .\.:\. \‘ignali
`
`Freer}: . Inniqqrmn‘ m r'muhfuufl'rm strange-«1m-
`interred drugs, {his midi shuns Imu' mmhimm'rm
`.m-urygim ,(r'u' mimam;Hrr‘rupmhr' unhhmfiex Hm!
`merger Impm'rrmr m'gum'i' i'eenfrnraei
`.r'immmr
`n'eeprm'x um prurfrir 1- puma-fir! mm'mmrar :jfli-rrs, in
`rw'm-e: hi- t'm'i'i'i'fflm mummr- nrrquz
`
`Antigen—Speeifie L'IH T Cells Regulate
`I’lmelian nl' Myelaill—lierived Suppresmir
`Cells in ('unm-r via llelrugmde Mllt‘
`(‘Iass ll Signaling
`II' in ‘mlm.
`Hl'illihis Karma]. :‘lll‘xllll Ni-Iusm.
`[‘jngi-ail
`l lieng. Jim Ill Hun-elm. and
`IIInIln- I. [-ahnlmu I:
`
`f’f'l't't-i'.’ Hm repel? ”shire-v.1" H Hrnh'rneru
`regarding Imu- mIr-Iram’dem-r-r! mpprr-wri a'i-Hn
`siimn'eu the mm m H} I “I
`I H'Hx m rrmr'i'i,
`.I'el'r'riimir ”_Im'li'm'iHr'r-tflrrn'fi Imp an Him I! m Married.
`”mm.- mmgeu apr'r rfir' farm». n} Hum- I H'H'u mm
`rmgrm'm Hn- mmnmaunplrm-wer effer I» n; uni-hm!
`iii-mu! mmrrr'wu ”fix.
`
`949
`
`I’rei‘is: This and} iih'nnfies the J'm‘i'rm' frmispm'n'r'
`.m "H (is r: r-n'h'r-m’ mm‘iuim- af'pSJ driven
`mr-mhm'ir r-rmri'nh- UH gifu'nfi six rim! recpi'mri'rm.
`and rims m'm pim'un'uin r‘r'i'ri'rriflfr'ar «imparting
`”magnum“ [II'FIQIT'ASIUH nip-1i rhfflr'r'i‘rif mun-rs.
`
`Mye l'ustlranseriptiunally Iniluees IIIFI
`['rntein and 'I'arget (iene I‘lxpressimi in
`Normal and Cancer Cells
`Megan Ii. line. Iari'tw M.
`.-\~;ea|lu. Mandi-up Kuln'.
`illltl Nit-hael
`I). ('uie
`
`f’r‘it'f- ..
`
`”I r' mwe_v.,rnw-x-~'."rm n. firmed In indm'ii'tm mi
`N I'UJ'I' r'r-guhmu' if! Iiimrn' III-pmm. highlighting n
`pi'ei'iumrfi um‘r'eUgmer! eflr‘eiru' puihli'rn fiir
`nm‘ogr'uie II'IIJI.\_‘;‘iIr'HHiHFH-‘ b} .Iiu'.
`
`PREVENTION AND EPIDEMIOLOGY
`
`958
`
`.r\ Positive Feedback Signaling Limp
`between ATM and the Vilumin I]
`IIeeelilnr Is Critical Iiir ('alleer
`('Iienmlirevenliml by Vitamin I)
`llm-i-Ju 'l'ing. Han-(1a Insulin-Karim.
`.‘w'hian _Iang ‘I':II1. lune-Wei HRH.
`'1'xL1-Illlu Lin.
`Wei-Hi Xeng._lui1ies Messing. 'I'znne-ji-ng Sheri.
`lie-Yin}; lian. Willis X. Li. lidwal'tl Messing. illIll
`I'i
`|-'en 1.ee
`
`Prefix: i-i'mh'ngs suggest Hm.“ i'ihmim .U prevents
`ermr'er In- xiimm’un'ug H pm'm'vr_fi‘r'tflmr'3'" signalling
`hm}; firm: the ei'hiim'n H n‘i'epmi' In {he ”All repair
`mm'him'ijr. im'reflxhig m- r_f,-'i'r'frHt'_i-‘.
`
`THERAPEUTICS, TARGETS, AND
`CHEMICAL BIOLOGY
`
`969
`
`Resistance to Selective IIIII‘II: Inhibition
`(Tan lie Mediated by Mmlesl Upstream
`I'alliway Activation
`|-'e
`Sn. William I]. liriulle)‘. (Jinngqing “Ellie.
`llllllp, Tang. Lizlmne, MI.
`lil'izlli Higgins,
`Kenneth Knliilh'k)‘. Kathryn Parkman.
`Min lung Kim. Kerstin 'I'i'mwei'. llil'llill'll _I. Lee.
`Kathleen ‘ieiinslaek. Jade ('ai‘ti'l‘. 'I'lminus Allin-rt,
`Sm'en Uei'nier. Iim linsinski. Milt‘hell Martin.
`Mar} Iillen Liimenx. Iirian l.l"¢[llti.
`llil\'IIl lleimlmmk. illlll {iideutl iinllag
`
`f’reri‘s: I-i'mi'r'iigs address the prey-m i'h'm'i'n!
`{bum-Hg." m prr'l'eii.‘ nr n'i-‘r'i'w' m'qiiiii'd i'ex'i'n'fmn'e
`m HHIIIHH HIM!” mmmmm. lefii'r'h rim premier
`{mil-eff”! M}! will h‘mwenf .‘p‘ir'mfleim'r i'r-x-pnmex m
`mrhmmim.
`
`979
`
`l'iitenlialimn of the Navel
`
`MOLECULAR AND CELLULAR
`
`PATHOBIOLOGY
`
`939
`
`Regulalinu al' Mommarlmxylale
`'I‘ranspurler ML'TI l'lxpressiun by 1:53
`Mediates Inward and Outward Lactale
`I-‘luxes in 'I‘nnmrs
`Romain liliilllll. I‘l't‘tli'i'jqul- \‘iigi'un. .-\|iue Menile.
`
`Mule |.e Irelmi. ['hamal Elie-«y. I'ii "e thin'eaux.
`Hula-[Ii lizard Naeni. .‘ltlll lllirjer I'I-I‘ull
`
`'I'npiiismllerase I lnliibilur
`Iudenoisoquinoline IMP—100 by the (‘ell
`('Iwekpuinl amt (‘th-(‘IikZ luliilulor
`:IZII77II2
`lilu-ellu M.
`
`-\r'i~. .Illll ‘i'i'I-l.
`
`l'lIIIIIIIII'I'
`
`I’rr't'is: Hm \Imn _m'rrl'irirv n pm“; u! r rim-rm Hmr
`H rmuhmnimu Hn'rrqil
`r-rmqirm'n' in! mm
`rrimmemi'r'm Inputsrauir’run' I mmmrm {aim
`I'hr'r'flflm'm Mame Im‘iiiliiruw mm in men- x1 neg-rm.
`i‘imi'I'I' i'i'fl iii'itr‘hs.
`
`
`
`AKQ. lineman. lwx whim In: (:fllir'm'Rl’seflfl'h
`
`Cancer Research
`
`

`

`—————__.——_..—.—
`
`990
`
`Ilislone lleneetylnse Inhibition
`tnereuses Levels oi ('holine Iiinase o
`and l’hosphoeholine I-‘neililating
`invasive [longing in Ilnnnm
`
`
`(‘aneers
`Monnia lieloln-elle-Button. \':Iil|::|
`lielen 'l'roi'. lioln'rl
`ll, le I'oele.
`.-\nne ('In'islnn- \\'ur1g i'e long.
`l’itj'Illf.
`|., taliznln-lli litt'lx'illll. lieollrey S.
`lulu: ii. (il‘illitlis. loo It. Judson. l’nnl \\'III‘ktII:III.
`Murlin U. Leaelt. nlnl inen I.i ('lnnn;
`
`.\r1nI:III.
`
`I’nir'is: Nomi: I 'nsn-r' hr'omoralr'rs offer r'rr'tr': 'ml mats
`rm- rlom'm' trials nitrogen?! drugs, as illustrated in
`this smrlr providing nm‘hrrm'strr- .mp‘rmttfin' the
`use of'plmspltrIr'lmlr'm' as H :‘rmrh'n’ute nmrrm’usn‘r‘
`l:r'tmirn'.lr'r_frn' imagine the plim‘mm'mlt mnm'r'
`response to Hill-ll" inhibitors.
`
`TUMOR AND STEM CELL BIOLOGY
`
`1001
`
`Ilysregnlution of lizrin
`I‘hospltorylution Prevents Metastasis
`and filters Cellular Metabolism in
`(Isl eosnreolna
`
`Ling lien. Hung-Hook Hung. Qing-ltong t‘hen.
`Ioseph Briggs. Jessien {'nssnrungll.
`Satish Srinirnsan. Miehuel 31. Lizardo.
`:illnlll'o Mendoza. .-\shle_\'
`i'. Xizl.
`N;1I".I_\'iltl Availhnni. lured Khan. and
`(‘Innnl Klnmnu
`
`l’rf’rris: 'l'ln's srmlr offers nrer‘lnmisnu' insights into
`the role of rt pleural regulator rlemefrrstrrsi'x that Hulls
`titepl'rtsmrr eel! membrane to the ”my firms/o 'lemn.
`mnl’ rim! “no net in port by linking melolmll'e um!
`respirator-i vapor-ill
`in nielmlrrn'r rnpm‘n’lfn.
`
`1013
`
`Hedgehog and Notch Signaling
`Regulate. Self-Ilenewal of
`Undifferentiated l’lcolnorphie
`Sareomas
`
`l'lnntg ‘i'l- Tale “one. illitgsiu Wei. Ilkt'tl Ililtl.
`Shillgo Hutu. Itonnk {ihunhnri :\'/.ut'ttier.
`Heather Whetstone. Itin'lnonrl I'oon. lim'i iln.
`|-'eitei Zlieng. I'ltil Khalil}, Weisln \\'
`
`I:I_\' S. Wonder. and Eleni-.Imin A. .\|rn:1n
`
`
`1 023
`
`l’rr-er's: Findings sneer-st on! omit More! {moment
`srr'nhjen-ern'
`.1 soft honor wort-1m- seen ohmic!
`u',u1'n.w'l'e{1 in .H'rr' elrn'i'h. not Him possible insights
`into its enlemrm'r origins to"development. n'ln'r'lr
`lime been lnlsror'r'r'olll (‘wrtr'ol'r'll'srrll
`
`M ant mary Gland Seleetire l-lseision of e-
`}rm Identifies Its Role in "II‘NJ‘ Splicing
`Honinr I\:ll:_\';n', thnnnno lino. Hnnlun'
`.-\r|tl}'tt.
`.\r|;1I1I lirlel. ‘t'olnnria ('m‘nrrnlains. \'.nn-~'s:I Rose.
`Mathew l'. ('nsintit‘o._lie Klnin. .\1ieh:lel I’. Lisatnti.
`I aim Nasini. l'nolo Furl inn. nlnl liir'liui’d (i. l'estell
`
`Hm- st'ml'r suggests strategies to ol’eo'ome
`Pr-er
`F't'.§tl."htltt'l’ tr:
`.‘IH-Jx Moose inhibitors. n'ln'rir m'e
`
`poise-“rill heme r'I'rrlmrtr‘rl in romeo! mots.
`
`LETTERS TO THE EDITOR
`
`1035
`
`1036
`
`Impact of lipitlteliul Organization on
`Myc Expression and :ielii'ily—ltetter
`Johanna I.
`|‘:IrlnIn-n :nnl _1II|In Klelstr'om
`
`impact of Epithelial llrgani ution on
`Mve [Expression and rte-tint}—
`Response
`llnvitl Simpson Helilttil Mnlllnsn'nnly. nlnl
`William I‘_ 't'nnsei'
`
`CORRECTIONS
`
`1037
`
`1038
`
`1 039
`
`Correction: l-anoglin Regulates
`L‘aneer—tilromal Cell Interactions in
`Prostate Tumors
`
`Correction: Sirloin I Is Unregulated in
`a Subset ol' liepnloeellnlar (‘nreinonlas
`where I! is Essential for 'l'elomere
`Mainlennnee and Tumor (‘ell Growth
`
`Correction: Long Noneoding llNr‘l
`“0TH": Regulates I’olyeomh-
`Dependent Chromatin Modification
`and Is Assoeint ed with l’oor Prognosis
`in Coloreetnl ('nneers
`
`
`
`ABOUT TH E COVER
`
`\"ennn‘nl'enilt reeenllj.’ (It'ltiet'eil HM approval for treating pzllients with
`-
`'
`l
`-
`.
`-
`.
`.
`..
`.
`Itlt'lilslzllit‘ melanoma harboring the “RAF meet-1 nmtulion. ‘l‘he
`”HM-"w" -tll'l\r'('ti uncontrolled prolllernllon is elleetn'ely hloeked hy
`Vennn'al'enili. reflected in the remnrknhle regressions observed in the elinie.
`However. most patients eventually relapse. and in litany instnnees.
`progression is nssoeinlell with renrtiration ol'l-ZRK signaling. as oliset'rell In
`high levels of |".|t|\‘ phosphm'ylution in tumor biopsies taken ill progression.
`The rover shows an example ol'n tumor iiiopsy token ill progression. 5n and
`I‘olleiigues iileltlili' a novel lot-ts mutation that mediates the sequiretl
`ri-sistnnee ol'nIelnnolnn eells to rettntratenih. Both MAI’K and I’litlx‘ pallnvnys
`are netire despite the presenee ol' drug. Combinations ol‘ rennirnlenih with
`either MICK or AK'I' inhibitors are allle to t)\'l.‘l‘('l)ttt(' this resistanee. providing,
`hope that these eoniltinnlions eonld mitigate disease relapse in patients. For
`
`rleloils. see the nrliele hr Sn and eollengnes on page 96‘] of this issue.
`
`
`V
`
`A Journal of the American Association for Cancer Research
`
`www.3acriournalsorg
`
`

`

`
`
`
`
`Microenvirorlnu.Ill .IrlI! lIIIIlIIIIIolIJIIII
`
`
`
`Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically
`
`Regulate T-oell Function to Promote Tumoral Immune
`
`Escape
`
`Seng—Hyong Woo'. Meghan E TuInis1. Monica V Goldberg“, Jaishree Bankoti'. Mark Selby“,
`ChristopherJ Nirsizhl“. Matthew L Bettini1, David M. Gravano1. Peter \logelR Chih Long Liu .
`Stephanie lTangsombalvisit). Joseph F Grosso'. George Netlo11 Matthew P Smeltzer3.Aloides Chaux
`PaulJ Utz"JCrng. Workman1. DrewM. Pardolli‘. AlanJ. Kormana. CharleeG. Drake“. and DarioAA. Vignali1
`
`I’ibetract
`
`IIII'III.‘
`I\IIIIIIII_1,
`in Humor.
`I'I‘IIIIIIIIIII'II III' lllllllllllt‘ L'HI'IIIII.‘
`lltillllitil‘ I'I-Ils Ill't‘ pivIIlItl
`IIIIIiIIiIuI‘y I'l‘I.‘l'|JIl)l'H (III
`ilIlIihituI'v I'l'(’l'|'lll||'.'&', t"l'|..-\--l ltIII‘gIIII‘d I'llIIiI‘IIIlI'
`|I_v ipiliIlIuI'nIIhl III-I'VIII.‘ as a IlunIiIIIIIIl ul'l'-I.'wilIf|I \I'IIIII‘ Itilll'l‘
`l‘t'l'l’|)llIl‘5 ‘IllI-II IIII I’D-l anIl l.I\(l-1’II‘.I-I-In tu fil’l'Vt' more while I'III-IIIIIIII
`liIIII’IiuIIII. IIIIWI-vvr. IIII! ('Kll'lll III synergy
`and t’tlllpul'tlll\'t‘ inli'I'III'liIIIII. III'th'I-n iIIIIilIilIu'y pathways i1](‘I'llll‘l‘l'l‘tfll'lilill largely IIIII-KIIIIIrI-Il. lll‘l‘I.‘. wI.‘ I‘I‘I'I'III
`IIIIIIIIIIIiVI'
`I‘Ut‘xl'lfl't'ifiittll ul' I'll-l
`IIIIIi IMI-‘I lll'l Iunlur-inlillmliI‘II-. l'll-l'
`IIIIII L'l'IH'
`'I' (‘t'llti
`iII
`lllft’l.‘ IlislinIfl
`lrIiIIsplanlalilt- lllllllJl'H. {III-III IIIIIi- |I\(i-'.IIIIIIli—I’Il— | IInliIIuIly III-.IllIllI.‘lll IIIIIII must miII- ul' I-IIIIIhliIIIII-Il luIIIIIII.
`thul onI‘laIgI‘lvlIIIIIiIItIIlIl III IIiIIgII-IIIIlilIIIIIv l I'l'Illll‘lt‘l‘ll. ”(‘Hpilt‘ nIiIIimal lll‘ll'lllll‘lfipillllllltigll'Sl’qlll‘lill‘Ill I'll- l and
`|.A(i-Mingle knuIkuIIl IItiII- IluIIl knockout IrIiII' IIlII'IIgIIII'Il III-Il—luII-IIIIIII- will: resultant Itllluil‘llllllll'fll' inlillrIIlII.‘
`in multiple uI'gIInII. leading to eventual IIlhIIlily. lluwuvzt-i l‘nql
`l’rI’IIH "
`IIIIII- IIIIIIwI-Il IIIIII'lII!Ii|_\' inI'rIIasoII
`HIII'ViIII [mm and the [more ul multiph- llauIIpIantahlI- lIIIIIIIIII. lIIeIIIIII-I'. llIIIHL' IIIIIIIIII. III-lino a IIlrIIIIg- NVHL'If'}
`III‘III'I'IIII tIII' l’|)-l and LN.- .1 Inllihitury pillhwu_\'II in IIIII'IWIIIIII' III IIIIIII III'II and minor ItIIliIII.ItIII. in IIIlIliIiIIlI. tho)-
`IIrIIuI- slrunglv Illal IIIIuI IIIIII‘kIIIlI- III IIII‘III' lllIlll‘t‘lJlCH I‘I-prI~I.I-III:.'
`i1. III'IIIIIlHil‘Ig IIuInhinaluI'ial strategy for t‘tlllt'l'l'.
`I.’III“.'III I'fI‘II:'26:!) 91'?—.'."I7. “"12”” I'lIIITH.
`
`Irltr oduI‘:IiOI‘I
`
`'I' l‘t‘ll-Ilit'tllillt'll :IuliIquIIr immune responses lll‘t' vssunlial
`l'III‘ I-iII-I'livI- Ill-II-Iiun ul'pl‘iIIIIII‘v I.IIIIIIIr II-II‘IIInII IIItII IIII' [malt-I'-
`
`Authors‘ IIM'IIIiIaIionI’I: ‘Departmenl ol immunology; “Veterinary PathologyI
`Core, ’Depnnrnerit ol Bioetalistlos. St. Jude Children's Research Hospital,
`MemphIs Tennessee. 4Dep'Ilth'ienle of Oncology. immunology and Urol-
`oqv; Immunology and Hemaloooiesis Division Johns Hopkins. Sidnev
`Klinmel Comprehenswe Cancer Center 'Departments 0! Oncology.
`Pathology I-Ind Urology; ”Department of Pathology Johns Hopkins Ul‘ll-
`veisily. Baltimore. Maryland;
`”BIoIogIILII Discover}.I California Bristol-
`Mvere- Squibb. Milpitas: and 'Department of Medicine Division of
`Immunology and Rheumalology Slanlord University School ol Medimne.
`Stanloru, California
`
`Note: Suppleinenlarv data for this article are available at Cancer Research
`Or'IlIne {tulip-.I‘I‘canoerres aacrjournalsorgn
`
`I_".I Irrenl addi'ees IorJoseph F. Groeso: Clinical Eliornarkersflmrnuno Oncol-
`ui1v, Bristol-Myers-Squibb, Pnnoeton. NJ.
`
`‘3.
`
`-l I Woo. ME. Turner. and MV. Goldberg contributed equally to this work.
`
`(1.1.5. Drake and BAA. VIgnaII share senior author-ship.
`
`Corresponding Authors: Dario AA. Vignali. Depanment of Immunology.
`.II'I. Jude Children's Research Hospital. Memphis TN. Phone. 901-595—
`:II3.31% Fox: 901 £395- 310?. E. mail: vignalilabifflstiude. org. and Charles G.
`Drake, Departments of Oncologv. Immunology and Urology.I Johns Hop—
`lui 15 Sidney Kimmel Compreheuswe Cancer Center. Baltimore. MD. E—mail:
`IJIIIake‘fl‘Ihrnledu
`doi; ll] I1{IBIDUUB-SAI?2.CAN-11-1620
`HUI I AII'IerIIran Assomation Ior Cancer Research.
`
`l 1. Although llll.‘qunuuv Iuslmu I‘IIII
`Iinn II-IIIinst IuI- laslsiIIIII.‘ l
`llI'lI'Il IIIIII IlI‘slIm IIIIIIignIIIII IIIlII. luInIIu l'fiL'cll'lL' vuIII-illauII'
`l}\'tI\-':11‘il‘l\Illl'l'll iIIlIinI.iI anII l'\ll iIIIIiI iuI~IhIII1isms l
`| — '1}. I“
`with IIIruniI \iral inlII lion 1.ll lumuI antigluu— I.'pI~I'I|iI' I'll-l
`and L‘Jill
`I I'I~l|:.' IlisplIII- Ilnptlltl‘d IVI‘llI'IIIII lunIliuII IIIIII an
`l'Kll'IlllrIilL'IIl
`|1lll'lltll\|‘lt' IIIIII'IIII-IIII‘i-III-Il lIv Ili‘t'l‘t'ilSt‘tl pruIluI'liIIu
`lll pmiull;Immatun-
`II'IIILinuII
`IIIIII
`II).p:III'SIIIIIISWI'DL'HH tu
`allllovnit- It’Slll'llllldlilll'l 1.)] This.Is l‘ill'tlllllt‘ll by evil t‘xlllllfiit'
`IIII-IhanisIuII. I.‘uIII as II-eulalui'v | tl‘llhl[M]. illIllII'l.'ll iIIlIiIIIIiI
`IIIIII-hanisms. «IIIII III. lllllilllltll'}' InIIII-I' IIII-I. tIIIit III-I III‘II'L'IJJII.III-II
`IIII I'xltIItIIIlI'Il. ItImur-inlillrating |_\'mp|iuI.'_\'iI_'II 1'|"||.]|.
`lI‘I
`t’lll‘l'l-
`l)l|1il|il)ll.llll‘5t‘ inhibitor}- IIIl'I'i‘IlllllHI‘l'IH rIIprI‘IIcIII :I lurluiIIIIhlII
`barrier to effective IIIIlilIIIIIIIr immunity [0— III].
`lnhihiturv receptors such us I‘ylulmir Il1-l)“l‘tlpll(ll’_\’ll."'ilSHtI
`I'iIIII-Il protein Ll lL"l'l..-\--l. (1)151! l. leuphIII'leI-III'IivIIIiuu III-III-
`II IIII‘ILI—i’I. (112211]. and prungIIImII'Il I’D-ll IlI~IIl|I l [I’ll-1.1.1121?”
`lllflt'llllli Ill multiple lIIvIIl~I III ensure appropriate l‘-I‘III| lIIIII'II-II-
`stasis. IIIlivI IliIIII. IIIIII lllilt‘lt‘llllillltlfl (I. II— l I}. lIIrllII-I llltIII‘.
`all
`.I
`inhibitory IIIIIII-I-ulvs aleu I‘IIIIllll‘IlIlt‘
`III II-II
`I-IIIIIIIIIiI
`regulation by IvuntrIIlliIIII'l'...L huiuIruslaIIIiI. IIIIII l'lltlt‘lllll‘l- Illl‘tll
`ailing iIIIluI-IIII
`'I‘...“ IiI'v L'ltl['tl'llt‘lll. and IIIiIiIII Itiny,
`lll'llllt’lllt
`I-I-ll IlitliII'IInlialiuu IInII
`lllllt‘lllltl
`lIJI—IO.
`lI-l.
`I‘ll.
`|l.It.I lIqu
`oI-III'IiIrIIIIv nI'IInipulIIteIl IIIiIrI~ ll'ldil‘tlll.‘ that ("ll A--| rI-pI‘I-III-nts
`IIIJIIIJI and indispensiblc'ull IIIvilI-LI' \\’lll‘l'lt'II. I’ll- l and |.Mi-
`.1 play mule IIulIIII-
`IIIIL'S in “humor IIgulatiuII.\Win-mare
`I'II'IIJ "
`IIIiI‘I‘ Ill‘t‘t‘lup II SI'VI'I'I.’
`lyl‘ll[‘Jllll[ll‘llllli.‘l‘illi\‘l’ IIiIIIIaSI‘
`IIIIII are usually InIIriIIIIIIIl by 1’. to -'1 works III'IIIII- l‘JIll- Pill?”
`
`
`
`wwvv aacrjournalsorg
`
`[flc IIIH'J'I‘I rm IIIIIIIIII'IIIII lI'rrI (littf't’rflmt’t‘trt‘it
`
`91?
`
`This material was copied
`at the NLM and may be
`So bject US Copyright Laws
`
`

`

`Woo el al.
`
`lwllil'l'l i‘III‘IIIII'H I’IJ- | } mire ll\"l' III-I'nml
`Hlllflll’
`:mli
`\‘uriuhlr'
`iIlIllliIIIe-IIIIHI-(I
`
`I irur while iliwvluriing
`(“sear-u-
`Illamili‘HIIIIiuIIx
`llI\|.|l."I' mil-(-
`
`depending (III gL-Iu‘lit' background:
`If’rfl'rl'f
`lieu-lull (liIIIIeLl calrtiiunrruplllIII- 5 In lit] weeks Hinge. wlle'I-us.
`I’II'I‘IH
`(‘5?lil.,-"II mil-(- (lt’\'l'lllll :I pl‘tiil‘lII‘IL-tl IIIIIIIH-lilu- I‘llll-
`tllllulllllilllilkl'h'IWI'I'f)lll(l|lll15llltll'\'{‘ll1|1l3l.22}.llllll'lilillll
`illnlell
`l-I-‘R-l
`{'S'Fllljh wire (in not
`(ll'\'l'l(l]} :un'
`tllfii‘ilfil’
`lllklllili'HlilllIDIIE-i wiIIIiII [he find year IIl'liIi- I'JIIJ.
`llvwnl Hllillivx |I;I\-'I-
`I'l'\'l'{lll'l.l
`[IIIII LAG-ll
`
`iillll
`
`I’ll-l
`
`I'II'I'
`
`| I'I ll
`lIIlIll llllltllllllRllllHIll'HllllfJ‘. |I \\'I'I.‘i-'Il\'tl lI'Rli’ll ily lMl’.-'\("l'
`I’rillilt‘ :Ii Ihe IHIHI. Ill llll'
`l lIIi\':'I'.\II\' IJl Mismllll'i {lk'llillt’l'
`ll].
`EIIUHI. ML'HH I'I'llf‘w u'l'r'r nlllllilll'll
`ll'lllli I.|’. r\lli.‘am {Mt-l‘illii'illl
`SIIIIIll-lxvllvrillg ['ulu't-I' L'I‘Illel'. NY].
`;IIIlllenIi¢'.-IlI-Il
`|I_\-
`Ill:-
`Il.-‘Il}|l. [Marl-h “LEUUJILIIIIII ll“\'l(‘[l in l.\ll'.-\t"l'
`I III The llr‘lllll.
`ill Ilw l iIIiw-I'wiII- nl' Miswuri I MIII‘l‘II IS. 'JIIIII}, HII l N I'l-llu \wre
`:Irigillllll)‘IIlIIIIiIII'II II'ImI LI’. .-\lli.~auII [ MI-Iliuriiil SilliIIl-kt’llt'l‘llllfli
`l'lll‘lt'l‘l' ('I'rllt‘l'. N5 1. Illllllillgll lllrhl'l'ellh ll:I\-‘I' lllll ln'l'll nul l1l'1l
`Iil‘llli’tl. llw}; livrl'nl'lll use (II'm'rilu-(l in I lll.‘ llll'l'llllll'l‘ in xi-rIgI-III-il-
`M] ITIlI'L‘ {l-I} IIIIIl
`II'uII-Il
`Irv |Ml'r\l"|
`I
`.‘II
`lll(‘ [{I‘II'III.
`.'II
`II"-
`l-IliI'I-I‘Hill' Ill. k-Iixrmlll'i l_l-'|.ll||lill‘_\’ 2‘). Bill 1
`I.
`
`How (‘yimnelryu inlraeellulllr eylukille filalilling. and
`eylukine analysis
`HiIIgII'
`t‘l’ll
`\‘llHIll'llHltlllH were prepared I'I'IIIII spleens. “Igni-
`Ilill. l)l'£|(‘l1llll.il|l(l il.\llli1l'_\'l_\'|llllll IIIIll('5.1III(l llllIllll‘h.('l‘llS \\'I'I'I‘
`Klélllll’ll willI lllllll'l’fii'l‘rll
`IIIlII-II-Il Illlllllllllll'fi {IliulegI-Iui.
`Ill)-
`I’IiIIHI-ienvv I'llalrnlillgvll.
`(Ir
`I-llinrzl'imlt'l‘xl
`(ll'lll
`IIIIIIII'xI‘II
`|I_\
`I-iIIII-I'
`|-'.-\I‘.‘i['u|iilur nr |..‘-i|i
`ll
`lluw l‘_\'l(|l|'ll'll'l' {RH}.
`I'III‘
`l'nl
`lll\\'llllL"t'llTI1I’:‘-I Iva'I-Ilseli:I'IJ-l IIEKI.5I.('IJHIIl511 l).?l. ('IJI l('
`lN-liHl. (1)115 [HIIIL ('Il'l-l
`llMT‘}. (.'lJ-l5ll."llil'.lll
`lll:\.’i-—hl§2].
`(‘IWI Hum-2n. I’ll
`I
`IIIMI’]
`:IIII.
`'I'L'I{-|i HIST-31):]. “LN-l
`llllSSl].
`ll"N-‘{ lXMlilL’l.
`'I'Nl“-U lMl’h-N'l'Z-ill).
`||.-|T ['ll'll
`lh'lllll}.
`I-Ipri’I Ilfilllll. uml LIKE-Ii
`l-l
`III-i"):
`rvl'.
`I-‘.|I.
`l-'nI'
`llIlI'ilI‘t‘llllliIl“ <'_\'lnkim' .Hlilillillg. mills \\'(‘T'I' :Il'l imlml \I'il ll IIIIIIr-
`lml
`I1!
`|'Il_\-'l'l5|illl' Iii lll‘(‘lill(’ll’i\r‘l.’\l
`|IJ[)II_I_:I"IIII.I|IlII:« iInIIIIIIl'I'iII
`[Gilli IIgl'IIIlJ I'III‘
`I
`lIIIlII'H iII
`llll' prim-lire iIl' {lulgil’lllg [313].
`prnl‘essvil Will] :I ('ylulix/l'yluperm llil
`lil'l].
`IIIIII HIIIIIII-Il
`ill-i
`lilllll'illl'tl. MI'HR‘III'L‘IIIUIII tIl'