From: Subject: Abstract | Glioma stem cells are more aggressive in recurrent tumors with malignant progression than in the primary tumor, and both can be maintained long-term in vitro Date: Sat, 8 Nov 2008 10:49:03 +0100 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C9418F.9D59DA10" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C9418F.9D59DA10 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.biomedcentral.com/1471-2407/8/304 =EF=BB=BF Abstract | Glioma stem = cells are more aggressive in recurrent tumors with malignant progression = than in the primary tumor, and both can be maintained long-term in = vitro

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Research article

Glioma stem cells are more aggressive in recurrent tumors with = malignant progression than in the primary tumor, and both can be=20 maintained long-term in vitro

Qiang Huang ,=20 Quan-Bin Zhang ,=20 Jun Dong ,=20 Yin-Yan Wu ,=20 Yun-Tian Shen ,=20 Yao-Dong Zhao ,=20 Yu-De Zhu ,=20 Yi Diao ,=20 Ai-Dong Wang and = Qing Lan

BMC Cancer 2008, = 8:304doi:10.1186/1471-2407-8-304


Published:	22 October 2008

Abstract (provisional)

Background

Despite the advances made during decades of research, the = mechanisms by=20 which glioma is initiated and established remain elusive. The = discovery of=20 glioma stem cells (GSCs) may help to elucidate the processes of=20 gliomagenesis with respect to their phenotype, differentiation and = tumorigenic capacity during initiation and progression. Research = on GSCs=20 is still in its infancy, so no definitive conclusions about their = role can=20 yet be drawn. To understand the biology of GSCs fully, it is = highly=20 desirable to establish permanent and biologically stable GSC = lines.

Methods

In the current study, GSCs were isolated from surgical = specimens of=20 primary and recurrent glioma in a patient whose malignancy had = progressed=20 during the previous six months. The GSCs were cryopreserved and=20 resuscitated periodically during long-term maintenance to = establish glioma=20 stem/progenitor cell (GSPC) lines, which were characterized by=20 immunofluorescence, flow cytometry and transmission electronic = microscopy.=20 The primary and recurrent GSPC lines were also compared in terms = of in=20 vivo tumorigenicity and invasiveness. Molecular genetic = differences=20 between the two lines were identified by array-based comparative = genomic=20 hybridization and further validated by real-time PCR.

Results

Two GSPC lines, SU-1 (primary) and SU-2 (recurrent), were = maintained in=20 vitro for more than 44 months and 38 months respectively. = Generally, the=20 potentials for proliferation, self-renewal and = multi-differentiation=20 remained relatively stable even after a prolonged series of = alternating=20 episodes of cryopreservation and resuscitation. Intracranial=20 transplantation of SU-1 cells produced relatively less invasive = tumor mass=20 in athymic nude mice, while SU-2 cells led to much more diffuse = and=20 aggressive lesions strikingly recapitulated their original tumors. = Neither=20 SU-1 nor SU-2 cells reached the terminal differentiation stage = under=20 conditions that would induce terminal differentiation in neural = stem=20 cells. The differentiation of most of the tumor cells seemed to be = blocked=20 at the progenitor cell phase: most of them expressed nestin but = only a few=20 co-expressed differentiation markers. Transmission electron = microscopy=20 showed that GSCs were at a primitive stage of differentiation with = low=20 autophagic activity. Array-based comparative genomic hybridization = revealed genetic alterations common to both SU-1 and SU-2, = including=20 amplification of the oncogene EGFR and deletion of the tumor = suppressor=20 PTEN, while some genetic alterations such as amplification of MTA1 = (metastasis associated gene 1) only occurred in SU-2.

Conclusion

The GSPC lines SU-1 and SU-2 faithfully retained the = characteristics of=20 their original tumors and provide a reliable resource for = investigating=20 the mechanisms of formation and recurrence of human gliomas with=20 progressive malignancy. Such investigations may eventually have = major=20 impacts on the understanding and treatment of gliomas.

The complete article is available = as a pro= visional=20 PDF. The fully formatted PDF and HTML versions are in=20 production. =

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=C2=A9 1999-2008 = BioMed Central Ltd=20 unless otherwise stated. Part of Springer Science+Business = Media.=20

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"; break; } =09 // This executes the replacement if (cond) { document.getElementById(id).innerHTML=3Dmovietext; link =3D false; } } //Functions related to FLV movies // Stopping the movie when another is started var currentItem; function getUpdate(typ,pr1,pr2,pid) { if (typ =3D=3D "state") { =09 // Play=20 if (pr1 =3D=3D 2) { =09 // Pause active movie if it is playing. if (currentItem !=3D null && currentItem !=3D pid) { thisMovie(currentItem).sendEvent('playpause'); } =09 // Save current movie currentItem =3D pid;=09 =09 // Flush active movie var on Stop (3) and Pause (0). } else if(pr1 =3D=3D 3 || pr1 =3D=3D 0) { = =20 currentItem =3D null; }=20 } }; // This is a javascript handler for the player and is always needed. function thisMovie(movieName) { if(navigator.appName.indexOf("Microsoft") !=3D -1) { return window[movieName]; } else { return document[movieName]; } }; // Replacing the jpeg with the movie var link =3D true; function playvideo(id,moviename,width,height) { if (document.getElementById) { var flvheight =3D height + 20; var so =3D new = SWFObject('http://www.biomedcentral.com/movies/mediaplayer.swf','js'+id,w= idth,flvheight,'7'); =20 = so.useExpressInstall('http://www.biomedcentral.com/movies/expressinstall.= swf');=20 so.addParam('allowfullscreen','true'); so.addParam('salign','lt'); so.addParam('quality','high'); so.addParam('scale','noscale'); so.addVariable('file',moviename); =20 so.addVariable('autostart','true'); so.addVariable('showdigits','false'); so.addVariable('useaudio','false'); so.addVariable('usefullscreen','true'); so.addVariable('showicons','false'); so.addVariable('enablejs','true'); so.addVariable('javascriptid','js'+id); = =20 so.addVariable('width',width); so.addVariable('height',flvheight); so.write(id); link =3D false; } } /** * SWFObject v1.5: Flash Player detection and embed - = http://blog.deconcept.com/swfobject/ * * SWFObject is (c) 2007 Geoff Stearns and is released under the MIT = License: * http://www.opensource.org/licenses/mit-license.php * */ if(typeof deconcept=3D=3D"undefined"){var deconcept=3Dnew = Object();}if(typeof = deconcept.util=3D=3D"undefined"){deconcept.util=3Dnew = Object();}if(typeof = deconcept.SWFObjectUtil=3D=3D"undefined"){deconcept.SWFObjectUtil=3Dnew = Object();}deconcept.SWFObject=3Dfunction(_1,id,w,h,_5,c,_7,_8,_9,_a){if(!= document.getElementById){return;}this.DETECT_KEY=3D_a?_a:"detectflash";th= is.skipDetect=3Ddeconcept.util.getRequestParameter(this.DETECT_KEY);this.= params=3Dnew Object();this.variables=3Dnew = Object();this.attributes=3Dnew = Array();if(_1){this.setAttribute("swf",_1);}if(id){this.setAttribute("id"= ,id);}if(w){this.setAttribute("width",w);}if(h){this.setAttribute("height= ",h);}if(_5){this.setAttribute("version",new = deconcept.PlayerVersion(_5.toString().split(".")));}this.installedVer=3Dd= econcept.SWFObjectUtil.getPlayerVersion();if(!window.opera&&document.all&= &this.installedVer.major>7){deconcept.SWFObject.doPrepUnload=3Dtrue;}if(c= ){this.addParam("bgcolor",c);}var = q=3D_7?_7:"high";this.addParam("quality",q);this.setAttribute("useExpress= Install",false);this.setAttribute("doExpressInstall",false);var = _c=3D(_8)?_8:window.location;this.setAttribute("xiRedirectUrl",_c);this.s= etAttribute("redirectUrl","");if(_9){this.setAttribute("redirectUrl",_9);= }};deconcept.SWFObject.prototype=3D{useExpressInstall:function(_d){this.x= iSWFPath=3D!_d?"expressinstall.swf":_d;this.setAttribute("useExpressInsta= ll",true);},setAttribute:function(_e,_f){this.attributes[_e]=3D_f;},getAt= tribute:function(_10){return = this.attributes[_10];},addParam:function(_11,_12){this.params[_11]=3D_12;= },getParams:function(){return = this.params;},addVariable:function(_13,_14){this.variables[_13]=3D_14;},g= etVariable:function(_15){return = this.variables[_15];},getVariables:function(){return = this.variables;},getVariablePairs:function(){var _16=3Dnew Array();var = key;var _18=3Dthis.getVariables();for(key in = _18){_16[_16.length]=3Dkey+"=3D"+_18[key];}return = _16;},getSWFHTML:function(){var = _19=3D"";if(navigator.plugins&&navigator.mimeTypes&&navigator.mimeTypes.l= ength){if(this.getAttribute("doExpressInstall")){this.addVariable("MMplay= erType","PlugIn");this.setAttribute("swf",this.xiSWFPath);}_19=3D"

0){_19+=3D"flashvar= s=3D\""+_1c+"\"";}_19+=3D"/>";}else{if(this.getAttribute("doExpressInstal= l")){this.addVariable("MMplayerType","ActiveX");this.setAttribute("swf",t= his.xiSWFPath);}_19=3D"

";}return = _19;},write:function(_20){if(this.getAttribute("useExpressInstall")){var = _21=3Dnew = deconcept.PlayerVersion([6,0,65]);if(this.installedVer.versionIsValid(_21= )&&!this.installedVer.versionIsValid(this.getAttribute("version"))){this.= setAttribute("doExpressInstall",true);this.addVariable("MMredirectURL",es= cape(this.getAttribute("xiRedirectUrl")));document.title=3Ddocument.title= .slice(0,47)+" - Flash Player = Installation";this.addVariable("MMdoctitle",document.title);}}if(this.ski= pDetect||this.getAttribute("doExpressInstall")||this.installedVer.version= IsValid(this.getAttribute("version"))){var n=3D(typeof = _20=3D=3D"string")?document.getElementById(_20):_20;n.innerHTML=3Dthis.ge= tSWFHTML();return = true;}else{if(this.getAttribute("redirectUrl")!=3D""){document.location.r= eplace(this.getAttribute("redirectUrl"));}}return = false;}};deconcept.SWFObjectUtil.getPlayerVersion=3Dfunction(){var = _23=3Dnew = deconcept.PlayerVersion([0,0,0]);if(navigator.plugins&&navigator.mimeType= s.length){var x=3Dnavigator.plugins["Shockwave = Flash"];if(x&&x.description){_23=3Dnew = deconcept.PlayerVersion(x.description.replace(/([a-zA-Z]|\s)+/,"").replac= e(/(\s+r|\s+b[0-9]+)/,".").split("."));}}else{if(navigator.userAgent&&nav= igator.userAgent.indexOf("Windows CE")>=3D0){var axo=3D1;var = _26=3D3;while(axo){try{_26++;axo=3Dnew = ActiveXObject("ShockwaveFlash.ShockwaveFlash."+_26);_23=3Dnew = deconcept.PlayerVersion([_26,0,0]);}catch(e){axo=3Dnull;}}}else{try{var = axo=3Dnew = ActiveXObject("ShockwaveFlash.ShockwaveFlash.7");}catch(e){try{var = axo=3Dnew ActiveXObject("ShockwaveFlash.ShockwaveFlash.6");_23=3Dnew = deconcept.PlayerVersion([6,0,21]);axo.AllowScriptAccess=3D"always";}catch= (e){if(_23.major=3D=3D6){return _23;}}try{axo=3Dnew = ActiveXObject("ShockwaveFlash.ShockwaveFlash");}catch(e){}}if(axo!=3Dnull= ){_23=3Dnew deconcept.PlayerVersion(axo.GetVariable("$version").split(" = ")[1].split(","));}}}return = _23;};deconcept.PlayerVersion=3Dfunction(_29){this.major=3D_29[0]!=3Dnull= ?parseInt(_29[0]):0;this.minor=3D_29[1]!=3Dnull?parseInt(_29[1]):0;this.r= ev=3D_29[2]!=3Dnull?parseInt(_29[2]):0;};deconcept.PlayerVersion.prototyp= e.versionIsValid=3Dfunction(fv){if(this.majorfv.major){return = true;}if(this.minorfv.minor){return true;}if(this.rev=3D0;i--){_2f[i].style.display=3D"none";for(var x in = _2f[i]){if(typeof = _2f[i][x]=3D=3D"function"){_2f[i][x]=3Dfunction(){};}}}};if(deconcept.SWF= Object.doPrepUnload){if(!deconcept.unloadSet){deconcept.SWFObjectUtil.pre= pUnload=3Dfunction(){__flash_unloadHandler=3Dfunction(){};__flash_savedUn= loadHandler=3Dfunction(){};window.attachEvent("onunload",deconcept.SWFObj= ectUtil.cleanupSWFs);};window.attachEvent("onbeforeunload",deconcept.SWFO= bjectUtil.prepUnload);deconcept.unloadSet=3Dtrue;}}if(!document.getElemen= tById&&document.all){document.getElementById=3Dfunction(id){return = document.all[id];};}var = getQueryParamValue=3Ddeconcept.util.getRequestParameter;var = FlashObject=3Ddeconcept.SWFObject;var SWFObject=3Ddeconcept.SWFObject; // CSSClass object used to add/delete classes from any element var CSSClass =3D {}; =20 CSSClass.is =3D function(e, c) // Check existence of class (c) in = element (e) { var classes =3D e.className; if (!classes) return false; =20 if (classes =3D=3D c) return true;=20 =20 return e.className.search("\\b" + c + "\\b") !=3D -1; }; CSSClass.add =3D function(e, c) // Add a new class { if (CSSClass.is(e, c)) return;=20 if (e.className) c =3D " " + c; =20 e.className +=3D c; =20 }; CSSClass.remove =3D function(e,c) // Remove existing class { =20 e.className =3D e.className.replace(new RegExp("\\b"+ c+"\\b\\s*", = "g"), ""); =09 if (e.value=3D=3De.defaultValue) {e.value=3D'';} }; // drop down banner ad functions function testMouse() // Detect mouse over banner ad { var IE =3D document.all?true:false if (!IE) document.captureEvents(Event.MOUSEMOVE) document.onmousemove =3D getMouseXY; var tempX =3D 0 var tempY =3D 0 function getMouseXY(e) { if (IE) { tempX =3D event.clientX + document.body.scrollLeft tempY =3D event.clientY + document.body.scrollTop } else { =20 tempX =3D e.pageX tempY =3D e.pageY } =20 =20 if (tempX < 0){tempX =3D 0} if (tempY < 0){tempY =3D 0} =20 =20 =20 =20 if (tempY > 78 || tempY < 15) // Adjust for different height ads = (currently 60px) { document.getElementById('newad').style.zIndex=3D1; }=20 else { document.getElementById('newad').style.zIndex=3D3; } } } function adjustAdMargin() // Remove margin from non-dropdown banner ad { var adHeight =3D document.getElementById('dropdown').offsetHeight ; if (adHeight =3D=3D 350) // This number is the height of the current = drop down ad { document.getElementById('dropdown').style.marginTop=3D"15px"; } =09 } window.onload =3D adjustAdMargin; // Check size of banner ad and adjusts = z-index // end drop down functions ------=_NextPart_000_0000_01C9418F.9D59DA10--