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Science 2 January = 2009:
Vol. 323. no.=20 5910, pp. 30 - 31
DOI: = 10.1126/science.323.5910.30

Prev= =20 | Tab= le=20 of Contents | Next= =20

News Focus

BRAIN CANCER:
A = Viral Link to=20 Glioblastoma?
Greg Miller

Circumstantial evidence hints that cytomegalovirus, a common=20 herpesvirus, may play a role in the aggressive brain cancer, but = big=20 questions remain

Delicate = operation.=20 Charles Cobbs removes a brain tumor at California Pacific = Medical=20 Center.
CREDIT: LACY ATKINS/SAN FRANCISCO=20 = CHRONICLE
S= AN=20 FRANCISCO, CALIFORNIA--Neurosurgeon Charles Cobbs is = trying to=20 remove as much of a brain tumor as possible without damaging = tissue=20 important for speech. He needs the patient's cooperation, so the=20 anesthesiologist dials down the propofol anesthetic and places a = laptop=20 computer on a stand near the patient's head. The 77-year-old man, = who has=20 a glioblastoma near the crease that separates the frontal and = temporal=20 lobes, slowly wakes up.
Images of familiar objects flash on the screen, and the patient = names=20 them while Cobbs electrically stimulates his exposed cortex with a = hand-held probe. "Cow, car, hairbrush," the man says. He sounds = groggy,=20 but the words are unslurred. Cobbs turns up the current for = stronger=20 stimulation and does another pass as the man counts to 50. = Satisfied that=20 the tumor can be safely resected, the surgical team here at the = California=20 Pacific Medical Center puts the patient back under, and Cobbs = scoops out a=20 bloody glob of tissue, most of which goes into a vial to be sent = to the=20 lab.
After the surgery, Cobbs is optimistic. Glioblastoma is the = worst grade=20 of malignant glioma, a relatively uncommon but deadly class of = brain=20 tumors that kills 97% of those diagnosed within 5 years. But Cobbs = says=20 the material he removed had the rubbery feel of dead tissue rather = than=20 the "grape jelly" consistency of a growing tumor. That would be = good news=20 for the patient, and Cobbs thinks it may also bode well for his = own=20 unorthodox hypothesis about malignant glioma.
Cobbs thinks the cancer may be caused, or at least spurred on, = by=20 cytomegalovirus (CMV), a common herpesvirus. Several years ago, = Cobbs=20 reported that malignant gliomas are rife with CMV, and he says = work by=20 other researchers supports his idea that the virus may be a potent = promoter of these cancers. His patient has been taking an = antiviral drug=20 called Valcyte, made by Roche Pharmaceuticals, in addition to = receiving=20 standard radiation and chemotherapy. Cobbs thinks drugs and other=20 therapies that target CMV may extend the lives of patients who = otherwise=20 have few options.
The idea is controversial and unproven. Why would such a common = virus=20 cause cancer in only a small subset of those infected? And why = have test=20 tube experiments so far failed to show that CMV transforms healthy = cells=20 into cancerous cells? These and other nettlesome questions beg for = answers=20 before Cobbs's theory can gain widespread acceptance.
Yet several researchers and clinicians who attended a meeting = Cobbs=20 organized in Boston last October say there is enough = circumstantial=20 evidence in support of the idea to merit serious attention. "It's = a=20 promising concept, and it gives us hope of new treatment = strategies for=20 this horrible disease," says Cecilia S=F6derberg-Naucl=E9r of the = Karolinska=20 Institute in Stockholm, Sweden. She and others have already begun = small=20 clinical trials with drugs and immunotherapy directed at CMV.
Counter to the mainstream
At age 45, Cobbs = still=20 has the rangy build of a collegiate rower, which he was at = Princeton=20 University. Soft-spoken and bespectacled, he doesn't come across = as a=20 rebel, although his thinking about malignant glioma has run = counter to the=20 mainstream. Cobbs did research as a medical resident suggesting = that these=20 tumors were "boiling cauldrons of inflammatory molecules," and he = wondered=20 whether this inflammation might somehow trigger the cancer or help = it=20 grow. It wasn't a fashionable idea at the time, and for a young=20 investigator, it was a risky avenue to pursue.
Reading Surely You're Joking, Mr. Feynman!, a memoir = written=20 by the iconoclastic physicist Richard Feynman, boosted his = confidence.=20 Cobbs says the message he took away from the book is that "your = job as a=20 scientist is to think for yourself and question what the herd is=20 thinking." Cobbs had a hunch that CMV might be just the sort of = virus to=20 lurk around and cause the kind of chronic inflammation he = suspected of=20 contributing to cancer. The virus infects for life, and mouse = studies have=20 found that it infects the neural stem cells thought to give rise = to=20 glioblastomas. To investigate, he and colleagues tested 27 = malignant=20 glioma samples for CMV proteins and genetic material. All were = positive,=20 the researchers reported in Cancer Research in 2002. = Samples of=20 noncancerous brain tissue tested negative.
Not everyone was convinced by the findings. In 2005, a team of=20 researchers at City of Hope Hospital in Duarte, California, = reported in=20 Modern Pathology that they'd failed to find CMV in glioma = samples. "I was kind of distressed and heartbroken," Cobbs = recalls. A team=20 at Duke University Medical Center in Durham, North Carolina, = wasn't=20 finding CMV in its samples, either. "We called [Cobbs] and said, = 'What's=20 the deal?'" says Duane Mitchell, a neuro-oncologist at Duke. Cobbs = suspected that the other researchers were using less sensitive = methods and=20 offered to visit both teams to demonstrate his technique. Only the = Duke=20 team took him up on it.
Since then, there have been several confirmations. Last = February,=20 Mitchell and colleagues reported finding CMV in more than 90% of = glioma=20 samples they examined; a team at M. D. Anderson Cancer Center in = Houston,=20 Texas, published similar findings a few months later; and=20 S=F6derberg-Naucl=E9r and colleagues have a forthcoming paper as = well.=20 "Without a question, the virus is there," says = S=F6derberg-Naucl=E9r. But is=20 it a bystander or an agent provocateur?
A suspicious resume
CMV is one of eight = human=20 herpesviruses; it infects at least half of the population in = developed=20 countries and nearly everyone in developing countries, where poor=20 sanitation and hygiene encourage its transmission. Although it = generally=20 doesn't cause problems in healthy adults, CMV is a common cause of = birth=20 defects, and it can cause a host of serious problems in = immunocompromised=20 people.
How it might trigger or abet cancer is not known, but there's = no=20 shortage of possibilities, says virologist Jay Nelson of Oregon = Health and=20 Science University in Portland. One way it could do this "is by = preventing=20 the immune system from taking the tumor out," he posits, because = CMV is=20 adept at manipulating signaling molecules on cell surfaces that = would=20 otherwise flag infected cells for destruction. Another possibility = is that=20 the virus helps sustain tumors by promoting angiogenesis, the = growth of=20 new blood vessels. Nelson's lab reported last year that = CMV-infected heart=20 cells churn out a slew of growth factors and other compounds that = spur=20 angiogenesis.
The virus also makes proteins that interfere with cellular = machinery=20 that normally prevents tumors, says Robert Kalejta, a cancer = biologist and=20 virologist at the University of Wisconsin, Madison. In 2003, = Kalejta and=20 colleagues reported that a CMV protein called pp71 helps break = down=20 retinoblastoma protein (Rb), a potent tumor suppressor. More = recently,=20 they identified a CMV enzyme called UL97 that inactivates Rb=20 (Science, 9 May 2008, p. 797)= .=20 "Clearly, these are two proteins that can do what's required" to = transform=20 healthy cells into tumor cells, Kalejta says. "The question is, = are they=20 really doing that in these cancers?"
Kalejta says he's intrigued but not yet convinced. He notes = that unlike=20 proven cancer-causing viruses such as human papilloma-virus and=20 Epstein-Barr virus, CMV has not been shown to transform healthy = cells into=20 cancerous cells. The lack of direct evidence that CMV can cause = cancer=20 remains an important caveat, Kalejta says.
Liliana Soroceanu, a neuroscientist who collaborates with Cobbs = at the=20 California Pacific Medical Center, hopes to gain clues about how = CMV might=20 contribute to malignant glioma by culturing cells from tumor = tissue Cobbs=20 has removed from patients. She plans to use a CMV gene chip = developed by=20 Nelson's team to examine which genes the virus turns on in = infected glioma=20 cells--and to see whether turning those genes off, using RNA = interference,=20 for example, slows the growth of cultured tumors.

Partners in = crime?=20 Cobbs suspects that malignant gliomas like this one may be = aided=20 by cytomegalovirus.
CREDIT: LACY ATKINS/SAN FRANCISCO=20 = CHRONICLE
B= edside=20 stories
Evidence of a link between CMV and glioma has = come=20 from the bedside as well as the lab bench. One serendipitous = finding comes=20 from a clinical trial with glioblastoma patients run by Robert = Prins and=20 colleagues at the University of California, Los Angeles. They have = been=20 testing a vaccine intended to train patients' immune systems to = attack=20 their tumors. To do this, they grow immune cells from each patient = in=20 culture, expose them to proteins from that patient's tumor, and = inject=20 them back into the patient.
As it happens, one patient responded to the vaccine by mounting = a=20 massive immune response against a CMV protein, the researchers = reported=20 last July in The New England Journal of Medicine. That = patient=20 has now survived nearly 6 years without a recurrence of the = cancer, longer=20 than 99% of patients who receive standard care, Prins says. (All = patients=20 in the trial received standard care--surgery, radiation, and=20 chemotherapy--in addition to the vaccine.) Although it's = impossible to=20 know if the vaccine is the reason, given the slim odds of = surviving that=20 long with glioblastoma, Prins thinks it's highly likely.
At Duke, Mitchell and colleagues are pursuing a similar = approach more=20 tightly focused on CMV. They are vaccinating glioblastoma patients = with=20 immune cells exposed to CMV proteins. The trial is intended to = assess the=20 safety of the treatment, but there are signs that it is having the = desired=20 effect. At November's meeting of the Society for Neuro-Oncology, = the=20 researchers reported that the vaccine had enhanced immune = responses=20 against CMV, and the 21 patients in the trial had a median = survival time=20 of more than 20 months. The median survival time so far for such = patients=20 is typically less than 15 months, Mitchell says.
At the Karolinska Institute, S=F6derberg-Naucl=E9r and = colleagues have just=20 completed a 2-year trial with Valcyte, the antiviral drug Cobbs's = patient=20 received. (Cobbs prescribed the drug off-label, not as part of a = clinical=20 trial.) The 42 patients with glioblastoma began taking Valcyte = after=20 surgeons had removed their tumors and researchers confirmed that = the=20 tumors were infected with CMV. Researchers used magnetic resonance = imaging=20 to look for signs that tumors grew back. The study is = double-blinded, so=20 the researchers don't yet know which patients received the drug = and which=20 received a placebo. Even so, S=F6derberg-Naucl=E9r is optimistic. = "We have=20 patients that looked extremely bad at the beginning that have = survived 2=20 years," she says. The trial concluded just before Christmas, and = the team=20 should know soon whether those patients received the drug--or just = a=20 remarkable stroke of good luck.
Cobbs says he's hopeful that if the Swedish trial goes well, = Roche will=20 fund a larger one. He insists he doesn't want to hype the evidence = for a=20 link between CMV and glioma but says he's gratified that other = researchers=20 are starting to take the idea seriously. "It may be a house of = cards, but=20 my gut tells me it might pan out to be something big time."

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:

Activation of Telomerase in Glioma Cells by Human = Cytomegalovirus:=20 Another Piece of the Puzzle.=20
J. Cinatl Jr, M. Nevels, C. Paulus, and M. Michaelis = (2009)
J=20 Natl Cancer Inst 101, 441-443 =
| Full=20 Text =BB | PDF = =BB=20

E-Letters:

Read = all E-Letters=

UL97: Old Enzyme, New Functions in Viral Ocogenesis = of Brain=20 Tumors=20
Francisco H. Felix, et al.=20
Science Online, 2 Feb 2009 [Full=20 text]

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To = view a=0A= copy of this license, visit = http://creativecommons.org/licenses/by-sa/2.5/ or=0A= send a letter to Creative Commons, 559 Nathan Abbott Way, Stanford, = California=0A= 94305, USA.=0A= =0A= Attribution: Leave my name and web address in this script intact.=0A= =0A= Not Supported in Opera=0A= ----------------------=0A= * user/password authentication=0A= * responseXML data member=0A= =0A= Not Fully Supported in Opera=0A= ----------------------------=0A= * async requests=0A= * abort()=0A= * getAllResponseHeaders(), getAllResponseHeader(header)=0A= =0A= */=0A= // IE support=0A= if (window.ActiveXObject && !window.XMLHttpRequest) {=0A= window.XMLHttpRequest =3D function() {=0A= var msxmls =3D new Array(=0A= 'Msxml2.XMLHTTP.5.0',=0A= 'Msxml2.XMLHTTP.4.0',=0A= 'Msxml2.XMLHTTP.3.0',=0A= 'Msxml2.XMLHTTP',=0A= 'Microsoft.XMLHTTP');=0A= for (var i =3D 0; i < msxmls.length; i++) {=0A= try {=0A= return new ActiveXObject(msxmls[i]);=0A= } catch (e) {=0A= }=0A= }=0A= return null;=0A= };=0A= }=0A= // Gecko support=0A= /* ;-) */=0A= // Opera support=0A= if (window.opera && !window.XMLHttpRequest) {=0A= window.XMLHttpRequest =3D function() {=0A= this.readyState =3D 0; 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i < this._headers.length; i++) {=0A= conn.setRequestProperty(this._headers[i].h, this._headers[i].v);=0A= }=0A= this._headers =3D [];=0A= if (this.method =3D=3D 'POST') {=0A= // POST data=0A= conn.setDoOutput(true);=0A= var wr =3D new = java.io.OutputStreamWriter(conn.getOutputStream(), this._getCharset());=0A= wr.write(data);=0A= wr.flush();=0A= wr.close();=0A= }=0A= // read response headers=0A= // NOTE: the getHeaderField() methods always return nulls for me :(=0A= var gotContentEncoding =3D false;=0A= var gotContentLength =3D false;=0A= var gotContentType =3D false;=0A= var gotDate =3D false;=0A= var gotExpiration =3D false;=0A= var gotLastModified =3D false;=0A= for (var i =3D 0; ; i++) {=0A= var hdrName =3D conn.getHeaderFieldKey(i);=0A= var hdrValue =3D conn.getHeaderField(i);=0A= if (hdrName =3D=3D null && hdrValue =3D=3D null) {=0A= break;=0A= }=0A= if (hdrName !=3D null) {=0A= this._headers[this._headers.length] =3D {h:hdrName, = v:hdrValue};=0A= switch (hdrName.toLowerCase()) {=0A= case 'content-encoding': gotContentEncoding =3D true; break;=0A= case 'content-length' : gotContentLength =3D true; break;=0A= case 'content-type' : gotContentType =3D true; break;=0A= case 'date' : gotDate =3D true; break;=0A= case 'expires' : gotExpiration =3D true; break;=0A= case 'last-modified' : gotLastModified =3D true; break;=0A= }=0A= }=0A= }=0A= // try to fill in any missing header information=0A= var val;=0A= val =3D conn.getContentEncoding();=0A= if (val !=3D null && !gotContentEncoding) = this._headers[this._headers.length] =3D {h:'Content-encoding', v:val};=0A= val =3D conn.getContentLength();=0A= if (val !=3D -1 && !gotContentLength) = this._headers[this._headers.length] =3D {h:'Content-length', v:val};=0A= val =3D conn.getContentType();=0A= if (val !=3D null && !gotContentType) = this._headers[this._headers.length] =3D {h:'Content-type', v:val};=0A= val =3D conn.getDate();=0A= if (val !=3D 0 && !gotDate) this._headers[this._headers.length] = =3D {h:'Date', v:(new Date(val)).toUTCString()};=0A= val =3D conn.getExpiration();=0A= if (val !=3D 0 && !gotExpiration) = this._headers[this._headers.length] =3D {h:'Expires', v:(new = Date(val)).toUTCString()};=0A= val =3D conn.getLastModified();=0A= if (val !=3D 0 && !gotLastModified) = this._headers[this._headers.length] =3D {h:'Last-modified', v:(new = Date(val)).toUTCString()};=0A= // read response data=0A= var reqdata =3D '';=0A= var stream =3D conn.getInputStream();=0A= if (stream) {=0A= var reader =3D new java.io.BufferedReader(new = java.io.InputStreamReader(stream, this._getCharset()));=0A= var line;=0A= while ((line =3D reader.readLine()) !=3D null) {=0A= if (this.readyState =3D=3D 2) {=0A= this.readyState =3D 3;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= }=0A= reqdata +=3D line + '\n';=0A= }=0A= reader.close();=0A= this.status =3D 200;=0A= this.statusText =3D 'OK';=0A= this.responseText =3D reqdata;=0A= this.readyState =3D 4;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= if (this.onload) {=0A= this.onload();=0A= }=0A= } else {=0A= // error=0A= this.status =3D 404;=0A= this.statusText =3D 'Not Found';=0A= this.responseText =3D '';=0A= this.readyState =3D 4;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= if (this.onerror) {=0A= this.onerror();=0A= }=0A= }=0A= };=0A= };=0A= }=0A= // ActiveXObject emulation=0A= if (!window.ActiveXObject && window.XMLHttpRequest) {=0A= window.ActiveXObject =3D function(type) {=0A= switch (type.toLowerCase()) {=0A= case 'microsoft.xmlhttp':=0A= case 'msxml2.xmlhttp':=0A= case 'msxml2.xmlhttp.3.0':=0A= case 'msxml2.xmlhttp.4.0':=0A= case 'msxml2.xmlhttp.5.0':=0A= return new XMLHttpRequest();=0A= }=0A= return null;=0A= };=0A= }=0A= ------=_NextPart_000_0004_01CA28A4.C0DA25B0 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://www.sciencemag.org/javascript/ajax/utility.js /************************************************************************= *****=0A= * javascript/ajax/utility.js=0A= *=0A= * Utility functions for working with XMLHttpRequest data.=0A= *=0A= * Copyright 2006 Board of Trustees of the Leland Stanford Junior = University.=0A= = *************************************************************************= ***/=0A= =0A= /*=0A= * Copy XML nodes into an HTMLElement. This effectively=0A= * clones XML markup which uses XHTML naming conventions=0A= * into an HTML DOM.=0A= */=0A= function copy_xml_to_html(src, dst) {=0A= if (src.nodeType =3D=3D 1) { /* Node.ELEMENT_NODE */=0A= var e =3D document.createElement(src.nodeName);=0A= for (var i =3D 0; i < src.childNodes.length; i++) {=0A= copy_xml_to_html(src.childNodes[i], e);=0A= }=0A= for (var i =3D 0; i < src.attributes.length; i++) {=0A= var n =3D src.attributes[i].name;=0A= var v =3D unescape_xml_string(src.attributes[i].value); =0A= e.setAttribute(n, v);=0A= if (n =3D=3D "class") {=0A= e.className =3D v;=0A= }=0A= else if (n =3D=3D "style") {=0A= set_css_style(v, e, "");=0A= }=0A= }=0A= dst.appendChild(e);=0A= }=0A= else if (src.nodeType =3D=3D 3) { /* Node.TEXT_NODE */=0A= dst.appendChild(document.createTextNode(src.nodeValue));=0A= }=0A= }=0A= =0A= /* =0A= * It is unclear that this is the right thing to be calling=0A= * from copy_xml_to_html, but it appears that Safari decides=0A= * to convert & to the NCR #, and then encodes that=0A= * NCR to &%26%2338;. So, I'm going to treat the DOM Attr=0A= * value as a plain string, and run our XML string input=0A= * through the decoding routine below.=0A= */=0A= function unescape_xml_string(s) {=0A= return s.replace(/'/g, "'")=0A= .replace(/'/g, "'")=0A= .replace(/"/g, "\"")=0A= .replace(/"/g, "\"")=0A= .replace(/>/g, ">")=0A= .replace(/>/g, ">")=0A= .replace(/</g, "<")=0A= .replace(/</g, "<")=0A= .replace(/&/g, "&")=0A= .replace(/&/g, "&");=0A= }=0A= =0A= /*=0A= * Parse set of CSS rules and apply them to an element.=0A= * This is quite horrifying, but I'm unable to determine=0A= * how else to handle this with IE 6. FireFox and other=0A= * sane browsers let you simply set the style attribute=0A= * or use e.style.setProperty(rule, value, priority),=0A= * IE 6 appears to have neither of these capabilities..=0A= */=0A= function set_css_style(css, e, priority) {=0A= var rules =3D css.split(";");=0A= for (var i =3D 0; i < rules.length; i++) {=0A= var nvpair =3D rules[i].split(":");=0A= if (nvpair.length =3D=3D 2) {=0A= try {=0A= var name =3D nvpair[0]; /* style attribute */=0A= var value =3D nvpair[1]; /* attribute value */=0A= =0A= /*=0A= * For each possible style attribute, set the=0A= * appropriate style property in the element.=0A= */=0A= if (name =3D=3D "background") {=0A= e.style.background =3D value;=0A= }=0A= else if (name =3D=3D "background-attachment") {=0A= e.style.backgroundAttachment =3D value;=0A= }=0A= else if (name =3D=3D "background-color") {=0A= e.style.backgroundColor =3D value;=0A= }=0A= else if (name =3D=3D "background-image") {=0A= e.style.backgroundImage =3D value;=0A= }=0A= else if (name =3D=3D "background-position") {=0A= e.style.backgroundPosition =3D value;=0A= }=0A= else if (name =3D=3D "background-position-x") {=0A= e.style.backgroundPositionX =3D value;=0A= }=0A= else if (name =3D=3D "background-position-y") {=0A= e.style.backgroundPositionY =3D value;=0A= }=0A= else if (name =3D=3D "background-repeat") {=0A= e.style.backgroundRepeat =3D value;=0A= }=0A= else if (name =3D=3D "behavior") {=0A= e.style.behavior =3D value;=0A= }=0A= else if (name =3D=3D "border") {=0A= e.style.border =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom") {=0A= e.style.borderBottom =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom-color") {=0A= e.style.borderBottomColor =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom-style") {=0A= e.style.borderBottomStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom-width") {=0A= e.style.borderBottomWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-collapse") {=0A= e.style.borderCollapse =3D value;=0A= }=0A= else if (name =3D=3D "border-color") {=0A= e.style.borderColor =3D value;=0A= }=0A= else if (name =3D=3D "border-left") {=0A= e.style.borderLeft =3D value;=0A= }=0A= else if (name =3D=3D "border-left-color") {=0A= e.style.borderLeftColor =3D value;=0A= }=0A= else if (name =3D=3D "border-left-style") {=0A= e.style.borderLeftStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-left-width") {=0A= e.style.borderLeftWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-right") {=0A= e.style.borderRight =3D value;=0A= }=0A= else if (name =3D=3D "border-right-color") {=0A= e.style.borderRightColor =3D value;=0A= }=0A= else if (name =3D=3D "border-right-style") {=0A= e.style.borderRightStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-right-width") {=0A= e.style.borderRightWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-style") {=0A= e.style.borderStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-top") {=0A= e.style.borderTop =3D value;=0A= }=0A= else if (name =3D=3D "border-top-color") {=0A= e.style.borderTopColor =3D value;=0A= }=0A= else if (name =3D=3D "border-top-style") {=0A= e.style.borderTopStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-top-width") {=0A= e.style.borderTopWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-width") {=0A= e.style.borderWidth =3D value;=0A= }=0A= else if (name =3D=3D "bottom") {=0A= e.style.bottom =3D value;=0A= }=0A= else if (name =3D=3D "clear") {=0A= e.style.clear =3D value;=0A= }=0A= else if (name =3D=3D "clip") {=0A= e.style.clip =3D value;=0A= }=0A= else if (name =3D=3D "color") {=0A= e.style.color =3D value;=0A= }=0A= else if (name =3D=3D "cssText") {=0A= e.style.Sets =3D value;=0A= }=0A= else if (name =3D=3D "cursor") {=0A= e.style.cursor =3D value;=0A= }=0A= else if (name =3D=3D "direction") {=0A= e.style.direction =3D value;=0A= }=0A= else if (name =3D=3D "display") {=0A= e.style.display =3D value;=0A= }=0A= else if (name =3D=3D "font") {=0A= e.style.font =3D value;=0A= }=0A= else if (name =3D=3D "font-family") {=0A= e.style.fontFamily =3D value;=0A= }=0A= else if (name =3D=3D "font-size") {=0A= e.style.fontSize =3D value;=0A= }=0A= else if (name =3D=3D "font-style") {=0A= e.style.fontStyle =3D value;=0A= }=0A= else if (name =3D=3D "font-variant") {=0A= e.style.fontVariant =3D value;=0A= }=0A= else if (name =3D=3D "font-weight") {=0A= e.style.fontWeight =3D value;=0A= }=0A= else if (name =3D=3D "height") {=0A= e.style.height =3D value;=0A= }=0A= else if (name =3D=3D "ime-mode") {=0A= e.style.imeMode =3D value;=0A= }=0A= else if (name =3D=3D "layout-flow") {=0A= e.style.layoutFlow =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid") {=0A= e.style.layoutGrid =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-char") {=0A= e.style.layoutGridChar =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-line") {=0A= e.style.layoutGridLine =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-mode") {=0A= e.style.layoutGridMode =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-type") {=0A= e.style.layoutGridType =3D value;=0A= }=0A= else if (name =3D=3D "left") {=0A= e.style.left =3D value;=0A= }=0A= else if (name =3D=3D "letter-spacing") {=0A= e.style.letterSpacing =3D value;=0A= }=0A= else if (name =3D=3D "line-break") {=0A= e.style.lineBreak =3D value;=0A= }=0A= else if (name =3D=3D "line-height") {=0A= e.style.lineHeight =3D value;=0A= }=0A= else if (name =3D=3D "list-style") {=0A= e.style.listStyle =3D value;=0A= }=0A= else if (name =3D=3D "list-style-image") {=0A= e.style.listStyleImage =3D value;=0A= }=0A= else if (name =3D=3D "list-style-position") {=0A= e.style.listStylePosition =3D value;=0A= }=0A= else if (name =3D=3D "list-style-type") {=0A= e.style.listStyleType =3D value;=0A= }=0A= else if (name =3D=3D "margin") {=0A= e.style.margin =3D value;=0A= }=0A= else if (name =3D=3D "margin-bottom") {=0A= e.style.marginBottom =3D value;=0A= }=0A= else if (name =3D=3D "margin-left") {=0A= e.style.marginLeft =3D value;=0A= }=0A= else if (name =3D=3D "margin-right") {=0A= e.style.marginRight =3D value;=0A= }=0A= else if (name =3D=3D "margin-top") {=0A= e.style.marginTop =3D value;=0A= }=0A= else if (name =3D=3D "min-height") {=0A= e.style.minHeight =3D value;=0A= }=0A= else if (name =3D=3D "overflow") {=0A= e.style.overflow =3D value;=0A= }=0A= else if (name =3D=3D "overflow-x") {=0A= e.style.overflowX =3D value;=0A= }=0A= else if (name =3D=3D "overflow-y") {=0A= e.style.overflowY =3D value;=0A= }=0A= else if (name =3D=3D "padding") {=0A= e.style.padding =3D value;=0A= }=0A= else if (name =3D=3D "padding-bottom") {=0A= e.style.paddingBottom =3D value;=0A= }=0A= else if (name =3D=3D "padding-left") {=0A= e.style.paddingLeft =3D value;=0A= }=0A= else if (name =3D=3D "padding-right") {=0A= e.style.paddingRight =3D value;=0A= }=0A= else if (name =3D=3D "padding-top") {=0A= e.style.paddingTop =3D value;=0A= }=0A= else if (name =3D=3D "page-break-after") {=0A= e.style.pageBreakAfter =3D value;=0A= }=0A= else if (name =3D=3D "page-break-before") {=0A= e.style.pageBreakBefore =3D value;=0A= }=0A= else if (name =3D=3D "pixelBottom") {=0A= e.style.pixelBottom =3D value;=0A= }=0A= else if (name =3D=3D "pixelHeight") {=0A= e.style.pixelHeight =3D value;=0A= }=0A= else if (name =3D=3D "pixelLeft") {=0A= e.style.pixelLeft =3D value;=0A= }=0A= else if (name =3D=3D "pixelRight") {=0A= e.style.pixelRight =3D value;=0A= }=0A= else if (name =3D=3D "pixelTop") {=0A= e.style.pixelTop =3D value;=0A= }=0A= else if (name =3D=3D "pixelWidth") {=0A= e.style.pixelWidth =3D value;=0A= }=0A= else if (name =3D=3D "posBottom") {=0A= e.style.posBottom =3D value;=0A= }=0A= else if (name =3D=3D "posHeight") {=0A= e.style.posHeight =3D value;=0A= }=0A= else if (name =3D=3D "position") {=0A= e.style.position =3D value;=0A= }=0A= else if (name =3D=3D "posLeft") {=0A= e.style.posLeft =3D value;=0A= }=0A= else if (name =3D=3D "posRight") {=0A= e.style.posRight =3D value;=0A= }=0A= else if (name =3D=3D "posTop") {=0A= e.style.posTop =3D value;=0A= }=0A= else if (name =3D=3D "posWidth") {=0A= e.style.posWidth =3D value;=0A= }=0A= else if (name =3D=3D "right") {=0A= e.style.right =3D value;=0A= }=0A= else if (name =3D=3D "ruby-align") {=0A= e.style.rubyAlign =3D value;=0A= }=0A= else if (name =3D=3D "ruby-overhang") {=0A= e.style.rubyOverhang =3D value;=0A= }=0A= else if (name =3D=3D "ruby-position") {=0A= e.style.rubyPosition =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-3dlight-color") {=0A= e.style.scrollbar3dLightColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-arrow-color") {=0A= e.style.scrollbarArrowColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-base-color") {=0A= e.style.scrollbarBaseColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-darkshadow-color") {=0A= e.style.scrollbarDarkShadowColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-face-color") {=0A= e.style.scrollbarFaceColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-highlight-color") {=0A= e.style.scrollbarHighlightColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-shadow-color") {=0A= e.style.scrollbarShadowColor =3D value;=0A= }=0A= else if (name =3D=3D "scrollbar-track-color") {=0A= e.style.scrollbarTrackColor =3D value;=0A= }=0A= else if (name =3D=3D "float") {=0A= e.style.styleFloat =3D value;=0A= }=0A= else if (name =3D=3D "table-layout") {=0A= e.style.tableLayout =3D value;=0A= }=0A= else if (name =3D=3D "text-align") {=0A= e.style.textAlign =3D value;=0A= }=0A= else if (name =3D=3D "text-align-last") {=0A= e.style.textAlignLast =3D value;=0A= }=0A= else if (name =3D=3D "text-autospace") {=0A= e.style.textAutospace =3D value;=0A= }=0A= else if (name =3D=3D "text-decoration") {=0A= e.style.textDecoration =3D value;=0A= }=0A= else if (name =3D=3D "textDecorationBlink") {=0A= e.style.textDecorationBlink =3D value;=0A= }=0A= else if (name =3D=3D "textDecorationLineThrough") {=0A= e.style.textDecorationLineThrough =3D value;=0A= }=0A= else if (name =3D=3D 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"vertical-align") {=0A= e.style.verticalAlign =3D value;=0A= }=0A= else if (name =3D=3D "visibility") {=0A= e.style.visibility =3D value;=0A= }=0A= else if (name =3D=3D "white-space") {=0A= e.style.whiteSpace =3D value;=0A= }=0A= else if (name =3D=3D "width") {=0A= e.style.width =3D value;=0A= }=0A= else if (name =3D=3D "word-break") {=0A= e.style.wordBreak =3D value;=0A= }=0A= else if (name =3D=3D "word-spacing") {=0A= e.style.wordSpacing =3D value;=0A= }=0A= else if (name =3D=3D "word-wrap") {=0A= e.style.wordWrap =3D value;=0A= }=0A= else if (name =3D=3D "writing-mode") {=0A= e.style.writingMode =3D value;=0A= }=0A= else if (name =3D=3D "z-index") {=0A= e.style.zIndex =3D value;=0A= }=0A= else if (name =3D=3D "zoom") {=0A= e.style.zoom =3D value;=0A= }=0A= }=0A= catch (e) {=0A= /* ignore error on attempt to set e.style.[property] */=0A= }=0A= }=0A= }=0A= }=0A= ------=_NextPart_000_0004_01CA28A4.C0DA25B0 Content-Type: application/octet-stream Content-Transfer-Encoding: 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BRAIN CANCER:
A = Viral Link to=20 Glioblastoma?

Circumstantial evidence hints that cytomegalovirus, a common=20 herpesvirus, may play a role in the aggressive brain cancer, but = big=20 questions remain

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BRAIN CANCER:A = Viral Link to=20 Glioblastoma?

Circumstantial evidence hints that cytomegalovirus, a common=20 herpesvirus, may play a role in the aggressive brain cancer, but = big=20 questions remain

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BRAIN CANCER:
A = Viral Link to=20 Glioblastoma?