Feng Zengkun

Scientists in Singapore haveopened a new frontier inthe fight against glioblasto-ma, a swift and deadly formof brain cancer.

Spreading quietly in the brain,the disease usually announces itselfin the form of fits and seizures inthe patient, or headaches due tothe tumour expanding and exert-ing pressure on the skull.

While the cancer is much rarerthan, say, breast and lung cancer, itis deadlier, killing most patientswithin 18 months even if theyhave surgery and chemotherapy.

In Singapore, there were 1,903cases of brain cancer between 1968and 2007.

In a stark reminder of patients’grim prospects, a 29-year-old USwoman was in the headlines global-ly last weekend for ending her lifeby doctor-assisted suicide, as shewanted to die on her own terms.

To help people like her, two sci-entists from the National Neuro-science Institute (NNI) in Singa-pore have been compiling a data-base of tumours removed from pa-tients here during surgery.

Over the past decade, they havebeen storing the physical samplesand looking into the tumours’ ge-netic information, which couldshed light on their weaknesses.

The brain tumour bank compris-es about 100 samples.

Senior research scientist CarolTang and Associate Professor Chris-topher Ang, head of neurosurgeryat NNI’s Singapore General Hospi-tal campus, have also developed away to reproduce the tumour cellsand implant them in mice so thatthey will grow exactly as they grewin the patients.

This is a breakthrough as scien-tists traditionally have only a finitesupply of cells from the original, ex-cised tumours for research andtests. Reproduced versions and cellsbought commercially are usually al-

tered and, when implanted inmice, do not reflect what happenedin patients.

Pharmaceutical companies canalso use the mice to test experimen-tal drugs, and use the results tofine-tune their clinical drug trialsso only patients with tumours thatcould respond take part in the tri-als.

“This will improve the trial re-sults so more cancer drugs make it

to the market,” said NNI’s Dr Ang.The institute has been working

with American drug company EliLilly on anti-brain cancer drugs.

Dr Tang said such a genetics-driven approach to diagnosing andtreating brain tumours is long over-due.

Currently, most doctors still relyon observation to identify the tu-mour type and decide on the treat-ment.

After surgery to remove the tu-mour, they usually put a sample un-der the microscope to identifywhat type it is through its features.

“But this method, called histolo-gy, is very subjective, and if the tu-mour is not the same throughout,some features may be missed,” shesaid.

Research in the United Stateshas shown that tumours that lookthe same may not be the same. It is

only by looking at their molecularbiology that scientists can detectdifferences, she added.

There are more than 100 typesof brain tumours, according to char-ity Cancer Research UK.

Such below-the-surface differ-ences could explain why some pa-tients respond to a drug while oth-ers do not, even if their tumourslook alike under the microscope.

The standard treatment for gliob-

lastomas now is surgery followedby radiation and chemotherapy,said Dr Ang.

“If the patient doesn’t respond,then you try random mixtures ofanother set of chemotherapydrugs, but you still won’t know ifthe patient will respond,” he said.

“Usually, the patient is so ill bythe second trial that he succumbsto the disease, so the window fortreatment is quite short.”

In September, a group of 27 neu-roscientists from around the worldcame to the same conclusions asthe NNI scientists.

The international scientists at ameeting in the Netherlands spon-sored by the International Societyof Neuropathologists, discussed ma-jor discoveries in the biology of cen-tral nervous system tumours,which include brain tumours.

The group recommended thatthe World Health Organisationtake into account the tumours’ ge-netic differences when it revises itsclassification. The last revision wasin 2007 and there is no specifieddate for the next one.

The scientists noted that re-search in the past decade had signif-icantly improved the biological un-derstanding of the molecular basisof human tumours.

“Brain tumours have shared inthis molecular revolution, and insome areas have been at the fore-front,” they said in a paper.

“Such information can have di-agnostic, prognostic and predictivevalue.”

Dr Tang believes the NNI’s re-search could eventually lead to pa-tients getting a more personaliseddiagnosis within days of surgery, sothat the most effective drugs can beprescribed.

Usually, when doctors talkabout genetic profiling, that in-volves looking at up to 800 gene sig-natures to see if the drugs willwork.

“That could take four to fivemonths, too much time and cost tobe useful for the patient,” she said.

Instead, the NNI will build onUS researchers’ work in mapping so-matic mutations, or changes in aperson’s DNA that occur afterbirth. A fairly comprehensive data-base of such mutations already ex-ists.

The idea is to establish a link be-tween the various tumour typesand somatic mutation patterns,and the effectiveness of drugsagainst the tumours.

Dr Tang said: “In the future, weshould be able to just test which so-matic mutations a patient has.

“That could take as little as aday, compared to months for thegene signatures. Then we can guesswhich drugs will be useful for thepatient, and hopefully get them bet-ter.”

zengkun@sph.com.sg

IN BRIEF

BURROWING INTO TUMOURS

Genes controlfat-busting bacteriaA person’s genetic makeupinfluences whether he is fat orthin by shaping which types ofmicrobes thrive in his body,according to a study led byCornell University in the UnitedStates and published in thejournal Cell.

By studying pairs of twins,researchers identified theChristensenellaceae bacterialfamily, which is more commonin lean individuals.

A member of this class ofbacteria – Christensenellaceaeminuta – was found to protectagainst weight gain whentransplanted into mice.

The findings pave the way forpersonalised probiotic therapiesthat could help reduce the riskof obesity-related diseases, basedon an individual’s geneticmakeup, said the university.

“If you look across thepopulation of gut bacteria andexplain abundances, there is ahost genetic component,” saidDr Ruth Ley, an associateprofessor of microbiology andthe paper’s senior author.

“Up until now, there hadbeen no direct evidence thatanything in the human gut wasunder that kind of geneticinfluence.”

Bugs ruled Earth wellbefore dinosaursWhen dinosaurs ruled the Earth,they were already being buggedby creatures that got here manymillions of years earlier:dragonflies and damselflies. Infact, the first creatures to take tothe skies did so 406 millionyears ago.

Rutgers University-Newarkbiologist Jessica Ware is part ofan international team of 100researchers that recentlycompleted a two-year project tomap the evolution of insectsusing molecular data.

They found that insectsoriginated at the same time asthe earliest terrestrial plants –about 480 million years ago –which suggests that insects andplants shaped the earliestterrestrial ecosystems together,said the university in astatement.

The team also found thatinsects developed wings longbefore any other animal, and atnearly the same time that landplants first grew substantiallyupwards to form forests.

While life on Earth began inthe water, the first creatures onland and in the air were insects,noted Dr Ware.

“Whatever people do, insectsdid it first. They waged war, theytook slaves, they learnt to workcooperatively, they flew, theyfarmed.”

The team, whose work hasbeen published in theprestigious journal Science,developed maps of the genomesof 1,200 insect species.

Allergy meds may begiving you an allergyThe very medication taken bypeople with allergies to relievetheir symptoms could causedifferent and sometimes worseallergic reactions.

And this development oftengoes undiagnosed, according toa presentation at the AnnualScientific Meeting of theAmerican College of Allergy,Asthma and Immunology.

For instance, a topicalsteroid’s job is to tameinflammation, but a personcould be having an allergicreaction to the medication itselfif the rash does not respond tothe treatment, gets worse withmedication, or improves at first,then flares up, said allergist LuzFonacier.

Other topical medicationsthat can cause allergies includeantibiotics and anaesthetics –some of which are found in lipbalms, and antifungals.

The sufferer often gets hivesor a rash, and a patch test can bedone to determine if he isallergic to the actual drug or toother ingredients such aspreservatives or fragrance.

Allergist Sami Bahna noted:“It’s surprising that the mainmedications used to relieveallergies can cause new allergiesor worsen already existingallergies.

“They are, therefore, rarelysuspected.”

Compiled by Chang Ai-Lien

PHOTO: LIM YAOHUI FOR THE SUNDAY TIMES

Dr Carol Tang and Dr Christopher Ang, both 45, in the NNI’s neuro-oncology laboratory with the FACS Aria, a high-speed flow cytometer routinely used forretrieving certain populations of cells in the mixed tumour cell environment. Their bank of brain tumours removed from patients here has about 100 samples.

Some tumours have clearlydefined boundaries in the brain.Others have finger-likeextensions into both brainhemispheres.

Over the past 10 years, seniorresearch scientist Carol Tang andAssociate Professor ChristopherAng from the NationalNeuroscience Institute (NNI)have seen it all when it comes tobrain tumours.

The pair have been steadilybuilding a well-respecteddatabase of some 100 braintumours removed from patientsduring surgery.

Brain cancer is uncommon in

Singapore, with 1,903 casesbetween 1968 and 2007.

So, unlike other repositoriesthat simply keep physicalsamples of the tumours, the NNIscientists also analysed thetumours’ genetic information tohelp shed light on theircharacteristics.

“After we collect the tumours,we separate them into four tofive sections,” said Dr Tang.

“We keep one section forhistology, several are formolecular evaluation, andanother to culture cells so we canuse them to recreate the tumoursin mice, an essential pre-clinicalanimal model,” she said.

She added that being able toreproduce the tumours wasimportant because, “in ascientific lab, people use thetissue to test their favouritehypotheses, which often leads tosample depletion”.

Prof Ang, who is head ofneurosurgery at NNI’s SingaporeGeneral Hospital campus,credited the good relationshipbetween NNI researchers andsurgeons for the supply oftumours to the database.

Dr Tang noted that a lot oftumours are necrotic (deadtissue). “When you remove thetumour, it is mostly unusable for

analysis. So we asked thesurgeons to please avoid thenecrotic pieces.”

Associate Professor John Kuo,director of the ComprehensiveBrain Tumour Programme at theUniversity of Wisconsin in theUnited States, called the NNIscientists’ work “world-class”.

“They are employingstate-of-the-art molecular andgenetic techniques, as well asusing those precious donatedtumour specimens and patienthistories, to make discoveriesabout the aberrant biologyunderlying cancer growth,” hesaid.

Feng Zengkun

Mesenchymal stem cells,which are found in the bonemarrow, can transformthemselves into cells whichproduce bone, cartilage, fator muscle, a trait thatscientists have tried toexploit for tissue repair.

Now, researchers from theSingapore-MIT Alliance forResearch and Technology(Smart) have developed away to isolate these rare cellsbased on physical traits suchas size and stiffness.

Here, the red stem cellwith a glowing greennucleus highlights the redcytoskeleton that makes acell stiff.

The scientists are startingtrials on patients with suchcells which they have siftedout, for bone marrowregeneration and repair.

‘Talking’ with Man’s best friend“We’ve developed a platform forcomputer-mediated communicationbetween humans and dogs thatopens the door to new avenues forinterpreting dogs’ behaviouralsignals and sending them clear andunambiguous cues in return. Wehave a fully functional prototype,but we’ll be refining the design aswe explore more and moreapplications for the platform.”DR DAVID ROBERTS, assistant professor of computerscience, North Carolina State University. He and hiscolleagues have developed a harness worn by the dog,which contains an array of technologies, includingsensors that not only track a dog’s physical well-being, but also can offer information about its emotional state, suchas whether it is excited or stressed. There are also speakers and vibrating motors that work alongside software totranslate human requests into signals on the harness. The researchers believe that the device could be used ineverything from search and rescue, to service dogs or training pets.

Beautiful Science

PHOTO: NORTH CAROLINA STATE UNIVERSITY

NNI duo banktumours removedduring surgeryand study their genes

PHOTO: SMART

PHOTO: AFP

Flying insects such as the dragonflyevolved 406 million years ago,developing wings long before anyother creature.

[ science ]

Cancer scientists’ brainwave

45thinkNovember 9, 2014 thesundaytimes