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Scientists find mutated genes related to 12 cancer types

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Scientists at the Washington University School of Medicine looking at 12 different types of cancer have identified 127 significantly mutated genes that appear to drive development of a range of tumors in the body. Those scientists hope the findings and more like them in the future could become part of standard cancer diagnosis.

Li Ding, PhD of the Genome Institute at Washington University

Li Ding, PhD of the Genome Institute at Washington University

Doctor Li Ding says the ability to identify those genes combined with additional research in the future could lead to a complete list of cancer genes responsible for all human cancers.

“Once we identify the specific mutation … we know which string the mutation is from … we can use existing drugs or develop novel therapy for treating the cancer.”

She says doctors can begin using the results found so far, while further research will look at more tumor samples and more cancers to look for more mutated genes.

“I believe that by increasing the sample size and increasing the tumor types we should be able to identify almost all the important cancer genes responsible for the development of different types of human cancers in the near future.”

A cancer gene panel set could be used upon diagnosis or after a patient has already been diagnosed.

Ding believes more important is that it could be used for cancer prognosis, making it another step toward more effective and individualized treatments. “Knowing after a patient has been diagnosed with cancer, then we can look at the specific mutations they have and develop a targeted therapy.”

The research utilizes advances that make analysis of cancer cells faster and cheaper.

Study compares cost-effectiveness of two brain tumor treatments

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A treatment for brain cancer in children that has been thought to be too expensive, isn’t, according to findings from a study Washington University researchers participated in.

Proton therapy delivers precise radiation doses to a tumor to spare healthy organs and tissues, making it safer than traditional photon therapy. Doctor Raymond Mailhot Vega with the Washington University School of Medicine says the hangup about using it has been the cost.

“Capital investment of construction of a facility has been approximated at $140-million dollars. That’s a huge investment to undertake especially in our climate of today. I think it’s important to demonstrate cost-effectiveness … whether it be to show that it is, or not.”

The study looked at treating medulloblastoma brain tumors, a type of fast-growing tumor that mainly effects children. It found that among several 18-year-olds assumed to have been diagnosed at age 5 the treatment decreased the risks of hearing loss, secondary malignancy and heart failure, resulting in a cost savings of more than 95 percent in study simulations.

“What it ultimately demonstrated was that proton therapy had been cost-effective, with the important caveat that this is with the best data available.”

Vega says the treatment might prove cost-effective and cost-saving for treating other types of cancer.

Discovery could lead to way to curb spread of Alzheimer’s, Parkinson’s diseases

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Research at Washington University in St. Louis could lead to a way to stop the spread of diseases like Parkinson’s and Alzheimer’s.

Clumps of corrupted tau protein are seen outside a nerve cell. Scientists have identified a receptor that lets these clumps enter the cell, causing the spread of the corruption. (Photo courtesy; Washington University).

Clumps of corrupted tau protein are seen outside a nerve cell. Scientists have identified a receptor that lets these clumps enter the cell, causing the spread of the corruption. (Photo courtesy; Washington University).

Researchers including a doctoral student have identified how a corrupted type of protein spreads through the brain potentially causing Alzheimer’s and Parkinson’s diseases and other brain-damaging disorders.

Neurology Professor Marc Diamond says the finding could be huge in battling those diseases.

“By understanding this mechanism it has opened up new possibilities to target these diseases with a completely different type of experimental strategy than has been used in the past.”

That protein attaches to cells via a particular receptor, in a process Diamond says would not take much to interrupt.

“You can take a small molecule that’s drug-like and that will block this process by interfering with the binding of these toxic aggregates with the cell surface.”

Unfortunately, Diamond says, there isn’t a drug to be used yet.

“None that we know of. There are drugs out there that have some of the properties that you’d want to see but in terms of a drug that would be safe to be given chronically and would get into the brain, there are none currently.”

Diamond says work will continue at the University to develop such a drug.

He adds, the findings could similarly help in fighting diseases in animals, such as that commonly called “mad cow disease.”

“The mechanisms that we are talking about here … the original ideas that we developed in my lab that we started testing about ten years ago were derived from understanding of what occurs in animals … those sorts of veterinary disorders could also in theory be treated by the same approach.”

The study can be found online in the Proceedings of the National Academy of Sciences.

 

Study suggests treatment of ear deformity could improve children’s school performance

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A study by researchers at the School of Medicine at Washington University in St. Louis has found that children with hearing loss in one ear due to a certain deformity can struggle in school and socially because of it.

A normal ear (top left) is compared with various external ear malformations common in children born with aural atresia, the absence of an external ear canal. The condition typically only affects one ear. (photo courtesy; the National Institutes of Health)

A normal ear (top left) is compared with various external ear malformations common in children born with aural atresia, the absence of an external ear canal. The condition typically only affects one ear. (photo courtesy; the National Institutes of Health)

The condition studied, aural atresia, refers to the absence or incomplete formation of an external ear canal. Of the children studied with that condition, about 40 percent needed speech therapy and a quarter have difficulties in school.

Doctor Judith Lieu, an Associate Professor at the Washington University School of Medicine in St. Louis, says one problem is hearing loss in one ear is often ignored because one working ear is thought to be enough for a child to learn and develop properly.

“We don’t want to have the assumption that [children] will do just fine in school and do just fine in terms of speech and language just because one ear hears normally.”

Lieu says this study suggests that adults need to take hearing loss in one ear of a child more seriously.

“We need to be vigilant, and as adults … parents, teachers, physicians … that we can help these children if they appear to be struggling or if they have some of these issues and think about that ear deformity or the hearing loss in the one ear as potentially playing a part in it.”

Lieu says such children might be perceived as “trouble students” as a result of their hearing problems.

“It can be quite noisy in a classroom when kids are busy and talking and chatting and if they are unable to hear well, they may be unable to pick out the teacher’s voice calling them back to attention or calling them back to a task, and so they may just proceed on and be perceived as not paying attention or not listening and having some behavioral issues.”

Lieu says once the problem is identified and recognized there are effective ways to deal with it, but she says more study is needed to determine how aggressively hearing loss in one ear of a child should be treated.

“I don’t want to state that every child needs a hearing aid when I know that hearing aid fitting is not a trivial thing and trying to teach a child to wear it, especially with the current cultural stigmas associated with a hearing device, I don’t want to make it so that every child has to wear it if it doesn’t help them.”

Further complicating matters, Lieu says, is that most private insurance will not cover hearing aids or devices.

“Children are more likely to receive a hearing aid or a device if they have Medicaid because it’s perceived to be a sensory issue so it’s kind of tied to disability, however that’s not universal.”

Lieu hopes to continue some of the additional study that she believes is needed, but says right now funding is difficult to come by because funding agencies don’t consider it a priority and federal research dollars are tight.

The research has been published in JAMA Otolaryngology.

Washington University researcher part of study of deadly viruses

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A researcher at Washington University in St. Louis will take part in a study to look for similarities in how humans respond to three potentially lethal viruses.

Washington University Professor of Medicine Michael Diamond, MD, PhD

Washington University Professor of Medicine Michael Diamond, MD, PhD

Washington University Professor of Medicine Michael Diamond is an expert on West Nile virus. He will work with researchers at the University of Wisconsin-Madison and the Pacific Northwest National Laboratories who will also study Ebola and influenza.

Diamond says those three ailments were chosen for their differences.

“They cause three different types of very severe disease, so we figured that would give us some insight into some of the pathways which were different. Yet we felt that because they’re all viruses, they replicate in a certain place in the cell, there would be some very conserved pathways which would be trying to restrict them, so there would be elements that would be similar and different.”

Diamond explains that finding similarities between the three could lead to new, more effective treatments useful against all three.

“For example, if you found certain pathways that were commonly activated and trying to restrict these very, very disparate viral infections, then that might be targets for new avenues for new, broad-spectrum antivirals.”

Developing such drugs has been difficult using more conventional methods. Diamond says this will use a “systems biology approach.”

“We look at it from a much higher point of view … we look at how the cells are changed in all of these different ways and then we would identify things that might be in common which could then be targeted.”

Diamond says he will meet his colleagues next month to begin laying out the roadmap for their work over the next five years.

“In the first couple of years we gather an enormous amount of information. We have a computational center that’s going to process this. We generate hypotheses about which of the genes may be important for controlling all three viruses together and which ones may be working specifically, and then the last three years of the grant we begin to test out and confirm and corroborate our hypotheses.”

The study is backed by an $18.3 million dollar grant from the National Institutes of Health.

Washington University the hub of worldwide trial of potential Alzheimer’s drugs (AUDIO)

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A worldwide study is about to begin of three drugs researchers hope will prevent Alzheimer’s disease. It is being orchestrated at Washington University School of Medicine in St. Louis.

The areas where the most Alzheimer’s plaques typically form are highlighted in red and yellow above. (Courtesy; Tammie Benzinger, MD, PhD, Tyler Blazey)

The principal investigator in the trial is Doctor Randall Bateman. He says three drugs have been selected.

“The goal of the trial is to use these drugs to counteract the biological effects of Alzheimer’s disease in these individuals.”

The people in the study have inherited mutations that cause early-onset Alzheimer’s. The study will see whether any of the drugs prevent a loss of cognition in those people.

Bateman says work with two of the drugs will start right away.

“Those are antibodies which target a protein which is believed to be the cause of Alzheimer’s disease in these individuals. That protein is called amyloid beta. Each of the antibodies acts in different ways and attacks different kinds of this protein to try to counteract the effects to treat the disease. A third compound is targeting the production of this amyloid beta protein, and it’s being proposed and is likely to start likely after the trial starts.”

Bateman says the first part of the study will last about two years. In the best case scenario, one or more of the drugs would have a significant impact and help the cognition of patients.

“In that case, we would support and have already discussed with the regulatory agencies the possibility of registering that drug for use by the population. That could happen any time there is a signal that comes up. Our expectation is that’s likely, if it were to happen, to occur within the five-year period of the trial. That being said, if the drug had a really miraculous effect on cognition it could be earlier than that.”

The trial will be conducted by the Dominantly Inherited Alzheimer’s Network Trials Unit (DIAN TU) at Washington University School of Medicine. Bateman says the strategy of this trial is different from most, that might test a single drug for effectiveness against a disease…

AUDIO:  Doctor Bateman explains how this story will be conducted, 1:31

Bateman says Alzheimer’s research has come a long way to be able to do this trial.

“It’s quite an exciting time in Alzheimer’s disease (research) where we now have the tools that we can look into the brain and see the changes of Alzheimer’s disease in real-time, as it’s happening. It’s those tools which have enabled and powered the possibility of being able to design and carry out this kind of an effective trial structure.”

See more at the University’s website.

Study: compound in red wine falls short for some health benefits

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One of the purported health benefits of red wine is called into question by a study done in St. Louis.

The findings of a recent Washington University study say a compound in red wine doesn’t deliver in one area of health benefits. (Photo: Robert Boston)

The study was not of red wine but of a compound found in it, resveratrol, that is also sold as a supplement. It is thought to improve insulin sensitivity, reduce risk of heart disease and increase longevity.

Doctor Samuel Klein is the Danforth Professor of Medicine and Nutritional Science and directs the Division of Geriatrics and Nutritional Science and the Center for Applied Research Sciences at the Washington University School of Medicine.  He says studies done on animals have supported some of the claimed benefits of consuming resveratrol, “but those were in metabolically unhealthy animals. We actually studied relatively metabolically healthy people, and when you give resveratrol to metabolically healthy animals there is no beneficial effect. We found a similar result in people … if you’re relatively healthy, there’s no benefit to consuming resveratrol.”

Klein says the finding does not dispute that resveratrol could be beneficial in other situations, such as in people who have metabolic abnormalities. “Those metabolic abnormalities would be blood sugar, increased blood pressure and abnormal blood lipids. So if you have abnormalities in those areas resveratrol might be healthy. We still need more study to really evaluate that more carefully and I think those studies are actually currently underway, and so we’ll get more data in the next one or two years.”

So, Klein says there is no reason for those who take resveratrol supplements to stop based on this finding. “I think if someone is taking resveratrol and they feel it’s helping them, they should continue, but if they’re metabolically healthy to begin with there doesn’t seem to be any obvious benefit at this time.”

As for red wine drinkers, he says, “They should keep drinking as much wine as possible.”

See the study online in Cell Metabolism.

Report: former OxyContin abusers switching to heroin (AUDIO)

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A researcher says a change in the formula of OxyContin to fight its abuse has had some success, but might have only driven many of its abusers to a worse drug.

Theodore J. Cicero, PhD (photos courtesy, Washington University School of Medicine and U.S. Drug Enforcement Administration)

In 2010, OxyContin was reformulated to make it harder to abuse. Professor Theodore Cicero at Washington University in St. Louis headed up a study that asked people entering drug rehab if they had been abusing OxyContin, and what they did after that reformulation.

“What our data suggests is they did not quit taking drugs. They still remained drug users, but they switched to an alternative medication such as oxymorphone, hydromorphone, fentanyl and in some cases they switched to heroin.”

See the report in the New England Journal of Medicine.

Cicero says this and other studies show that drug abuse doesn’t just stop, it shifts from one substance to another. He says the way to fight it is to address demand.

“Interdiction efforts to stop the flow of drugs into the drug abuse culture in this country have largely failed to decrease the supply. As long as there’s this demand out there, there’s going to be some way to supply addicts with the drugs they’re looking for. Our study really begs for more research and more study of intervention and prevention techniques.”

He says the answer is to keep attacking supply, but focus more on attacking demand. “What we do as we develop policies nationwide is to recognize that yes, limiting the supply is not a bad thing, it’s a good thing, but we need to in some way or other decrease the demand side. That is a very difficult task and that’s why there’s been so little progress made in that area.”

Cicero says heroin is a far more dangerous, affordable and unpredictable drug than OxyContin. “Once you start to buy heroin, you’re buying a powder form … it’s always cut by the dealers down to as little as five percent pure. What this makes for is a great deal of difficulty in estimating what dose you’re taking. So in contrast to the legal drugs where you’re certain of dose, you are very uncertain with heroin about what dose is acceptable and what you’re going to inevitably lead to is overdose.”

The data is still being evaluated but Cicero felt it was important to get the early results out. “This trend toward increases in heroin use is important enough that we want to get the word out to physicians, regulatory officials and the public, so they can be aware of what’s happening.” 

The report appears as a letter to the editor in the New England Journal of Medicine.

AUDIO:  Mike Lear interviews Professor Theodore Cicero, PhD