This is default featured slide 1 title
This is default featured slide 2 title
This is default featured slide 3 title
This is default featured slide 4 title
This is default featured slide 5 title
 

Monthly Archives: November 2016

Precision medicine advances pediatric brain tumor diagnosis

Precision medicine — in which diagnosis and treatments are keyed to the genetic susceptibilities of individual cancers — has advanced to the point where it can now impact the care of a majority of children with brain tumors, a new study by investigators at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center suggests.

In the largest clinical study to date of genetic abnormalities in pediatric brain tumors, researchers performed clinical testing on more than 200 tumor samples and found that a majority had genetic irregularities that could influence how the disease was diagnosed and/or treated with approved drugs or agents being evaluated in clinical trials. The findings, reported online by the journal Neuro-Oncology, demonstrate that testing pediatric brain tumor tissue for genetic abnormalities is clinically feasible and that in many cases the results can guide patients’ treatment.

The need for new approaches to treating brain cancer in children is urgent, the study authors say. “Although there has been a great deal of progress over the past 30 years in improving survival rates for children with cancer, advances in pediatric brain cancer haven’t been as dramatic,” says co-lead author Pratiti Bandopadhayay, MBBS, PhD, of Dana-Farber/Boston Children’s. “In a recent study, brain tumors accounted for 25 percent of all pediatric deaths attributed to cancer. In addition, many of the current therapies can result in long-term difficulties in cognitive or physical functioning.”

Since emerging from research labs more than a decade ago, targeted therapies for cancer have significantly improved the treatment of certain types of leukemia, digestive system tumors, and breast cancer, among other malignancies. The new study is unique in that it reports on the largest collection of pediatric brain tumors to be genetically profiled as patients came to clinic. Pathologists and cytogeneticists performed the testing in a federally approved clinical laboratory — certified under Clinical Laboratory Improvement Amendments (CLIA) as the only type of labs in the United States whose findings can guide patient treatment. Dana-Farber/Boston Children’s, the researchers noted, is one of the few centers in the country to regularly analyze the genetics of patients’ pediatric brain tumors.

The researchers plumbed the genomes of 203 pediatric brain tumor samples, representing all major subtypes of the disease. They analyzed 117 of the samples with OncoPanel testing, a technology that sequences the exomes — the sections of DNA that hold the blueprints for making specific cell proteins — for irregularities in 300 cancer-related genes. They also studied 146 samples tested with OncoCopy, which examines how many copies of genes are missing or overabundant within the tumor cells. Sixty samples underwent both forms of testing ,which allowed researchers to explore whether combining the two tests was more powerful than each alone.

Of the samples tested by OncoPanel, 56 percent harbored genetic abnormalities that were clinically relevant — that could impact a patient’s diagnosis or be targeted by drugs already in clinical use or under study in clinical trials. (Many of these drugs cross the blood-brain barrier, the dense web of cells that can prevent medicines from exiting the bloodstream to reach the brain.) Among the findings:

  • Alterations were found in the gene BRAF, one of the most commonly mutated genes in pediatric brain tumors, and one for which several targeted drugs are being tested.
  • The two-pronged testing approach revealed clinically relevant abnormalities in 89 percent of medulloblastomas, which account for nearly a fifth of all brain tumors in children. Combining the two tests was found to be particularly useful for these patients.

“The importance of genomic profiling in the diagnosis and treatment of pediatric brain cancers is reflected in the World Health Organization’s recent decision to classify such tumors by the genetic alterations within them, rather than by broad tumor type” says study co-senior author Susan Chi, MD, of Dana-Farber/Boston Children’s. “Targeted therapies are likely to be most effective when they’re matched to specific abnormalities within tumor cells. Our findings show that precision medicine for pediatric brain tumors can now be a reality.”

Brain stimulation used like a scalpel

Northwestern Medicine scientists showed for the first time that non-invasive brain stimulation can be used like a scalpel, rather than like a hammer, to cause a specific improvement in precise memory.

Precise memory, rather than general memory, is critical for knowing details such as the specific color, shape and location of a building you are looking for, rather than simply knowing the part of town it’s in. This type of memory is crucial for normal functioning, and it is often lost in people with serious memory disorders.

“We show that it is possible to target the portion of the brain responsible for this type of memory and to improve it,” said lead author Joel Voss, assistant professor of medical social sciences at Northwestern University Feinberg School of Medicine. “People with brain injuries have problems with precise memory as do individuals with dementia, and so our findings could be useful in developing new treatments for these conditions.”

By stimulating the brain network responsible for spatial memory with powerful electromagnets, scientists improved the precision of people’s memory for identifying locations. This benefit lasted a full 24 hours after receiving stimulation and corresponded to changes in brain activity.

“We improved people’s memory in a very specific and important way a full day after we stimulated their brains,” Voss said.

The paper was published Jan. 19 in Current Biology.

The research enhances scientific understanding of how memory can be improved using noninvasive stimulation. Most previous studies of noninvasive brain stimulation have found only very general and short-lived effects on thinking abilities, rather than highly specific and long-lasting effects on an ability such as precise memory.

The scientists used MRI to identify memory-related brain networks then stimulated them with noninvasive electromagnetic stimulation. Detailed memory tests were used to show that this improved spatial precision memory, and EEG was used to show that these memory improvements corresponded to indicators of improved brain network function.

How rescue proteins dispose of harmful messages?

During protein synthesis, the genetic information stored in a gene’s DNA is translated into proteins. This process takes place inside veritable macromolecular machines known as ribosomes, and starts by transcribing genetic information from a cell’s DNA into transportable units known as messenger RNAs (mRNAs). These units, which contain detailed instructions for the synthesis of specific proteins, are then read and translated by ribosomes into proteins. Defective mRNAs will result in aberrant, potentially harmful proteins; an efficient process for recognizing and disposing of such mRNAs is therefore essential.

As part of their study, researchers led by Dr. Tarek Hilal from Charité’s Institute of Medical Physics and Biophysics studied mRNAs that lack ‘stop codons’ — genetic stop signs that signal the end of protein synthesis. Attempts to decode and translate such ‘nonstop-mRNAs’ leads to a complete stalling of the ribosomal machinery, resulting in effectively blocking continued protein synthesis. Using cryo-electron microscopy to study the structure of such ribosome-mRNA complexes, the researchers were able to show the manner in which special rescue proteins (Dom34 and Hbs1) recognize such stalled ribosomes, thereby initiating the splitting of the arrested complex and the degradation of the faulty mRNA. The rescue proteins recognize arrested ribosomes by detecting, and binding to, conserved locations normally occupied by mRNA. This direct competition-based approach ensures that only ribosomes with aberrant mRNAs are targeted.

“Research into the effects of aberrant mRNAs and the consequences of inadequate degradation is becoming increasingly significant,” says Dr. Hilal. He adds: “Aberrant mRNAs have been found to be particularly common in patients with neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). Gaining an understanding of the relevant cellular control mechanisms on a molecular level may help us to develop new treatment approaches.”

Help AmeriCares Save Lives in Japan

More than a week after the terrifying earthquake and tsunami struck Japan, accounts of both devastation and hope keep rolling in. As the official death toll has climbed to more than 18,000, inspiring survival stories — such as that of teenager Jin Abe and his grandmother Sumi, who were trapped in a collapsed wooden home in Ishinomaki for nine days before rescue workers heard Jin’s cries for help — have surfaced too.

Such survivors need our help now more than ever, and it’s not too late to contribute. Everyday Health members have so far donated almost $30,000 in aid to AmeriCares, a non-profit aid organization with an emergency response team on the ground in Tokyo and Sendai setting up deliveries of crucial supplies to people who lost their homes and everything they own. AmeriCares’ emergency response manager Michelle Jackson’s first-person account reaffirms why we need to keep giving.

“At one shelter, a doctor pleaded for more medicines and supplies, saying that people are getting very anxious,” says Jackson, who arrived the day after the earthquake and is overseeing a small team to identify the needs of the nearly 300,000 Japanese people living in shelters (often without heat and power) to ensure they get health care.

Jackson says that families packed into small shelters are worried about the possible spread of infectious diseases, and how they’ll get resupplied with the crucial medications they need to take regularly. For example, one woman requires seven medications to treat her hypertension, diabetes, high cholesterol, and other health problems. Since the evacuation, she’s only been able to take three. At another shelter, the AmeriCares team encountered people who haven’t had access to any of their medications for a week.

At one hospital in Fukushima (within a 12.5-mile radius of the nuclear plant), just 12 staff members of the 200 regularly employed there remain to care for the elderly patients who could not be evacuated.

It’s these people — who have lost their homes and family members and who are going without medications, blankets, and daily essentials — who gravely need our help.

To contribute money to help meet these critical needs, go to Americares.org or text “Live” to 25383 to make a $10 donation.