ScienceDaily (Jan. 5, 2012) — A national clinical trial testing the efficacy of a novel brain tumor vaccine has begun at Wake Forest Baptist Medical Center, the only facility in the Southeast to participate. The vaccine will be tested in patients with newly diagnosed glioblastoma multiforme (GBM), the most aggressive and highest grade malignant glioma. Wake Forest Baptist will treat a minimum of 25 patients in this randomized, placebo-controlled phase II clinical trial of ICT-107. A total of 20 sites across the country are participating in the trial to test the safety and efficacy of this novel cancer vaccine.
All patients enrolled in the study will receive the current standard treatment for GBM, which includes surgery followed by radiation and chemotherapy. Two thirds of the participants will then also get the experimental vaccine treatment, which will be administered in the post radiation phase of treatment, while the others will get a "dummy," or placebo vaccine in addition to standard therapy.
"This vaccine is for newly-diagnosed patients," said Glenn Lesser, M.D., a professor of internal medicine, hematology-oncology, at Wake Forest Baptist and principal investigator for the study. "Scientifically, it's a very well designed study and we are excited to participate in this clinical trial. We've been asked to participate based on our reputation as an outstanding brain tumor center and the expertise our center has with bringing novel therapies and novel therapeutics to patients."
The approach with this particular vaccine is unique, Lesser added, because it is targeting the antigens or proteins that are present on glioma stem cells, whereas other treatment approaches mostly target differentiated tumor cells.
"The antigens used in this vaccine target the tumor stem cells -- the handful of cells that keep the tumor alive and dividing. Most of the cells we kill with standard treatment are likely not the ones driving the tumor growth. If the stem cells aren't targeted, they keep generating more tumors."
According to the biotechnology company that is conducting the trial, the Phase I clinical study of ICT-107 in GBM involved 16 newly-diagnosed patients who received the vaccine in addition to standard therapy -- surgery, radiation and chemotherapy. Those patients demonstrated a one-year overall survival of 100 percent and a two-year survival of 80 percent. Although only a small number of patients were treated, these results compare favorably with historical 61percent one-year and 26 percent two-year survival with standard care alone.
Vaccines for brain tumors are new and experimental, said Lesser, but are gaining more attention in the glioma world. "Vaccines are a way to harness the body's own defenses -- which are usually used to ward off or control infections like the flu -- to fight cancer cells instead," Lesser explained. "It is a way of presenting antigens or proteins normally found on the surface of the cancer cells to the immune system so that immune cells can seek out and kill those cancer cells anywhere in the body. This is not unlike giving a piece of clothing to a bloodhound and then letting it loose to find a missing person."
Wake Forest Baptist is also involved in another brain tumor vaccine trial for patients with low-grade or slower growing gliomas. Among the targets of both of these vaccines is a new protein found on the surface of glioma cells discovered by Waldemar Debinski, M.D., Ph.D, director of the Wake Forest Baptist Brain Tumor Center of Excellence.
"Early studies of vaccines for patients with brain tumors are showing promising results," Lesser said. "We want to help definitively determine how good these novel therapies really are for patients."
Saturday, January 7, 2012
What Determines the Capacity of Short-Term Memory?
ScienceDaily (Dec. 15, 2011) — Short-term memory plays a crucial role in how our consciousness operates. Several years ago a hypothesis has been formulated, according to which capacity of short-term memory depends in a special way on two cycles of brain electric activity. Scientists from the Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw have now demonstrated this experimentally for the first time.
A human being can consciously process from five to nine pieces of information simultaneously. During processing these pieces of information remain in the short-term memory. In 1995 researchers from Brandeis University in Waltham suggested that the capacity of short-term memory could depend on two bands of brain's electric activity: theta and gamma waves. However, only now, through carefully designed experiments conducted at the Nencki Experimental Biology Institute of the Polish Academy of Sciences (Nencki Institute) in Warsaw, it was possible to unambiguously prove that such a relationship really exists.
For an electroencephalography exam (EEG) several electrodes are placed on patient's head. The recorded brain electric signals contain waves of different frequencies, among other theta waves with the frequency of 4-7 Hz and gamma waves with the frequency of 25-50 Hz. It has been known for some time that these waves are used for retaining information in the brain. It was observed for example that the amplitudes of theta and gamma waves increased when people were forced to store more information in short-term memory.
"The hypothesis formulated by Lisman and Idiart in 1995 assumes that we are able to memorise as many 'bites' of information, as there are gamma cycles for one theta cycle. Research to date provided only indirect support for this hypothesis," say psychologist Jan Kamiński, PhD student from the Nencki Institute and main author of experiments conducted by the team of Prof. Andrzej Wróbel in cooperation with Dr. Aneta Brzezicka from the Warsaw School of Social Sciences and Humanities.
A 'bite' of information refers to its portion in memory. A 'bite' may be a number, letter, idea, situation, picture or smell. "Designing experiments on the capacity of memory one needs to be very careful not to make it too easy for the subject to group many 'bites' into one," stresses Kamiński and as an example gives the following sequence of letters: 2, 0, 1, 1. "Such four 'bites' of information are easy to group into the number corresponding to current year. Instead of four bites of information we are left with just one."
Interpreting the length of theta and gamma waves from EEG recording is not easy either. These waves are not directly visible in the EEG signal. Kamiński proposed a new method of determining them. Researchers recorded brain's electric activity in seventeen volunteers resting with closed eyes for five minutes. Next they filtered the signals and analysed not the cycles themselves but their correlations. Only based on discovered correlations the ratio of the length of theta wave to gamma wave was determined and the likely capacity of verbal short-term memory was determined.
Following the EEG recording, the volunteers, were subjected to classic short-term memory capacity test. It consisted of repeated display of longer and longer sequences of numbers. Each number was presented for one second. Then volunteers had to reconstruct the sequence from memory. At first the sequence consisted of three numbers but at the end of the exam of as many as nine. "We have observed that the longer the theta cycles, the more information 'bites' the subject was able to remember; the longer the gamma cycle, the less the subject remembered. Next we determined the correlation between the results of the tests and estimates from the EEG measurements. Just as expected the correlation turned out to be very high and it confirmed the hypothesis of Lisman and Idiart," says Kamiński.
Capacity of short-term memory impacts the effects of reasoning -- the greater the capacity, the better the effects. Currently researchers conduct studies on developing the most effective ways of training short-term memory.
A human being can consciously process from five to nine pieces of information simultaneously. During processing these pieces of information remain in the short-term memory. In 1995 researchers from Brandeis University in Waltham suggested that the capacity of short-term memory could depend on two bands of brain's electric activity: theta and gamma waves. However, only now, through carefully designed experiments conducted at the Nencki Experimental Biology Institute of the Polish Academy of Sciences (Nencki Institute) in Warsaw, it was possible to unambiguously prove that such a relationship really exists.
For an electroencephalography exam (EEG) several electrodes are placed on patient's head. The recorded brain electric signals contain waves of different frequencies, among other theta waves with the frequency of 4-7 Hz and gamma waves with the frequency of 25-50 Hz. It has been known for some time that these waves are used for retaining information in the brain. It was observed for example that the amplitudes of theta and gamma waves increased when people were forced to store more information in short-term memory.
"The hypothesis formulated by Lisman and Idiart in 1995 assumes that we are able to memorise as many 'bites' of information, as there are gamma cycles for one theta cycle. Research to date provided only indirect support for this hypothesis," say psychologist Jan Kamiński, PhD student from the Nencki Institute and main author of experiments conducted by the team of Prof. Andrzej Wróbel in cooperation with Dr. Aneta Brzezicka from the Warsaw School of Social Sciences and Humanities.
A 'bite' of information refers to its portion in memory. A 'bite' may be a number, letter, idea, situation, picture or smell. "Designing experiments on the capacity of memory one needs to be very careful not to make it too easy for the subject to group many 'bites' into one," stresses Kamiński and as an example gives the following sequence of letters: 2, 0, 1, 1. "Such four 'bites' of information are easy to group into the number corresponding to current year. Instead of four bites of information we are left with just one."
Interpreting the length of theta and gamma waves from EEG recording is not easy either. These waves are not directly visible in the EEG signal. Kamiński proposed a new method of determining them. Researchers recorded brain's electric activity in seventeen volunteers resting with closed eyes for five minutes. Next they filtered the signals and analysed not the cycles themselves but their correlations. Only based on discovered correlations the ratio of the length of theta wave to gamma wave was determined and the likely capacity of verbal short-term memory was determined.
Following the EEG recording, the volunteers, were subjected to classic short-term memory capacity test. It consisted of repeated display of longer and longer sequences of numbers. Each number was presented for one second. Then volunteers had to reconstruct the sequence from memory. At first the sequence consisted of three numbers but at the end of the exam of as many as nine. "We have observed that the longer the theta cycles, the more information 'bites' the subject was able to remember; the longer the gamma cycle, the less the subject remembered. Next we determined the correlation between the results of the tests and estimates from the EEG measurements. Just as expected the correlation turned out to be very high and it confirmed the hypothesis of Lisman and Idiart," says Kamiński.
Capacity of short-term memory impacts the effects of reasoning -- the greater the capacity, the better the effects. Currently researchers conduct studies on developing the most effective ways of training short-term memory.
Thursday, June 9, 2011
Moderate to Intense Exercise May Protect the Brain
Older people who regularly exercise at a moderate to intense level may be less likely to develop the small brain lesions, sometimes referred to as "silent strokes," that are the first sign of cerebrovascular disease, according to a new study published in the June 8, 2011, online issue of Neurology®, the medical journal of the American Academy of Neurology (AAN).
"These 'silent strokes' are more significant than the name implies, because they have been associated with an increased risk of falls and impaired mobility, memory problems and even dementia, as well as stroke," said study author Joshua Z. Willey, MD, MS, of Columbia University in New York and a member of the American Academy of Neurology. "Encouraging older people to take part in moderate to intense exercise may be an important strategy for keeping their brains healthy."
The study involved 1,238 people who had never had a stroke. Participants completed a questionnaire about how often and how intensely they exercised at the beginning of the study and then had MRI scans of their brains an average of six years later, when they were an average of 70 years old.
A total of 43 percent of the participants reported that they had no regular exercise; 36 percent engaged in regular light exercise, such as golf, walking, bowling or dancing; and 21 percent engaged in regular moderate to intense exercise, such as hiking, tennis, swimming, biking, jogging or racquetball.
The brain scans showed that 197 of the participants, or 16 percent, had small brain lesions, or infarcts, called silent strokes. People who engaged in moderate to intense exercise were 40 percent less likely to have the silent strokes than people who did no regular exercise. The results remained the same after the researchers took into account other vascular risk factors such as high blood pressure, high cholesterol and smoking. There was no difference between those who engaged in light exercise and those who did not exercise.
"Of course, light exercise has many other beneficial effects, and these results should not discourage people from doing light exercise," Willey said.
The study also showed that the benefit of moderate to intense exercise on brain health was not apparent for people with Medicaid or no health insurance. People who exercised regularly at a moderate to intense level who had Medicaid or no health insurance were no less likely to have silent infarcts than people who did no regular exercise. "It may be that the overall life difficulties for people with no insurance or on Medicaid lessens the protective effect of regular exercise," Willey said.
The study was supported by the National Institute of Neurological Disorders and Stroke.
Story Source:
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by American Academy of Neurology.
"These 'silent strokes' are more significant than the name implies, because they have been associated with an increased risk of falls and impaired mobility, memory problems and even dementia, as well as stroke," said study author Joshua Z. Willey, MD, MS, of Columbia University in New York and a member of the American Academy of Neurology. "Encouraging older people to take part in moderate to intense exercise may be an important strategy for keeping their brains healthy."
The study involved 1,238 people who had never had a stroke. Participants completed a questionnaire about how often and how intensely they exercised at the beginning of the study and then had MRI scans of their brains an average of six years later, when they were an average of 70 years old.
A total of 43 percent of the participants reported that they had no regular exercise; 36 percent engaged in regular light exercise, such as golf, walking, bowling or dancing; and 21 percent engaged in regular moderate to intense exercise, such as hiking, tennis, swimming, biking, jogging or racquetball.
The brain scans showed that 197 of the participants, or 16 percent, had small brain lesions, or infarcts, called silent strokes. People who engaged in moderate to intense exercise were 40 percent less likely to have the silent strokes than people who did no regular exercise. The results remained the same after the researchers took into account other vascular risk factors such as high blood pressure, high cholesterol and smoking. There was no difference between those who engaged in light exercise and those who did not exercise.
"Of course, light exercise has many other beneficial effects, and these results should not discourage people from doing light exercise," Willey said.
The study also showed that the benefit of moderate to intense exercise on brain health was not apparent for people with Medicaid or no health insurance. People who exercised regularly at a moderate to intense level who had Medicaid or no health insurance were no less likely to have silent infarcts than people who did no regular exercise. "It may be that the overall life difficulties for people with no insurance or on Medicaid lessens the protective effect of regular exercise," Willey said.
The study was supported by the National Institute of Neurological Disorders and Stroke.
Story Source:
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by American Academy of Neurology.
Monday, November 1, 2010
Three-Dimensional Maps Of Brain Wiring
ScienceDaily (Oct. 29, 2010) — A team of researchers at the Eindhoven University of Technology has developed a software tool that physicians can use to easily study the wiring of the brains of their patients. The tool converts MRI scans using special techniques to three-dimensional images. This now makes it possible to view a total picture of the winding roads and their contacts without having to operate. Researcher Vesna Prčkovska defended her PhD thesis on this subject last week.
To know accurately where the main nerve bundles in the brain are located is of immense importance for neurosurgeons, explains Bart ter Haar Romenij (professor of Biomedical Image Analysis, at the Department of Biomedical Engineering). As an example he cites 'deep brain stimulation', with which vibration seizures in patients with Parkinson's disease can be suppressed. "With this new tool, you can determine exactly where to place the stimulation electrode in the brain. The guiding map has been improved: because we now see the roads on the map, we know better where to stick the needle." The technique may also yield many new insights into neurological and psychiatric disorders. And it is important for brain surgeons to know in advance where the critical nerve bundles are, to avoid damaging them.
The accuracy of the tool is a great step forward. Especially intersections of nerve bundles were difficult to identify till now. Ter Haar Romenij: "You can now see for the first time the spaghetti-like structures and their connections." We are far from seeing all brain connections; there are many more smaller compounds in the brains, who are not seen by the new tool. A microscope observed them. "But you cannot, of course, dissect a live patient into slices for under a microscope," the professor smiles.
The tool was developed by TU/e researcher Anna Vilanova, with her PhD students Vesna Prčkovska, Tim Peeters and Paulo Rodrigues. A demonstration of the package can be found on YouTube (see link below). The tool is based on a recently developed technology called HARDI (High Angular Resolution Diffusion Imaging). The MRI measuring technique for HARDI was already there, the research team took care of the processing, interpretation and interactive visualization of these very complex data, so that doctors can get to work.
Bart ter Haar Romenij expects that the tool can be ready at relatively short notice for use in the hospital within a few years. "We need to validate the package. We now need to prove that the images match reality." Also, there is still work to do on the speed of the corresponding MRI scan. For a detailed view, a patient needs to be one hour in the scanner, which is too long. Moreover, the tool is already widely in use by other scientists, says the professor.
The research was supported by NWO (Dutch Organization for Scientific Research). The thesis of Vesna Prčkovska is titled: High Angular Resolution Diffusion Imaging, Processing & Visualization. She graduated on October 20, 2010.
Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.
To know accurately where the main nerve bundles in the brain are located is of immense importance for neurosurgeons, explains Bart ter Haar Romenij (professor of Biomedical Image Analysis, at the Department of Biomedical Engineering). As an example he cites 'deep brain stimulation', with which vibration seizures in patients with Parkinson's disease can be suppressed. "With this new tool, you can determine exactly where to place the stimulation electrode in the brain. The guiding map has been improved: because we now see the roads on the map, we know better where to stick the needle." The technique may also yield many new insights into neurological and psychiatric disorders. And it is important for brain surgeons to know in advance where the critical nerve bundles are, to avoid damaging them.
The accuracy of the tool is a great step forward. Especially intersections of nerve bundles were difficult to identify till now. Ter Haar Romenij: "You can now see for the first time the spaghetti-like structures and their connections." We are far from seeing all brain connections; there are many more smaller compounds in the brains, who are not seen by the new tool. A microscope observed them. "But you cannot, of course, dissect a live patient into slices for under a microscope," the professor smiles.
The tool was developed by TU/e researcher Anna Vilanova, with her PhD students Vesna Prčkovska, Tim Peeters and Paulo Rodrigues. A demonstration of the package can be found on YouTube (see link below). The tool is based on a recently developed technology called HARDI (High Angular Resolution Diffusion Imaging). The MRI measuring technique for HARDI was already there, the research team took care of the processing, interpretation and interactive visualization of these very complex data, so that doctors can get to work.
Bart ter Haar Romenij expects that the tool can be ready at relatively short notice for use in the hospital within a few years. "We need to validate the package. We now need to prove that the images match reality." Also, there is still work to do on the speed of the corresponding MRI scan. For a detailed view, a patient needs to be one hour in the scanner, which is too long. Moreover, the tool is already widely in use by other scientists, says the professor.
The research was supported by NWO (Dutch Organization for Scientific Research). The thesis of Vesna Prčkovska is titled: High Angular Resolution Diffusion Imaging, Processing & Visualization. She graduated on October 20, 2010.
Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.
Thursday, October 7, 2010
Neuroscience Research May Help Patients Recover from Brain Injury
ScienceDaily (Oct. 5, 2010) — New neuroscience research by life scientists from UCLA and Australia may potentially help people who have lost their ability to remember due to brain injury or disease.
By examining how we learn and store memories, these scientists have shown that the way the brain first captures and encodes a situation or event is quite different from how it processes subsequent similar events.
The study is published in the Sept. 29 edition of the online journal PLoS ONE, a publication of the Public Library of Science
Memories are formed in the part of the brain known as the hippocampus, a seahorse-shaped structure that plays critical roles in processing, storing and recalling information. The hippocampus is very susceptible to damage through stroke or lack of oxygen and is critically involved in Alzheimer's disease, said study co-author Michael Fanselow, a UCLA professor of psychology and a member of the UCLA Brain Research Institute.
When a memory is first formed, a small protein involved in synaptic transmission -- the NMDA receptor -- is indispensable to the process, said study co-author Bryce Vissel, a group leader of the neuroscience research program at Sydney's Garvan Institute of Medical Research. Activation of the NMDA receptor allows calcium to enter a neuron, and calcium permeability enables a chain of molecular reactions that help encode experience and consolidate memory, Fanselow and Vissel said.
Learning theorists have assumed that learning cannot occur without NMDA receptors. But the new findings show that NMDA receptors are not essential in "second-learning," when the rules of "first-learning" are applied to new yet similar scenarios. Instead, another class of receptors known as AMPA receptors, also calcium permeable, appears to take up the task.
Although the findings are still preliminary, Fanselow is optimistic about what it could mean for people whose memory formation has been impaired. "The system we are working with is one that we know is critically involved in Alzheimer's disease and other kinds of brain deficit memory impairment," he said. "This is just the start. We have uncovered a mechanism that contributes to learning and memory, and we now have to figure out what to do with it. When is it important normally? When can we harness it to take over function when the normal mechanisms aren't working? Can we use it to have some protective effect in conditions like Alzheimer's disease, where neurons are dying? Can we stimulate these pathways and keep them participating in memories?
"We can see that we might now have a target for drugs that are different from the standard class of cognitive enhancers," he added. "We can see the possibilities for different styles of training that better activate this newly discovered mechanism."
If the processes involved in second-stage learning can be mimicked therapeutically, he said, the health benefits potentially could be substantial. Fanselow and Vissel have worked closely over the last six years, along with Thomas O'Dell, a UCLA professor of physiology at the David Geffen School of Medicine at UCLA, to unravel the two different synaptic mechanisms and their meanings.
"When we started this research, we knew that the NMDA receptor was implicated in learning and memory, and we decided to see if we could mimic its process through another receptor system," said Vissel, a molecular neuroscientist. "Instead of having to create a new receptor system, we discovered one already in existence -- one that was NMDA-independent. This amounted to uncovering a whole new mechanism of learning."
By examining how we learn and store memories, these scientists have shown that the way the brain first captures and encodes a situation or event is quite different from how it processes subsequent similar events.
The study is published in the Sept. 29 edition of the online journal PLoS ONE, a publication of the Public Library of Science
Memories are formed in the part of the brain known as the hippocampus, a seahorse-shaped structure that plays critical roles in processing, storing and recalling information. The hippocampus is very susceptible to damage through stroke or lack of oxygen and is critically involved in Alzheimer's disease, said study co-author Michael Fanselow, a UCLA professor of psychology and a member of the UCLA Brain Research Institute.
When a memory is first formed, a small protein involved in synaptic transmission -- the NMDA receptor -- is indispensable to the process, said study co-author Bryce Vissel, a group leader of the neuroscience research program at Sydney's Garvan Institute of Medical Research. Activation of the NMDA receptor allows calcium to enter a neuron, and calcium permeability enables a chain of molecular reactions that help encode experience and consolidate memory, Fanselow and Vissel said.
Learning theorists have assumed that learning cannot occur without NMDA receptors. But the new findings show that NMDA receptors are not essential in "second-learning," when the rules of "first-learning" are applied to new yet similar scenarios. Instead, another class of receptors known as AMPA receptors, also calcium permeable, appears to take up the task.
Although the findings are still preliminary, Fanselow is optimistic about what it could mean for people whose memory formation has been impaired. "The system we are working with is one that we know is critically involved in Alzheimer's disease and other kinds of brain deficit memory impairment," he said. "This is just the start. We have uncovered a mechanism that contributes to learning and memory, and we now have to figure out what to do with it. When is it important normally? When can we harness it to take over function when the normal mechanisms aren't working? Can we use it to have some protective effect in conditions like Alzheimer's disease, where neurons are dying? Can we stimulate these pathways and keep them participating in memories?
"We can see that we might now have a target for drugs that are different from the standard class of cognitive enhancers," he added. "We can see the possibilities for different styles of training that better activate this newly discovered mechanism."
If the processes involved in second-stage learning can be mimicked therapeutically, he said, the health benefits potentially could be substantial. Fanselow and Vissel have worked closely over the last six years, along with Thomas O'Dell, a UCLA professor of physiology at the David Geffen School of Medicine at UCLA, to unravel the two different synaptic mechanisms and their meanings.
"When we started this research, we knew that the NMDA receptor was implicated in learning and memory, and we decided to see if we could mimic its process through another receptor system," said Vissel, a molecular neuroscientist. "Instead of having to create a new receptor system, we discovered one already in existence -- one that was NMDA-independent. This amounted to uncovering a whole new mechanism of learning."
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