[Source: TGen] - The Translational Genomics Research Institute (TGen), Scottsdale Healthcare and Mayo Clinic are testing a new drug that could help cancer patients by stimulating the immune system.
Clinical trials of the drug VTX-2337 are being conducted at TGen Clinical Research Services at Scottsdale Healthcare, a partnership of Phoenix-based TGen and Scottsdale-based Scottsdale Healthcare Corp., and at Mayo Clinic in Arizona.
Dr. Ramesh Ramanathan, Medical Director of TGen Clincal Research Services at Scottsdale Healthcare, said the new drug appears promising.
"VTX-2337 is a new, novel, small molecule aimed at stimulating the immune cells in the blood, lymph nodes, and in and around the tumor. It represents an exciting new class of agents for cancer therapy with good preclinical evidence of activity," Dr. Ramanathan said.
The Phase I trial, a yearlong first-in-humans test, will study the drug's safety. If successful, a Phase II trial will test the drug's effectiveness on tumors.
A weakened immune system is often the result of advanced cancer. The hope is that this new drug will actually help enable the immune system to slow down the growth of tumors, and perhaps even shrink them, Dr. Ramanathan said.
VTX-2337 is the first drug of its kind developed by San Diego-based VentiRx Pharmaceuticals Inc. The biopharmaceutical company is focused on the development of new Toll-Like Receptor 8 (TLR8) agonists, which are small molecules that prompt a response in the body's immune system. The drugs are intended to treat cancer, respiratory and autoimmune diseases.
"VentiRx is very excited to be working with TGen, Scottsdale Healthcare and Mayo Clinic on this important and novel program," said Michael Kamdar, Executive Vice President and Chief Business Officer at VentiRx. "Entering Phase I clinical trials represents a significant milestone for VentiRx and our TLR efforts in that we have rapidly advanced into a clinical development company with a novel molecule that may play an important role and have broad application in the treatment of cancer."
VTX-2337 is a small molecule TLR8 agonist that is expected to be used in combination with standard of care for the treatment of patients with cancer. Preclinical evaluation of VTX-2337 suggests that it may play a key role in augmenting the innate arm of the immune system.
There are two broad components of the immune system, the innate arm, and the adaptive arm. Both generally aim to eliminate viruses and bacteria.
-- The innate arm senses infectious agents as they infect the body by recognizing structures they have in common, such as lipids, proteins, sugars, and nucleic acids (DNA and RNA). This is an initial rapid response, which is not precise but potent.
-- The adaptive arm of the immune system is instructed by the innate arm to devise more specific responses to unique components of the invading pathogens. This is a more precise response and takes longer, especially when an infectious agent is encountered for the first time.
The first clinical trial at TCRS at Scottsdale Healthcare will investigate the safety and pharmacology of multiple doses of VTX-2337 in patients with late-stage cancer. For more information about this clinical trial, please call Joyce Ingold, R.N., research patient care coordinator for Scottsdale Healthcare, at 480-323-1339.
The clinical trial coordinator for Mayo Clinic is Dianna Boughter, who can be reached at 480-301-9875.
"VTX-2337 is the first selective TLR8 compound to reach the clinic, and we are hopeful that modulation of the innate immune response will provide a benefit to patients in a number of oncology indications," said Dr. Robert Hershberg, Executive Vice President and Chief Medical Officer at VentiRx.
Showing posts with label Mayo Clinic. Show all posts
Showing posts with label Mayo Clinic. Show all posts
Friday, December 19, 2008
Monday, November 3, 2008
Chronic Headaches? 'Medication Overuse Headaches' Surprisingly Common
[Source: ScienceDaily] - There is a critical need to review current treatment strategies for the increasingly common problem of medication overuse headaches (MOH), according to a series of international papers in the November issue of Cephalalgia.
“MOH is associated with severe disability, unmet treatment need and little clinical data to support current management strategies” says neurology expert Professor David W Dodick from the Mayo Clinic College of Medicine, Arizona, USA.
His overview also highlights the need for greater research into the condition - in particular the role that migraine medication can play in the withdrawal process. It is accompanied by papers on how the condition is tackled in Denmark, Germany, Moldova, Japan, Spain, Canada, India and Taiwan.
MOH, previously known as rebound headache, drug-induced headache or drug-misuse headache, is a headache that occurs at least 15 days a month when patients overuse medication.
“Tolerance to the analgesic effect of the acute medication develops over time, consumption may increase and patients may show withdrawal symptoms when they stop the overused mediation” explains Professor Dodick. “We estimate that the condition affects one in every 100 adults and one in every 200 adolescents worldwide, which is a considerable number.
“For example, in the USA 60 per cent of people with chronic daily headaches attending
headache clinics have MOH. Data from a physician study suggests that it may be the third most frequent type of headache after migraines and tension-type headaches. And a Norwegian study found that people were seven times more likely to suffer from chronic headaches if they used analgesics daily or almost daily for more than a month.”
Despite being very common, there are no standardised treatment guidelines for MOH, partly due to the small number of controlled clinical trials that have addressed the treatment of this condition.
However, recent research suggests that the traditional approach of not providing new treatment strategies until patients have been through detoxification may not be the best clinical option.
“Data from recent trials indicate that treatments developed to prevent migraine may prove effective if they are used in patients with MOH before the overused medicine is withdrawn” says Professor Dodick.
“This points to the need for clinical trials to re-evaluate current strategies and find the best way forward.”
The international papers that accompany Dr Dodick’s overview show that MOH is a common problem, but the incidence, causes and treatment vary from country to country.
•Just under a quarter of the MOH cases seen at Taipei Veterans General Hospital in Taiwan are caused by people overusing cold cure preparations. Dr Shuu-Jiun Wang points out that 100 brands are currently available in Taiwan and he and his colleagues frequently see patients who have taken the whole 60ml bottle rather than the 10ml recommended dose. The problem is more common in people with lower education levels. Other common causes of MOH, which affect one in 100 Taiwanese people, include analgesics, with or without caffeine.
•Dr Zaza Katsarava from the University of Essen in Germany reports that new rules that enable healthcare plans to sign contracts with headache centres to provide day care centre withdrawal programmes have reduced MOH relapse rates in the country. He says that studies lasting from three to five years have indicated that relapse rates range from 34 to 48 per cent.
•Medication overuse is a major clinical problem and a significant source of headache-related disability in Canada, according to Professor Werner J Becker from the University of Calgary. He believes that it will take a concerted effort by the public, health professionals and healthcare funders to provide better prevention and treatment for MOH. But he points out: “It can at times be difficult for patients to find a physician who will expend the time, energy and skill to help them escape from the prison of medication overuse.”
•MOH is a serious problem in Spain, especially among middle-aged women, says Professor Julio Pascual from the University Hospital at Salamanca. He advocates an active detection and treatment approach, pointing out that in his experience this can lead to long-term improvements in more than half of MOH cases. However he adds that patients with primary headache can often be biologically, and possibly genetically, predisposed to developing chronic daily headaches regardless of analgesic use, making the drugs the consequence, not the cause of daily headaches.
•Dr Rigmor Jensen from the University of Copenhagen, Denmark, says that MOH has become a greater problem in Scandinavia over the last decade and is now the third most prevalent form of headache after tension type headaches and migraine. “A long-standing tradition of restrictive use of painkillers is changing and in general the use of simple analgesics and combination drugs has steadily increased in Denmark” she says.
The drugs that cause MOH may vary from country to country says Dr Rie Kanki from Kitasato University in Kanagawa, Japan, as their market availability may differ and people’s attitudes can be greatly affected by cultural attitudes. For example codeine and barbiturates, which are used in combination analgesics in the USA and Europe, are not available in Japan. Dr Kanki says that patient education is essential and that the growing number of headache specialists in Japan is making it easier to seek expert advice.
People living in Moldova often face psychological, cultural and religious barriers to drug use, according to Dr Ion Moldovanu from the State Medical and Pharmaceutical University in Chisinau. He reports that a clinical study of chronic migraine patients found that the two-thirds who did not have MOH expressed significantly greater phobias about the effects of drugs. Because of this they used fewer drugs than the third of patients who did have MOH.
Limited clinical data suggests that MOH is not as prevalent in India as it is in Europe and the US, reports Dr K Ravishankar from the Lilavati Hospital and Research Centre in Mumbai. He suggests this could be because people tend to use pain balms, delay medication and use alternative medicine. However, he says that more population-based studies are needed in the country, where access to healthcare is difficult and costly and headaches are not a priority compared with AIDS, Malaria and TB.
“It is clear from the papers in this issue of Cephalalgia that MOH is a common universal problem and that many countries face unique challenges due to the drugs that are available, patient and physician attitudes and the different health care delivery systems” says Dr Dodick, who will take over as Editor-in-Chief of Cephalalgia in January 2009.
“However, the overwhelming consensus is that MOH is a growing problem that has a major negative impact on health-related quality of life. It is important to identify patients with a high frequency of headaches, who are at high risk of MOH, as early as possible and initiate measures to reduce the consumption of acute pain medication.
“This is an important series of papers as it illustrates the global public health burden imposed by MOH and identifies the unique underlying factors that contribute to MOH in different countries, as well as country-specific barriers to treatment.
“The expert authors have also highlighted the need for systematic and concerted research efforts to better understand the mechanisms and most effective treatment strategies for MOH, stressing that this is a major priority in the field of headache medicine.”
“MOH is associated with severe disability, unmet treatment need and little clinical data to support current management strategies” says neurology expert Professor David W Dodick from the Mayo Clinic College of Medicine, Arizona, USA.
His overview also highlights the need for greater research into the condition - in particular the role that migraine medication can play in the withdrawal process. It is accompanied by papers on how the condition is tackled in Denmark, Germany, Moldova, Japan, Spain, Canada, India and Taiwan.
MOH, previously known as rebound headache, drug-induced headache or drug-misuse headache, is a headache that occurs at least 15 days a month when patients overuse medication.
“Tolerance to the analgesic effect of the acute medication develops over time, consumption may increase and patients may show withdrawal symptoms when they stop the overused mediation” explains Professor Dodick. “We estimate that the condition affects one in every 100 adults and one in every 200 adolescents worldwide, which is a considerable number.
“For example, in the USA 60 per cent of people with chronic daily headaches attending
headache clinics have MOH. Data from a physician study suggests that it may be the third most frequent type of headache after migraines and tension-type headaches. And a Norwegian study found that people were seven times more likely to suffer from chronic headaches if they used analgesics daily or almost daily for more than a month.”
Despite being very common, there are no standardised treatment guidelines for MOH, partly due to the small number of controlled clinical trials that have addressed the treatment of this condition.
However, recent research suggests that the traditional approach of not providing new treatment strategies until patients have been through detoxification may not be the best clinical option.
“Data from recent trials indicate that treatments developed to prevent migraine may prove effective if they are used in patients with MOH before the overused medicine is withdrawn” says Professor Dodick.
“This points to the need for clinical trials to re-evaluate current strategies and find the best way forward.”
The international papers that accompany Dr Dodick’s overview show that MOH is a common problem, but the incidence, causes and treatment vary from country to country.
•Just under a quarter of the MOH cases seen at Taipei Veterans General Hospital in Taiwan are caused by people overusing cold cure preparations. Dr Shuu-Jiun Wang points out that 100 brands are currently available in Taiwan and he and his colleagues frequently see patients who have taken the whole 60ml bottle rather than the 10ml recommended dose. The problem is more common in people with lower education levels. Other common causes of MOH, which affect one in 100 Taiwanese people, include analgesics, with or without caffeine.
•Dr Zaza Katsarava from the University of Essen in Germany reports that new rules that enable healthcare plans to sign contracts with headache centres to provide day care centre withdrawal programmes have reduced MOH relapse rates in the country. He says that studies lasting from three to five years have indicated that relapse rates range from 34 to 48 per cent.
•Medication overuse is a major clinical problem and a significant source of headache-related disability in Canada, according to Professor Werner J Becker from the University of Calgary. He believes that it will take a concerted effort by the public, health professionals and healthcare funders to provide better prevention and treatment for MOH. But he points out: “It can at times be difficult for patients to find a physician who will expend the time, energy and skill to help them escape from the prison of medication overuse.”
•MOH is a serious problem in Spain, especially among middle-aged women, says Professor Julio Pascual from the University Hospital at Salamanca. He advocates an active detection and treatment approach, pointing out that in his experience this can lead to long-term improvements in more than half of MOH cases. However he adds that patients with primary headache can often be biologically, and possibly genetically, predisposed to developing chronic daily headaches regardless of analgesic use, making the drugs the consequence, not the cause of daily headaches.
•Dr Rigmor Jensen from the University of Copenhagen, Denmark, says that MOH has become a greater problem in Scandinavia over the last decade and is now the third most prevalent form of headache after tension type headaches and migraine. “A long-standing tradition of restrictive use of painkillers is changing and in general the use of simple analgesics and combination drugs has steadily increased in Denmark” she says.
The drugs that cause MOH may vary from country to country says Dr Rie Kanki from Kitasato University in Kanagawa, Japan, as their market availability may differ and people’s attitudes can be greatly affected by cultural attitudes. For example codeine and barbiturates, which are used in combination analgesics in the USA and Europe, are not available in Japan. Dr Kanki says that patient education is essential and that the growing number of headache specialists in Japan is making it easier to seek expert advice.
People living in Moldova often face psychological, cultural and religious barriers to drug use, according to Dr Ion Moldovanu from the State Medical and Pharmaceutical University in Chisinau. He reports that a clinical study of chronic migraine patients found that the two-thirds who did not have MOH expressed significantly greater phobias about the effects of drugs. Because of this they used fewer drugs than the third of patients who did have MOH.
Limited clinical data suggests that MOH is not as prevalent in India as it is in Europe and the US, reports Dr K Ravishankar from the Lilavati Hospital and Research Centre in Mumbai. He suggests this could be because people tend to use pain balms, delay medication and use alternative medicine. However, he says that more population-based studies are needed in the country, where access to healthcare is difficult and costly and headaches are not a priority compared with AIDS, Malaria and TB.
“It is clear from the papers in this issue of Cephalalgia that MOH is a common universal problem and that many countries face unique challenges due to the drugs that are available, patient and physician attitudes and the different health care delivery systems” says Dr Dodick, who will take over as Editor-in-Chief of Cephalalgia in January 2009.
“However, the overwhelming consensus is that MOH is a growing problem that has a major negative impact on health-related quality of life. It is important to identify patients with a high frequency of headaches, who are at high risk of MOH, as early as possible and initiate measures to reduce the consumption of acute pain medication.
“This is an important series of papers as it illustrates the global public health burden imposed by MOH and identifies the unique underlying factors that contribute to MOH in different countries, as well as country-specific barriers to treatment.
“The expert authors have also highlighted the need for systematic and concerted research efforts to better understand the mechanisms and most effective treatment strategies for MOH, stressing that this is a major priority in the field of headache medicine.”
Monday, September 15, 2008
International TGen-led team finds link between brain protein and Alzheimer's disease
[Source: TGen] - Investigators at the Translational Genomics Research Institute (TGen) today announced a link between the brain protein KIBRA and Alzheimer's disease, a discovery that could lead to promising new treatments for this memory-robbing disorder.
The new discovery builds on a previous TGen-led study published in the prestigious journal Science, which showed a genetic link between KIBRA and memory in healthy adults.
In the new study, TGen researchers found that carriers of a memory-enhancing flavor of the KIBRA gene had a 25 percent lower risk of developing Alzheimer's disease.
The findings were reported Saturday in the online edition of Neurobiology of Aging, a Philadelphia-based peer-review journal that generally focuses on how aging affects the nervous system.
"This research suggests that KIBRA, and possibly some of the proteins with which it interacts, may play a role in Alzheimer's disease," said Dr. Matthew Huentelman, an investigator in TGen's Neurogenomics Division and the paper's senior author.
The critical difference found in KIBRA, a protein so named because it is commonly found in the kidneys and brain, was that those individuals with the T-allele gene were less likely to develop Alzheimer's than those with the C-allele. Alleles are those genetic markers – A, C, G or T – that determine such inherited traits as eye and hair color, or susceptibility to disease.
"We are now beginning to dig deeper regarding the genetic sequence of KIBRA in individuals carrying, and not carrying, the T-allele. We believe this variation causes a potential lifelong difference in the total levels of KIBRA in the brain, and that this may influence one's risk for Alzheimer's," said Huentelman, who led a team that worked with several Arizona institutions, as well as other national and international universities and research institutions.
Dr. Eric Reiman, clinical director of TGen's Neurogenomics Division and executive director of the Banner Alzheimer's Institute, said, "This study suggests a link between the inherited genes involved in normal human memory and the predisposition to Alzheimer's disease."
"It provides promising new targets at which to aim new treatments to stave off Alzheimer's and improve memory," said Reiman, who also is director of the Arizona Alzheimer's Consortium and a contributor to the study.
The findings announced today are built on a 2006 study led by collaborative teams from Arizona and Zurich, Switzerland, and published in the journal Science. That pioneering TGen research revealed a link between KIBRA and memory, in which healthy adults with the KIBRA T-allele performed better on memory tests than those without this gene.
In the most recent analysis, Huentelman's team confirmed a link between KIBRA and Alzheimer's in three different ways:
Using TGen's powerful analytic tools to find a genetic association between the KIBRA gene and Alzheimer's disease, comparing more than 1,700 living and deceased people, with and without the disorder.
Using gene expression tools to find that KIBRA, and genes for other molecules that interact with KIBRA, were significantly altered in the neurons of people who had Alzheimer's disease, but not in individuals without the disorder.
Using a brain imaging technique called positron emission tomography (PET) to find that cognitively-normal, late-middle-aged people lacking the protective T-allele gene had reduced activity in parts of the brain usually affected by Alzheimer's.
Genetic association studyIn a study of 702 deceased persons diagnosed with Alzheimer's, and 1,026 living and deceased persons with and without Alzheimer's, researchers found that non-carriers of the KIBRA T-allele had increased risk of late-onset Alzheimer's.
The genotyped samples came from five centers, including three European organizations representing German, Dutch and Norwegian populations.
Gene expression studyThe gene expression study examined tissues from six regions of the brain among 47 deceased individuals. The brain tissue samples were provided by three Alzheimer's disease centers: Washington University in St. Louis, Mo.; Duke University in Durham, N.C.; and Sun Health Research Institute in Sun City, Ariz.
KIBRA, and a subset of other molecules directly interacting with it, were significantly altered in regions of the brain involved in Alzheimer's disease pathology. The regions investigated included the hippocampus, entorhinal cortex, posterior cingulate cortex, middle temporal gyrus, and superior frontal gyrus. However, they were not altered in a region of the brain typically unaffected by the disease -- the primary visual cortex.
Positron Emission Tomography scans
PET scans of 67 non-carriers of the KIBRA T-allele, and 69 carriers -- all with close relatives diagnosed with Alzheimer's -- showed that non-carriers exhibited, on average, similar alterations in the metabolic activity of key brain regions known to be altered in the earliest stages of the disease. All 136 individuals were mentally-normal, late-middle-aged Phoenix-area volunteers solicited from newspaper advertisements. They ranged in age from 47 to 68, with an average age of 55.
Scans showed that individuals without the KIBRA T-allele -- those with only KIBRA C-alleles from their mother and from their father -- had less metabolic brain activity when compared to those individuals carrying the T-allele -- from either their mother or father, or both. These differences were found in the precuneus and posterior cingulated regions of the brain affected in the earliest stages of Alzheimer's.
Previous work led by Reiman illustrated a similar finding when individuals were grouped according to whether they carried the most powerful genetic indicator for Alzheimer's -- the epsilon 4 allele of apolipoprotein E. In the current study, the effects of this allele were controlled for, yet similar observations were made. This suggests that KIBRA may play a role in a convergent biological risk pathway for the disease.
###
ParticipantsTGen's Jason Corneveaux and Dr. Winnie S. Liang were the paper's first authors.
Other Arizona participants in the study were: Arizona Alzheimer's Consortium, Banner Alzheimer's Institute, Sun Health Research Institute, St. Joseph's Hospital, Arizona State University, Mayo Clinic Arizona, and the University of Arizona's departments of Psychiatry, Radiology, and its Evelyn F. McKnight Brain Institute.
Other U.S. participants included: University of Miami, the National Institute on Aging, and the Mayo Clinic Rochester.
International collaborators included: the Netherlands Institute for Neurosciences, Netherlands; the Norwegian University of Science and Technology, and St. Olav's Hospital, Norway; the University of Bonn, Germany; and the University of Basel, Switzerland.
The new discovery builds on a previous TGen-led study published in the prestigious journal Science, which showed a genetic link between KIBRA and memory in healthy adults.
In the new study, TGen researchers found that carriers of a memory-enhancing flavor of the KIBRA gene had a 25 percent lower risk of developing Alzheimer's disease.
The findings were reported Saturday in the online edition of Neurobiology of Aging, a Philadelphia-based peer-review journal that generally focuses on how aging affects the nervous system.
"This research suggests that KIBRA, and possibly some of the proteins with which it interacts, may play a role in Alzheimer's disease," said Dr. Matthew Huentelman, an investigator in TGen's Neurogenomics Division and the paper's senior author.
The critical difference found in KIBRA, a protein so named because it is commonly found in the kidneys and brain, was that those individuals with the T-allele gene were less likely to develop Alzheimer's than those with the C-allele. Alleles are those genetic markers – A, C, G or T – that determine such inherited traits as eye and hair color, or susceptibility to disease.
"We are now beginning to dig deeper regarding the genetic sequence of KIBRA in individuals carrying, and not carrying, the T-allele. We believe this variation causes a potential lifelong difference in the total levels of KIBRA in the brain, and that this may influence one's risk for Alzheimer's," said Huentelman, who led a team that worked with several Arizona institutions, as well as other national and international universities and research institutions.
Dr. Eric Reiman, clinical director of TGen's Neurogenomics Division and executive director of the Banner Alzheimer's Institute, said, "This study suggests a link between the inherited genes involved in normal human memory and the predisposition to Alzheimer's disease."
"It provides promising new targets at which to aim new treatments to stave off Alzheimer's and improve memory," said Reiman, who also is director of the Arizona Alzheimer's Consortium and a contributor to the study.
The findings announced today are built on a 2006 study led by collaborative teams from Arizona and Zurich, Switzerland, and published in the journal Science. That pioneering TGen research revealed a link between KIBRA and memory, in which healthy adults with the KIBRA T-allele performed better on memory tests than those without this gene.
In the most recent analysis, Huentelman's team confirmed a link between KIBRA and Alzheimer's in three different ways:
Using TGen's powerful analytic tools to find a genetic association between the KIBRA gene and Alzheimer's disease, comparing more than 1,700 living and deceased people, with and without the disorder.
Using gene expression tools to find that KIBRA, and genes for other molecules that interact with KIBRA, were significantly altered in the neurons of people who had Alzheimer's disease, but not in individuals without the disorder.
Using a brain imaging technique called positron emission tomography (PET) to find that cognitively-normal, late-middle-aged people lacking the protective T-allele gene had reduced activity in parts of the brain usually affected by Alzheimer's.
Genetic association studyIn a study of 702 deceased persons diagnosed with Alzheimer's, and 1,026 living and deceased persons with and without Alzheimer's, researchers found that non-carriers of the KIBRA T-allele had increased risk of late-onset Alzheimer's.
The genotyped samples came from five centers, including three European organizations representing German, Dutch and Norwegian populations.
Gene expression studyThe gene expression study examined tissues from six regions of the brain among 47 deceased individuals. The brain tissue samples were provided by three Alzheimer's disease centers: Washington University in St. Louis, Mo.; Duke University in Durham, N.C.; and Sun Health Research Institute in Sun City, Ariz.
KIBRA, and a subset of other molecules directly interacting with it, were significantly altered in regions of the brain involved in Alzheimer's disease pathology. The regions investigated included the hippocampus, entorhinal cortex, posterior cingulate cortex, middle temporal gyrus, and superior frontal gyrus. However, they were not altered in a region of the brain typically unaffected by the disease -- the primary visual cortex.
Positron Emission Tomography scans
PET scans of 67 non-carriers of the KIBRA T-allele, and 69 carriers -- all with close relatives diagnosed with Alzheimer's -- showed that non-carriers exhibited, on average, similar alterations in the metabolic activity of key brain regions known to be altered in the earliest stages of the disease. All 136 individuals were mentally-normal, late-middle-aged Phoenix-area volunteers solicited from newspaper advertisements. They ranged in age from 47 to 68, with an average age of 55.
Scans showed that individuals without the KIBRA T-allele -- those with only KIBRA C-alleles from their mother and from their father -- had less metabolic brain activity when compared to those individuals carrying the T-allele -- from either their mother or father, or both. These differences were found in the precuneus and posterior cingulated regions of the brain affected in the earliest stages of Alzheimer's.
Previous work led by Reiman illustrated a similar finding when individuals were grouped according to whether they carried the most powerful genetic indicator for Alzheimer's -- the epsilon 4 allele of apolipoprotein E. In the current study, the effects of this allele were controlled for, yet similar observations were made. This suggests that KIBRA may play a role in a convergent biological risk pathway for the disease.
###
ParticipantsTGen's Jason Corneveaux and Dr. Winnie S. Liang were the paper's first authors.
Other Arizona participants in the study were: Arizona Alzheimer's Consortium, Banner Alzheimer's Institute, Sun Health Research Institute, St. Joseph's Hospital, Arizona State University, Mayo Clinic Arizona, and the University of Arizona's departments of Psychiatry, Radiology, and its Evelyn F. McKnight Brain Institute.
Other U.S. participants included: University of Miami, the National Institute on Aging, and the Mayo Clinic Rochester.
International collaborators included: the Netherlands Institute for Neurosciences, Netherlands; the Norwegian University of Science and Technology, and St. Olav's Hospital, Norway; the University of Bonn, Germany; and the University of Basel, Switzerland.
Friday, September 5, 2008
Improved Statistical Tool To Rank Sickest Patients Waiting For Liver Transplants
[Source: ScienceDaily] - Mayo Clinic researchers have developed an improved statistical model that could help ensure that the sickest patients receive liver transplants first.
Researchers found that including serum sodium concentration in the statistical model now used could reduce by 7 percent the number of patients (as many as 50 people) who die each year while waiting for a liver transplant. Serum sodium levels can be measured with a blood test.
The study will be published in the Sept. 4, 2008, issue of the New England Journal of Medicine.
"The subset of patients with the lowest sodium blood levels is not served well by the current system," says W. Ray Kim, M.D., liver transplant physician at Mayo Clinic and lead researcher on the study. Low serum sodium occurs in patients with advanced liver disease, who frequently have a large amount of ascites (fluid in abdomen), a serious complication of liver cirrhosis.
In the United States, the United Network for Organ Sharing (UNOS), a nonprofit, scientific and educational organization, administers the distribution of organs from deceased donors to patients waiting for transplants.
In 2001, Mayo Clinic researchers developed the formula used to rank patients waiting for livers from deceased donors. Called the Model for End-Stage Liver Disease (MELD), it was adopted by UNOS in 2002. The highest MELD scores indicate the sickest patients, who are placed at the top of the transplant waiting list.
"The addition of sodium to MELD would be a relatively modest improvement," says Dr. Kim.
"Since low serum sodium does not affect the majority of patients, we didn't pick it up in our original work. However, we have discovered that in those affected, low sodium has a substantial impact on mortality. This impact is particularly large in patients with low MELD, who would be placed low on the waiting list under the current system."
How the study was done. In this observational study, researchers analyzed patient data collected upon UNOS registration for liver transplantation. In 2005, there were 6,769 patients placed on the list. Of those, 422 died and 1,781 underwent liver transplant within 90 days. Based on these data, researchers created a new statistical model that incorporates serum sodium and MELD.
The new model was verified by using waiting-patient data from 2006, when 477 patients died within three months of placement on the waiting list. "By factoring in sodium, researchers predicted that about 7 percent of deaths of waiting patients would have had considerably higher priority for transplant, and it may have prevented their deaths," says Dr. Kim.
More than 400 patients receive liver transplants at Mayo Clinic's sites in Minnesota, Florida and Arizona each year. Mayo Clinic is the most experienced liver transplant center in the nation, with some of the highest survival rates in the world.
Other Mayo Clinic researchers involved in this study include Walter Kremers, Ph.D.; Russell Wiesner, M.D.; Patrick Kamath, M.D.; Joanne Benson; and Terry Therneau, Ph.D.
Researchers found that including serum sodium concentration in the statistical model now used could reduce by 7 percent the number of patients (as many as 50 people) who die each year while waiting for a liver transplant. Serum sodium levels can be measured with a blood test.
The study will be published in the Sept. 4, 2008, issue of the New England Journal of Medicine.
"The subset of patients with the lowest sodium blood levels is not served well by the current system," says W. Ray Kim, M.D., liver transplant physician at Mayo Clinic and lead researcher on the study. Low serum sodium occurs in patients with advanced liver disease, who frequently have a large amount of ascites (fluid in abdomen), a serious complication of liver cirrhosis.
In the United States, the United Network for Organ Sharing (UNOS), a nonprofit, scientific and educational organization, administers the distribution of organs from deceased donors to patients waiting for transplants.
In 2001, Mayo Clinic researchers developed the formula used to rank patients waiting for livers from deceased donors. Called the Model for End-Stage Liver Disease (MELD), it was adopted by UNOS in 2002. The highest MELD scores indicate the sickest patients, who are placed at the top of the transplant waiting list.
The MELD score is based on three standard laboratory tests:
Total serum bilirubin concentration, indicated by jaundice- International normalized ratio for the prothrombin time, which measures the blood's ability to clot
- Serum creatinine concentration, an indicator of renal (kidney) function
"The addition of sodium to MELD would be a relatively modest improvement," says Dr. Kim.
"Since low serum sodium does not affect the majority of patients, we didn't pick it up in our original work. However, we have discovered that in those affected, low sodium has a substantial impact on mortality. This impact is particularly large in patients with low MELD, who would be placed low on the waiting list under the current system."
How the study was done. In this observational study, researchers analyzed patient data collected upon UNOS registration for liver transplantation. In 2005, there were 6,769 patients placed on the list. Of those, 422 died and 1,781 underwent liver transplant within 90 days. Based on these data, researchers created a new statistical model that incorporates serum sodium and MELD.
The new model was verified by using waiting-patient data from 2006, when 477 patients died within three months of placement on the waiting list. "By factoring in sodium, researchers predicted that about 7 percent of deaths of waiting patients would have had considerably higher priority for transplant, and it may have prevented their deaths," says Dr. Kim.
More than 400 patients receive liver transplants at Mayo Clinic's sites in Minnesota, Florida and Arizona each year. Mayo Clinic is the most experienced liver transplant center in the nation, with some of the highest survival rates in the world.
Other Mayo Clinic researchers involved in this study include Walter Kremers, Ph.D.; Russell Wiesner, M.D.; Patrick Kamath, M.D.; Joanne Benson; and Terry Therneau, Ph.D.
Monday, July 14, 2008
Mayo Clinic Proceedings examines link between bacteria in the digestive system and obesity
[Source: EUREKALERT , John Murphy, newsbureau@mayo.edu] - Obesity is more than a cosmetic concern because it increases a persons risk for developing high blood pressure, diabetes and many other serious health problems. Its well understood that consuming more calories than you expend through exercise and daily activities causes weight gain. But with about one in every three American adults now considered obese, researchers are attempting to identify additional factors that affect a persons tendency to gain and retain excess weight. In the April issue of Mayo Clinic Proceedings, researchers from Mayo Clinic Arizona and Arizona State University examine the role that bacteria in the human gastrointestinal tract play in regulating weight and the development of obesity.
Known as gut microbiota, the trillions of bacteria that populate the human gastrointestinal tract perform a variety of chores. These friendly microbes help extract calories from what we eat, help store these calories for later use, and provide energy and nutrients for the production of new bacteria to continue this work.
According to John DiBaise, M.D., a Mayo Clinic Arizona gastroenterologist and lead author of the Mayo Clinic Proceedings article, several animal studies suggest that gut microbiota are involved in regulating weight and that modifying these bacteria could one day be a treatment option for obesity.
One study cited by the authors observed that young, conventionally-reared mice have a significantly higher body fat content than a laboratory-bred, germ-free strain of mice that lack these bacteria, even though they consumed less food than their germ-free counterparts. When the same research group transplanted gut microbiota from normal mice into germ-free mice, the germ-free mice experienced a 60 percent increase in body fat within two weeks, without any increase in food consumption or obvious differences in energy expenditure.
Another animal study reviewed by the authors focused on the gene content of the gut microbiota in mice. Finding more end products of fermentation and fewer calories in the feces of obese mice led researchers to speculate that the gut microbiota in the obese mice help extract additional calories from ingested food.
These results suggest that differences exist in the gut microbiota of obese versus lean mice, raising the possibility that the manipulation of gut microbiota could be a useful strategy for regulating energy balance in obese people, says Dr. DiBaise.
Although information on the link between gut microbiota and obesity in human subjects is more limited, the authors present some evidence supporting this connection. One study cited placed 12 obese participants in a weight-loss program for a year, randomly assigning them to either a fat-restricted or carbohydrate-restricted, low-calorie diet. Researchers noted distinct differences between lean and obese participants when they monitored the type and number of bacteria found in participants stool samples before and after the diet changes.
Another study cited followed children from birth to age 7 and analyzed stool samples collected at 6 and 12 months. The children who were normal weight at age 7 had distinctly different bacteria in their samples from those collected from overweight-obese children, suggesting that differences in the composition of the gut microbiota precede overweight-obesity.
Dr. DiBaise says that much more research is needed to clarify a number of issues related to the relationship between the gut microbiota and obesity. Future studies need to establish whether the small changes in caloric extraction seen in recent studies can produce measurable weight differences in humans.
Known as gut microbiota, the trillions of bacteria that populate the human gastrointestinal tract perform a variety of chores. These friendly microbes help extract calories from what we eat, help store these calories for later use, and provide energy and nutrients for the production of new bacteria to continue this work.
According to John DiBaise, M.D., a Mayo Clinic Arizona gastroenterologist and lead author of the Mayo Clinic Proceedings article, several animal studies suggest that gut microbiota are involved in regulating weight and that modifying these bacteria could one day be a treatment option for obesity.
One study cited by the authors observed that young, conventionally-reared mice have a significantly higher body fat content than a laboratory-bred, germ-free strain of mice that lack these bacteria, even though they consumed less food than their germ-free counterparts. When the same research group transplanted gut microbiota from normal mice into germ-free mice, the germ-free mice experienced a 60 percent increase in body fat within two weeks, without any increase in food consumption or obvious differences in energy expenditure.
Another animal study reviewed by the authors focused on the gene content of the gut microbiota in mice. Finding more end products of fermentation and fewer calories in the feces of obese mice led researchers to speculate that the gut microbiota in the obese mice help extract additional calories from ingested food.
These results suggest that differences exist in the gut microbiota of obese versus lean mice, raising the possibility that the manipulation of gut microbiota could be a useful strategy for regulating energy balance in obese people, says Dr. DiBaise.
Although information on the link between gut microbiota and obesity in human subjects is more limited, the authors present some evidence supporting this connection. One study cited placed 12 obese participants in a weight-loss program for a year, randomly assigning them to either a fat-restricted or carbohydrate-restricted, low-calorie diet. Researchers noted distinct differences between lean and obese participants when they monitored the type and number of bacteria found in participants stool samples before and after the diet changes.
Another study cited followed children from birth to age 7 and analyzed stool samples collected at 6 and 12 months. The children who were normal weight at age 7 had distinctly different bacteria in their samples from those collected from overweight-obese children, suggesting that differences in the composition of the gut microbiota precede overweight-obesity.
Dr. DiBaise says that much more research is needed to clarify a number of issues related to the relationship between the gut microbiota and obesity. Future studies need to establish whether the small changes in caloric extraction seen in recent studies can produce measurable weight differences in humans.
Tuesday, April 22, 2008
Experts get $6.6 mil for Alzheimer's work
[Source: Ken Alltucker, The Arizona Republic] - Scientists at Banner Alzheimer's Institute and the Mayo Clinic in Arizona have secured a $6.6 million federal grant to study the brains of people who carry a genetic risk for developing Alzheimer's disease.
The National Institute on Aging grant will allow researchers to use brain-scanning technology to monitor the brains of 200 healthy people who either carry or lack APOE4, a critical gene linked to Alzheimer's disease found in one of four people.
If local researchers can track brain changes before participants get Alzheimer's, it may yield valuable clues to develop a vaccine for a disease that afflicts 5.2 million Americans.
"We want to detect early brain changes in relation to different levels of risk for Alzheimer's," said Dr. Eric M. Reiman, executive director of Banner Alzheimer's Institute and the study's principal investigator. "We believe the data and findings will become increasingly important over time."
The grant is the latest federal-funding coup for Arizona scientists studying Alzheimer's.
The Arizona Alzheimer's Consortium, a group of seven Arizona research groups including Banner and Mayo Clinic, has secured more than $75 million in research grants over the past decade.
Other Arizona consortium members aiding the brain-scanning study include Arizona State University, University of Arizona and the Translational Genomics Research Institute.
Reiman and Dr. Richard Caselli, chairman of Mayo Arizona's department of neurology, had already secured more than $6 million in federal grants over the past nine years for the study.
The new grant will allow researchers to increase the study size from 160 people to 200. A majority of the 40 new recruits will likely be of Latino descent, giving the study a more robust mix of ethnicities.
Researchers will use positron-emission tomography and magnetic-resonance-imaging scans to track and predict the loss of memory and thinking ability of its patients.
The National Institute on Aging grant will allow researchers to use brain-scanning technology to monitor the brains of 200 healthy people who either carry or lack APOE4, a critical gene linked to Alzheimer's disease found in one of four people.
If local researchers can track brain changes before participants get Alzheimer's, it may yield valuable clues to develop a vaccine for a disease that afflicts 5.2 million Americans.
"We want to detect early brain changes in relation to different levels of risk for Alzheimer's," said Dr. Eric M. Reiman, executive director of Banner Alzheimer's Institute and the study's principal investigator. "We believe the data and findings will become increasingly important over time."
The grant is the latest federal-funding coup for Arizona scientists studying Alzheimer's.
The Arizona Alzheimer's Consortium, a group of seven Arizona research groups including Banner and Mayo Clinic, has secured more than $75 million in research grants over the past decade.
Other Arizona consortium members aiding the brain-scanning study include Arizona State University, University of Arizona and the Translational Genomics Research Institute.
Reiman and Dr. Richard Caselli, chairman of Mayo Arizona's department of neurology, had already secured more than $6 million in federal grants over the past nine years for the study.
The new grant will allow researchers to increase the study size from 160 people to 200. A majority of the 40 new recruits will likely be of Latino descent, giving the study a more robust mix of ethnicities.
Researchers will use positron-emission tomography and magnetic-resonance-imaging scans to track and predict the loss of memory and thinking ability of its patients.
Wednesday, April 16, 2008
Multiple Myeloma Research Consortium and Sunesis Pharmaceuticals Present Data On SNS-032 At American Association of Cancer Research Annual Meeting
[Source Genetic Engineering News] - The Multiple Myeloma Research Consortium (MMRC) in collaboration with Sunesis Pharmaceuticals presented preclinical data on the activity of Sunesis' cell cycle inhibitor, SNS-032, in multiple myeloma cell assays and animal models. The data was presented orally at the 2008 Annual Meeting of the American Association of Cancer Research.
Suzanne Trudel, MD, Assistant Professor, University Health Network (UHN) in Toronto, Canada, and Project Leader for the MMRC Validation Team, which performed the studies, presented data showing that SNS-032 demonstrated growth inhibitory effects in different multiple myeloma cell lines as well as myeloma cells prepared from patient samples. In addition, SNS-032 demonstrated activity in a transgenic animal model with multiple myeloma characteristics similar to those observed in humans. These studies, resulting from extensive collaborative efforts between the MMRC, Emory University's Winship Cancer Institute and Sunesis demonstrated preclinical, single-agent activity of SNS-032 in multiple myeloma and support its further investigation as a potential therapeutic candidate. SNS-032, a potent and selective inhibitor of cyclin-dependent kinases (CDKs) 2, 7 and 9, is currently in a Phase 1 clinical trial in patients with chronic lymphocytic leukemia (CLL) or multiple myeloma.
"Sunesis is proud to collaborate with the MMRC and the Validation Team to advance this important clinical program in the quest for a cure for multiple myeloma. It highlights the importance of collaborations between industry and oncology field experts in order to more rapidly and appropriately evaluate new treatments for cancer therapy," said Rachael Hawtin, PhD, Associate Director, Biology, Sunesis.
The MMRC Validation Team, composed of leading myeloma scientists from the Dana-Farber Cancer Institute, Mayo Clinic-Scottsdale, H. Lee Moffitt Cancer Center and UHN, tests compounds in a variety of multiple myeloma cell-based systems and animal models. The team represents a unique research and development model, typically not included in foundation activities, with the major goal of prioritizing compounds to enter myeloma clinical trials by testing their preclinical activity in myeloma specific systems.
"The team is very encouraged by the success of the first project to enter the MMRC validation model and the selection of this research as an oral presentation at the AACR. The results demonstrate modest single agent activity in mice," says Dr. Trudel
Suzanne Trudel, MD, Assistant Professor, University Health Network (UHN) in Toronto, Canada, and Project Leader for the MMRC Validation Team, which performed the studies, presented data showing that SNS-032 demonstrated growth inhibitory effects in different multiple myeloma cell lines as well as myeloma cells prepared from patient samples. In addition, SNS-032 demonstrated activity in a transgenic animal model with multiple myeloma characteristics similar to those observed in humans. These studies, resulting from extensive collaborative efforts between the MMRC, Emory University's Winship Cancer Institute and Sunesis demonstrated preclinical, single-agent activity of SNS-032 in multiple myeloma and support its further investigation as a potential therapeutic candidate. SNS-032, a potent and selective inhibitor of cyclin-dependent kinases (CDKs) 2, 7 and 9, is currently in a Phase 1 clinical trial in patients with chronic lymphocytic leukemia (CLL) or multiple myeloma.
"Sunesis is proud to collaborate with the MMRC and the Validation Team to advance this important clinical program in the quest for a cure for multiple myeloma. It highlights the importance of collaborations between industry and oncology field experts in order to more rapidly and appropriately evaluate new treatments for cancer therapy," said Rachael Hawtin, PhD, Associate Director, Biology, Sunesis.
The MMRC Validation Team, composed of leading myeloma scientists from the Dana-Farber Cancer Institute, Mayo Clinic-Scottsdale, H. Lee Moffitt Cancer Center and UHN, tests compounds in a variety of multiple myeloma cell-based systems and animal models. The team represents a unique research and development model, typically not included in foundation activities, with the major goal of prioritizing compounds to enter myeloma clinical trials by testing their preclinical activity in myeloma specific systems.
"The team is very encouraged by the success of the first project to enter the MMRC validation model and the selection of this research as an oral presentation at the AACR. The results demonstrate modest single agent activity in mice," says Dr. Trudel
Wednesday, April 2, 2008
Retired NFL Players At Increased Risk For Heart Problems, Mayo Clinic Finds
[Source: ScienceDaily ] - Screening for cardiovascular problems in elite-level football players should begin in high school and continue throughout the lives of college and professional players. Mayo Clinic physicians based that conclusion on the results of their new study of the cardiovascular health of 233 retired National Football League (NFL) players.
The Mayo data showed that 82 percent of NFL players under age 50 had abnormal narrowing and blockages in arteries, compared to the general population of the same age. This finding suggests that the former athletes face increased risk of experiencing high blood pressure, heart attack or stroke. The report on research conducted by the Mayo Clinic Arizona group will be presented next week at the American College of Cardiology Annual Scientific Session in Chicago.
Significance of the Mayo Clinic Study
This is the first and largest study to measure comprehensive cardiovascular performance measures on retired NFL athletes, ages 35 to 65. Its findings add to the emerging portrait of poor heart health among this group of retired athletes. The findings also suggest that players as young as high school age who are engaged in serious competitive-conference level of training and play may benefit from regular cardiovascular screening. "What we hope to emphasize with our findings is that all NFL players -- retired or not -- need to undergo cardiovascular health evaluation because they may have changes in heart and vessel conditions that we can treat so they don't experience problems later in life," says Robert Hurst, M.D., Mayo Clinic cardiologist and lead researcher.
Adds chair of cardiovascular diseases at Mayo Clinic in Arizona and researcher Bijoy Khandheria, M.D.: "Cardiovascular screening is readily available and needs to become a routine part of serious football players' health care, beginning at the high school level for those who are engaged in a highly competitive and rigorous level of training and play."
Football and Heart Problems
Previous research by various institutions and investigators in recent years showed concerning health trends:
- Retired NFL players are more prone to obesity and obstructive sleep apnea than the general population.
Retired NFL players have an increased rate of metabolic syndrome, a condition increasingly linked to excess weight and lack of activity, which can lead to type 2 diabetes.
Higher mortality is reported in linemen, as compared to people in the general population of the same age who are not professional football players.
Research is needed to determine the causes.
Observing these serious trends, the Mayo Clinic researchers undertook the study to define vascular health and, by association, cardiovascular risk in retired NFL players. To determine vascular health, the Mayo team conducted multisite screening events with the help of players' associations. Investigators measured the internal diameter of the carotid artery. They also assessed plaque deposits which can block blood flow.
The most striking results showed that:
In players less than 50 years old, 82 percent had either plaque or carotid narrowing greater than the 75th percentile of the population, adjusted for age, sex and race. This represents a dangerous level of narrowing that could lead to a catastrophic reduction of blood flow resulting in heart attack or stroke.
Heart disease had not been previously diagnosed in these players. Nor had they experienced symptoms of heart disease, such as chest pain upon exertion.
As a result, the players did not know that they were at serious risk of heart attack or stroke, or that they needed to make lifestyle changes or start medical therapy to improve the capacity of their cardiovascular systems to maintain blood flow.
The Mayo research team concluded that because test results showed evidence of asymptomatic narrowing of the arteries -- called atherosclerosis -- the retired NFL players are at abnormally high risk for an adverse cardiovascular event, as compared with people of the same age in the general population. In addition, the high incidence of plaque found in players' vessels suggests that the increased narrowing is not solely due to increased body mass index. Further research is needed to explain this. In the meantime, football players will benefit from regular cardiovascular screening. "Effective therapies are available to help players avoid serious cardiovascular problems later in life, but players need to take that first step of seeking out screening programs to identify those at risk," Dr. Khandheria says.
Collaboration and Support
Other Mayo Clinic researchers are Erik Wissner, M.D.; Robert Burke, M.D.; and Chris Kendall, all of Mayo Clinic, Scottsdale/Phoenix, Ariz. Their work was supported by Mayo Foundation for Medical Education and Research.
Adapted from materials provided by Mayo Clinic.
New Resuscitation Approach For Out-of-hospital Cardiac Arrest Associated With Increased Survival, Study Shows
[Source: ScienceDaily ] - Patients who had cardiac arrests outside of the hospital setting and were treated with a resuscitation approach designed to limit interruption of chest compressions, termed minimally interrupted cardiac resuscitation (MICR), were more likely to survive than those patients who received standard treatments, according to a new study.
"Out-of-hospital cardiac arrest is a major public health problem and a leading cause of death," the authors write. "Although early defibrillation with automated external defibrillators improves survival, early defibrillation is rare and few patients with out-of-hospital cardiac arrest survive. In 2004, the average survival of patients with out-of-hospital cardiac arrest was 3 percent in the state of Arizona."
MICR, previously referred to as cardiocerebral resuscitation, is a new approach to out-of-hospital cardiac arrest for emergency medical services (EMS) personnel. MICR focuses on maximizing blood flow to the heart and brain through a series of coordinated interventions, and includes an initial series of 200 uninterrupted chest compressions, rhythm analysis with a single shock, 200 immediate post-shock chest compressions before pulse check or rhythm re-analysis, early administration of epinephrine (adrenaline, used to stimulate the heart), and delayed endotracheal intubation (placement of a flexible plastic tube into the trachea for the purpose of ventilating the lungs).
Bentley J. Bobrow, M.D., of Mayo Clinic, Scottsdale, Ariz., and colleagues investigated whether MICR would improve survival from out-of-hospital cardiac arrest. Patients with out-of-hospital cardiac arrests in two metropolitan cities in Arizona before and after MICR training of fire department emergency medical personnel were assessed. In a second analysis of protocol compliance, patients from the two metropolitan cities and 60 additional fire departments in Arizona who actually received MICR were compared with patients who did not receive MICR but received standard advanced life support.
Among the 886 patients with cardiac arrest in the two metropolitan cities, survival-to-hospital discharge increased from 4 of 218 patients (1.8 percent) in the before MICR training group to 36 of 668 patients (5.4 percent) in the after MICR training group. In the subgroup of 174 patients with a witnessed cardiac arrest and ventricular fibrillation (chaotic, irregular heart rhythm that results in little or no circulation but that may respond to defibrillation), survival increased from 2 of 43 patients (4.7 percent) in the before MICR training group to 23 of 131 patients (17.6 percent) in the after MICR training group.
For the protocol compliance analysis, overall survival-to-hospital discharge occurred in 69 of 1,799 patients (3.8 percent) who did not receive MICR and in 60 of 661 (9.1 percent) who received MICR. Survival with witnessed ventricular fibrillation and cardiac arrest occurred in 46 of 387 patients (11.9 percent) who did not receive MICR and in 40 of 141 patients (28.4 percent) who received MICR.
"Why should MICR be associated with improved outcomes after out-of-hospital cardiac arrest" One major contributor to the poor survival rates of patients with out-of-hospital cardiac arrest is prolonged inadequate myocardial and cerebral perfusion. During resuscitation efforts, the forward blood flow produced by chest compressions is so marginal that any interruption of chest compressions is extremely [harmful], especially for favorable neurological outcomes. Excessive interruptions of chest compressions by pre-hospital personnel are common. Therefore, MICR emphasizes uninterrupted chest compressions," the authors write.
"In this study, survival-to-hospital discharge of patients with an out-of-hospital cardiac arrest improved significantly after implementation of MICR as an alternate EMS protocol. These findings require confirmation in randomized trials."
Journal reference: JAMA. 2008;299[10]:1158-1165.
Editorial: Progress in Resuscitation
In an accompanying editorial, Mary Ann Peberdy, M.D., and Joseph P. Ornato, M.D., of Virginia Commonwealth University, Richmond, comment on the findings of Bobrow and colleagues.
"Although the concept of MICR needs further scientific evaluation, perhaps in the form of a randomized, controlled, clinical trial with precise documentation of protocol compliance, these details are likely not important factors to the numerous additional survivors who are back home with their families after the implementation of this new protocol. Progress in improving survival after cardiac arrest is most commonly made by a gradual evolution of science and its translation into clinical medicine rather than single, earth-shattering revolutions. This study ... represents confirmation that the quality of CPR, particularly the need for minimally interrupted chest compression and the lesser importance of positive pressure ventilation [receiving oxygen under pressure by a mechanical respirator], is a meaningful development in the evolution of resuscitation science."
Editorial reference: JAMA. 2008;299[10]:1188-1190.
Adapted from materials provided by JAMA and Archives Journals.
"Out-of-hospital cardiac arrest is a major public health problem and a leading cause of death," the authors write. "Although early defibrillation with automated external defibrillators improves survival, early defibrillation is rare and few patients with out-of-hospital cardiac arrest survive. In 2004, the average survival of patients with out-of-hospital cardiac arrest was 3 percent in the state of Arizona."
MICR, previously referred to as cardiocerebral resuscitation, is a new approach to out-of-hospital cardiac arrest for emergency medical services (EMS) personnel. MICR focuses on maximizing blood flow to the heart and brain through a series of coordinated interventions, and includes an initial series of 200 uninterrupted chest compressions, rhythm analysis with a single shock, 200 immediate post-shock chest compressions before pulse check or rhythm re-analysis, early administration of epinephrine (adrenaline, used to stimulate the heart), and delayed endotracheal intubation (placement of a flexible plastic tube into the trachea for the purpose of ventilating the lungs).
Bentley J. Bobrow, M.D., of Mayo Clinic, Scottsdale, Ariz., and colleagues investigated whether MICR would improve survival from out-of-hospital cardiac arrest. Patients with out-of-hospital cardiac arrests in two metropolitan cities in Arizona before and after MICR training of fire department emergency medical personnel were assessed. In a second analysis of protocol compliance, patients from the two metropolitan cities and 60 additional fire departments in Arizona who actually received MICR were compared with patients who did not receive MICR but received standard advanced life support.
Among the 886 patients with cardiac arrest in the two metropolitan cities, survival-to-hospital discharge increased from 4 of 218 patients (1.8 percent) in the before MICR training group to 36 of 668 patients (5.4 percent) in the after MICR training group. In the subgroup of 174 patients with a witnessed cardiac arrest and ventricular fibrillation (chaotic, irregular heart rhythm that results in little or no circulation but that may respond to defibrillation), survival increased from 2 of 43 patients (4.7 percent) in the before MICR training group to 23 of 131 patients (17.6 percent) in the after MICR training group.
For the protocol compliance analysis, overall survival-to-hospital discharge occurred in 69 of 1,799 patients (3.8 percent) who did not receive MICR and in 60 of 661 (9.1 percent) who received MICR. Survival with witnessed ventricular fibrillation and cardiac arrest occurred in 46 of 387 patients (11.9 percent) who did not receive MICR and in 40 of 141 patients (28.4 percent) who received MICR.
"Why should MICR be associated with improved outcomes after out-of-hospital cardiac arrest" One major contributor to the poor survival rates of patients with out-of-hospital cardiac arrest is prolonged inadequate myocardial and cerebral perfusion. During resuscitation efforts, the forward blood flow produced by chest compressions is so marginal that any interruption of chest compressions is extremely [harmful], especially for favorable neurological outcomes. Excessive interruptions of chest compressions by pre-hospital personnel are common. Therefore, MICR emphasizes uninterrupted chest compressions," the authors write.
"In this study, survival-to-hospital discharge of patients with an out-of-hospital cardiac arrest improved significantly after implementation of MICR as an alternate EMS protocol. These findings require confirmation in randomized trials."
Journal reference: JAMA. 2008;299[10]:1158-1165.
Editorial: Progress in Resuscitation
In an accompanying editorial, Mary Ann Peberdy, M.D., and Joseph P. Ornato, M.D., of Virginia Commonwealth University, Richmond, comment on the findings of Bobrow and colleagues.
"Although the concept of MICR needs further scientific evaluation, perhaps in the form of a randomized, controlled, clinical trial with precise documentation of protocol compliance, these details are likely not important factors to the numerous additional survivors who are back home with their families after the implementation of this new protocol. Progress in improving survival after cardiac arrest is most commonly made by a gradual evolution of science and its translation into clinical medicine rather than single, earth-shattering revolutions. This study ... represents confirmation that the quality of CPR, particularly the need for minimally interrupted chest compression and the lesser importance of positive pressure ventilation [receiving oxygen under pressure by a mechanical respirator], is a meaningful development in the evolution of resuscitation science."
Editorial reference: JAMA. 2008;299[10]:1188-1190.
Adapted from materials provided by JAMA and Archives Journals.
Could Changing The Bacteria In Your Digestive System Be An Obesity Treatment?
[Source: ScienceDaily ] - Obesity is more than a cosmetic concern because it increases a person's risk for developing high blood pressure, diabetes and many other serious health problems. It's well understood that consuming more calories than you expend through exercise and daily activities causes weight gain. But with about one in every three American adults now considered obese, researchers are attempting to identify additional factors that affect a person's tendency to gain and retain excess weight.
In the April issue of Mayo Clinic Proceedings, researchers from Mayo Clinic Arizona and Arizona State University examine the role that bacteria in the human gastrointestinal tract play in regulating weight and the development of obesity.
Known as gut microbiota, the trillions of bacteria that populate the human gastrointestinal tract perform a variety of chores. These "friendly" microbes help extract calories from what we eat, help store these calories for later use, and provide energy and nutrients for the production of new bacteria to continue this work.
According to John DiBaise, M.D., a Mayo Clinic Arizona gastroenterologist and lead author of the Mayo Clinic Proceedings article, several animal studies suggest that gut microbiota are involved in regulating weight and that modifying these bacteria could one day be a treatment option for obesity.
One study cited by the authors observed that young, conventionally-reared mice have a significantly higher body fat content than a laboratory-bred, germ-free strain of mice that lack these bacteria, even though they consumed less food than their germ-free counterparts. When the same research group transplanted gut microbiota from normal mice into germ-free mice, the germ-free mice experienced a 60 percent increase in body fat within two weeks, without any increase in food consumption or obvious differences in energy expenditure.
Another animal study reviewed by the authors focused on the gene content of the gut microbiota in mice. Finding more end products of fermentation and fewer calories in the feces of obese mice led researchers to speculate that the gut microbiota in the obese mice help extract additional calories from ingested food.
"These results suggest that differences exist in the gut microbiota of obese versus lean mice, raising the possibility that the manipulation of gut microbiota could be a useful strategy for regulating energy balance in obese people," says Dr. DiBaise.
Although information on the link between gut microbiota and obesity in human subjects is more limited, the authors present some evidence supporting this connection. One study cited placed 12 obese participants in a weight-loss program for a year, randomly assigning them to either a fat-restricted or carbohydrate-restricted, low-calorie diet. Researchers noted distinct differences between lean and obese participants when they monitored the type and number of bacteria found in participants' stool samples before and after the diet changes.
Another study cited followed children from birth to age 7 and analyzed stool samples collected at 6 and 12 months. The children who were normal weight at age 7 had distinctly different bacteria in their samples from those collected from overweight-obese children, suggesting that differences in the composition of the gut microbiota precede overweight-obesity.
Dr. DiBaise says that much more research is needed to clarify a number of issues related to the relationship between the gut microbiota and obesity. Future studies need to establish whether the small changes in caloric extraction seen in recent studies can produce measurable weight differences in humans. Second, researchers need to prove or disprove the possible relationship between the gut microbiota and the regulation of weight.
"In particular, it is essential to demonstrate unequivocally whether differences in gut microbiota in obese versus lean people are the cause or the result of obesity," says Dr. DiBaise.
Finally, the authors note that the next wave of research should explore the safety and feasibility of modifying the gut microbiota in clinical trials involving humans.
"Although clearly no substitute for proper diet and exercise, manipulation of the gut microbiota may represent a novel approach for treating obesity that has few adverse effects," says Dr. DiBaise.
Other authors of this article include: Husen Zhang, Ph.D., Rosa Krajmalnik-Brown, Ph.D., and Bruce Rittmann, Ph.D., from Arizona State University; and Mayo Clinic Arizona researchers Michael Crowell, Ph.D. and G. Anton Decker, M.B.B.Ch.
Adapted from materials provided by Mayo Clinic, via EurekAlert!, a service of AAAS.
In the April issue of Mayo Clinic Proceedings, researchers from Mayo Clinic Arizona and Arizona State University examine the role that bacteria in the human gastrointestinal tract play in regulating weight and the development of obesity.
Known as gut microbiota, the trillions of bacteria that populate the human gastrointestinal tract perform a variety of chores. These "friendly" microbes help extract calories from what we eat, help store these calories for later use, and provide energy and nutrients for the production of new bacteria to continue this work.
According to John DiBaise, M.D., a Mayo Clinic Arizona gastroenterologist and lead author of the Mayo Clinic Proceedings article, several animal studies suggest that gut microbiota are involved in regulating weight and that modifying these bacteria could one day be a treatment option for obesity.
One study cited by the authors observed that young, conventionally-reared mice have a significantly higher body fat content than a laboratory-bred, germ-free strain of mice that lack these bacteria, even though they consumed less food than their germ-free counterparts. When the same research group transplanted gut microbiota from normal mice into germ-free mice, the germ-free mice experienced a 60 percent increase in body fat within two weeks, without any increase in food consumption or obvious differences in energy expenditure.
Another animal study reviewed by the authors focused on the gene content of the gut microbiota in mice. Finding more end products of fermentation and fewer calories in the feces of obese mice led researchers to speculate that the gut microbiota in the obese mice help extract additional calories from ingested food.
"These results suggest that differences exist in the gut microbiota of obese versus lean mice, raising the possibility that the manipulation of gut microbiota could be a useful strategy for regulating energy balance in obese people," says Dr. DiBaise.
Although information on the link between gut microbiota and obesity in human subjects is more limited, the authors present some evidence supporting this connection. One study cited placed 12 obese participants in a weight-loss program for a year, randomly assigning them to either a fat-restricted or carbohydrate-restricted, low-calorie diet. Researchers noted distinct differences between lean and obese participants when they monitored the type and number of bacteria found in participants' stool samples before and after the diet changes.
Another study cited followed children from birth to age 7 and analyzed stool samples collected at 6 and 12 months. The children who were normal weight at age 7 had distinctly different bacteria in their samples from those collected from overweight-obese children, suggesting that differences in the composition of the gut microbiota precede overweight-obesity.
Dr. DiBaise says that much more research is needed to clarify a number of issues related to the relationship between the gut microbiota and obesity. Future studies need to establish whether the small changes in caloric extraction seen in recent studies can produce measurable weight differences in humans. Second, researchers need to prove or disprove the possible relationship between the gut microbiota and the regulation of weight.
"In particular, it is essential to demonstrate unequivocally whether differences in gut microbiota in obese versus lean people are the cause or the result of obesity," says Dr. DiBaise.
Finally, the authors note that the next wave of research should explore the safety and feasibility of modifying the gut microbiota in clinical trials involving humans.
"Although clearly no substitute for proper diet and exercise, manipulation of the gut microbiota may represent a novel approach for treating obesity that has few adverse effects," says Dr. DiBaise.
Other authors of this article include: Husen Zhang, Ph.D., Rosa Krajmalnik-Brown, Ph.D., and Bruce Rittmann, Ph.D., from Arizona State University; and Mayo Clinic Arizona researchers Michael Crowell, Ph.D. and G. Anton Decker, M.B.B.Ch.
Adapted from materials provided by Mayo Clinic, via EurekAlert!, a service of AAAS.
Monday, March 24, 2008
Mayo Clinic cancer model to speed up drug research
[SOurce: Kate Nolan, The Arizona Republic] - Mayo Clinic Arizona scientists recently completed research that may speed development of new treatments for multiple myeloma, a common type of blood cancer.After a six-year effort, Mayo researchers in Scottsdale proved that a gene called MYC is instrumental in converting a benign tumor called MGUS into one that eventually becomes myeloma.A team of 12 scientists led by Dr. Leif Bergsagel were able to create a model of the disease in mice through genetic engineering. Bergsagel is a widely recognized authority on the genetic roots of the disease.
"This model helps us understand the genetic properties that lead to multiple myeloma and provides a framework for developing better therapies," Bergsagel said.Until this project, efforts to produce models that could genetically replicate the formation of myeloma had failed.
The model can streamline research in several ways.
• Scientists can observe the disease closely under various conditions.
• The model can identify the specific mutations that lead to cancer, which can help scientists better understand what's going on with patients.
• Researchers can test new treatments on real cancer cells, without human risk.
"This model helps us understand the genetic properties that lead to multiple myeloma and provides a framework for developing better therapies," Bergsagel said.Until this project, efforts to produce models that could genetically replicate the formation of myeloma had failed.
The model can streamline research in several ways.
• Scientists can observe the disease closely under various conditions.
• The model can identify the specific mutations that lead to cancer, which can help scientists better understand what's going on with patients.
• Researchers can test new treatments on real cancer cells, without human risk.
Wednesday, March 12, 2008
Institutional networks lays groundwork for biotech boom
[Source: Kate Nolan, The Arizona Republic] - If Arizona's long-predicted biotech boom ever happens, one thing the Northeast Valley will be able to say is: "We're ready."The biomedical industry here has more strategic alliances than the United Nations Security Council. Mayo Clinic, Scottsdale Healthcare, University of Arizona, Arizona State University, the Translational Genomics Research Institute (TGen) and the International Genomics Consortium - all are networked through a system of pacts and contracts.
Some of the deals have born even more entities, such as MAC5, a collaboration by Mayo and ASU's Biodesign Institute; and TD2, a Mayo-TGen deal.With those links in place, it seemed like a re-run recently when Mayo Clinic and TGen announced a new research collaboration. Didn't they already do that in 2003? Back then, TGen and the entire Mayo organization - which includes a giant headquarters in Minnesota and a smaller one in Florida, in addition to local campuses in Phoenix and Scottsdale - agreed to explore possible collaborations.
Deal ensures cancer research
The new deal, said Dr. Rafael Fonseca, who heads the Arizona division of the Mayo Clinic Cancer Center, is a whole lot tighter. And is focused only on cancer."We had to find ways to enhance our relationship with TGen," he said, sounding curiously like a listing on eHarmony. What they came up with appears to be the institutional version of moving in together.In the new deal, 30 TGen researchers will become members of the Mayo Clinic Cancer Center, one of the 39 comprehensive cancer centers sanctioned by the National Cancer Institute, which also signs off on the doctors and researchers named as members.Mayo's triple-site cancer center has 300 members, so TGen's scientists will constitute 10 percent.The deal not only plays to each institution's needs and strengths, but constitutes a sort of pre-nuptial agreement that could save the relationship in future endeavors."All institutions are protective when it comes to intellectual property," said Fonseca. Typically in collaborations, researchers come up with a project and then arduously have to draft an agreement vetted by lawyers; it can take a while."Having an existing relationship, with templates for these agreements," speeds things up, Fonseca said. But that's merely a convenience.
Goal: Quick patient treatment
Fonseca said the core reason the cancer center and TGen are exchanging vows is their mutual goal: getting treatments to patients faster."The word synergy is used sometimes quite loosely, but this is one case where it really applies," he said.Fonseca, known for his research in multiple myeloma, has worked with TGen researchers since coming to Mayo Scottsdale five years ago."I was the main broker for making this happen," he said. He wanted his colleagues to know what TGen can do."They are a powerhouse in research abilities and tools. They can sequence more genes than anybody in the world. They have a high through-put way of shutting down thousands of genes at once," he said with a fervor that, to the unschooled, translated to: Whatever he's talking about, it must be Big Time in medical research."Mayo clearly has top abilities at the clinical level. It's a perfect marriage," Fonseca said.For him, research has to pass the "handshake test," meaning it must have a "human set of information" connected to it.
Focus kept on the patients
"The Mayo-TGen collaboration will always be based on 'why.' Why isn't this patient doing better? Why has this patient changed? I'm actually very passionate about this," Fonseca said."Trent is also obsessed with making the link to the bedside," he said, referring to Dr. Jeffrey Trent, the internationally recognized scientist who conceived of TGen and is now its president and scientific director."Jeff says TGen isn't a technology-driven company. He's more like: I have this technology and these scientists. Can't we help predict who will relapse from a tumor? "We think that's huge. That's why we could align so well," Fonseca said.He expects to start naming TGen members to the cancer center in January.Trent will be among them.
Some of the deals have born even more entities, such as MAC5, a collaboration by Mayo and ASU's Biodesign Institute; and TD2, a Mayo-TGen deal.With those links in place, it seemed like a re-run recently when Mayo Clinic and TGen announced a new research collaboration. Didn't they already do that in 2003? Back then, TGen and the entire Mayo organization - which includes a giant headquarters in Minnesota and a smaller one in Florida, in addition to local campuses in Phoenix and Scottsdale - agreed to explore possible collaborations.
Deal ensures cancer research
The new deal, said Dr. Rafael Fonseca, who heads the Arizona division of the Mayo Clinic Cancer Center, is a whole lot tighter. And is focused only on cancer."We had to find ways to enhance our relationship with TGen," he said, sounding curiously like a listing on eHarmony. What they came up with appears to be the institutional version of moving in together.In the new deal, 30 TGen researchers will become members of the Mayo Clinic Cancer Center, one of the 39 comprehensive cancer centers sanctioned by the National Cancer Institute, which also signs off on the doctors and researchers named as members.Mayo's triple-site cancer center has 300 members, so TGen's scientists will constitute 10 percent.The deal not only plays to each institution's needs and strengths, but constitutes a sort of pre-nuptial agreement that could save the relationship in future endeavors."All institutions are protective when it comes to intellectual property," said Fonseca. Typically in collaborations, researchers come up with a project and then arduously have to draft an agreement vetted by lawyers; it can take a while."Having an existing relationship, with templates for these agreements," speeds things up, Fonseca said. But that's merely a convenience.
Goal: Quick patient treatment
Fonseca said the core reason the cancer center and TGen are exchanging vows is their mutual goal: getting treatments to patients faster."The word synergy is used sometimes quite loosely, but this is one case where it really applies," he said.Fonseca, known for his research in multiple myeloma, has worked with TGen researchers since coming to Mayo Scottsdale five years ago."I was the main broker for making this happen," he said. He wanted his colleagues to know what TGen can do."They are a powerhouse in research abilities and tools. They can sequence more genes than anybody in the world. They have a high through-put way of shutting down thousands of genes at once," he said with a fervor that, to the unschooled, translated to: Whatever he's talking about, it must be Big Time in medical research."Mayo clearly has top abilities at the clinical level. It's a perfect marriage," Fonseca said.For him, research has to pass the "handshake test," meaning it must have a "human set of information" connected to it.
Focus kept on the patients
"The Mayo-TGen collaboration will always be based on 'why.' Why isn't this patient doing better? Why has this patient changed? I'm actually very passionate about this," Fonseca said."Trent is also obsessed with making the link to the bedside," he said, referring to Dr. Jeffrey Trent, the internationally recognized scientist who conceived of TGen and is now its president and scientific director."Jeff says TGen isn't a technology-driven company. He's more like: I have this technology and these scientists. Can't we help predict who will relapse from a tumor? "We think that's huge. That's why we could align so well," Fonseca said.He expects to start naming TGen members to the cancer center in January.Trent will be among them.
Thursday, December 20, 2007
Mayo Clinic study shows potential for new drug treatment for multiple myeloma
[Source: Mayo Clinic] - Mayo Clinic researchers today presented results of a phase II trial that shows potential to help patients with multiple myeloma, an incurable cancer of the white blood cells affecting more than 50,000 patients in the U.S.
“For newly-diagnosed multiple myeloma patients, this new drug treatment provides a more frequent, rapid and deep response, compared with earlier treatment options,” said Craig B. Reeder, M.D., a Mayo Clinic hematologist/oncologist and lead investigator of the study. “This is the first time we have studied this treatment in newly-diagnosed patients with this condition. This new treatment proved to be very successful.”
The research team studied 30 patients enrolled in the trial who were administered a drug regimen using cyclophosphamide, bortezomib and dexamethasone (Cybor-D). That combination showed an improved response over the drug therapy used historically – lenalidomide-dexamethasone (L-Dex).
The 30 trial patients were administered Cybor-D. A control group of 34 patients was treated with L-Dex. Findings reveal that Cybor-D produced a higher rate of good or complete responses than the L-Dex.
Cybor-D was found to produce a rapid initial decline and reduction in M protein, an antibody protein that can build up in the bone marrow and cause the blood to thicken or damage the kidneys.
Other Mayo Clinic researchers contributing to the study included Rafael Fonseca, M.D.; Leif Bergsagel, M.D.; S. Vincent Rajkumar, M.D.; Jacy Boesiger; Christine Chen; Martha Lacy, M.D.; Keith Stewart, M.B.Ch.B.; Joseph Hentz and Nicholas Pirooz. Researchers from Princess Margaret Hospital in Toronto, Ontario, also contributed to the study.
Findings were reported by Dr. Reeder at the American Society of Hematology’s annual meeting in Atlanta Dec. 8-11, 2007.
“For newly-diagnosed multiple myeloma patients, this new drug treatment provides a more frequent, rapid and deep response, compared with earlier treatment options,” said Craig B. Reeder, M.D., a Mayo Clinic hematologist/oncologist and lead investigator of the study. “This is the first time we have studied this treatment in newly-diagnosed patients with this condition. This new treatment proved to be very successful.”
The research team studied 30 patients enrolled in the trial who were administered a drug regimen using cyclophosphamide, bortezomib and dexamethasone (Cybor-D). That combination showed an improved response over the drug therapy used historically – lenalidomide-dexamethasone (L-Dex).
The 30 trial patients were administered Cybor-D. A control group of 34 patients was treated with L-Dex. Findings reveal that Cybor-D produced a higher rate of good or complete responses than the L-Dex.
Cybor-D was found to produce a rapid initial decline and reduction in M protein, an antibody protein that can build up in the bone marrow and cause the blood to thicken or damage the kidneys.
Other Mayo Clinic researchers contributing to the study included Rafael Fonseca, M.D.; Leif Bergsagel, M.D.; S. Vincent Rajkumar, M.D.; Jacy Boesiger; Christine Chen; Martha Lacy, M.D.; Keith Stewart, M.B.Ch.B.; Joseph Hentz and Nicholas Pirooz. Researchers from Princess Margaret Hospital in Toronto, Ontario, also contributed to the study.
Findings were reported by Dr. Reeder at the American Society of Hematology’s annual meeting in Atlanta Dec. 8-11, 2007.
Wednesday, July 11, 2007
Biodesign Institute leads innovative project to prevent breast cancer
[Source: Joe Caspermeyer, Biodesign Institute] -- Biodesign Institute researchers have received nearly $9 million in grants to develop a preventive vaccine against cancer. Stephen Albert Johnston, PhD, director of the institute’s Center for Innovations in Medicine, will focus his research project on breast cancer. Johnston is one of only two recipients in the nation bestowed with a five-year, $7.5 million grant from the Department of Defense’s Innovator Award, funded through its Breast Cancer Research Program. His Biodesign research colleague, Douglas Lake, PhD, will lead a three-year $1.2 million project from the W. M. Keck Foundation to take the basic technology and see whether it could be applied to several other forms of cancer.
Yvette Ruiz and Douglas Lake discuss their latest efforts to uncover cancer protein signatures as part of a Biodesign Institute and Mayo Clinic cancer vaccine project. The project has received nearly $9 million in funds from a Department of Defense ’Innovator Award’ and the W.M. Keck Foundation.
Cancer is the second leading cause of death in the U.S., with an estimated 1.45 million cases of cancer diagnosed this year. More than 560,000 people will die from the disease. Breast cancer is the second leading cause of death in women. The Department of Defense, using appropriations from a congressionally directed medical research program, has sought to eradicate breast cancer by funding innovative, high-impact research through a partnership of scientists and consumers. The Innovator Award recognizes individuals who have a "history of visionary scholarship, leadership and creativity."
“Breast cancer’s course is often long and devastating and, despite advances in diagnosis and treatment, one in five women still succumb to the disease,” said Johnston. “It’s time to fundamentally rethink how we approach this problem. Our goal, based on some promising preliminary results, is to see if we can make a vaccine that would be given to all adult women to prevent the occurrence of breast cancer”
Johnston notes that the most successful medical intervention in history has been the development of vaccines against infectious disease. “Developing a cancer vaccine would be the perfect solution, not only in eliminating cancer mortality, but also potentially some of the costs of diagnosis and treatment.”
The W.M. Keck Foundation Award will further push the boundaries of cancer vaccine research by laying the groundwork for breakthrough discoveries to broaden the team’s approach to other cancers. “It’s been well-established that cancers create foreign proteins that the immune system can recognize,” said Douglas Lake, who will lead the Keck Foundation project. “If we could pre-immunize an individual with a collection of proteins that effectively represent any foreign protein that a breast tumor would produce, the immune system would arm itself against breast cancer,” said Lake. “And, if the platform technology proves successful, it could be applied to other cancers.”
The Biodesign Institute duo will lead a highly interdisciplinary team of scientists and clinicians, which involves renowned collaborators from other institutions including: Laurence Miller, MD, Mayo Clinic director for research and Richard Smith, PhD, chief scientist at Pacific Northwest National Labs. The research team, utilizing the latest advances in genomics, proteomics and immunology, wants to find a number of common signatures that occur across a wide spectrum of breast tumors. “This has truly been a collaborative effort, with significant contributions from both organizations,” according to Miller. “I am thrilled that this is going forward, and am also pleased to see this important project launching our joint efforts in the Mayo Clinic/ASU Center for Cancer-related Convergence, Cooperation and Collaboration (MAC5).”
The research work will be performed at the Biodesign Institute’s Center for Innovations in Medicine and Mayo Clinic’s new Collaborative Research Building. This project is the first major initiative undertaken under the MAC5 umbrella partnership. Earlier, the organizations invested seed funds including private funding from Mayo and ASU funding made possible by the Arizona voter-approved, Proposition 301 Technology Research and Infrastructure Fund (TRIF). The funds allowed Johnston’s team to launch the project and obtain the initial supportive data. Space has been allocated at research facilities at the Biodesign Institute and on the Scottsdale campus of Mayo Clinic, with additional faculty and clinicians being hired to support the project.
To find common elements in breast cancer and other tumors, the research team will use patient and normal samples from extensive tissue banks at the Mayo Clinic. The team will develop new techniques to identify small protein fragments, or peptides, found in breast cancer cell lines and primary tumors. “The key is that these peptides have to trigger an immune response against breast tumors but not in normal cells,” said Johnston.
Johnston knows demonstrating their approach will be a significant challenge. But he has been encouraged by recent mouse studies in his lab, which have identified peptides that have shown protection against breast cancer. Lake is advancing these preliminary mouse studies by identifying peptides from human tumors that are candidates for a cancer vaccine. “We believe the technology and knowledge base now exists to determine whether or not this idea is feasible,” said Johnston. “If we are successful in our approach, we hope to bring a vaccine candidate to clinical trials by the end of the grant period.”
Yvette Ruiz and Douglas Lake discuss their latest efforts to uncover cancer protein signatures as part of a Biodesign Institute and Mayo Clinic cancer vaccine project. The project has received nearly $9 million in funds from a Department of Defense ’Innovator Award’ and the W.M. Keck Foundation.
Cancer is the second leading cause of death in the U.S., with an estimated 1.45 million cases of cancer diagnosed this year. More than 560,000 people will die from the disease. Breast cancer is the second leading cause of death in women. The Department of Defense, using appropriations from a congressionally directed medical research program, has sought to eradicate breast cancer by funding innovative, high-impact research through a partnership of scientists and consumers. The Innovator Award recognizes individuals who have a "history of visionary scholarship, leadership and creativity."
“Breast cancer’s course is often long and devastating and, despite advances in diagnosis and treatment, one in five women still succumb to the disease,” said Johnston. “It’s time to fundamentally rethink how we approach this problem. Our goal, based on some promising preliminary results, is to see if we can make a vaccine that would be given to all adult women to prevent the occurrence of breast cancer”
Johnston notes that the most successful medical intervention in history has been the development of vaccines against infectious disease. “Developing a cancer vaccine would be the perfect solution, not only in eliminating cancer mortality, but also potentially some of the costs of diagnosis and treatment.”
The W.M. Keck Foundation Award will further push the boundaries of cancer vaccine research by laying the groundwork for breakthrough discoveries to broaden the team’s approach to other cancers. “It’s been well-established that cancers create foreign proteins that the immune system can recognize,” said Douglas Lake, who will lead the Keck Foundation project. “If we could pre-immunize an individual with a collection of proteins that effectively represent any foreign protein that a breast tumor would produce, the immune system would arm itself against breast cancer,” said Lake. “And, if the platform technology proves successful, it could be applied to other cancers.”
The Biodesign Institute duo will lead a highly interdisciplinary team of scientists and clinicians, which involves renowned collaborators from other institutions including: Laurence Miller, MD, Mayo Clinic director for research and Richard Smith, PhD, chief scientist at Pacific Northwest National Labs. The research team, utilizing the latest advances in genomics, proteomics and immunology, wants to find a number of common signatures that occur across a wide spectrum of breast tumors. “This has truly been a collaborative effort, with significant contributions from both organizations,” according to Miller. “I am thrilled that this is going forward, and am also pleased to see this important project launching our joint efforts in the Mayo Clinic/ASU Center for Cancer-related Convergence, Cooperation and Collaboration (MAC5).”
The research work will be performed at the Biodesign Institute’s Center for Innovations in Medicine and Mayo Clinic’s new Collaborative Research Building. This project is the first major initiative undertaken under the MAC5 umbrella partnership. Earlier, the organizations invested seed funds including private funding from Mayo and ASU funding made possible by the Arizona voter-approved, Proposition 301 Technology Research and Infrastructure Fund (TRIF). The funds allowed Johnston’s team to launch the project and obtain the initial supportive data. Space has been allocated at research facilities at the Biodesign Institute and on the Scottsdale campus of Mayo Clinic, with additional faculty and clinicians being hired to support the project.
To find common elements in breast cancer and other tumors, the research team will use patient and normal samples from extensive tissue banks at the Mayo Clinic. The team will develop new techniques to identify small protein fragments, or peptides, found in breast cancer cell lines and primary tumors. “The key is that these peptides have to trigger an immune response against breast tumors but not in normal cells,” said Johnston.
Johnston knows demonstrating their approach will be a significant challenge. But he has been encouraged by recent mouse studies in his lab, which have identified peptides that have shown protection against breast cancer. Lake is advancing these preliminary mouse studies by identifying peptides from human tumors that are candidates for a cancer vaccine. “We believe the technology and knowledge base now exists to determine whether or not this idea is feasible,” said Johnston. “If we are successful in our approach, we hope to bring a vaccine candidate to clinical trials by the end of the grant period.”
Sunday, July 8, 2007
Valley team hopes to develop 1st preventive breast-cancer vaccine
[Source: Kate Nolan, The Arizona Republic] -- An Arizona mission to invent the first preventive cancer vaccine is being armed by the U.S. Department of Defense. Dr. Stephen Johnston won a five-year, $7.5 million "Innovator Award" from the Defense Department's Breast Cancer Research Program, according to an announcement planned today by Arizona State University's Biodesign Institute and Mayo Clinic. The grant supports efforts toward a breast-cancer vaccine by 15 researchers at MAC5, a partnership between Mayo Clinic in Scottsdale and ASU in Tempe.
Researchers plan to use common proteins among breast cancers to vaccinate against attacking cancer cells. No cancer vaccines exist. However, the HPV vaccine prevents an infectious disease related to cervical cancer."Now I can concentrate more on science than raising money," said Johnston, director of the institute's Center for Innovations in Medicine. A growing view that cancer research has not been innovative enough, may have positively influenced the Defense Department's decision, Johnston said."Conceptually, this idea is out far enough that we're not sure it will work," Johnston said, adding that the venture could lead to a vaccine against all major cancers.The research team includes Dr. Laurence Miller, director of research at Mayo , and Dr. Richard Smith, chief scientist at Pacific Northwest National Labs in Richland, Wash.
Researchers plan to use common proteins among breast cancers to vaccinate against attacking cancer cells. No cancer vaccines exist. However, the HPV vaccine prevents an infectious disease related to cervical cancer."Now I can concentrate more on science than raising money," said Johnston, director of the institute's Center for Innovations in Medicine. A growing view that cancer research has not been innovative enough, may have positively influenced the Defense Department's decision, Johnston said."Conceptually, this idea is out far enough that we're not sure it will work," Johnston said, adding that the venture could lead to a vaccine against all major cancers.The research team includes Dr. Laurence Miller, director of research at Mayo , and Dr. Richard Smith, chief scientist at Pacific Northwest National Labs in Richland, Wash.
Wednesday, June 6, 2007
Research Team Identifies New Alzheimer's Gene
Research Team Identifies New Alzheimer’s Gene
Source: TGen
A study comparing more genetic markers in the DNA of people with and without Alzheimer’s disease than ever before has enabled researchers to identify a common gene that appears to increase a person's risk for developing Alzheimer's disease. The finding, announced today by researchers at the Translational Genomics Research Institute (TGen), Banner Alzheimer's Institute, Kronos Science Laboratory and their collaborative partners, suggests that the gene - called GAB2 - modifies an individual's risk when associated with other genes, including APOE4. The study results appear in the June 7 issue of the prestigious peer-reviewed journal, Neuron.
Alzheimer's disease is the most common form of disabling memory and thinking problems in older people. The progressive neurological disorder afflicts an estimated 5 million Americans, a number expected to triple by 2050. "We have entered a new era in medical research. Today's technologies permit us to survey a sufficient number of letters throughout the human genome to provide a clearer picture of how life works and ultimately allow better clinical management of patients," said Dr. Dietrich Stephan, Director of TGen's Neurogenomics Division and the paper's senior author, "These new, robust tools may eventually allow us to improve our ability to diagnose Alzheimer's disease, even before it strikes."
To date, the most significant gene found to predispose an individual to late onset Alzheimer's (LOAD) has been APOE4. In this latest study, researchers from seven organizations contributed to the genome-wide scan using Affymetrix microarray technology. The team screened the DNA from 1,400 individuals who had been clinically assessed with Alzheimer's prior death, and simultaneously examined more than 500,000 SNPs or genetic variations to characterize and confirm additional LOAD susceptibility genes. The search revealed GAB2.
Based on the genetics of this and other neuroscientific findings, researchers suggest the healthy form of the GAB2 gene may protect brain cells from developing tangles, one of the hallmarks of Alzheimer's disease. If the findings are confirmed, this discovery could provide a target for future Alzheimer's therapeutic drugs. "We hope that this study, along with the genome-wide genetics studies to come, will contribute to the clarification of Alzheimer's risk factors and disease mechanisms, the discovery of promising new disease-slowing and prevention therapies, and the identification of patients and at-risk people most likely to benefit from those treatments," said Dr. Eric Reiman, the study's first author and Executive Director of the Banner Alzheimer's Institute.
After finding an association between a form of the GAB2 gene and Alzheimer's disease in three separate groups, the researchers showed that the GAB2 gene is unusually active in vulnerable brain cells from Alzheimer's patients and that the GAB2 protein produced by this gene is present in those brain cells containing tangles. When the researchers silenced GAB2 in preliminary studies it increased a molecular process thought to play an important role in the development of tangles. Based on these findings, the researchers hypothesize that GAB2 might function under normal conditions to compensate for the harmful effects of APOE4 and other genes in older people and that the GAB2 risk gene lacks this protective effect.
The study, funded by Kronos Science Laboratory, an affiliate of Phoenix-based Kronos Optimal Health Company, will enable Kronos to develop a test that aids in clinical diagnosis and help determine a person's genetic predisposition for developing Alzheimer’s disease. "This discovery allows us to accelerate the development process for creating a new diagnostic test that is capable of detecting the presence of GAB2, and may ultimately help millions of individuals reach a more informed decision regarding the most appropriate type and timing of treatment," said Dr. Chris Heward, President of Kronos Science Laboratory.
Until recently, researchers lacked the technology to examine the genetic components of a disease at such a high-level of detail. By utilizing the Affymetrix 500K Arrays, the study's researchers rapidly produced a genetic map of each brain tissue sample and isolated the GAB2 gene relatively quickly. "This Alzheimer's disease breakthrough is another powerful example of a fundamental life science discovery made by an Affymetrix customer. Our latest microarray technology continues to accelerate research at an unprecedented pace by enabling scientists to better identify the specific genetic variations associated with complex diseases," said Kevin King, President of Life Sciences Business and Executive Vice President at Affymetrix.
In addition to surveying an unprecedented number of genetic markers in each person's DNA, the researchers capitalized on extremely rigorous criteria to determine whether or not their volunteers had Alzheimer's. For instance, the study included more than 1000 brain donors confirmed to either have Alzheimer's disease or be free of the disorder at autopsy. This study resulted in a comprehensive set of high-quality data to be made publicly available to the research community. The researchers believe that deposition of this data set in the public domain will open a new era in Alzheimer research. When a scientist suspects a particular gene or pathway maybe implicated in Alzheimer's disease, they will use these data to see if there is genetic evidence supporting their idea. Reviewing these data in an hour will permit them to save months of work and thousands of dollars to achieve the same result. Moreover, it paves the way for even more advanced studies using larger sample populations, more powerful array chips that can distinguish more genetic markers, and more sophisticated methods of analyzing the data.
Study participants included TGen, Kronos Science Laboratory, Banner Alzheimer's Institute, Mayo Clinic Scottsdale, the Netherlands Brain Bank, Sun Health Research Institute, the University of Arizona, Arizona State University, the Arizona Alzheimer's Consortium, and several Alzheimer's Disease Centers supported by the National Institutes of Health's National Institute of Aging.
Source: TGen
A study comparing more genetic markers in the DNA of people with and without Alzheimer’s disease than ever before has enabled researchers to identify a common gene that appears to increase a person's risk for developing Alzheimer's disease. The finding, announced today by researchers at the Translational Genomics Research Institute (TGen), Banner Alzheimer's Institute, Kronos Science Laboratory and their collaborative partners, suggests that the gene - called GAB2 - modifies an individual's risk when associated with other genes, including APOE4. The study results appear in the June 7 issue of the prestigious peer-reviewed journal, Neuron.
Alzheimer's disease is the most common form of disabling memory and thinking problems in older people. The progressive neurological disorder afflicts an estimated 5 million Americans, a number expected to triple by 2050. "We have entered a new era in medical research. Today's technologies permit us to survey a sufficient number of letters throughout the human genome to provide a clearer picture of how life works and ultimately allow better clinical management of patients," said Dr. Dietrich Stephan, Director of TGen's Neurogenomics Division and the paper's senior author, "These new, robust tools may eventually allow us to improve our ability to diagnose Alzheimer's disease, even before it strikes."
To date, the most significant gene found to predispose an individual to late onset Alzheimer's (LOAD) has been APOE4. In this latest study, researchers from seven organizations contributed to the genome-wide scan using Affymetrix microarray technology. The team screened the DNA from 1,400 individuals who had been clinically assessed with Alzheimer's prior death, and simultaneously examined more than 500,000 SNPs or genetic variations to characterize and confirm additional LOAD susceptibility genes. The search revealed GAB2.
Based on the genetics of this and other neuroscientific findings, researchers suggest the healthy form of the GAB2 gene may protect brain cells from developing tangles, one of the hallmarks of Alzheimer's disease. If the findings are confirmed, this discovery could provide a target for future Alzheimer's therapeutic drugs. "We hope that this study, along with the genome-wide genetics studies to come, will contribute to the clarification of Alzheimer's risk factors and disease mechanisms, the discovery of promising new disease-slowing and prevention therapies, and the identification of patients and at-risk people most likely to benefit from those treatments," said Dr. Eric Reiman, the study's first author and Executive Director of the Banner Alzheimer's Institute.
After finding an association between a form of the GAB2 gene and Alzheimer's disease in three separate groups, the researchers showed that the GAB2 gene is unusually active in vulnerable brain cells from Alzheimer's patients and that the GAB2 protein produced by this gene is present in those brain cells containing tangles. When the researchers silenced GAB2 in preliminary studies it increased a molecular process thought to play an important role in the development of tangles. Based on these findings, the researchers hypothesize that GAB2 might function under normal conditions to compensate for the harmful effects of APOE4 and other genes in older people and that the GAB2 risk gene lacks this protective effect.
The study, funded by Kronos Science Laboratory, an affiliate of Phoenix-based Kronos Optimal Health Company, will enable Kronos to develop a test that aids in clinical diagnosis and help determine a person's genetic predisposition for developing Alzheimer’s disease. "This discovery allows us to accelerate the development process for creating a new diagnostic test that is capable of detecting the presence of GAB2, and may ultimately help millions of individuals reach a more informed decision regarding the most appropriate type and timing of treatment," said Dr. Chris Heward, President of Kronos Science Laboratory.
Until recently, researchers lacked the technology to examine the genetic components of a disease at such a high-level of detail. By utilizing the Affymetrix 500K Arrays, the study's researchers rapidly produced a genetic map of each brain tissue sample and isolated the GAB2 gene relatively quickly. "This Alzheimer's disease breakthrough is another powerful example of a fundamental life science discovery made by an Affymetrix customer. Our latest microarray technology continues to accelerate research at an unprecedented pace by enabling scientists to better identify the specific genetic variations associated with complex diseases," said Kevin King, President of Life Sciences Business and Executive Vice President at Affymetrix.
In addition to surveying an unprecedented number of genetic markers in each person's DNA, the researchers capitalized on extremely rigorous criteria to determine whether or not their volunteers had Alzheimer's. For instance, the study included more than 1000 brain donors confirmed to either have Alzheimer's disease or be free of the disorder at autopsy. This study resulted in a comprehensive set of high-quality data to be made publicly available to the research community. The researchers believe that deposition of this data set in the public domain will open a new era in Alzheimer research. When a scientist suspects a particular gene or pathway maybe implicated in Alzheimer's disease, they will use these data to see if there is genetic evidence supporting their idea. Reviewing these data in an hour will permit them to save months of work and thousands of dollars to achieve the same result. Moreover, it paves the way for even more advanced studies using larger sample populations, more powerful array chips that can distinguish more genetic markers, and more sophisticated methods of analyzing the data.
Study participants included TGen, Kronos Science Laboratory, Banner Alzheimer's Institute, Mayo Clinic Scottsdale, the Netherlands Brain Bank, Sun Health Research Institute, the University of Arizona, Arizona State University, the Arizona Alzheimer's Consortium, and several Alzheimer's Disease Centers supported by the National Institutes of Health's National Institute of Aging.
Monday, June 4, 2007
Mayo Clinic - Spread of breast cancer to lungs in asthma patients may be prevented by use of common inhalers
Researchers at Mayo Clinic in Arizona suggest there may be a link between asthma and the spread of cancer in breast cancer patients. Importantly, using available inhaler medications could reduce potential metastasis to the lungs in breast cancer patients who have asthma. The study was conducted in mice and supported by examination of breast cancer patient records. The results, according to the researchers, offer a biological link: Activation of cells that line blood vessels is required for the movement of pro-inflammatory white blood cells (which occurs in asthma) and for the movement of circulating cancer cells from the blood into lung tissue.
In the study, mice that were exposed to an allergen commonly used in mouse asthma studies and then injected with melanoma cells were compared to control groups of mice that did not suffer from allergic asthma. The allergen-induced pulmonary inflammation in the asthmatic mice was associated with an almost 400 percent increase in lung metastasis in these animals. But in mice treated with a medication currently available to asthma patients that reduces their lung inflammation (corticosteroids self-administered using hand-held inhalers), the rate of metastasis fell to that seen in mice that were not exposed to an allergen.
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In the study, mice that were exposed to an allergen commonly used in mouse asthma studies and then injected with melanoma cells were compared to control groups of mice that did not suffer from allergic asthma. The allergen-induced pulmonary inflammation in the asthmatic mice was associated with an almost 400 percent increase in lung metastasis in these animals. But in mice treated with a medication currently available to asthma patients that reduces their lung inflammation (corticosteroids self-administered using hand-held inhalers), the rate of metastasis fell to that seen in mice that were not exposed to an allergen.
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Friday, June 1, 2007
Alliance Aims to Boost Biomedicine
Arizona’s bioscience efforts continue to grow through an extensive, statewide collaborative network of initiatives. Now, research capabilities are being allied around the state in a new effort to improve medical diagnostics and human health.
The Arizona Proteomics Alliance (AZPA), a statewide consortium, has been formed to advance the emergent science of proteomics, a science whose broad vision is to understand the biological role of the complete set of proteins in the human body, or proteome. The initiative combines the expertise of nine leading Arizona institutions, including ASU, Banner Health, Barrow Neurological Institute, Carl T. Hayden Veterans Affairs Medical Center, Intrinsic Bioprobes Inc., Mayo Clinic, Sun Health Research Institute, Translational Genomics Research Institute (TGen) and the University of Arizona (U of A). “This alliance places Arizona in the forefront of proteomics research capabilities and will no doubt have broad impact on biomedical research and personalized medicine,” said Jeff Trent, president and scientific director of TGen.
AZPA promotes a team approach to solving problems of significant biomedical interest, according to Michael Mobley, administrative director of AZPA and associate director of the Biodesign Institute at ASU. The alliance will advance the role of proteomics research in the understanding of human health and disease by creating a network of scientists who share resources and expertise.
“AZPA facilitates access to technical and intellectual resources that are rarely surpassed within the United States, and provides the state with a distinct competitive advantage in this field,” says Serrine Lau, scientific director of AZPA, director of Southwest Environmental Health Sciences Center at the U of A’s College of Pharmacy, and a member of U of A’s BIO5 Institute. “We are pleased that the resources of the Arizona Proteomics Consortium at U of A will be part of this state-wide alliance,” Lau says.
The Mayo Clinic is also expecting to be able to expand its efforts and bring new diagnostic and treatment options to its patients as part of the proteomics initiative, according to Laurence Miller, director of research and the cancer center at the Arizona Mayo Clinic. “The alliance will put Arizona in a stronger position to compete for federal and private research funding,” Mobley says.
The effort builds on the vast knowledge generated by the Human Genome Project, which has mapped roughly 25,000 genes. Each gene codes for the production of protein, but with all the modifications possible to both the gene transcript and protein, the human body could have well over a million different proteins, according to the Human Proteome Initiative. This entourage of proteins, the proteome, is ultimately responsible for everything, good or bad, related to human health and disease. Developing tests to rapidly obtain protein profiles as a predictive marker for disease or identifying therapeutic targets benefit health care and medicine.
Leslie Tolbert, vice president for research, graduate studies and economic development at U of A, said that the pooling of technologies statewide would allow researchers to maximize capabilities and minimize costs in a field that requires the development of new research methods. For example, this collaborative effort is expected to foster an expansion of the cancer research initiative at Banner Health, the state’s largest hospital system, says Susan Edwards, president of the Arizona region for Banner Health. A unifying research approach within the alliance is “integrative proteomics,” which involves advancing the processes, methods and technologies that elucidate the role of proteins within an integrated understanding of human biology, according to Mark Hayes, director of Arizona Applied NanoSensors in the College of Liberal Arts and Sciences at ASU. “This means developing proteomics research capabilities so that they are complementary to other advancing fields like genomics, bioinformatics and clinical research,” says Hayes, who was an early champion for the expansion of regional proteomics and the formation of this alliance.
The alliance has just launched a Web site (http://www.integrativeproteomics.org/) where researchers can exchange information about resources and the important problems they are working together to solve. “Collaboration is one of the things that sets Arizona science apart from other states, where competition is more often the rule,” says Joseph Rogers, president and senior scientist of the Sun Health Research Institute. The important partnerships formed in proteomics are expected to not only expand research efforts and improve chances for greater funding, but also to promote the future recruitment and training of talented individuals for the field of health care in Arizona.
The Arizona Proteomics Alliance (AZPA), a statewide consortium, has been formed to advance the emergent science of proteomics, a science whose broad vision is to understand the biological role of the complete set of proteins in the human body, or proteome. The initiative combines the expertise of nine leading Arizona institutions, including ASU, Banner Health, Barrow Neurological Institute, Carl T. Hayden Veterans Affairs Medical Center, Intrinsic Bioprobes Inc., Mayo Clinic, Sun Health Research Institute, Translational Genomics Research Institute (TGen) and the University of Arizona (U of A). “This alliance places Arizona in the forefront of proteomics research capabilities and will no doubt have broad impact on biomedical research and personalized medicine,” said Jeff Trent, president and scientific director of TGen.
AZPA promotes a team approach to solving problems of significant biomedical interest, according to Michael Mobley, administrative director of AZPA and associate director of the Biodesign Institute at ASU. The alliance will advance the role of proteomics research in the understanding of human health and disease by creating a network of scientists who share resources and expertise.
“AZPA facilitates access to technical and intellectual resources that are rarely surpassed within the United States, and provides the state with a distinct competitive advantage in this field,” says Serrine Lau, scientific director of AZPA, director of Southwest Environmental Health Sciences Center at the U of A’s College of Pharmacy, and a member of U of A’s BIO5 Institute. “We are pleased that the resources of the Arizona Proteomics Consortium at U of A will be part of this state-wide alliance,” Lau says.
The Mayo Clinic is also expecting to be able to expand its efforts and bring new diagnostic and treatment options to its patients as part of the proteomics initiative, according to Laurence Miller, director of research and the cancer center at the Arizona Mayo Clinic. “The alliance will put Arizona in a stronger position to compete for federal and private research funding,” Mobley says.
The effort builds on the vast knowledge generated by the Human Genome Project, which has mapped roughly 25,000 genes. Each gene codes for the production of protein, but with all the modifications possible to both the gene transcript and protein, the human body could have well over a million different proteins, according to the Human Proteome Initiative. This entourage of proteins, the proteome, is ultimately responsible for everything, good or bad, related to human health and disease. Developing tests to rapidly obtain protein profiles as a predictive marker for disease or identifying therapeutic targets benefit health care and medicine.
Leslie Tolbert, vice president for research, graduate studies and economic development at U of A, said that the pooling of technologies statewide would allow researchers to maximize capabilities and minimize costs in a field that requires the development of new research methods. For example, this collaborative effort is expected to foster an expansion of the cancer research initiative at Banner Health, the state’s largest hospital system, says Susan Edwards, president of the Arizona region for Banner Health. A unifying research approach within the alliance is “integrative proteomics,” which involves advancing the processes, methods and technologies that elucidate the role of proteins within an integrated understanding of human biology, according to Mark Hayes, director of Arizona Applied NanoSensors in the College of Liberal Arts and Sciences at ASU. “This means developing proteomics research capabilities so that they are complementary to other advancing fields like genomics, bioinformatics and clinical research,” says Hayes, who was an early champion for the expansion of regional proteomics and the formation of this alliance.
The alliance has just launched a Web site (http://www.integrativeproteomics.org/) where researchers can exchange information about resources and the important problems they are working together to solve. “Collaboration is one of the things that sets Arizona science apart from other states, where competition is more often the rule,” says Joseph Rogers, president and senior scientist of the Sun Health Research Institute. The important partnerships formed in proteomics are expected to not only expand research efforts and improve chances for greater funding, but also to promote the future recruitment and training of talented individuals for the field of health care in Arizona.
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