Adipose tissue

Preclinical research raises the prospect of more effective treatments for cachexia, a profound wasting of fat and muscle that can increase the risk of death in cancer patients.

In mouse models, an antibody effectively improved or prevented symptoms of cachexia.

The antibody inhibited the effects of parathyroid hormone-related protein (PTHrP), which is released from many types of cancer cells.

The researchers said their findings, published in Nature, are the first to explain in detail how PTHrP from tumors switches on a thermogenic process in fatty tissues, resulting in unhealthy weight loss.

The team carried out 2 experiments using mice that developed lung tumors and cachexia. In the first, a polyclonal antibody that specifically neutralizes PTHrP prevented cachexia almost completely, while untreated animals became mildly cachexic.

Anti-PTHrP treatment prevented the shrinkage of fat droplets. It blocked thermogenic gene expression in epididymal white adipose tissue, interscapular brown adipose tissue, and inguinal white adipose tissue, which suggests thermogenesis has a causal role in fat wasting.

Treatment with the anti-PTHrP antibody also lowered oxygen consumption in the mice, increased their physical activity, and reduced their heat production.

In the second experiment, the researchers treated mice with the anti-PTHrP antibody until they observed severe cachexia in control animals. The antibody significantly preserved muscle mass, which was evident by improved grip strength and in situ muscle contraction.

“You would have expected, based on our first experiments in cell culture, that blocking PTHrP in the mice would reduce browning of the fat,” said study author Bruce Spiegelman, PhD, of the Dana-Farber Cancer Institute in Boston.

“But we were surprised that it also affected the loss of muscle mass and improved health.”

Additional experiments, in which the researchers injected PTHrP into healthy and tumor-bearing mice, suggested that PTHrP alone doesn’t directly cause muscle wasting. But blocking the protein’s activity still prevents cachexia.

Thus, the role of PTHrP “is definitely not the whole answer” to the riddle of cachexia, Dr Spiegelman noted. Furthermore, it may turn out that the PTHrP mechanism is responsible for cachexia in only a subset of cancer patients.

The researchers analyzed blood samples from 47 cachexic patients with lung or colon cancer. And they found increased levels of PTHrP in 17 of the patients. Those patients had significantly lower lean body mass and were producing more heat energy at rest than the other patients in the group.

Dr Spiegelman noted that, before they test the anti-PTHrP antibody in clinical trials, clinicians would likely want to determine if the protein is elevated in certain cancers and determine which patients would be good candidates for the treatment.

Adipose tissue

Preclinical research raises the prospect of more effective treatments for cachexia, a profound wasting of fat and muscle that can increase the risk of death in cancer patients.

In mouse models, an antibody effectively improved or prevented symptoms of cachexia.

The antibody inhibited the effects of parathyroid hormone-related protein (PTHrP), which is released from many types of cancer cells.

The researchers said their findings, published in Nature, are the first to explain in detail how PTHrP from tumors switches on a thermogenic process in fatty tissues, resulting in unhealthy weight loss.

The team carried out 2 experiments using mice that developed lung tumors and cachexia. In the first, a polyclonal antibody that specifically neutralizes PTHrP prevented cachexia almost completely, while untreated animals became mildly cachexic.

Anti-PTHrP treatment prevented the shrinkage of fat droplets. It blocked thermogenic gene expression in epididymal white adipose tissue, interscapular brown adipose tissue, and inguinal white adipose tissue, which suggests thermogenesis has a causal role in fat wasting.

Treatment with the anti-PTHrP antibody also lowered oxygen consumption in the mice, increased their physical activity, and reduced their heat production.

In the second experiment, the researchers treated mice with the anti-PTHrP antibody until they observed severe cachexia in control animals. The antibody significantly preserved muscle mass, which was evident by improved grip strength and in situ muscle contraction.

“You would have expected, based on our first experiments in cell culture, that blocking PTHrP in the mice would reduce browning of the fat,” said study author Bruce Spiegelman, PhD, of the Dana-Farber Cancer Institute in Boston.

“But we were surprised that it also affected the loss of muscle mass and improved health.”

Additional experiments, in which the researchers injected PTHrP into healthy and tumor-bearing mice, suggested that PTHrP alone doesn’t directly cause muscle wasting. But blocking the protein’s activity still prevents cachexia.

Thus, the role of PTHrP “is definitely not the whole answer” to the riddle of cachexia, Dr Spiegelman noted. Furthermore, it may turn out that the PTHrP mechanism is responsible for cachexia in only a subset of cancer patients.

The researchers analyzed blood samples from 47 cachexic patients with lung or colon cancer. And they found increased levels of PTHrP in 17 of the patients. Those patients had significantly lower lean body mass and were producing more heat energy at rest than the other patients in the group.

Dr Spiegelman noted that, before they test the anti-PTHrP antibody in clinical trials, clinicians would likely want to determine if the protein is elevated in certain cancers and determine which patients would be good candidates for the treatment.

Adipose tissue

Preclinical research raises the prospect of more effective treatments for cachexia, a profound wasting of fat and muscle that can increase the risk of death in cancer patients.

In mouse models, an antibody effectively improved or prevented symptoms of cachexia.

The antibody inhibited the effects of parathyroid hormone-related protein (PTHrP), which is released from many types of cancer cells.

The researchers said their findings, published in Nature, are the first to explain in detail how PTHrP from tumors switches on a thermogenic process in fatty tissues, resulting in unhealthy weight loss.

The team carried out 2 experiments using mice that developed lung tumors and cachexia. In the first, a polyclonal antibody that specifically neutralizes PTHrP prevented cachexia almost completely, while untreated animals became mildly cachexic.

Anti-PTHrP treatment prevented the shrinkage of fat droplets. It blocked thermogenic gene expression in epididymal white adipose tissue, interscapular brown adipose tissue, and inguinal white adipose tissue, which suggests thermogenesis has a causal role in fat wasting.

Treatment with the anti-PTHrP antibody also lowered oxygen consumption in the mice, increased their physical activity, and reduced their heat production.

In the second experiment, the researchers treated mice with the anti-PTHrP antibody until they observed severe cachexia in control animals. The antibody significantly preserved muscle mass, which was evident by improved grip strength and in situ muscle contraction.

“You would have expected, based on our first experiments in cell culture, that blocking PTHrP in the mice would reduce browning of the fat,” said study author Bruce Spiegelman, PhD, of the Dana-Farber Cancer Institute in Boston.

“But we were surprised that it also affected the loss of muscle mass and improved health.”

Additional experiments, in which the researchers injected PTHrP into healthy and tumor-bearing mice, suggested that PTHrP alone doesn’t directly cause muscle wasting. But blocking the protein’s activity still prevents cachexia.

Thus, the role of PTHrP “is definitely not the whole answer” to the riddle of cachexia, Dr Spiegelman noted. Furthermore, it may turn out that the PTHrP mechanism is responsible for cachexia in only a subset of cancer patients.

The researchers analyzed blood samples from 47 cachexic patients with lung or colon cancer. And they found increased levels of PTHrP in 17 of the patients. Those patients had significantly lower lean body mass and were producing more heat energy at rest than the other patients in the group.

Dr Spiegelman noted that, before they test the anti-PTHrP antibody in clinical trials, clinicians would likely want to determine if the protein is elevated in certain cancers and determine which patients would be good candidates for the treatment.

Lab mouse

Scientists say they’ve generated a mouse model that supports the transplantation of human hematopoietic stem cells (HSCs), despite the species barrier and without the need for irradiation.

The group used a mutation of the Kit receptor in the mouse stem cells to facilitate the engraftment of human cells.

In this model, human HSCs can expand and differentiate into all blood cell types without any additional treatment.

Even cells of the innate immune system that are not typically found in “humanized” mice were efficiently generated in this mouse.

Furthermore, the stem cells can be maintained in the mouse over a longer period of time.

The researchers reported these results in Cell Stem Cell.

“Our goal was to develop an optimal model for the transplantation and study of human blood stem cells,” said study author Claudia Waskow, PhD, of Technische Universität Dresden in Germany.

To achieve optimal stem cell engraftment, she and her colleagues introduced a naturally occurring mutation of the Kit receptor into mice lacking a functional immune system.

In this way, the team circumvented the 2 major obstacles of HSC transplantation: the rejection by the recipient’s immune system and the absence of free niche space for the incoming donor stem cells in the recipient’s bone marrow.

The Kit mutation in the new mouse model impairs the recipient’s stem cell compartment in such a way that the endogenous HSCs can be easily replaced by human donor stem cells with a functional Kit receptor.

The researchers said this replacement works so efficiently that irradiation can be completely omitted, allowing the study of human blood development in a physiological setting. The model can now be used to study diseases of the human blood and immune system or to test new treatment options.

The results of this research also show that the Kit receptor is important for the function of human HSCs, notably in a transplant setting. The researchers said future studies will focus on using this knowledge to improve conditioning therapy for patients undergoing HSC transplant.

Lab mouse

Scientists say they’ve generated a mouse model that supports the transplantation of human hematopoietic stem cells (HSCs), despite the species barrier and without the need for irradiation.

The group used a mutation of the Kit receptor in the mouse stem cells to facilitate the engraftment of human cells.

In this model, human HSCs can expand and differentiate into all blood cell types without any additional treatment.

Even cells of the innate immune system that are not typically found in “humanized” mice were efficiently generated in this mouse.

Furthermore, the stem cells can be maintained in the mouse over a longer period of time.

The researchers reported these results in Cell Stem Cell.

“Our goal was to develop an optimal model for the transplantation and study of human blood stem cells,” said study author Claudia Waskow, PhD, of Technische Universität Dresden in Germany.

To achieve optimal stem cell engraftment, she and her colleagues introduced a naturally occurring mutation of the Kit receptor into mice lacking a functional immune system.

In this way, the team circumvented the 2 major obstacles of HSC transplantation: the rejection by the recipient’s immune system and the absence of free niche space for the incoming donor stem cells in the recipient’s bone marrow.

The Kit mutation in the new mouse model impairs the recipient’s stem cell compartment in such a way that the endogenous HSCs can be easily replaced by human donor stem cells with a functional Kit receptor.

The researchers said this replacement works so efficiently that irradiation can be completely omitted, allowing the study of human blood development in a physiological setting. The model can now be used to study diseases of the human blood and immune system or to test new treatment options.

The results of this research also show that the Kit receptor is important for the function of human HSCs, notably in a transplant setting. The researchers said future studies will focus on using this knowledge to improve conditioning therapy for patients undergoing HSC transplant.

Lab mouse

Scientists say they’ve generated a mouse model that supports the transplantation of human hematopoietic stem cells (HSCs), despite the species barrier and without the need for irradiation.

The group used a mutation of the Kit receptor in the mouse stem cells to facilitate the engraftment of human cells.

In this model, human HSCs can expand and differentiate into all blood cell types without any additional treatment.

Even cells of the innate immune system that are not typically found in “humanized” mice were efficiently generated in this mouse.

Furthermore, the stem cells can be maintained in the mouse over a longer period of time.

The researchers reported these results in Cell Stem Cell.

“Our goal was to develop an optimal model for the transplantation and study of human blood stem cells,” said study author Claudia Waskow, PhD, of Technische Universität Dresden in Germany.

To achieve optimal stem cell engraftment, she and her colleagues introduced a naturally occurring mutation of the Kit receptor into mice lacking a functional immune system.

In this way, the team circumvented the 2 major obstacles of HSC transplantation: the rejection by the recipient’s immune system and the absence of free niche space for the incoming donor stem cells in the recipient’s bone marrow.

The Kit mutation in the new mouse model impairs the recipient’s stem cell compartment in such a way that the endogenous HSCs can be easily replaced by human donor stem cells with a functional Kit receptor.

The researchers said this replacement works so efficiently that irradiation can be completely omitted, allowing the study of human blood development in a physiological setting. The model can now be used to study diseases of the human blood and immune system or to test new treatment options.

The results of this research also show that the Kit receptor is important for the function of human HSCs, notably in a transplant setting. The researchers said future studies will focus on using this knowledge to improve conditioning therapy for patients undergoing HSC transplant.

COPENHAGEN – The location of cerebral microbleeds appears to be strongly associated with dementia subtypes, perhaps reflecting the disorders’ underlying pathologies.

"This regional association with dementia subtypes is consistent with the hypothesis that lobar cerebral microbleeds reflect cerebral amyloid angiopathy, which is consistent with Alzheimer’s disease, while those in deep areas reflect hypertensive arteriopathy, which is important in vascular dementia," Lenore Launer, Ph.D., said at the Alzheimer’s Association International Conference 2014.

Dr. Launer, chief of the neuroepidemiology section in the laboratory of epidemiology and population science at the National Institute on Aging, and her colleagues examined the relationship between incident microbleeds and dementia in the AGES (Age, Gene/Environment Susceptibility) Reykjavik Study.

The population-based study is a project of the Icelandic Heart Association. It was established in 1967 and has followed more than 9,000 people, all of whom were born between 1907 and 1935. In 2000, the group partnered with the National Institute on Aging to further study diseases of old age, with an emphasis on imaging.

Since then, participants have undergone extensive phenotyping and repeat brain imaging to look specifically at cerebral microbleeds, infarcts, white-matter hyperintensities, and whole-brain volume.

Dr. Launer’s study comprised 2,482 people who were without stroke or dementia at baseline and who had complete brain MRI data during two 5-year periods: 2002-2006 and 2007-2011.

At baseline, patients’ mean age was 75 years. About 25% were carriers of the apolipoprotein E epsilon 4 allele. Hypertension was common (77% of patients). Almost a third of patients (29%) had brain infarct–like lesions, 11% had white-matter hyperintensities, and 16% had cerebral microbleeds.

Over the study period, 458 (18%) of the cohort’s patients developed new microbleeds, with 30% of those developing multiple bleeds. Of those new microbleeds, 64% were strictly lobar, with 1-15 bleeds per person. The remainder were deep lesions, numbering 1-19 per person.

There were 111 new dementia cases; of those, 83 were diagnosed as Alzheimer’s and 17 as vascular dementia. The rest were designated as "other dementia."

Two multivariate regression analyses examined the relationship between microbleed location and dementia subtype. Both controlled for a number of clinical and demographic factors. The first analysis included age, gender, and baseline cerebral microbleeds. The second analysis included all of those factors, plus education, depression, baseline vascular risk factors (hypertension, smoking, diabetes, body mass index, and total cholesterol), and baseline MRI markers (infarcts, total brain volume, and hyperintense lesions).

In the fully adjusted model, microbleed location showed a significant relationship with dementia subtypes. Lobar microbleeds were associated with a doubling in the risk of Alzheimer’s disease, while deep bleeds increased the risk of vascular dementia sixfold.

"It’s difficult to disentangle the temporal relationship here," Dr. Launer said. "But incident cerebral microbleeds may indicate more severe small-vessel disease, and be the thing that pushes a person off the cliff into the clinical presentation of dementia."

The Icelandic Heart Association and the National Institute on Aging sponsored the study. As a government employee, Dr. Launer has no financial disclosures.

[email protected]

On Twitter @alz_gal

COPENHAGEN – The location of cerebral microbleeds appears to be strongly associated with dementia subtypes, perhaps reflecting the disorders’ underlying pathologies.

"This regional association with dementia subtypes is consistent with the hypothesis that lobar cerebral microbleeds reflect cerebral amyloid angiopathy, which is consistent with Alzheimer’s disease, while those in deep areas reflect hypertensive arteriopathy, which is important in vascular dementia," Lenore Launer, Ph.D., said at the Alzheimer’s Association International Conference 2014.

Dr. Launer, chief of the neuroepidemiology section in the laboratory of epidemiology and population science at the National Institute on Aging, and her colleagues examined the relationship between incident microbleeds and dementia in the AGES (Age, Gene/Environment Susceptibility) Reykjavik Study.

The population-based study is a project of the Icelandic Heart Association. It was established in 1967 and has followed more than 9,000 people, all of whom were born between 1907 and 1935. In 2000, the group partnered with the National Institute on Aging to further study diseases of old age, with an emphasis on imaging.

Since then, participants have undergone extensive phenotyping and repeat brain imaging to look specifically at cerebral microbleeds, infarcts, white-matter hyperintensities, and whole-brain volume.

Dr. Launer’s study comprised 2,482 people who were without stroke or dementia at baseline and who had complete brain MRI data during two 5-year periods: 2002-2006 and 2007-2011.

At baseline, patients’ mean age was 75 years. About 25% were carriers of the apolipoprotein E epsilon 4 allele. Hypertension was common (77% of patients). Almost a third of patients (29%) had brain infarct–like lesions, 11% had white-matter hyperintensities, and 16% had cerebral microbleeds.

Over the study period, 458 (18%) of the cohort’s patients developed new microbleeds, with 30% of those developing multiple bleeds. Of those new microbleeds, 64% were strictly lobar, with 1-15 bleeds per person. The remainder were deep lesions, numbering 1-19 per person.

There were 111 new dementia cases; of those, 83 were diagnosed as Alzheimer’s and 17 as vascular dementia. The rest were designated as "other dementia."

Two multivariate regression analyses examined the relationship between microbleed location and dementia subtype. Both controlled for a number of clinical and demographic factors. The first analysis included age, gender, and baseline cerebral microbleeds. The second analysis included all of those factors, plus education, depression, baseline vascular risk factors (hypertension, smoking, diabetes, body mass index, and total cholesterol), and baseline MRI markers (infarcts, total brain volume, and hyperintense lesions).

In the fully adjusted model, microbleed location showed a significant relationship with dementia subtypes. Lobar microbleeds were associated with a doubling in the risk of Alzheimer’s disease, while deep bleeds increased the risk of vascular dementia sixfold.

"It’s difficult to disentangle the temporal relationship here," Dr. Launer said. "But incident cerebral microbleeds may indicate more severe small-vessel disease, and be the thing that pushes a person off the cliff into the clinical presentation of dementia."

The Icelandic Heart Association and the National Institute on Aging sponsored the study. As a government employee, Dr. Launer has no financial disclosures.

[email protected]

On Twitter @alz_gal

COPENHAGEN – The location of cerebral microbleeds appears to be strongly associated with dementia subtypes, perhaps reflecting the disorders’ underlying pathologies.

"This regional association with dementia subtypes is consistent with the hypothesis that lobar cerebral microbleeds reflect cerebral amyloid angiopathy, which is consistent with Alzheimer’s disease, while those in deep areas reflect hypertensive arteriopathy, which is important in vascular dementia," Lenore Launer, Ph.D., said at the Alzheimer’s Association International Conference 2014.

Dr. Launer, chief of the neuroepidemiology section in the laboratory of epidemiology and population science at the National Institute on Aging, and her colleagues examined the relationship between incident microbleeds and dementia in the AGES (Age, Gene/Environment Susceptibility) Reykjavik Study.

The population-based study is a project of the Icelandic Heart Association. It was established in 1967 and has followed more than 9,000 people, all of whom were born between 1907 and 1935. In 2000, the group partnered with the National Institute on Aging to further study diseases of old age, with an emphasis on imaging.

Since then, participants have undergone extensive phenotyping and repeat brain imaging to look specifically at cerebral microbleeds, infarcts, white-matter hyperintensities, and whole-brain volume.

Dr. Launer’s study comprised 2,482 people who were without stroke or dementia at baseline and who had complete brain MRI data during two 5-year periods: 2002-2006 and 2007-2011.

At baseline, patients’ mean age was 75 years. About 25% were carriers of the apolipoprotein E epsilon 4 allele. Hypertension was common (77% of patients). Almost a third of patients (29%) had brain infarct–like lesions, 11% had white-matter hyperintensities, and 16% had cerebral microbleeds.

Over the study period, 458 (18%) of the cohort’s patients developed new microbleeds, with 30% of those developing multiple bleeds. Of those new microbleeds, 64% were strictly lobar, with 1-15 bleeds per person. The remainder were deep lesions, numbering 1-19 per person.

There were 111 new dementia cases; of those, 83 were diagnosed as Alzheimer’s and 17 as vascular dementia. The rest were designated as "other dementia."

Two multivariate regression analyses examined the relationship between microbleed location and dementia subtype. Both controlled for a number of clinical and demographic factors. The first analysis included age, gender, and baseline cerebral microbleeds. The second analysis included all of those factors, plus education, depression, baseline vascular risk factors (hypertension, smoking, diabetes, body mass index, and total cholesterol), and baseline MRI markers (infarcts, total brain volume, and hyperintense lesions).

In the fully adjusted model, microbleed location showed a significant relationship with dementia subtypes. Lobar microbleeds were associated with a doubling in the risk of Alzheimer’s disease, while deep bleeds increased the risk of vascular dementia sixfold.

"It’s difficult to disentangle the temporal relationship here," Dr. Launer said. "But incident cerebral microbleeds may indicate more severe small-vessel disease, and be the thing that pushes a person off the cliff into the clinical presentation of dementia."

The Icelandic Heart Association and the National Institute on Aging sponsored the study. As a government employee, Dr. Launer has no financial disclosures.

[email protected]

On Twitter @alz_gal

Adults who consumed high levels of omega-3 polyunsaturated fatty acids showed a markedly reduced risk of developing amyotrophic lateral sclerosis in a pooled analysis of five large prospective cohort studies that assessed diet.

Diet-derived omega-3 polyunsaturated fatty acids (PUFAs) are known to have neuroprotective effects, and those present in neural plasma membranes can modulate oxidative stress, excitotoxicity, and inflammation. But no prospective studies have explored a possible relationship between omega-3 PUFA intake and amyotrophic lateral sclerosis (ALS) risk, according to Kathryn C. Fitzgerald of the department of nutrition, Harvard School of Public Health, Boston, and her associates.

© Suprijono Suharjoto - Fotolia.com

In a study published July 14 in JAMA Neurology, Ms. Fitzgerald and her colleagues pooled data from the Health Professionals Follow-up Study, the Nurses’ Health Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health-AARP Diet and Health Study. A total of 995 ALS patients were identified among 1,002,082 participants in these studies. The five studies included detailed dietary information and tracked the occurrence of ALS in the study participants through the National Death Index.

Omega-3 PUFA intake in the highest quintile of consumption at a median of 2.11 g/day was associated with a 34% reduced risk of developing ALS, compared with the lowest quintile of consumption at a median of 0.94 g/day. This finding was consistent across all five studies. This means that adding 0.5% of energy from omega-3 PUFAs and maintaining a constant intake of omega-6 fatty acids while reducing the intake of other types of fat would reduce ALS risk by 34%. Consumption of alpha-linolenic acid, another PUFA, also was associated with significantly reduced risk of developing ALS. In contrast, consumption of omega-6 PUFAs, consumption of linolenic acid, total energy intake, and percentage of energy from other types of fat showed no association with ALS risk, the investigators said (JAMA Neurol. 2014 July 14 [doi:10.1001/jamaneurol.2014.1214]).

Foods that are rich in omega-3 PUFAs include fatty fish (salmon, sardines, tuna, herring) and fish oils; vegetable oils (corn, safflower, canola, soy, and flaxseed oils); and nuts and seeds (walnuts, chia seeds, butternuts, and sunflower seeds). Further studies are needed to confirm this protective effect in ALS and to determine whether patients who already have the disease would benefit from the addition of omega-3 PUFAs to their diets, Ms. Fitzgerald and her associates added.

The findings from Ms. Fitzgerald and her associates are persuasive and consistent with earlier suggestions that PUFAs may play a role in other neurodegenerative conditions, Dr. Michael Swash said in a related editorial (JAMA Neurol. 2014 July 14 [doi:10.1001/jamaneurol.2014.1894]).

"Ideas on long-term risk-susceptibility factors are very much welcomed in trying to unravel the mystery that is ALS. Now, in addition to genetic factors, there are the following five risk factors to work on: male sex, smoking status, BMI, physical exercise, and dietary intake of PUFAs," said Dr. Swash of the Royal London Hospital, Queen Mary University of London, and the Institute of Neuroscience at the University of Lisbon.

This study was supported by the National Institute of Neurological Diseases and Stroke, the National Cancer Institute, and the ALS Therapy Alliance Foundation. The study authors and Dr. Swash had no financial disclosures.

Adults who consumed high levels of omega-3 polyunsaturated fatty acids showed a markedly reduced risk of developing amyotrophic lateral sclerosis in a pooled analysis of five large prospective cohort studies that assessed diet.

Diet-derived omega-3 polyunsaturated fatty acids (PUFAs) are known to have neuroprotective effects, and those present in neural plasma membranes can modulate oxidative stress, excitotoxicity, and inflammation. But no prospective studies have explored a possible relationship between omega-3 PUFA intake and amyotrophic lateral sclerosis (ALS) risk, according to Kathryn C. Fitzgerald of the department of nutrition, Harvard School of Public Health, Boston, and her associates.

© Suprijono Suharjoto - Fotolia.com

In a study published July 14 in JAMA Neurology, Ms. Fitzgerald and her colleagues pooled data from the Health Professionals Follow-up Study, the Nurses’ Health Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health-AARP Diet and Health Study. A total of 995 ALS patients were identified among 1,002,082 participants in these studies. The five studies included detailed dietary information and tracked the occurrence of ALS in the study participants through the National Death Index.

Omega-3 PUFA intake in the highest quintile of consumption at a median of 2.11 g/day was associated with a 34% reduced risk of developing ALS, compared with the lowest quintile of consumption at a median of 0.94 g/day. This finding was consistent across all five studies. This means that adding 0.5% of energy from omega-3 PUFAs and maintaining a constant intake of omega-6 fatty acids while reducing the intake of other types of fat would reduce ALS risk by 34%. Consumption of alpha-linolenic acid, another PUFA, also was associated with significantly reduced risk of developing ALS. In contrast, consumption of omega-6 PUFAs, consumption of linolenic acid, total energy intake, and percentage of energy from other types of fat showed no association with ALS risk, the investigators said (JAMA Neurol. 2014 July 14 [doi:10.1001/jamaneurol.2014.1214]).

Foods that are rich in omega-3 PUFAs include fatty fish (salmon, sardines, tuna, herring) and fish oils; vegetable oils (corn, safflower, canola, soy, and flaxseed oils); and nuts and seeds (walnuts, chia seeds, butternuts, and sunflower seeds). Further studies are needed to confirm this protective effect in ALS and to determine whether patients who already have the disease would benefit from the addition of omega-3 PUFAs to their diets, Ms. Fitzgerald and her associates added.

The findings from Ms. Fitzgerald and her associates are persuasive and consistent with earlier suggestions that PUFAs may play a role in other neurodegenerative conditions, Dr. Michael Swash said in a related editorial (JAMA Neurol. 2014 July 14 [doi:10.1001/jamaneurol.2014.1894]).

"Ideas on long-term risk-susceptibility factors are very much welcomed in trying to unravel the mystery that is ALS. Now, in addition to genetic factors, there are the following five risk factors to work on: male sex, smoking status, BMI, physical exercise, and dietary intake of PUFAs," said Dr. Swash of the Royal London Hospital, Queen Mary University of London, and the Institute of Neuroscience at the University of Lisbon.

This study was supported by the National Institute of Neurological Diseases and Stroke, the National Cancer Institute, and the ALS Therapy Alliance Foundation. The study authors and Dr. Swash had no financial disclosures.

Adults who consumed high levels of omega-3 polyunsaturated fatty acids showed a markedly reduced risk of developing amyotrophic lateral sclerosis in a pooled analysis of five large prospective cohort studies that assessed diet.

Diet-derived omega-3 polyunsaturated fatty acids (PUFAs) are known to have neuroprotective effects, and those present in neural plasma membranes can modulate oxidative stress, excitotoxicity, and inflammation. But no prospective studies have explored a possible relationship between omega-3 PUFA intake and amyotrophic lateral sclerosis (ALS) risk, according to Kathryn C. Fitzgerald of the department of nutrition, Harvard School of Public Health, Boston, and her associates.

© Suprijono Suharjoto - Fotolia.com

In a study published July 14 in JAMA Neurology, Ms. Fitzgerald and her colleagues pooled data from the Health Professionals Follow-up Study, the Nurses’ Health Study, the Cancer Prevention Study II Nutrition Cohort, the Multiethnic Cohort Study, and the National Institutes of Health-AARP Diet and Health Study. A total of 995 ALS patients were identified among 1,002,082 participants in these studies. The five studies included detailed dietary information and tracked the occurrence of ALS in the study participants through the National Death Index.

Omega-3 PUFA intake in the highest quintile of consumption at a median of 2.11 g/day was associated with a 34% reduced risk of developing ALS, compared with the lowest quintile of consumption at a median of 0.94 g/day. This finding was consistent across all five studies. This means that adding 0.5% of energy from omega-3 PUFAs and maintaining a constant intake of omega-6 fatty acids while reducing the intake of other types of fat would reduce ALS risk by 34%. Consumption of alpha-linolenic acid, another PUFA, also was associated with significantly reduced risk of developing ALS. In contrast, consumption of omega-6 PUFAs, consumption of linolenic acid, total energy intake, and percentage of energy from other types of fat showed no association with ALS risk, the investigators said (JAMA Neurol. 2014 July 14 [doi:10.1001/jamaneurol.2014.1214]).

Foods that are rich in omega-3 PUFAs include fatty fish (salmon, sardines, tuna, herring) and fish oils; vegetable oils (corn, safflower, canola, soy, and flaxseed oils); and nuts and seeds (walnuts, chia seeds, butternuts, and sunflower seeds). Further studies are needed to confirm this protective effect in ALS and to determine whether patients who already have the disease would benefit from the addition of omega-3 PUFAs to their diets, Ms. Fitzgerald and her associates added.

The findings from Ms. Fitzgerald and her associates are persuasive and consistent with earlier suggestions that PUFAs may play a role in other neurodegenerative conditions, Dr. Michael Swash said in a related editorial (JAMA Neurol. 2014 July 14 [doi:10.1001/jamaneurol.2014.1894]).

"Ideas on long-term risk-susceptibility factors are very much welcomed in trying to unravel the mystery that is ALS. Now, in addition to genetic factors, there are the following five risk factors to work on: male sex, smoking status, BMI, physical exercise, and dietary intake of PUFAs," said Dr. Swash of the Royal London Hospital, Queen Mary University of London, and the Institute of Neuroscience at the University of Lisbon.

This study was supported by the National Institute of Neurological Diseases and Stroke, the National Cancer Institute, and the ALS Therapy Alliance Foundation. The study authors and Dr. Swash had no financial disclosures.

 

 

Patient receiving chemotherapy

Credit: Rhoda Baer

 

Differences in treatment access and quality may explain why survival rates vary widely for European patients with hematologic malignancies, researchers have reported in The Lancet Oncology.

“The good news is that 5-year survival for most cancers of the blood has increased over the past 11 years, most likely reflecting the approval of new targeted drugs in the early 2000s . . . ,” said Milena Sant, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy.

“But there continue to be persistent differences between regions. For example, the uptake and use of new technologies and effective treatments has been far slower in eastern Europe than other regions. This might have contributed to the large differences in the management and outcomes of patients.”

Dr Sant and her colleagues uncovered these differences by analyzing data from 30 cancer registries covering all patients diagnosed in 20 European countries.*

The researchers compared changes in 5-year survival for 560,444 adults (aged 15 years and older) who were diagnosed with 11 lymphoid and myeloid cancers between 1997 and 2008, and followed up to the end of 2008.

Some cancers have shown particularly large increases in survival between 1997-1999 and 2006-2008, such as follicular lymphoma (59% to 74%), diffuse large B-cell lymphoma (42% to 55%), chronic myeloid leukemia (32% to 54%), and acute promyelocytic leukemia (50% to 62%).

The greatest improvements in survival have been in northern, central, and eastern Europe, even though adults in eastern Europe (where survival in 1997 was the lowest) continue to have lower survival for most hematologic malignancies than elsewhere.

Survival gains have been lower in southern Europe and the UK. For example, improvements in 5-year chronic myeloid leukemia survival in northern Europe (29% to 60%) and central Europe (34% to 65%) have been persistently higher than in the UK (35% to 56%) and southern Europe (37% to 55%).

Overall, the risk of death within 5 years from diagnosis fell significantly for all malignancies except myelodysplastic syndromes. But not all regions have seen such improvements.

For example, compared with the UK, the excess risk of death was significantly higher in eastern Europe than in other regions for most of the cancers investigated, but significantly lower in northern Europe.

The researchers said the most likely reasons for continuing geographical differences in survival are inequalities in the provision of care and in the availability and use of new treatments.

“We know that rituximab, imatinib, thalidomide, and bortezomib were first made available for general use in Europe in 1997, 2001, 1998, and 2003, respectively,” the researchers wrote.

“The years following general release of these drugs coincided with large increases in survival for chronic myeloid leukemia, diffuse large B-cell lymphoma, and follicular lymphoma, with a smaller but still significant survival increase for multiple myeloma plasmacytoma.”

However, they pointed out that the uptake and use of these drugs has not been uniform across Europe. For example, market uptake of rituximab, imatinib, and bortezomib was lower in eastern Europe than elsewhere and might explain the consistently lower survival in this region.

Writing in a linked comment article, Alastair Munro, MD, of the University of Dundee Medical School in Scotland, questioned whether improvements in survival can be attributed to drugs alone.

He said that better understanding of the conclusions from this study (called EUROCARE-5) requires additional information about changes affecting survival according to disease categories, the distribution of histological subtypes and their relation with the age distribution of the population, the distribution of stages at diagnosis, and the timing of active intervention for indolent tumors.

*The areas included in the study were northern Europe (Denmark, Iceland, and Norway), the UK (England, Northern Ireland, Scotland, and Wales), central Europe (Austria, France, Germany, Switzerland, and The Netherlands), eastern Europe (Bulgaria, Estonia, Lithuania, Poland, and Slovakia), and southern Europe (Italy, Malta, and Slovenia).

 

 

Patient receiving chemotherapy

Credit: Rhoda Baer

 

Differences in treatment access and quality may explain why survival rates vary widely for European patients with hematologic malignancies, researchers have reported in The Lancet Oncology.

“The good news is that 5-year survival for most cancers of the blood has increased over the past 11 years, most likely reflecting the approval of new targeted drugs in the early 2000s . . . ,” said Milena Sant, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy.

“But there continue to be persistent differences between regions. For example, the uptake and use of new technologies and effective treatments has been far slower in eastern Europe than other regions. This might have contributed to the large differences in the management and outcomes of patients.”

Dr Sant and her colleagues uncovered these differences by analyzing data from 30 cancer registries covering all patients diagnosed in 20 European countries.*

The researchers compared changes in 5-year survival for 560,444 adults (aged 15 years and older) who were diagnosed with 11 lymphoid and myeloid cancers between 1997 and 2008, and followed up to the end of 2008.

Some cancers have shown particularly large increases in survival between 1997-1999 and 2006-2008, such as follicular lymphoma (59% to 74%), diffuse large B-cell lymphoma (42% to 55%), chronic myeloid leukemia (32% to 54%), and acute promyelocytic leukemia (50% to 62%).

The greatest improvements in survival have been in northern, central, and eastern Europe, even though adults in eastern Europe (where survival in 1997 was the lowest) continue to have lower survival for most hematologic malignancies than elsewhere.

Survival gains have been lower in southern Europe and the UK. For example, improvements in 5-year chronic myeloid leukemia survival in northern Europe (29% to 60%) and central Europe (34% to 65%) have been persistently higher than in the UK (35% to 56%) and southern Europe (37% to 55%).

Overall, the risk of death within 5 years from diagnosis fell significantly for all malignancies except myelodysplastic syndromes. But not all regions have seen such improvements.

For example, compared with the UK, the excess risk of death was significantly higher in eastern Europe than in other regions for most of the cancers investigated, but significantly lower in northern Europe.

The researchers said the most likely reasons for continuing geographical differences in survival are inequalities in the provision of care and in the availability and use of new treatments.

“We know that rituximab, imatinib, thalidomide, and bortezomib were first made available for general use in Europe in 1997, 2001, 1998, and 2003, respectively,” the researchers wrote.

“The years following general release of these drugs coincided with large increases in survival for chronic myeloid leukemia, diffuse large B-cell lymphoma, and follicular lymphoma, with a smaller but still significant survival increase for multiple myeloma plasmacytoma.”

However, they pointed out that the uptake and use of these drugs has not been uniform across Europe. For example, market uptake of rituximab, imatinib, and bortezomib was lower in eastern Europe than elsewhere and might explain the consistently lower survival in this region.

Writing in a linked comment article, Alastair Munro, MD, of the University of Dundee Medical School in Scotland, questioned whether improvements in survival can be attributed to drugs alone.

He said that better understanding of the conclusions from this study (called EUROCARE-5) requires additional information about changes affecting survival according to disease categories, the distribution of histological subtypes and their relation with the age distribution of the population, the distribution of stages at diagnosis, and the timing of active intervention for indolent tumors.

*The areas included in the study were northern Europe (Denmark, Iceland, and Norway), the UK (England, Northern Ireland, Scotland, and Wales), central Europe (Austria, France, Germany, Switzerland, and The Netherlands), eastern Europe (Bulgaria, Estonia, Lithuania, Poland, and Slovakia), and southern Europe (Italy, Malta, and Slovenia).

 

 

Patient receiving chemotherapy

Credit: Rhoda Baer

 

Differences in treatment access and quality may explain why survival rates vary widely for European patients with hematologic malignancies, researchers have reported in The Lancet Oncology.

“The good news is that 5-year survival for most cancers of the blood has increased over the past 11 years, most likely reflecting the approval of new targeted drugs in the early 2000s . . . ,” said Milena Sant, MD, of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy.

“But there continue to be persistent differences between regions. For example, the uptake and use of new technologies and effective treatments has been far slower in eastern Europe than other regions. This might have contributed to the large differences in the management and outcomes of patients.”

Dr Sant and her colleagues uncovered these differences by analyzing data from 30 cancer registries covering all patients diagnosed in 20 European countries.*

The researchers compared changes in 5-year survival for 560,444 adults (aged 15 years and older) who were diagnosed with 11 lymphoid and myeloid cancers between 1997 and 2008, and followed up to the end of 2008.

Some cancers have shown particularly large increases in survival between 1997-1999 and 2006-2008, such as follicular lymphoma (59% to 74%), diffuse large B-cell lymphoma (42% to 55%), chronic myeloid leukemia (32% to 54%), and acute promyelocytic leukemia (50% to 62%).

The greatest improvements in survival have been in northern, central, and eastern Europe, even though adults in eastern Europe (where survival in 1997 was the lowest) continue to have lower survival for most hematologic malignancies than elsewhere.

Survival gains have been lower in southern Europe and the UK. For example, improvements in 5-year chronic myeloid leukemia survival in northern Europe (29% to 60%) and central Europe (34% to 65%) have been persistently higher than in the UK (35% to 56%) and southern Europe (37% to 55%).

Overall, the risk of death within 5 years from diagnosis fell significantly for all malignancies except myelodysplastic syndromes. But not all regions have seen such improvements.

For example, compared with the UK, the excess risk of death was significantly higher in eastern Europe than in other regions for most of the cancers investigated, but significantly lower in northern Europe.

The researchers said the most likely reasons for continuing geographical differences in survival are inequalities in the provision of care and in the availability and use of new treatments.

“We know that rituximab, imatinib, thalidomide, and bortezomib were first made available for general use in Europe in 1997, 2001, 1998, and 2003, respectively,” the researchers wrote.

“The years following general release of these drugs coincided with large increases in survival for chronic myeloid leukemia, diffuse large B-cell lymphoma, and follicular lymphoma, with a smaller but still significant survival increase for multiple myeloma plasmacytoma.”

However, they pointed out that the uptake and use of these drugs has not been uniform across Europe. For example, market uptake of rituximab, imatinib, and bortezomib was lower in eastern Europe than elsewhere and might explain the consistently lower survival in this region.

Writing in a linked comment article, Alastair Munro, MD, of the University of Dundee Medical School in Scotland, questioned whether improvements in survival can be attributed to drugs alone.

He said that better understanding of the conclusions from this study (called EUROCARE-5) requires additional information about changes affecting survival according to disease categories, the distribution of histological subtypes and their relation with the age distribution of the population, the distribution of stages at diagnosis, and the timing of active intervention for indolent tumors.

*The areas included in the study were northern Europe (Denmark, Iceland, and Norway), the UK (England, Northern Ireland, Scotland, and Wales), central Europe (Austria, France, Germany, Switzerland, and The Netherlands), eastern Europe (Bulgaria, Estonia, Lithuania, Poland, and Slovakia), and southern Europe (Italy, Malta, and Slovenia).

Thrombus

Credit: Kevin MacKenzie

The US Food and Drug Administration (FDA) has placed a hold on patient enrollment and dosing of drugs under investigation in the phase 3 REGULATE-PCI trial.

The trial is a comparison of the reversible thrombin inhibitor bivalirudin and the Revolixys Kit—a 2-component system consisting of pegnivacogin, an anticoagulant aptamer targeting coagulation Factor IXa, and its complementary oligonucleotide active control agent, anivamersen—in patients undergoing percutaneous coronary intervention (PCI).

The company sponsoring the REGULATE-PCI trial, Regado Biosciences, had voluntarily halted enrollment prior to the FDA’s announcement. The FDA’s clinical hold formalizes its involvement in any decision to re-initiate enrollment and dosing in the trial in the future.

Regado stopped enrollment after its Data Safety Monitoring Board (DSMB) started an unplanned review of the study data. The board has said the review is focusing on serious adverse events and allergic reactions.

“[W]e remain blinded to REGULATE-PCI study data and are awaiting the outcome of the full safety and efficacy analysis, including an analysis of benefit/risk ratio, being performed by our DSMB,” said David J Mazzo, PhD, CEO of Regado.

“Any recommendation to re-initiate patient enrollment in REGULATE-PCI will be based on the DSMB’s conclusions and would always be implemented in agreement with FDA.”

The REGULATE-PCI trial is a comparison of the Revolixys Kit (formerly known as REG-1) with bivalirudin (Angiomax) in patients undergoing PCI. The goal is to enroll 13,200 patients, and 3234 have been enrolled to date.

Eligible patients are those receiving PCI electively or for the treatment of unstable angina or non-ST elevated myocardial infarction.

Patients randomized to the Revolixys arm receive pegnivacogin at a dose of 1 mg/kg along with an 80% reversal dose of anivamersen. The timing of the remaining 20% is at the discretion of the treating physician.

The trial is powered to show superiority in efficacy and noninferiority in safety of the Revolixys Kit compared to bivalirudin. The study’s primary endpoint is a composite of death, nonfatal myocardial infarction, nonfatal stroke, and urgent target lesion revascularization through day 3 post-PCI.

For more details, visit clinicaltrials.gov.

Thrombus

Credit: Kevin MacKenzie

The US Food and Drug Administration (FDA) has placed a hold on patient enrollment and dosing of drugs under investigation in the phase 3 REGULATE-PCI trial.

The trial is a comparison of the reversible thrombin inhibitor bivalirudin and the Revolixys Kit—a 2-component system consisting of pegnivacogin, an anticoagulant aptamer targeting coagulation Factor IXa, and its complementary oligonucleotide active control agent, anivamersen—in patients undergoing percutaneous coronary intervention (PCI).

The company sponsoring the REGULATE-PCI trial, Regado Biosciences, had voluntarily halted enrollment prior to the FDA’s announcement. The FDA’s clinical hold formalizes its involvement in any decision to re-initiate enrollment and dosing in the trial in the future.

Regado stopped enrollment after its Data Safety Monitoring Board (DSMB) started an unplanned review of the study data. The board has said the review is focusing on serious adverse events and allergic reactions.

“[W]e remain blinded to REGULATE-PCI study data and are awaiting the outcome of the full safety and efficacy analysis, including an analysis of benefit/risk ratio, being performed by our DSMB,” said David J Mazzo, PhD, CEO of Regado.

“Any recommendation to re-initiate patient enrollment in REGULATE-PCI will be based on the DSMB’s conclusions and would always be implemented in agreement with FDA.”

The REGULATE-PCI trial is a comparison of the Revolixys Kit (formerly known as REG-1) with bivalirudin (Angiomax) in patients undergoing PCI. The goal is to enroll 13,200 patients, and 3234 have been enrolled to date.

Eligible patients are those receiving PCI electively or for the treatment of unstable angina or non-ST elevated myocardial infarction.

Patients randomized to the Revolixys arm receive pegnivacogin at a dose of 1 mg/kg along with an 80% reversal dose of anivamersen. The timing of the remaining 20% is at the discretion of the treating physician.

The trial is powered to show superiority in efficacy and noninferiority in safety of the Revolixys Kit compared to bivalirudin. The study’s primary endpoint is a composite of death, nonfatal myocardial infarction, nonfatal stroke, and urgent target lesion revascularization through day 3 post-PCI.

For more details, visit clinicaltrials.gov.

Thrombus

Credit: Kevin MacKenzie

The US Food and Drug Administration (FDA) has placed a hold on patient enrollment and dosing of drugs under investigation in the phase 3 REGULATE-PCI trial.

The trial is a comparison of the reversible thrombin inhibitor bivalirudin and the Revolixys Kit—a 2-component system consisting of pegnivacogin, an anticoagulant aptamer targeting coagulation Factor IXa, and its complementary oligonucleotide active control agent, anivamersen—in patients undergoing percutaneous coronary intervention (PCI).

The company sponsoring the REGULATE-PCI trial, Regado Biosciences, had voluntarily halted enrollment prior to the FDA’s announcement. The FDA’s clinical hold formalizes its involvement in any decision to re-initiate enrollment and dosing in the trial in the future.

Regado stopped enrollment after its Data Safety Monitoring Board (DSMB) started an unplanned review of the study data. The board has said the review is focusing on serious adverse events and allergic reactions.

“[W]e remain blinded to REGULATE-PCI study data and are awaiting the outcome of the full safety and efficacy analysis, including an analysis of benefit/risk ratio, being performed by our DSMB,” said David J Mazzo, PhD, CEO of Regado.

“Any recommendation to re-initiate patient enrollment in REGULATE-PCI will be based on the DSMB’s conclusions and would always be implemented in agreement with FDA.”

The REGULATE-PCI trial is a comparison of the Revolixys Kit (formerly known as REG-1) with bivalirudin (Angiomax) in patients undergoing PCI. The goal is to enroll 13,200 patients, and 3234 have been enrolled to date.

Eligible patients are those receiving PCI electively or for the treatment of unstable angina or non-ST elevated myocardial infarction.

Patients randomized to the Revolixys arm receive pegnivacogin at a dose of 1 mg/kg along with an 80% reversal dose of anivamersen. The timing of the remaining 20% is at the discretion of the treating physician.

The trial is powered to show superiority in efficacy and noninferiority in safety of the Revolixys Kit compared to bivalirudin. The study’s primary endpoint is a composite of death, nonfatal myocardial infarction, nonfatal stroke, and urgent target lesion revascularization through day 3 post-PCI.

For more details, visit clinicaltrials.gov.

Berries are rich in antioxidants

Two researchers have offered an explanation as to why antioxidants are not effective in fighting cancers and suggested a way to change that.

The duo proposed that antioxidants from supplements or dietary sources are proving ineffective because they are not acting where reactive oxygen species (ROS) are produced.

So therapies that directly inhibit the production of mitochondrial- and NADPH oxidase-derived ROS, or that scavenge ROS at these sites, may be more effective.

David Tuveson, MD, PhD, of the Cold Spring Harbor Laboratory in New York, and Navdeep S. Chandel, PhD, of the Feinberg School of Medicine at Northwestern University in Chicago, detailed these theories in a report published in The New England Journal of Medicine.

The pair’s insights are based on recent advances in understanding the cell system that establishes a natural balance between oxidizing and antioxidizing compounds.

Oxidants like hydrogen peroxide are manufactured within cells and are essential in small quantities. But oxidants are toxic in large amounts, and cells naturally generate their own antioxidants to neutralize oxidants.

It has seemed logical, therefore, to boost a person’s intake of antioxidants to counter the effects of hydrogen peroxide and other similarly toxic ROS. All the more because cancer cells are known to generate higher levels of ROS to help feed their abnormal growth.

However, Drs Tuveson and Chandel proposed that taking antioxidant pills or eating foods rich in antioxidants may be failing to show a beneficial effect against cancer because antioxidants do not act where tumor-promoting ROS are produced—at mitochondria.

Rather, supplements and dietary antioxidants tend to accumulate at scattered distant sites in the cell, “leaving tumor-promoting ROS relatively unperturbed.”

Therefore, the authors suggested therapies that directly inhibit the production of mitochondrial- and NADPH oxidase-derived ROS, or that scavenge ROS at these sites, will be more effective than dietary antioxidants.

An alternative approach

Drs Tuveson and Chandel also proposed an alternative approach: disabling antioxidants in cancer cells. They noted that quantities of both ROS and natural antioxidants are higher in cancer cells. The higher levels of antioxidants are a natural defense by cancer cells to keep their higher levels of oxidants in check so that growth can continue.

In fact, therapies that raise the levels of oxidants in cells can be beneficial, whereas those that act as antioxidants may further stimulate the cancer cells.

So the authors suggested that genetic or pharmacologic inhibition of antioxidant proteins—a concept tested successfully in rodent models of lung and pancreatic cancers—may be a useful therapeutic approach in humans.

The key challenge is to identify antioxidant proteins and pathways in cells that are used only by cancer cells and not by healthy cells. Impeding antioxidant production in healthy cells will upset the delicate redox balance upon which normal cellular function depends.

So it seems research is needed to profile antioxidant pathways in tumor and adjacent normal cells, to identify possible therapeutic targets.

Berries are rich in antioxidants

Two researchers have offered an explanation as to why antioxidants are not effective in fighting cancers and suggested a way to change that.

The duo proposed that antioxidants from supplements or dietary sources are proving ineffective because they are not acting where reactive oxygen species (ROS) are produced.

So therapies that directly inhibit the production of mitochondrial- and NADPH oxidase-derived ROS, or that scavenge ROS at these sites, may be more effective.

David Tuveson, MD, PhD, of the Cold Spring Harbor Laboratory in New York, and Navdeep S. Chandel, PhD, of the Feinberg School of Medicine at Northwestern University in Chicago, detailed these theories in a report published in The New England Journal of Medicine.

The pair’s insights are based on recent advances in understanding the cell system that establishes a natural balance between oxidizing and antioxidizing compounds.

Oxidants like hydrogen peroxide are manufactured within cells and are essential in small quantities. But oxidants are toxic in large amounts, and cells naturally generate their own antioxidants to neutralize oxidants.

It has seemed logical, therefore, to boost a person’s intake of antioxidants to counter the effects of hydrogen peroxide and other similarly toxic ROS. All the more because cancer cells are known to generate higher levels of ROS to help feed their abnormal growth.

However, Drs Tuveson and Chandel proposed that taking antioxidant pills or eating foods rich in antioxidants may be failing to show a beneficial effect against cancer because antioxidants do not act where tumor-promoting ROS are produced—at mitochondria.

Rather, supplements and dietary antioxidants tend to accumulate at scattered distant sites in the cell, “leaving tumor-promoting ROS relatively unperturbed.”

Therefore, the authors suggested therapies that directly inhibit the production of mitochondrial- and NADPH oxidase-derived ROS, or that scavenge ROS at these sites, will be more effective than dietary antioxidants.

An alternative approach

Drs Tuveson and Chandel also proposed an alternative approach: disabling antioxidants in cancer cells. They noted that quantities of both ROS and natural antioxidants are higher in cancer cells. The higher levels of antioxidants are a natural defense by cancer cells to keep their higher levels of oxidants in check so that growth can continue.

In fact, therapies that raise the levels of oxidants in cells can be beneficial, whereas those that act as antioxidants may further stimulate the cancer cells.

So the authors suggested that genetic or pharmacologic inhibition of antioxidant proteins—a concept tested successfully in rodent models of lung and pancreatic cancers—may be a useful therapeutic approach in humans.

The key challenge is to identify antioxidant proteins and pathways in cells that are used only by cancer cells and not by healthy cells. Impeding antioxidant production in healthy cells will upset the delicate redox balance upon which normal cellular function depends.

So it seems research is needed to profile antioxidant pathways in tumor and adjacent normal cells, to identify possible therapeutic targets.

Berries are rich in antioxidants

Two researchers have offered an explanation as to why antioxidants are not effective in fighting cancers and suggested a way to change that.

The duo proposed that antioxidants from supplements or dietary sources are proving ineffective because they are not acting where reactive oxygen species (ROS) are produced.

So therapies that directly inhibit the production of mitochondrial- and NADPH oxidase-derived ROS, or that scavenge ROS at these sites, may be more effective.

David Tuveson, MD, PhD, of the Cold Spring Harbor Laboratory in New York, and Navdeep S. Chandel, PhD, of the Feinberg School of Medicine at Northwestern University in Chicago, detailed these theories in a report published in The New England Journal of Medicine.

The pair’s insights are based on recent advances in understanding the cell system that establishes a natural balance between oxidizing and antioxidizing compounds.

Oxidants like hydrogen peroxide are manufactured within cells and are essential in small quantities. But oxidants are toxic in large amounts, and cells naturally generate their own antioxidants to neutralize oxidants.

It has seemed logical, therefore, to boost a person’s intake of antioxidants to counter the effects of hydrogen peroxide and other similarly toxic ROS. All the more because cancer cells are known to generate higher levels of ROS to help feed their abnormal growth.

However, Drs Tuveson and Chandel proposed that taking antioxidant pills or eating foods rich in antioxidants may be failing to show a beneficial effect against cancer because antioxidants do not act where tumor-promoting ROS are produced—at mitochondria.

Rather, supplements and dietary antioxidants tend to accumulate at scattered distant sites in the cell, “leaving tumor-promoting ROS relatively unperturbed.”

Therefore, the authors suggested therapies that directly inhibit the production of mitochondrial- and NADPH oxidase-derived ROS, or that scavenge ROS at these sites, will be more effective than dietary antioxidants.

An alternative approach

Drs Tuveson and Chandel also proposed an alternative approach: disabling antioxidants in cancer cells. They noted that quantities of both ROS and natural antioxidants are higher in cancer cells. The higher levels of antioxidants are a natural defense by cancer cells to keep their higher levels of oxidants in check so that growth can continue.

In fact, therapies that raise the levels of oxidants in cells can be beneficial, whereas those that act as antioxidants may further stimulate the cancer cells.

So the authors suggested that genetic or pharmacologic inhibition of antioxidant proteins—a concept tested successfully in rodent models of lung and pancreatic cancers—may be a useful therapeutic approach in humans.

The key challenge is to identify antioxidant proteins and pathways in cells that are used only by cancer cells and not by healthy cells. Impeding antioxidant production in healthy cells will upset the delicate redox balance upon which normal cellular function depends.

So it seems research is needed to profile antioxidant pathways in tumor and adjacent normal cells, to identify possible therapeutic targets.

Recalled product

Image courtesy of Hospira

Hospira, Inc., has announced a US-wide, user-level recall of one lot of Lactated Ringers and 5% Dextrose Injection, USP, 1000 mL, Flexible Container (NDC 0409-7929-09, Lot 35-118-JT).

The company confirmed a report of particulate within the solution of the primary container. It was a filamentous-like structured particulate indicative of mold.

An analysis of the primary container and overwrap revealed a puncture that had caused the container to leak.

Intravenous administration of a non-sterile product can result in infections that may be life-threatening and could result in prolonged hospitalization or organ failure.

However, Hospira has not received reports of any adverse events associated with this issue for this lot and has not identified any quality issues with retention samples for this lot.

Lactated Ringers and 5% Dextrose Injection is indicated for parenteral replacement of extracellular losses of fluid and electrolytes, with or without minimal carbohydrate calories, as required by the clinical condition of the patient.

The product is packaged in 1000mL flexible containers, 1 container per overwrap, and 12 overwrapped containers in each case. The lot number is located in the upper left hand side of the primary container.

This lot (35-118-JT) was distributed nationwide—from December 2013 through February 2014—to hospitals, clinics, wholesalers, and distributors.

Anyone with an existing inventory should stop use and distribution, quarantine the product immediately, and call Stericycle at 1-888-912-8457 (8am to 5pm EST, Monday through Friday) to arrange for the return of the product.

For medical inquiries, contact Hospira Medical Communications at 1-800-615-0187 (available 24 hours a day, 7 days per week) or [email protected].

To report adverse events or product complaints, contact Hospira Global

Complaint Management at 1-800-441-4100 (8am to 5pm CT, Monday through Friday) or

[email protected].

Adverse events or quality problems can also be reported to the Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

Recalled product

Image courtesy of Hospira

Hospira, Inc., has announced a US-wide, user-level recall of one lot of Lactated Ringers and 5% Dextrose Injection, USP, 1000 mL, Flexible Container (NDC 0409-7929-09, Lot 35-118-JT).

The company confirmed a report of particulate within the solution of the primary container. It was a filamentous-like structured particulate indicative of mold.

An analysis of the primary container and overwrap revealed a puncture that had caused the container to leak.

Intravenous administration of a non-sterile product can result in infections that may be life-threatening and could result in prolonged hospitalization or organ failure.

However, Hospira has not received reports of any adverse events associated with this issue for this lot and has not identified any quality issues with retention samples for this lot.

Lactated Ringers and 5% Dextrose Injection is indicated for parenteral replacement of extracellular losses of fluid and electrolytes, with or without minimal carbohydrate calories, as required by the clinical condition of the patient.

The product is packaged in 1000mL flexible containers, 1 container per overwrap, and 12 overwrapped containers in each case. The lot number is located in the upper left hand side of the primary container.

This lot (35-118-JT) was distributed nationwide—from December 2013 through February 2014—to hospitals, clinics, wholesalers, and distributors.

Anyone with an existing inventory should stop use and distribution, quarantine the product immediately, and call Stericycle at 1-888-912-8457 (8am to 5pm EST, Monday through Friday) to arrange for the return of the product.

For medical inquiries, contact Hospira Medical Communications at 1-800-615-0187 (available 24 hours a day, 7 days per week) or [email protected].

To report adverse events or product complaints, contact Hospira Global

Complaint Management at 1-800-441-4100 (8am to 5pm CT, Monday through Friday) or

[email protected].

Adverse events or quality problems can also be reported to the Food and Drug Administration’s MedWatch Adverse Event Reporting Program.

Recalled product

Image courtesy of Hospira

Hospira, Inc., has announced a US-wide, user-level recall of one lot of Lactated Ringers and 5% Dextrose Injection, USP, 1000 mL, Flexible Container (NDC 0409-7929-09, Lot 35-118-JT).

The company confirmed a report of particulate within the solution of the primary container. It was a filamentous-like structured particulate indicative of mold.

An analysis of the primary container and overwrap revealed a puncture that had caused the container to leak.

Intravenous administration of a non-sterile product can result in infections that may be life-threatening and could result in prolonged hospitalization or organ failure.

However, Hospira has not received reports of any adverse events associated with this issue for this lot and has not identified any quality issues with retention samples for this lot.

Lactated Ringers and 5% Dextrose Injection is indicated for parenteral replacement of extracellular losses of fluid and electrolytes, with or without minimal carbohydrate calories, as required by the clinical condition of the patient.

The product is packaged in 1000mL flexible containers, 1 container per overwrap, and 12 overwrapped containers in each case. The lot number is located in the upper left hand side of the primary container.

This lot (35-118-JT) was distributed nationwide—from December 2013 through February 2014—to hospitals, clinics, wholesalers, and distributors.

Anyone with an existing inventory should stop use and distribution, quarantine the product immediately, and call Stericycle at 1-888-912-8457 (8am to 5pm EST, Monday through Friday) to arrange for the return of the product.

For medical inquiries, contact Hospira Medical Communications at 1-800-615-0187 (available 24 hours a day, 7 days per week) or [email protected].

To report adverse events or product complaints, contact Hospira Global

Complaint Management at 1-800-441-4100 (8am to 5pm CT, Monday through Friday) or

[email protected].

Adverse events or quality problems can also be reported to the Food and Drug Administration’s MedWatch Adverse Event Reporting Program.