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Assay can detect counterfeit malaria drugs
Credit: CDC
A new assay can be used to determine if a product actually contains the antimalarial drug artesunate, according to a paper published in the journal Talanta.
The testing system looks about as simple, and is almost as cheap, as a sheet of paper.
But it’s actually a colorimetric assay consumers could use to tell whether or not they are getting the medication they paid for—artesunate.
The assay also verifies that an adequate level of the drug is present.
“There are laboratory methods to analyze medications such as this, but they often are not available or widely used in the developing world, where malaria kills thousands of people every year,” said study author Vincent Remcho, PhD, of Oregon State University in Corvallis.
“What we need are inexpensive, accurate assays that can detect adulterated pharmaceuticals in the field, simple enough that anyone can use them. Our technology should provide that.”
The technology is an application of microfluidics in which a film is impressed onto paper that can then detect the presence and level of artesunate in a product.
A single pill can be crushed and dissolved in water. When a drop of the solution is placed on the paper, it turns yellow if the drug is present. The intensity of the color indicates the level of the drug, which can be compared to a simple color chart.
The system can also include another step. The researchers created an iPhone app that could be used to measure the color and tell with an even higher degree of accuracy both the presence and level of artesunate.
“This is conceptually similar to what we do with integrated circuit chips in computers, but we’re pushing fluids around instead of electrons, to reveal chemical information that’s useful to us,” Dr Remcho said. “Chemical communication is how Mother Nature does it, and the long-term applications of this approach really are mind-blowing.”
Aside from ensuring patients receive the appropriate treatment, the assay could help government officials combat the larger problem of drug counterfeiting. Researchers have found that, in some places in the developing world, more than 80% of outlets are selling counterfeit pharmaceuticals.
Dr Remcho and his colleagues also believe their technique could be expanded for a wide range of other medical conditions, pharmaceutical and diagnostic tests, pathogen detection, environmental analysis, and other uses. 
Credit: CDC
A new assay can be used to determine if a product actually contains the antimalarial drug artesunate, according to a paper published in the journal Talanta.
The testing system looks about as simple, and is almost as cheap, as a sheet of paper.
But it’s actually a colorimetric assay consumers could use to tell whether or not they are getting the medication they paid for—artesunate.
The assay also verifies that an adequate level of the drug is present.
“There are laboratory methods to analyze medications such as this, but they often are not available or widely used in the developing world, where malaria kills thousands of people every year,” said study author Vincent Remcho, PhD, of Oregon State University in Corvallis.
“What we need are inexpensive, accurate assays that can detect adulterated pharmaceuticals in the field, simple enough that anyone can use them. Our technology should provide that.”
The technology is an application of microfluidics in which a film is impressed onto paper that can then detect the presence and level of artesunate in a product.
A single pill can be crushed and dissolved in water. When a drop of the solution is placed on the paper, it turns yellow if the drug is present. The intensity of the color indicates the level of the drug, which can be compared to a simple color chart.
The system can also include another step. The researchers created an iPhone app that could be used to measure the color and tell with an even higher degree of accuracy both the presence and level of artesunate.
“This is conceptually similar to what we do with integrated circuit chips in computers, but we’re pushing fluids around instead of electrons, to reveal chemical information that’s useful to us,” Dr Remcho said. “Chemical communication is how Mother Nature does it, and the long-term applications of this approach really are mind-blowing.”
Aside from ensuring patients receive the appropriate treatment, the assay could help government officials combat the larger problem of drug counterfeiting. Researchers have found that, in some places in the developing world, more than 80% of outlets are selling counterfeit pharmaceuticals.
Dr Remcho and his colleagues also believe their technique could be expanded for a wide range of other medical conditions, pharmaceutical and diagnostic tests, pathogen detection, environmental analysis, and other uses.
Credit: CDC
A new assay can be used to determine if a product actually contains the antimalarial drug artesunate, according to a paper published in the journal Talanta.
The testing system looks about as simple, and is almost as cheap, as a sheet of paper.
But it’s actually a colorimetric assay consumers could use to tell whether or not they are getting the medication they paid for—artesunate.
The assay also verifies that an adequate level of the drug is present.
“There are laboratory methods to analyze medications such as this, but they often are not available or widely used in the developing world, where malaria kills thousands of people every year,” said study author Vincent Remcho, PhD, of Oregon State University in Corvallis.
“What we need are inexpensive, accurate assays that can detect adulterated pharmaceuticals in the field, simple enough that anyone can use them. Our technology should provide that.”
The technology is an application of microfluidics in which a film is impressed onto paper that can then detect the presence and level of artesunate in a product.
A single pill can be crushed and dissolved in water. When a drop of the solution is placed on the paper, it turns yellow if the drug is present. The intensity of the color indicates the level of the drug, which can be compared to a simple color chart.
The system can also include another step. The researchers created an iPhone app that could be used to measure the color and tell with an even higher degree of accuracy both the presence and level of artesunate.
“This is conceptually similar to what we do with integrated circuit chips in computers, but we’re pushing fluids around instead of electrons, to reveal chemical information that’s useful to us,” Dr Remcho said. “Chemical communication is how Mother Nature does it, and the long-term applications of this approach really are mind-blowing.”
Aside from ensuring patients receive the appropriate treatment, the assay could help government officials combat the larger problem of drug counterfeiting. Researchers have found that, in some places in the developing world, more than 80% of outlets are selling counterfeit pharmaceuticals.
Dr Remcho and his colleagues also believe their technique could be expanded for a wide range of other medical conditions, pharmaceutical and diagnostic tests, pathogen detection, environmental analysis, and other uses.
Model reveals how to target cancer’s weaknesses
Credit: PNAS
A new model suggests we should be targeting cancers’ weaknesses instead of their strengths.
An article in BioEssays proposes that cancers form when recently evolved genes are damaged, and cancer cells have to revert to using older, inappropriate genetic pathways.
So we should create treatments that take advantage of capabilities humans have developed more recently—such as the adaptive immune system—instead of trying to target older capabilities—such as the innate immune system and cell proliferation.
“The rapid proliferation of cancer cells is an ancient, default capability that became regulated during the evolution of multicellularity about a billion years ago,” said study author Charley Lineweaver, PhD, of The Australian National University in Canberra.
“Our model suggests that cancer progression is the accumulation of damage to the more recently acquired genes. Without the regulation of these recent genes, cell physiology reverts to earlier programs, such as unregulated cell proliferation.”
To develop their model, Dr Lineweaver and his colleagues turned to knowledge uncovered by genome sequencing in a range of our distant relatives, including fish, coral, and sponges.
This knowledge has allowed scientists to establish the order in which genes evolved and is the basis of the new therapeutic implications of the model, Dr Lineweaver said.
He noted that the standard model of cancer development suggests that selection produces the acquired capabilities of cancer—such as sustained proliferative signaling and evading apoptosis—and they evolve during the lifetime of the patient.
But Dr Lineweaver’s model suggests the capabilities of cancer are acquired atavisms. They are activated during early embryogenesis and wound healing and reactivated inappropriately during carcinogenesis.
The most recent capabilities—mammalian and vertebrate capabilities—are the least entrenched in cancer. So they should be targeted with therapy.
The older capabilities—last eukaryotic common ancestor (LECA) capabilities, stem eukaryote capabilities, and the earliest evolved capabilities—are maintained in cancer and are therefore difficult to target.
For example, some human ATP binding cassette (ABC) transporters are ancient, and some are quite recent. Dr Lineweaver and his colleagues found that older ABC proteins were more likely to be active in cancer.
So the researchers believe we should create treatments that can be expelled by the newer ABC transporters. That way, normal cells will expel the treatment, but cancer cells will not.
Another potential treatment avenue, according to Dr Lineweaver, is targeting the adaptive immune system.
“The adaptive immune system that humans have has evolved relatively recently, and it seems cancer cells do not have the ability to talk to and be protected by it,” he noted.
“The new therapeutic strategies we are proposing target these weaknesses. These strategies are very different from current therapies, which attack cancer’s strength—its ability to proliferate rapidly.”
Credit: PNAS
A new model suggests we should be targeting cancers’ weaknesses instead of their strengths.
An article in BioEssays proposes that cancers form when recently evolved genes are damaged, and cancer cells have to revert to using older, inappropriate genetic pathways.
So we should create treatments that take advantage of capabilities humans have developed more recently—such as the adaptive immune system—instead of trying to target older capabilities—such as the innate immune system and cell proliferation.
“The rapid proliferation of cancer cells is an ancient, default capability that became regulated during the evolution of multicellularity about a billion years ago,” said study author Charley Lineweaver, PhD, of The Australian National University in Canberra.
“Our model suggests that cancer progression is the accumulation of damage to the more recently acquired genes. Without the regulation of these recent genes, cell physiology reverts to earlier programs, such as unregulated cell proliferation.”
To develop their model, Dr Lineweaver and his colleagues turned to knowledge uncovered by genome sequencing in a range of our distant relatives, including fish, coral, and sponges.
This knowledge has allowed scientists to establish the order in which genes evolved and is the basis of the new therapeutic implications of the model, Dr Lineweaver said.
He noted that the standard model of cancer development suggests that selection produces the acquired capabilities of cancer—such as sustained proliferative signaling and evading apoptosis—and they evolve during the lifetime of the patient.
But Dr Lineweaver’s model suggests the capabilities of cancer are acquired atavisms. They are activated during early embryogenesis and wound healing and reactivated inappropriately during carcinogenesis.
The most recent capabilities—mammalian and vertebrate capabilities—are the least entrenched in cancer. So they should be targeted with therapy.
The older capabilities—last eukaryotic common ancestor (LECA) capabilities, stem eukaryote capabilities, and the earliest evolved capabilities—are maintained in cancer and are therefore difficult to target.
For example, some human ATP binding cassette (ABC) transporters are ancient, and some are quite recent. Dr Lineweaver and his colleagues found that older ABC proteins were more likely to be active in cancer.
So the researchers believe we should create treatments that can be expelled by the newer ABC transporters. That way, normal cells will expel the treatment, but cancer cells will not.
Another potential treatment avenue, according to Dr Lineweaver, is targeting the adaptive immune system.
“The adaptive immune system that humans have has evolved relatively recently, and it seems cancer cells do not have the ability to talk to and be protected by it,” he noted.
“The new therapeutic strategies we are proposing target these weaknesses. These strategies are very different from current therapies, which attack cancer’s strength—its ability to proliferate rapidly.”
Credit: PNAS
A new model suggests we should be targeting cancers’ weaknesses instead of their strengths.
An article in BioEssays proposes that cancers form when recently evolved genes are damaged, and cancer cells have to revert to using older, inappropriate genetic pathways.
So we should create treatments that take advantage of capabilities humans have developed more recently—such as the adaptive immune system—instead of trying to target older capabilities—such as the innate immune system and cell proliferation.
“The rapid proliferation of cancer cells is an ancient, default capability that became regulated during the evolution of multicellularity about a billion years ago,” said study author Charley Lineweaver, PhD, of The Australian National University in Canberra.
“Our model suggests that cancer progression is the accumulation of damage to the more recently acquired genes. Without the regulation of these recent genes, cell physiology reverts to earlier programs, such as unregulated cell proliferation.”
To develop their model, Dr Lineweaver and his colleagues turned to knowledge uncovered by genome sequencing in a range of our distant relatives, including fish, coral, and sponges.
This knowledge has allowed scientists to establish the order in which genes evolved and is the basis of the new therapeutic implications of the model, Dr Lineweaver said.
He noted that the standard model of cancer development suggests that selection produces the acquired capabilities of cancer—such as sustained proliferative signaling and evading apoptosis—and they evolve during the lifetime of the patient.
But Dr Lineweaver’s model suggests the capabilities of cancer are acquired atavisms. They are activated during early embryogenesis and wound healing and reactivated inappropriately during carcinogenesis.
The most recent capabilities—mammalian and vertebrate capabilities—are the least entrenched in cancer. So they should be targeted with therapy.
The older capabilities—last eukaryotic common ancestor (LECA) capabilities, stem eukaryote capabilities, and the earliest evolved capabilities—are maintained in cancer and are therefore difficult to target.
For example, some human ATP binding cassette (ABC) transporters are ancient, and some are quite recent. Dr Lineweaver and his colleagues found that older ABC proteins were more likely to be active in cancer.
So the researchers believe we should create treatments that can be expelled by the newer ABC transporters. That way, normal cells will expel the treatment, but cancer cells will not.
Another potential treatment avenue, according to Dr Lineweaver, is targeting the adaptive immune system.
“The adaptive immune system that humans have has evolved relatively recently, and it seems cancer cells do not have the ability to talk to and be protected by it,” he noted.
“The new therapeutic strategies we are proposing target these weaknesses. These strategies are very different from current therapies, which attack cancer’s strength—its ability to proliferate rapidly.”
More RNs are delaying retirement, study shows
chemo to a cancer patient
Credit: Rhoda Baer
The nursing workforce in the US has grown substantially in recent years, and this is only partly due to an increase in nursing graduates, according to a new study.
The research revealed that registered nurses (RNs) are putting off retirement for longer than they have in the past.
From 1991 to 2012, 24% of RNs who were working at age 50 remained working as late as age 69. From 1969 to 1990, however, only 9% of nurses were still working at age 69.
These findings appear in Health Affairs.
“We estimate this trend accounts for about a quarter of an unexpected surge in the supply of registered nurses that the nation has experienced in recent years,” said study author David Auerbach, PhD, of RAND Corporation in Boston. “This may provide advantages to parts of the US healthcare system.”
The researchers noted that the RN workforce has surpassed forecasts from a decade ago, growing to 2.7 million in 2012 instead of peaking at 2.2 million as predicted. While much of the difference is the result of a surge in new nursing graduates, the size of the workforce is particularly sensitive to changes in retirement age.
Dr Auerbach and his colleagues uncovered the trend of delaying retirement by analyzing data from the Current Population Survey and the American Community Survey.
The team included all respondents aged 23 to 69 who reported being employed as an RN during the week of the relevant survey from 1969 to 2012. There were 70,724 RNs who responded to the Current Population Survey and 307,187 who responded to the American Community Survey.
The researchers found that, from 1969 to 1990, for a given number of RNs working at age 50, 47% were still working at age 62. From 1991 to 2012, 74% of RNs were working at age 62.
The trend of RNs delaying retirement, which largely predates the recent recession, extended nursing careers by 2.5 years after age 50 and increased the 2012 RN workforce by 136,000 people, according to the researchers.
The team said the reasons older RNs are working longer is unclear, but it is likely part of an overall trend that has seen more Americans—particularly women—stay in the workforce longer because of lengthening life expectancy and the satisfaction they derive from employment.
chemo to a cancer patient
Credit: Rhoda Baer
The nursing workforce in the US has grown substantially in recent years, and this is only partly due to an increase in nursing graduates, according to a new study.
The research revealed that registered nurses (RNs) are putting off retirement for longer than they have in the past.
From 1991 to 2012, 24% of RNs who were working at age 50 remained working as late as age 69. From 1969 to 1990, however, only 9% of nurses were still working at age 69.
These findings appear in Health Affairs.
“We estimate this trend accounts for about a quarter of an unexpected surge in the supply of registered nurses that the nation has experienced in recent years,” said study author David Auerbach, PhD, of RAND Corporation in Boston. “This may provide advantages to parts of the US healthcare system.”
The researchers noted that the RN workforce has surpassed forecasts from a decade ago, growing to 2.7 million in 2012 instead of peaking at 2.2 million as predicted. While much of the difference is the result of a surge in new nursing graduates, the size of the workforce is particularly sensitive to changes in retirement age.
Dr Auerbach and his colleagues uncovered the trend of delaying retirement by analyzing data from the Current Population Survey and the American Community Survey.
The team included all respondents aged 23 to 69 who reported being employed as an RN during the week of the relevant survey from 1969 to 2012. There were 70,724 RNs who responded to the Current Population Survey and 307,187 who responded to the American Community Survey.
The researchers found that, from 1969 to 1990, for a given number of RNs working at age 50, 47% were still working at age 62. From 1991 to 2012, 74% of RNs were working at age 62.
The trend of RNs delaying retirement, which largely predates the recent recession, extended nursing careers by 2.5 years after age 50 and increased the 2012 RN workforce by 136,000 people, according to the researchers.
The team said the reasons older RNs are working longer is unclear, but it is likely part of an overall trend that has seen more Americans—particularly women—stay in the workforce longer because of lengthening life expectancy and the satisfaction they derive from employment.
chemo to a cancer patient
Credit: Rhoda Baer
The nursing workforce in the US has grown substantially in recent years, and this is only partly due to an increase in nursing graduates, according to a new study.
The research revealed that registered nurses (RNs) are putting off retirement for longer than they have in the past.
From 1991 to 2012, 24% of RNs who were working at age 50 remained working as late as age 69. From 1969 to 1990, however, only 9% of nurses were still working at age 69.
These findings appear in Health Affairs.
“We estimate this trend accounts for about a quarter of an unexpected surge in the supply of registered nurses that the nation has experienced in recent years,” said study author David Auerbach, PhD, of RAND Corporation in Boston. “This may provide advantages to parts of the US healthcare system.”
The researchers noted that the RN workforce has surpassed forecasts from a decade ago, growing to 2.7 million in 2012 instead of peaking at 2.2 million as predicted. While much of the difference is the result of a surge in new nursing graduates, the size of the workforce is particularly sensitive to changes in retirement age.
Dr Auerbach and his colleagues uncovered the trend of delaying retirement by analyzing data from the Current Population Survey and the American Community Survey.
The team included all respondents aged 23 to 69 who reported being employed as an RN during the week of the relevant survey from 1969 to 2012. There were 70,724 RNs who responded to the Current Population Survey and 307,187 who responded to the American Community Survey.
The researchers found that, from 1969 to 1990, for a given number of RNs working at age 50, 47% were still working at age 62. From 1991 to 2012, 74% of RNs were working at age 62.
The trend of RNs delaying retirement, which largely predates the recent recession, extended nursing careers by 2.5 years after age 50 and increased the 2012 RN workforce by 136,000 people, according to the researchers.
The team said the reasons older RNs are working longer is unclear, but it is likely part of an overall trend that has seen more Americans—particularly women—stay in the workforce longer because of lengthening life expectancy and the satisfaction they derive from employment.
New insight into MYC-induced lymphoma
Credit: Juha Klefstrom
Investigators have identified biological signatures in lymphoma cells that can be traced back to the original oncogene.
The team analyzed mouse models and patient samples of MYC-induced lymphoma. And they discovered lipid signatures that corresponded with the level of MYC expression.
The investigators believe this discovery could be the first step toward developing a technique to identify the origin of lymphomas and other malignancies.
They described their discovery in PNAS.
“The same cancer can occur because of different genes, but, in certain cases, the aggressiveness and the type of treatment actually depend a lot on what oncogene caused that cancer,” said study author Livia Eberlin, PhD, of Stanford University in California.
With that in mind, she and her colleagues looked at MYC, an oncogene that’s responsible for approximately half of all human cancers. They wanted to find a biological signature that would trace the mutating cancer cells back to the original oncogene.
“When cancer takes place, the cell loves to gobble up glucose—that’s a sugar—and glutamine,” said Richard Zare, PhD, also of Stanford. “It takes those and makes different lipids—different fatty molecules than what it normally makes.”
So the investigators set out to evaluate changes in lipid profiles in MYC-induced lymphoma. They compared lipid signatures in MYC-induced transgenic mouse models to those in normal control mice.
The team identified 104 molecular ions that were either increased or decreased in the MYC lymphoma models compared to controls. And 86 of these ions were complex phospholipids.
Most of the lipids that were increased in lymphoma were glycerophosphoglycerols and cardiolipins, with a higher content of monounsaturated fatty acids when compared with controls.
To determine if these findings might also apply to humans, the investigators examined 15 samples from lymphoma patients.
The samples had varying expression levels of MYC oncoprotein, and the team observed distinct lipid profiles in lymphomas with high and low MYC expression. This included many of the lipid species they had identified in the animal models of MYC-induced lymphoma.
The investigators said their results suggest a relationship between specific lipid species and the overexpression of MYC. And this information could have both diagnostic and prognostic applications.
Credit: Juha Klefstrom
Investigators have identified biological signatures in lymphoma cells that can be traced back to the original oncogene.
The team analyzed mouse models and patient samples of MYC-induced lymphoma. And they discovered lipid signatures that corresponded with the level of MYC expression.
The investigators believe this discovery could be the first step toward developing a technique to identify the origin of lymphomas and other malignancies.
They described their discovery in PNAS.
“The same cancer can occur because of different genes, but, in certain cases, the aggressiveness and the type of treatment actually depend a lot on what oncogene caused that cancer,” said study author Livia Eberlin, PhD, of Stanford University in California.
With that in mind, she and her colleagues looked at MYC, an oncogene that’s responsible for approximately half of all human cancers. They wanted to find a biological signature that would trace the mutating cancer cells back to the original oncogene.
“When cancer takes place, the cell loves to gobble up glucose—that’s a sugar—and glutamine,” said Richard Zare, PhD, also of Stanford. “It takes those and makes different lipids—different fatty molecules than what it normally makes.”
So the investigators set out to evaluate changes in lipid profiles in MYC-induced lymphoma. They compared lipid signatures in MYC-induced transgenic mouse models to those in normal control mice.
The team identified 104 molecular ions that were either increased or decreased in the MYC lymphoma models compared to controls. And 86 of these ions were complex phospholipids.
Most of the lipids that were increased in lymphoma were glycerophosphoglycerols and cardiolipins, with a higher content of monounsaturated fatty acids when compared with controls.
To determine if these findings might also apply to humans, the investigators examined 15 samples from lymphoma patients.
The samples had varying expression levels of MYC oncoprotein, and the team observed distinct lipid profiles in lymphomas with high and low MYC expression. This included many of the lipid species they had identified in the animal models of MYC-induced lymphoma.
The investigators said their results suggest a relationship between specific lipid species and the overexpression of MYC. And this information could have both diagnostic and prognostic applications.
Credit: Juha Klefstrom
Investigators have identified biological signatures in lymphoma cells that can be traced back to the original oncogene.
The team analyzed mouse models and patient samples of MYC-induced lymphoma. And they discovered lipid signatures that corresponded with the level of MYC expression.
The investigators believe this discovery could be the first step toward developing a technique to identify the origin of lymphomas and other malignancies.
They described their discovery in PNAS.
“The same cancer can occur because of different genes, but, in certain cases, the aggressiveness and the type of treatment actually depend a lot on what oncogene caused that cancer,” said study author Livia Eberlin, PhD, of Stanford University in California.
With that in mind, she and her colleagues looked at MYC, an oncogene that’s responsible for approximately half of all human cancers. They wanted to find a biological signature that would trace the mutating cancer cells back to the original oncogene.
“When cancer takes place, the cell loves to gobble up glucose—that’s a sugar—and glutamine,” said Richard Zare, PhD, also of Stanford. “It takes those and makes different lipids—different fatty molecules than what it normally makes.”
So the investigators set out to evaluate changes in lipid profiles in MYC-induced lymphoma. They compared lipid signatures in MYC-induced transgenic mouse models to those in normal control mice.
The team identified 104 molecular ions that were either increased or decreased in the MYC lymphoma models compared to controls. And 86 of these ions were complex phospholipids.
Most of the lipids that were increased in lymphoma were glycerophosphoglycerols and cardiolipins, with a higher content of monounsaturated fatty acids when compared with controls.
To determine if these findings might also apply to humans, the investigators examined 15 samples from lymphoma patients.
The samples had varying expression levels of MYC oncoprotein, and the team observed distinct lipid profiles in lymphomas with high and low MYC expression. This included many of the lipid species they had identified in the animal models of MYC-induced lymphoma.
The investigators said their results suggest a relationship between specific lipid species and the overexpression of MYC. And this information could have both diagnostic and prognostic applications.
How federal budget cuts are affecting research
Credit: Rhoda Baer
A new report suggests recent budget cuts to federal health programs in the US have had some negative consequences for hematology researchers.
The Coalition for Health Funding, an alliance of more than 90 public health advocacy organizations, invited scientists, public health advocates, and others to share stories of how they have been hurt by the budget cuts.
The resulting report is titled “Faces of Austerity, How Budget Cuts Hurt America’s Health.”
It details the negative effects the cuts have had on scientific discovery and innovation, scientists and health practitioners, health and social services, and government programs designed to respond to health hazards and natural disasters.
Among the stories included in the report are 2 from members of the American Society of Hematology (ASH), who detail how a decade of flat funding for the National Institutes of Health (NIH) and a 5% budget cut in 2013 have shuttered labs and jeopardized tomorrow’s treatments.
“Most people I know have been affected,” said Debra Newman, PhD, an investigator at BloodCenter of Wisconsin in Milwaukee.
“Their research funding has decreased and, consequently, so has the size of their laboratories because they cannot afford to employ the same number of staff. Talented investigators have started to leave research and go on to other things because they can’t support a research operation without money to run it.”
The other ASH member story is that of Christopher Porter, MD, a pediatric hematologist/oncologist at Children’s Hospital Colorado in Aurora. Despite receiving an excellent score on an NIH grant application, Dr Porter was denied funding in 2013 amid budget cuts.
“My lab had been able to report exciting preliminary data, but we really needed supplemental funds to keep this project moving,” he said. “While our initial application to NIH scored high enough to have received funding in previous years, it was not within the current funding range.”
Drs Newman and Porter are among the first recipients of ASH Bridge Grants, awards first offered in 2012 for investigators who applied for competitive grants from NIH but were denied funding due to cuts. The awards are intended to “bridge” investigators to their next NIH grant.
While such supplementary grant funding programs are helpful, they cannot replace critical NIH funding that has been cut for hematology research, according to ASH.
“When biomedical research is under-funded, everybody loses,” said ASH President Linda J. Burns, MD, of the University of Minnesota.
“Scientists are forced to slow or suspend research because they no longer have the resources to continue searching for new treatments, and even cures, for some of the world’s deadliest diseases. We continue to urge Congress to support a balanced approach to deficit reduction that does not include further cuts to critical biomedical research and public health and safety programs.”
“Faces of Austerity” is available online at www.cutshurt.org. A related report, “Faces of Austerity: How Budget Cuts Have Made Us Sicker, Poorer, and Less Safe,” was published last November.
Credit: Rhoda Baer
A new report suggests recent budget cuts to federal health programs in the US have had some negative consequences for hematology researchers.
The Coalition for Health Funding, an alliance of more than 90 public health advocacy organizations, invited scientists, public health advocates, and others to share stories of how they have been hurt by the budget cuts.
The resulting report is titled “Faces of Austerity, How Budget Cuts Hurt America’s Health.”
It details the negative effects the cuts have had on scientific discovery and innovation, scientists and health practitioners, health and social services, and government programs designed to respond to health hazards and natural disasters.
Among the stories included in the report are 2 from members of the American Society of Hematology (ASH), who detail how a decade of flat funding for the National Institutes of Health (NIH) and a 5% budget cut in 2013 have shuttered labs and jeopardized tomorrow’s treatments.
“Most people I know have been affected,” said Debra Newman, PhD, an investigator at BloodCenter of Wisconsin in Milwaukee.
“Their research funding has decreased and, consequently, so has the size of their laboratories because they cannot afford to employ the same number of staff. Talented investigators have started to leave research and go on to other things because they can’t support a research operation without money to run it.”
The other ASH member story is that of Christopher Porter, MD, a pediatric hematologist/oncologist at Children’s Hospital Colorado in Aurora. Despite receiving an excellent score on an NIH grant application, Dr Porter was denied funding in 2013 amid budget cuts.
“My lab had been able to report exciting preliminary data, but we really needed supplemental funds to keep this project moving,” he said. “While our initial application to NIH scored high enough to have received funding in previous years, it was not within the current funding range.”
Drs Newman and Porter are among the first recipients of ASH Bridge Grants, awards first offered in 2012 for investigators who applied for competitive grants from NIH but were denied funding due to cuts. The awards are intended to “bridge” investigators to their next NIH grant.
While such supplementary grant funding programs are helpful, they cannot replace critical NIH funding that has been cut for hematology research, according to ASH.
“When biomedical research is under-funded, everybody loses,” said ASH President Linda J. Burns, MD, of the University of Minnesota.
“Scientists are forced to slow or suspend research because they no longer have the resources to continue searching for new treatments, and even cures, for some of the world’s deadliest diseases. We continue to urge Congress to support a balanced approach to deficit reduction that does not include further cuts to critical biomedical research and public health and safety programs.”
“Faces of Austerity” is available online at www.cutshurt.org. A related report, “Faces of Austerity: How Budget Cuts Have Made Us Sicker, Poorer, and Less Safe,” was published last November.
Credit: Rhoda Baer
A new report suggests recent budget cuts to federal health programs in the US have had some negative consequences for hematology researchers.
The Coalition for Health Funding, an alliance of more than 90 public health advocacy organizations, invited scientists, public health advocates, and others to share stories of how they have been hurt by the budget cuts.
The resulting report is titled “Faces of Austerity, How Budget Cuts Hurt America’s Health.”
It details the negative effects the cuts have had on scientific discovery and innovation, scientists and health practitioners, health and social services, and government programs designed to respond to health hazards and natural disasters.
Among the stories included in the report are 2 from members of the American Society of Hematology (ASH), who detail how a decade of flat funding for the National Institutes of Health (NIH) and a 5% budget cut in 2013 have shuttered labs and jeopardized tomorrow’s treatments.
“Most people I know have been affected,” said Debra Newman, PhD, an investigator at BloodCenter of Wisconsin in Milwaukee.
“Their research funding has decreased and, consequently, so has the size of their laboratories because they cannot afford to employ the same number of staff. Talented investigators have started to leave research and go on to other things because they can’t support a research operation without money to run it.”
The other ASH member story is that of Christopher Porter, MD, a pediatric hematologist/oncologist at Children’s Hospital Colorado in Aurora. Despite receiving an excellent score on an NIH grant application, Dr Porter was denied funding in 2013 amid budget cuts.
“My lab had been able to report exciting preliminary data, but we really needed supplemental funds to keep this project moving,” he said. “While our initial application to NIH scored high enough to have received funding in previous years, it was not within the current funding range.”
Drs Newman and Porter are among the first recipients of ASH Bridge Grants, awards first offered in 2012 for investigators who applied for competitive grants from NIH but were denied funding due to cuts. The awards are intended to “bridge” investigators to their next NIH grant.
While such supplementary grant funding programs are helpful, they cannot replace critical NIH funding that has been cut for hematology research, according to ASH.
“When biomedical research is under-funded, everybody loses,” said ASH President Linda J. Burns, MD, of the University of Minnesota.
“Scientists are forced to slow or suspend research because they no longer have the resources to continue searching for new treatments, and even cures, for some of the world’s deadliest diseases. We continue to urge Congress to support a balanced approach to deficit reduction that does not include further cuts to critical biomedical research and public health and safety programs.”
“Faces of Austerity” is available online at www.cutshurt.org. A related report, “Faces of Austerity: How Budget Cuts Have Made Us Sicker, Poorer, and Less Safe,” was published last November.
Method forces cells to devour dying neighbors
engulfed dying cells (purple)
Credit: Toru Komatsu
A two-pronged approach can prompt phagocytosis in inert cells, according to a paper published in Science Signaling.
Researchers manipulated HeLa cells, which typically cannot perform phagocytosis, by activating one protein inside the cells and expressing another protein on the cells’ surface. This forced the cells to engulf apoptotic Jurkat T cells.
So the researchers believe this technique could be used as a targeted therapy, with engineered cells consuming unwanted cells.
“Our goal is to build artificial cells programmed to eat up dangerous junk in the body, which could be anything from bacteria to the amyloid-beta plaques that cause Alzheimer’s to the body’s own rogue cancer cells,” said study author Takanari Inoue, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.
“By figuring out how to get normally inert cells to recognize and engulf dying cells, we’ve taken an important step in that direction.”
Dr Inoue and his colleagues set out to “strip down” phagocytosis, determining the minimum tools one cell needs to eat another. Their first task was to induce the HeLa cells to attach to nearby dying cells—apoptotic Jurkat T cells—by getting the right receptors to the HeLa cells’ surface.
The researchers knew that part of a receptor protein called MFG-E8 would recognize and stick to a distress signal on the surface of dying cells, and coaxing the HeLa cells to make the protein fragment was straightforward.
To get the fragment, termed C2, onto the outside of the cells, the team found a way to stick it to another protein that was bound for the cell’s surface, thus taking advantage of the cell’s own transportation system.
As a result, up to 6 apoptotic Jurkat T cells stuck to each HeLa cell. The bad news was that the HeLa cells weren’t actually eating the T cells.
Fortunately, the researchers already had an idea about what to try next. Previous research had shown that activating the Rac gene could cause a cell to engulf beads stuck to its surface.
Sure enough, the team found that HeLa cells with both surface C2 and activated Rac swallowed the apoptotic cells readily.
“We’ve shown it’s possible to endow ordinary cells with the power to do something unique: take on the role of a specialized macrophage,” Dr Inoue said.
He cautioned, however, that the researchers don’t believe the engulfed cells are being broken down. Getting the HeLa cells to finish the process of phagocytosis will be one of the group’s next steps.
engulfed dying cells (purple)
Credit: Toru Komatsu
A two-pronged approach can prompt phagocytosis in inert cells, according to a paper published in Science Signaling.
Researchers manipulated HeLa cells, which typically cannot perform phagocytosis, by activating one protein inside the cells and expressing another protein on the cells’ surface. This forced the cells to engulf apoptotic Jurkat T cells.
So the researchers believe this technique could be used as a targeted therapy, with engineered cells consuming unwanted cells.
“Our goal is to build artificial cells programmed to eat up dangerous junk in the body, which could be anything from bacteria to the amyloid-beta plaques that cause Alzheimer’s to the body’s own rogue cancer cells,” said study author Takanari Inoue, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.
“By figuring out how to get normally inert cells to recognize and engulf dying cells, we’ve taken an important step in that direction.”
Dr Inoue and his colleagues set out to “strip down” phagocytosis, determining the minimum tools one cell needs to eat another. Their first task was to induce the HeLa cells to attach to nearby dying cells—apoptotic Jurkat T cells—by getting the right receptors to the HeLa cells’ surface.
The researchers knew that part of a receptor protein called MFG-E8 would recognize and stick to a distress signal on the surface of dying cells, and coaxing the HeLa cells to make the protein fragment was straightforward.
To get the fragment, termed C2, onto the outside of the cells, the team found a way to stick it to another protein that was bound for the cell’s surface, thus taking advantage of the cell’s own transportation system.
As a result, up to 6 apoptotic Jurkat T cells stuck to each HeLa cell. The bad news was that the HeLa cells weren’t actually eating the T cells.
Fortunately, the researchers already had an idea about what to try next. Previous research had shown that activating the Rac gene could cause a cell to engulf beads stuck to its surface.
Sure enough, the team found that HeLa cells with both surface C2 and activated Rac swallowed the apoptotic cells readily.
“We’ve shown it’s possible to endow ordinary cells with the power to do something unique: take on the role of a specialized macrophage,” Dr Inoue said.
He cautioned, however, that the researchers don’t believe the engulfed cells are being broken down. Getting the HeLa cells to finish the process of phagocytosis will be one of the group’s next steps.
engulfed dying cells (purple)
Credit: Toru Komatsu
A two-pronged approach can prompt phagocytosis in inert cells, according to a paper published in Science Signaling.
Researchers manipulated HeLa cells, which typically cannot perform phagocytosis, by activating one protein inside the cells and expressing another protein on the cells’ surface. This forced the cells to engulf apoptotic Jurkat T cells.
So the researchers believe this technique could be used as a targeted therapy, with engineered cells consuming unwanted cells.
“Our goal is to build artificial cells programmed to eat up dangerous junk in the body, which could be anything from bacteria to the amyloid-beta plaques that cause Alzheimer’s to the body’s own rogue cancer cells,” said study author Takanari Inoue, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland.
“By figuring out how to get normally inert cells to recognize and engulf dying cells, we’ve taken an important step in that direction.”
Dr Inoue and his colleagues set out to “strip down” phagocytosis, determining the minimum tools one cell needs to eat another. Their first task was to induce the HeLa cells to attach to nearby dying cells—apoptotic Jurkat T cells—by getting the right receptors to the HeLa cells’ surface.
The researchers knew that part of a receptor protein called MFG-E8 would recognize and stick to a distress signal on the surface of dying cells, and coaxing the HeLa cells to make the protein fragment was straightforward.
To get the fragment, termed C2, onto the outside of the cells, the team found a way to stick it to another protein that was bound for the cell’s surface, thus taking advantage of the cell’s own transportation system.
As a result, up to 6 apoptotic Jurkat T cells stuck to each HeLa cell. The bad news was that the HeLa cells weren’t actually eating the T cells.
Fortunately, the researchers already had an idea about what to try next. Previous research had shown that activating the Rac gene could cause a cell to engulf beads stuck to its surface.
Sure enough, the team found that HeLa cells with both surface C2 and activated Rac swallowed the apoptotic cells readily.
“We’ve shown it’s possible to endow ordinary cells with the power to do something unique: take on the role of a specialized macrophage,” Dr Inoue said.
He cautioned, however, that the researchers don’t believe the engulfed cells are being broken down. Getting the HeLa cells to finish the process of phagocytosis will be one of the group’s next steps.
Technique allows for early cancer diagnosis
Credit: Максим Кукушкин
Immunosignaturing can allow for early detection of multiple myeloma and a range of other cancers, according to research published in PNAS.
Immunosignaturing involves profiling the entire population of antibodies circulating in the blood at a given time.
The method allowed researchers to distinguish 14 separate diseases, including 12 cancers, from one another and from healthy controls. The specificity was greater than 98% for each diagnosis.
“For years, we’ve seen remarkable results from immunosignatures, but introducing the technology to the scientific community has required a lot of patience,” said study author Phillip Stafford, PhD, of Arizona State University in Tempe.
The technique relies on a microarray consisting of thousands of random sequence peptides, imprinted on a glass slide. When a tiny droplet of blood (less than a microliter is needed) is spread across the microarray, antibodies in the blood selectively bind with individual peptides, forming a portrait of immune activity—an immunosignature.
Because the peptide sequences are random and not related to any naturally occurring disease antigens, the immunosignatures are “disease agnostic,” which means a single platform is potentially applicable to multiple disease types.
With their research, Dr Stafford and his colleagues put this claim to the test. The team first “trained” the system to calibrate results and establish reference immunosignatures using 20 samples each from 5 cancer patient cohorts, along with 20 non-cancer patients.
Once reference immunosignatures were established, the researchers tested the technique in a blind evaluation of 120 independent samples covering the same diseases. The results demonstrated 95% accuracy.
To further assess the diagnostic power of immunosignaturing, the team tested more than 1500 historical samples comprising 14 different diseases. This included 12 cancers, such as breast, brain, and multiple myeloma.
The average diagnostic accuracy of immunosignaturing was greater than 98% for each diagnosis, which suggests the method is suitable for the simultaneous classification of multiple diseases.
In a pairwise test against healthy control samples, multiple myeloma samples displayed the most significantly different peptides by t test. Of the top 100 peptides selected in this way, only breast cancer showed no overlap with any other disease.
Nevertheless, the researchers were able to distinguish the 14 separate diseases from one another, as well as from healthy controls, through immunosignatures.
Dr Stafford and his colleagues said these results suggest that immunosignatures provide an attractive means of capturing disease complexity. They offer a marked improvement over traditional methods in which one-to-one molecular recognition events are measured and a small number of analytes can be evaluated.
Furthermore, the technology is flexible in terms of handling and processing, the team said. A dried sample of blood, collected on filter paper and mailed to a study facility, can be used to generate an immunosignature.
The researchers also pointed out that the microarray chip used for this study contains 10,000 imprinted peptides, and this allows for enhanced sensitivity, owing to the large number of different possible signals elicited.
However, a significant improvement in immunosignaturing sensitivity and accuracy might be achieved through new chip technology. The team is currently developing a chip imprinted with more than 100,000 peptides.
Credit: Максим Кукушкин
Immunosignaturing can allow for early detection of multiple myeloma and a range of other cancers, according to research published in PNAS.
Immunosignaturing involves profiling the entire population of antibodies circulating in the blood at a given time.
The method allowed researchers to distinguish 14 separate diseases, including 12 cancers, from one another and from healthy controls. The specificity was greater than 98% for each diagnosis.
“For years, we’ve seen remarkable results from immunosignatures, but introducing the technology to the scientific community has required a lot of patience,” said study author Phillip Stafford, PhD, of Arizona State University in Tempe.
The technique relies on a microarray consisting of thousands of random sequence peptides, imprinted on a glass slide. When a tiny droplet of blood (less than a microliter is needed) is spread across the microarray, antibodies in the blood selectively bind with individual peptides, forming a portrait of immune activity—an immunosignature.
Because the peptide sequences are random and not related to any naturally occurring disease antigens, the immunosignatures are “disease agnostic,” which means a single platform is potentially applicable to multiple disease types.
With their research, Dr Stafford and his colleagues put this claim to the test. The team first “trained” the system to calibrate results and establish reference immunosignatures using 20 samples each from 5 cancer patient cohorts, along with 20 non-cancer patients.
Once reference immunosignatures were established, the researchers tested the technique in a blind evaluation of 120 independent samples covering the same diseases. The results demonstrated 95% accuracy.
To further assess the diagnostic power of immunosignaturing, the team tested more than 1500 historical samples comprising 14 different diseases. This included 12 cancers, such as breast, brain, and multiple myeloma.
The average diagnostic accuracy of immunosignaturing was greater than 98% for each diagnosis, which suggests the method is suitable for the simultaneous classification of multiple diseases.
In a pairwise test against healthy control samples, multiple myeloma samples displayed the most significantly different peptides by t test. Of the top 100 peptides selected in this way, only breast cancer showed no overlap with any other disease.
Nevertheless, the researchers were able to distinguish the 14 separate diseases from one another, as well as from healthy controls, through immunosignatures.
Dr Stafford and his colleagues said these results suggest that immunosignatures provide an attractive means of capturing disease complexity. They offer a marked improvement over traditional methods in which one-to-one molecular recognition events are measured and a small number of analytes can be evaluated.
Furthermore, the technology is flexible in terms of handling and processing, the team said. A dried sample of blood, collected on filter paper and mailed to a study facility, can be used to generate an immunosignature.
The researchers also pointed out that the microarray chip used for this study contains 10,000 imprinted peptides, and this allows for enhanced sensitivity, owing to the large number of different possible signals elicited.
However, a significant improvement in immunosignaturing sensitivity and accuracy might be achieved through new chip technology. The team is currently developing a chip imprinted with more than 100,000 peptides.
Credit: Максим Кукушкин
Immunosignaturing can allow for early detection of multiple myeloma and a range of other cancers, according to research published in PNAS.
Immunosignaturing involves profiling the entire population of antibodies circulating in the blood at a given time.
The method allowed researchers to distinguish 14 separate diseases, including 12 cancers, from one another and from healthy controls. The specificity was greater than 98% for each diagnosis.
“For years, we’ve seen remarkable results from immunosignatures, but introducing the technology to the scientific community has required a lot of patience,” said study author Phillip Stafford, PhD, of Arizona State University in Tempe.
The technique relies on a microarray consisting of thousands of random sequence peptides, imprinted on a glass slide. When a tiny droplet of blood (less than a microliter is needed) is spread across the microarray, antibodies in the blood selectively bind with individual peptides, forming a portrait of immune activity—an immunosignature.
Because the peptide sequences are random and not related to any naturally occurring disease antigens, the immunosignatures are “disease agnostic,” which means a single platform is potentially applicable to multiple disease types.
With their research, Dr Stafford and his colleagues put this claim to the test. The team first “trained” the system to calibrate results and establish reference immunosignatures using 20 samples each from 5 cancer patient cohorts, along with 20 non-cancer patients.
Once reference immunosignatures were established, the researchers tested the technique in a blind evaluation of 120 independent samples covering the same diseases. The results demonstrated 95% accuracy.
To further assess the diagnostic power of immunosignaturing, the team tested more than 1500 historical samples comprising 14 different diseases. This included 12 cancers, such as breast, brain, and multiple myeloma.
The average diagnostic accuracy of immunosignaturing was greater than 98% for each diagnosis, which suggests the method is suitable for the simultaneous classification of multiple diseases.
In a pairwise test against healthy control samples, multiple myeloma samples displayed the most significantly different peptides by t test. Of the top 100 peptides selected in this way, only breast cancer showed no overlap with any other disease.
Nevertheless, the researchers were able to distinguish the 14 separate diseases from one another, as well as from healthy controls, through immunosignatures.
Dr Stafford and his colleagues said these results suggest that immunosignatures provide an attractive means of capturing disease complexity. They offer a marked improvement over traditional methods in which one-to-one molecular recognition events are measured and a small number of analytes can be evaluated.
Furthermore, the technology is flexible in terms of handling and processing, the team said. A dried sample of blood, collected on filter paper and mailed to a study facility, can be used to generate an immunosignature.
The researchers also pointed out that the microarray chip used for this study contains 10,000 imprinted peptides, and this allows for enhanced sensitivity, owing to the large number of different possible signals elicited.
However, a significant improvement in immunosignaturing sensitivity and accuracy might be achieved through new chip technology. The team is currently developing a chip imprinted with more than 100,000 peptides.
A novel method of blood cell production
stem cells to form endothelium
(green), then blood cells (red)
Credit: Irina Elcheva
and Akhilesh Kumar
Researchers have reported a new method for creating human blood cells in the lab, and they believe the approach is safer and more reliable than its predecessors.
The team determined how blood cells are made at the earliest stages of development; namely, 2 genetic programs are responsible for turning pluripotent stem cells into blood cells.
This discovery gave the researchers the tools to make an array of blood cells themselves, using transcription factors.
“This is the first demonstration of the production of different kinds of cells from human pluripotent stem cells using transcription factors,” said Igor Slukvin, MD, PhD, of the University of Wisconsin-Madison.
He and his colleagues described this method in Nature Communications.
During development, blood cells emerge in the aorta. There, blood cells, including hematopoietic stem cells, are generated by budding from hemogenic endothelial cells.
Dr Slukvin and his colleagues found that 2 distinct groups of transcription factors—pan-myeloid (ETV2 and GATA2) and erythro-megakaryocytic (GATA2 and TAL1)—directly convert human pluripotent stem cells into hemogenic endothelial cells.
These cells then develop into blood cells with pan-myeloid or erythro-megakaryocytic potential.
“By overexpressing just 2 transcription factors, we can, in the laboratory dish, reproduce the sequence of events we see in the embryo,” Dr Slukvin said.
Furthermore, the method could produce blood cells in abundance. For every million stem cells, the researchers were able to produce 30 million blood cells.
The team noted that a critical aspect of this work is the use of modified messenger RNA to direct stem cells toward particular developmental fates.
This approach makes it possible to induce cells without introducing any genetic artifacts. So this method of blood cell production is safer than other methods, according to the researchers.
“You can do it without a virus, and genome integrity is not affected,” Dr Slukvin noted.
He added that his group is still working on a method for producing hematopoietic stem cells in the lab.
“We still don’t know how to do that,” he said. “But our new approach to making blood cells will give us an opportunity to model their development in a dish and identify novel hematopoietic stem cell factors.”
stem cells to form endothelium
(green), then blood cells (red)
Credit: Irina Elcheva
and Akhilesh Kumar
Researchers have reported a new method for creating human blood cells in the lab, and they believe the approach is safer and more reliable than its predecessors.
The team determined how blood cells are made at the earliest stages of development; namely, 2 genetic programs are responsible for turning pluripotent stem cells into blood cells.
This discovery gave the researchers the tools to make an array of blood cells themselves, using transcription factors.
“This is the first demonstration of the production of different kinds of cells from human pluripotent stem cells using transcription factors,” said Igor Slukvin, MD, PhD, of the University of Wisconsin-Madison.
He and his colleagues described this method in Nature Communications.
During development, blood cells emerge in the aorta. There, blood cells, including hematopoietic stem cells, are generated by budding from hemogenic endothelial cells.
Dr Slukvin and his colleagues found that 2 distinct groups of transcription factors—pan-myeloid (ETV2 and GATA2) and erythro-megakaryocytic (GATA2 and TAL1)—directly convert human pluripotent stem cells into hemogenic endothelial cells.
These cells then develop into blood cells with pan-myeloid or erythro-megakaryocytic potential.
“By overexpressing just 2 transcription factors, we can, in the laboratory dish, reproduce the sequence of events we see in the embryo,” Dr Slukvin said.
Furthermore, the method could produce blood cells in abundance. For every million stem cells, the researchers were able to produce 30 million blood cells.
The team noted that a critical aspect of this work is the use of modified messenger RNA to direct stem cells toward particular developmental fates.
This approach makes it possible to induce cells without introducing any genetic artifacts. So this method of blood cell production is safer than other methods, according to the researchers.
“You can do it without a virus, and genome integrity is not affected,” Dr Slukvin noted.
He added that his group is still working on a method for producing hematopoietic stem cells in the lab.
“We still don’t know how to do that,” he said. “But our new approach to making blood cells will give us an opportunity to model their development in a dish and identify novel hematopoietic stem cell factors.”
stem cells to form endothelium
(green), then blood cells (red)
Credit: Irina Elcheva
and Akhilesh Kumar
Researchers have reported a new method for creating human blood cells in the lab, and they believe the approach is safer and more reliable than its predecessors.
The team determined how blood cells are made at the earliest stages of development; namely, 2 genetic programs are responsible for turning pluripotent stem cells into blood cells.
This discovery gave the researchers the tools to make an array of blood cells themselves, using transcription factors.
“This is the first demonstration of the production of different kinds of cells from human pluripotent stem cells using transcription factors,” said Igor Slukvin, MD, PhD, of the University of Wisconsin-Madison.
He and his colleagues described this method in Nature Communications.
During development, blood cells emerge in the aorta. There, blood cells, including hematopoietic stem cells, are generated by budding from hemogenic endothelial cells.
Dr Slukvin and his colleagues found that 2 distinct groups of transcription factors—pan-myeloid (ETV2 and GATA2) and erythro-megakaryocytic (GATA2 and TAL1)—directly convert human pluripotent stem cells into hemogenic endothelial cells.
These cells then develop into blood cells with pan-myeloid or erythro-megakaryocytic potential.
“By overexpressing just 2 transcription factors, we can, in the laboratory dish, reproduce the sequence of events we see in the embryo,” Dr Slukvin said.
Furthermore, the method could produce blood cells in abundance. For every million stem cells, the researchers were able to produce 30 million blood cells.
The team noted that a critical aspect of this work is the use of modified messenger RNA to direct stem cells toward particular developmental fates.
This approach makes it possible to induce cells without introducing any genetic artifacts. So this method of blood cell production is safer than other methods, according to the researchers.
“You can do it without a virus, and genome integrity is not affected,” Dr Slukvin noted.
He added that his group is still working on a method for producing hematopoietic stem cells in the lab.
“We still don’t know how to do that,” he said. “But our new approach to making blood cells will give us an opportunity to model their development in a dish and identify novel hematopoietic stem cell factors.”
FDA warns of non-sterile drugs
Credit: Bill Branson
The US Food and Drug Administration (FDA) is alerting healthcare professionals not to use sterile drugs produced by Unique Pharmaceuticals Ltd., as they may be contaminated.
Healthcare professionals should immediately check their medical supplies and quarantine any sterile drug products from Unique Pharmaceuticals, a compounding outsourcing facility in Temple, Texas.
Administration of a non-sterile product may result in serious infection or death.
Unique Pharmaceuticals’ products were distributed nationwide. Most of the product labels include: “Unique Pharmaceuticals, Temple TX USA 76502.”
FDA investigators conducted 2 recent inspections of the Unique Pharmaceuticals facility and observed unsanitary conditions that resulted in a lack of sterility assurance.
The inspections revealed sterility failures in several lots of products intended to be sterile, recurring environmental contamination problems, and poor sterile production practices.
The FDA previously asked the company to recall all non-expired lots of sterile drug products, but the company refused to do so. The FDA has now issued a formal request for Unique Pharmaceuticals to recall all non-expired lots of its sterile products currently on the market.
The FDA has also asked the company to cease sterile compounding operations until sufficient corrections are made at its facility. Unique Pharmaceuticals has refused this request as well.
To date, the FDA is not aware of reports of illness associated with the use of Unique Pharmaceuticals’ products.
Patients who have received any drug product produced by Unique Pharmaceuticals and have concerns should contact their healthcare professional.
Professionals and consumers may report adverse events or quality problems associated with the use of Unique Pharmaceuticals’ products to the FDA’s MedWatch Adverse Event Reporting Program.
Unique Pharmaceuticals is registered under section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA) as an outsourcing facility. The Drug Quality and Security Act, signed into law on November 27, 2013, added a new section 503B to the FDCA. Under section 503B, a compounder can elect to become an outsourcing facility.
Outsourcing facilities must comply with current good manufacturing practice requirements, will be subject to inspection by the FDA according to a risk-based schedule, and must meet certain other requirements, such as reporting adverse events and providing the FDA with certain information about the products they compound.
Credit: Bill Branson
The US Food and Drug Administration (FDA) is alerting healthcare professionals not to use sterile drugs produced by Unique Pharmaceuticals Ltd., as they may be contaminated.
Healthcare professionals should immediately check their medical supplies and quarantine any sterile drug products from Unique Pharmaceuticals, a compounding outsourcing facility in Temple, Texas.
Administration of a non-sterile product may result in serious infection or death.
Unique Pharmaceuticals’ products were distributed nationwide. Most of the product labels include: “Unique Pharmaceuticals, Temple TX USA 76502.”
FDA investigators conducted 2 recent inspections of the Unique Pharmaceuticals facility and observed unsanitary conditions that resulted in a lack of sterility assurance.
The inspections revealed sterility failures in several lots of products intended to be sterile, recurring environmental contamination problems, and poor sterile production practices.
The FDA previously asked the company to recall all non-expired lots of sterile drug products, but the company refused to do so. The FDA has now issued a formal request for Unique Pharmaceuticals to recall all non-expired lots of its sterile products currently on the market.
The FDA has also asked the company to cease sterile compounding operations until sufficient corrections are made at its facility. Unique Pharmaceuticals has refused this request as well.
To date, the FDA is not aware of reports of illness associated with the use of Unique Pharmaceuticals’ products.
Patients who have received any drug product produced by Unique Pharmaceuticals and have concerns should contact their healthcare professional.
Professionals and consumers may report adverse events or quality problems associated with the use of Unique Pharmaceuticals’ products to the FDA’s MedWatch Adverse Event Reporting Program.
Unique Pharmaceuticals is registered under section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA) as an outsourcing facility. The Drug Quality and Security Act, signed into law on November 27, 2013, added a new section 503B to the FDCA. Under section 503B, a compounder can elect to become an outsourcing facility.
Outsourcing facilities must comply with current good manufacturing practice requirements, will be subject to inspection by the FDA according to a risk-based schedule, and must meet certain other requirements, such as reporting adverse events and providing the FDA with certain information about the products they compound.
Credit: Bill Branson
The US Food and Drug Administration (FDA) is alerting healthcare professionals not to use sterile drugs produced by Unique Pharmaceuticals Ltd., as they may be contaminated.
Healthcare professionals should immediately check their medical supplies and quarantine any sterile drug products from Unique Pharmaceuticals, a compounding outsourcing facility in Temple, Texas.
Administration of a non-sterile product may result in serious infection or death.
Unique Pharmaceuticals’ products were distributed nationwide. Most of the product labels include: “Unique Pharmaceuticals, Temple TX USA 76502.”
FDA investigators conducted 2 recent inspections of the Unique Pharmaceuticals facility and observed unsanitary conditions that resulted in a lack of sterility assurance.
The inspections revealed sterility failures in several lots of products intended to be sterile, recurring environmental contamination problems, and poor sterile production practices.
The FDA previously asked the company to recall all non-expired lots of sterile drug products, but the company refused to do so. The FDA has now issued a formal request for Unique Pharmaceuticals to recall all non-expired lots of its sterile products currently on the market.
The FDA has also asked the company to cease sterile compounding operations until sufficient corrections are made at its facility. Unique Pharmaceuticals has refused this request as well.
To date, the FDA is not aware of reports of illness associated with the use of Unique Pharmaceuticals’ products.
Patients who have received any drug product produced by Unique Pharmaceuticals and have concerns should contact their healthcare professional.
Professionals and consumers may report adverse events or quality problems associated with the use of Unique Pharmaceuticals’ products to the FDA’s MedWatch Adverse Event Reporting Program.
Unique Pharmaceuticals is registered under section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA) as an outsourcing facility. The Drug Quality and Security Act, signed into law on November 27, 2013, added a new section 503B to the FDCA. Under section 503B, a compounder can elect to become an outsourcing facility.
Outsourcing facilities must comply with current good manufacturing practice requirements, will be subject to inspection by the FDA according to a risk-based schedule, and must meet certain other requirements, such as reporting adverse events and providing the FDA with certain information about the products they compound.
Antibody may treat cancer cachexia
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.
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.
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.