One factor that determines how at risk an individual is of developing late-onset Alzheimer disease (AD) is the version of the APOE gene that they carry - those carrying the gene that enables them to make the apoE4 form of the apoE protein are at increased risk and those carrying the gene that enables them to make the apoE2 form are at decreased risk. It has been hypothesized that increasing the amount of lipid (fat) associated with apoE by overexpressing the protein ABCA1 might decrease amyloid deposition in the brain, the hallmark of AD. Evidence to support this hypothesis has now been generated in mice by David Holtzman and colleagues at Washington University School of Medicine, St Louis.
In this study, mice that provide a model of AD (PDAPP mice) were engineered to overexpress the protein ABCA1 in the brain. These mice had characteristics almost identical to PDAPP mice lacking apoE - they had decreased amyloid deposition in the brain compared with normal PDAPP mice. As the PDAPP mice overexpressing ABCA1 in the brain were shown to have increased amounts of lipid associated with apoE, the authors concluded the hypothesis that an ABCA1-mediated increase in the amount of lipid associated with apoE would decrease amyloid deposition in the brain was correct. Furthermore, they suggested that approaches to increase the function of ABCA1 in the brain might be of benefit to individuals with, or at risk of developing, AD.
Title: Overexpression of ABCA1 reduces amyloid deposition in the PDAPP mouse model of Alzheimer disease
Author: David M. Holtzman
Washington University School of Medicine, St Louis, Missouri, USA.
Source: Karen Honey
Journal of Clinical Investigation
вторник, 19 июля 2011 г.
суббота, 16 июля 2011 г.
Developing Methods To Separate The Brain's Good And Bad Iron To Combat Parkinson's And Alzheimer's
Duke University chemists are developing ways to bind up iron in the brain to combat the neurological devastation of Parkinson's and Alzheimer's diseases. The key is to weed out potentially destructive forms of iron that generate harmful free radicals while leaving benign forms of iron alone to carry out vital functions in the body.
"Using existing chelating (metal-binding) molecules to target iron in the brain can be tricky," said Katherine Franz, an assistant chemistry professor at Duke, because iron is essential to the body. "We want to go after only the iron that is causing the damage. We don't want to pull the iron out of healthy sites."
During the American Chemical Society's August 2007 national meeting in Boston, Franz described her work with graduate student Louise Charkoudian to formulate sensitive chemical sentinels they call "pro-chelators." Those are metal-binding agents wrapped in chemical "cages" so they can enter the brain and wait in reserve until they encounter a site of potential damage.
Such a site contains both iron and the molecule hydrogen peroxide. The reaction between these two players -- known as a "Fenton reaction" -- can lead to the production of a highly reactive oxygen-containing chemical group called a hydroxyl radical, Franz said.
These toxic chemical radicals can cause oxidative stress in brain cells that has been associated with Parkinson's and Alzheimer's as well as other age-related maladies such as macular degeneration in the eyes, she said.
The pro-chelators that Franz described at the ACS meeting contain phenols that wear chemical "masks" around themselves to keep them from binding with benign forms of iron or other metals, such as those found in some essential enzymes. But the presence of excessive amounts of hydrogen peroxide will trigger an unmasking, allowing the phenols to sop up and inactivate the bad iron, she said.
Franz and Charkoudian described their first formula for a pro-chelator in a report printed in the Sept. 27, 2006, issue of the Journal of the American Chemical Society. The work is being supported by the Parkinson's Disease Foundation and Duke University.
Franz's talk at the society's latest national meeting concentrated on a second generation of pro-chelator compounds that are better tailored in both sensitivity and response time to the brain's chemical environment, she said.
A report on those newer compounds is also pending in the journal Dalton Transactions and includes contributions by post-doctoral associate David Pham and Duke undergraduate students Ashley Kwon and Abbey Vangeloff.
While their previous experiments have been in laboratory glassware, the Duke pair has now begun working with living cells.
"That work looks promising," Franz said. "It looks like we're seeing iron binding only when we increase the levels of hydrogen peroxide. This level of peroxide normally kills cells, but we are seeing cell survival with the pro-chelators, so we're very excited."
Source: Monte Basgall
Duke University
"Using existing chelating (metal-binding) molecules to target iron in the brain can be tricky," said Katherine Franz, an assistant chemistry professor at Duke, because iron is essential to the body. "We want to go after only the iron that is causing the damage. We don't want to pull the iron out of healthy sites."
During the American Chemical Society's August 2007 national meeting in Boston, Franz described her work with graduate student Louise Charkoudian to formulate sensitive chemical sentinels they call "pro-chelators." Those are metal-binding agents wrapped in chemical "cages" so they can enter the brain and wait in reserve until they encounter a site of potential damage.
Such a site contains both iron and the molecule hydrogen peroxide. The reaction between these two players -- known as a "Fenton reaction" -- can lead to the production of a highly reactive oxygen-containing chemical group called a hydroxyl radical, Franz said.
These toxic chemical radicals can cause oxidative stress in brain cells that has been associated with Parkinson's and Alzheimer's as well as other age-related maladies such as macular degeneration in the eyes, she said.
The pro-chelators that Franz described at the ACS meeting contain phenols that wear chemical "masks" around themselves to keep them from binding with benign forms of iron or other metals, such as those found in some essential enzymes. But the presence of excessive amounts of hydrogen peroxide will trigger an unmasking, allowing the phenols to sop up and inactivate the bad iron, she said.
Franz and Charkoudian described their first formula for a pro-chelator in a report printed in the Sept. 27, 2006, issue of the Journal of the American Chemical Society. The work is being supported by the Parkinson's Disease Foundation and Duke University.
Franz's talk at the society's latest national meeting concentrated on a second generation of pro-chelator compounds that are better tailored in both sensitivity and response time to the brain's chemical environment, she said.
A report on those newer compounds is also pending in the journal Dalton Transactions and includes contributions by post-doctoral associate David Pham and Duke undergraduate students Ashley Kwon and Abbey Vangeloff.
While their previous experiments have been in laboratory glassware, the Duke pair has now begun working with living cells.
"That work looks promising," Franz said. "It looks like we're seeing iron binding only when we increase the levels of hydrogen peroxide. This level of peroxide normally kills cells, but we are seeing cell survival with the pro-chelators, so we're very excited."
Source: Monte Basgall
Duke University
среда, 13 июля 2011 г.
Unfolding The Genetic Code
It turns out that sequencing the human genome - determining the order of DNA building blocks -- has not completely cracked the code of how DNA directs various cellular processes. In addition to the sequence of the base pairs, the instructions are in the packaging - how DNA is folded within a cell.
Virginia Tech researchers used novel methodology and the university's System X supercomputer to carry out what is probably the first simulation that explores full range of motions of a DNA strand of 147 base pairs, the length that is required to form the fundamental unit of DNA packing in the living cells -- the nucleosome. Contrary to a long-held belief that DNA is hard to bend, the simulation shows in crisp atomic detail that DNA is considerably more flexible than commonly thought.
The research is published in the December issue of the Biophysical Journal, in the article "A Computational Study of Nucleosomal DNA Flexibility," by Jory Zmuda Ruscio of Leesburg, Va., a Ph.D. student in the Genetics, Bioinformatics and Computational Biology Program at Virginia Tech, and Alexey Onufriev of Blacksburg, assistant professor of computer sciences and physics at Virginia Tech. They have been invited to do a platform presentation at the 51st Biophysical Society Annual Meeting in Baltimore in March.
There is about 12 feet of DNA in a human cell but it is packaged into nucleosomes - lengths of 147 base pairs each wrapped around eight special proteins. A nucleosome looks kind of like the lumpy beginning of a rubber-band ball. Or maybe more like a lumpy worm coil. Uncoiled, the worm wiggles, flexes, and even kinks, according to a simulation performed on System X.
As we know from watching forensic detective shows on TV, the DNA in all of an individual's cells is identical. The DNA in fingernail cells is exactly the same as in muscle. Yet the cells are different. "This is because, roughly speaking, the DNA in different cell types is packed differently and the complexes it forms with the surrounding proteins are in different positions, so only the relevant part of the code can be read at a time," said Onufriev. "Although nobody knows exactly how it happens, you can imagine reading only what you can see on a part of a crumpled newspaper."
The traditional view is that DNA is relatively rigid and that considerable energy is required when it needs to be bent to form protein-DNA complexes. However, recent experiments (Nature, Aug. 17, 2006) have begun to challenge that view. "The famous double-helix may be much more flexible than previously thought," said Onufriev.
The Virginia Tech research responded to this debate. Using 128 of System X's 1,100 processors, the research resulted in a System X movie revealing DNA wiggling like a worm, showing greater flexibility than expected from the traditional view. The DNA packing in the nucleosome is also found to be surprisingly loose. "The implication is that it may not cost much energy to bend the DNA - even to bend sharply," said Onufriev.
The methodology that is making it possible is based on the so-called "implicit solvent" approach being developed by Onufriev. "Biology does not happen in a vacuum," he said. "We are 75 percent water, and the effect of the water environment must be taken into account when studying biomolecules."
Previous simulations were often slowed because they accounted for the water that is present in living systems. For instance, in early studies of protein folding, only a few percent of the computing effort was being spent on the activity of the protein while the rest accounted for the activity of the surrounding fluids. The "implicit solvent" approach accounts for the role of water on average, but the movements of individual water molecules are not predicted, freeing computation capacity for simulation of whatever protein is being studied.
"Experiment cannot always probe atomic detail of living molecules because they are too small and often move too fast, said Onufriev. "But we can combine computational power with good algorithms to simulate these motions at high (atom-scale) resolution.
"It is an exciting time to do molecular modeling," he said. "The computing power and the methodology have come to the point that we can begin to fully probe biology on timescales very relevant to living things - such as DNA packing."
Virginia Tech's System X supercomputer was critical to this research, he said. "It was the combination of its sheer compute power with the algorithmic advantages that made it possible to run molecular simulations on that scale."
So far, the Virginia Tech research team addressed the question of how flexible the DNA is, which is only a small piece of the "second part of the genetic code" puzzle, Onufriev said. "However, this small piece should pave the way to addressing bigger questions, such as 'Exactly how is the tightly packed genetic content read by cellular machines"'"
"Atomic level simulations can complement experimentation and narrow competing theories," said Onufriev. "For systems as large as the nucleosome, simulations using virtual water may be the only practical way to estimate the stability of various confirmations," he said.
How DNA bends and flexes is critical for many cellular processes including cell differentiation and DNA replication. Although also observed in recent experiments, this unusual DNA flexibility is still unexplained. "Now seeing that DNA is not as hard to bend may lead to radical changes in our perspective," said Onufriev. "We are using these detailed pictures to see exactly how DNA bends and to understand the details of the mechanism behind it, something that is very hard or impossible to do experimentally."
Onufriev and his group of biochemistry, physics, biology, and other computer science researchers received a $1.1 million grant from the National Institutes of Health to develop high performance computing methodology to create molecular models and to probe in atomic detail the mechanisms of biology.
The purpose of the NIH award is to develop the methodology for computer simulations of complex biological processes and address the question of the atomic mechanism of DNA flexibility, Onufriev said. "This research may not only provide fundamental insights into how life works at the molecular level, but also has applications in drug discovery and in particular for rational drug design, which is an important consideration for the NIH."
Contact: Susan Trulove
Virginia Tech
Virginia Tech researchers used novel methodology and the university's System X supercomputer to carry out what is probably the first simulation that explores full range of motions of a DNA strand of 147 base pairs, the length that is required to form the fundamental unit of DNA packing in the living cells -- the nucleosome. Contrary to a long-held belief that DNA is hard to bend, the simulation shows in crisp atomic detail that DNA is considerably more flexible than commonly thought.
The research is published in the December issue of the Biophysical Journal, in the article "A Computational Study of Nucleosomal DNA Flexibility," by Jory Zmuda Ruscio of Leesburg, Va., a Ph.D. student in the Genetics, Bioinformatics and Computational Biology Program at Virginia Tech, and Alexey Onufriev of Blacksburg, assistant professor of computer sciences and physics at Virginia Tech. They have been invited to do a platform presentation at the 51st Biophysical Society Annual Meeting in Baltimore in March.
There is about 12 feet of DNA in a human cell but it is packaged into nucleosomes - lengths of 147 base pairs each wrapped around eight special proteins. A nucleosome looks kind of like the lumpy beginning of a rubber-band ball. Or maybe more like a lumpy worm coil. Uncoiled, the worm wiggles, flexes, and even kinks, according to a simulation performed on System X.
As we know from watching forensic detective shows on TV, the DNA in all of an individual's cells is identical. The DNA in fingernail cells is exactly the same as in muscle. Yet the cells are different. "This is because, roughly speaking, the DNA in different cell types is packed differently and the complexes it forms with the surrounding proteins are in different positions, so only the relevant part of the code can be read at a time," said Onufriev. "Although nobody knows exactly how it happens, you can imagine reading only what you can see on a part of a crumpled newspaper."
The traditional view is that DNA is relatively rigid and that considerable energy is required when it needs to be bent to form protein-DNA complexes. However, recent experiments (Nature, Aug. 17, 2006) have begun to challenge that view. "The famous double-helix may be much more flexible than previously thought," said Onufriev.
The Virginia Tech research responded to this debate. Using 128 of System X's 1,100 processors, the research resulted in a System X movie revealing DNA wiggling like a worm, showing greater flexibility than expected from the traditional view. The DNA packing in the nucleosome is also found to be surprisingly loose. "The implication is that it may not cost much energy to bend the DNA - even to bend sharply," said Onufriev.
The methodology that is making it possible is based on the so-called "implicit solvent" approach being developed by Onufriev. "Biology does not happen in a vacuum," he said. "We are 75 percent water, and the effect of the water environment must be taken into account when studying biomolecules."
Previous simulations were often slowed because they accounted for the water that is present in living systems. For instance, in early studies of protein folding, only a few percent of the computing effort was being spent on the activity of the protein while the rest accounted for the activity of the surrounding fluids. The "implicit solvent" approach accounts for the role of water on average, but the movements of individual water molecules are not predicted, freeing computation capacity for simulation of whatever protein is being studied.
"Experiment cannot always probe atomic detail of living molecules because they are too small and often move too fast, said Onufriev. "But we can combine computational power with good algorithms to simulate these motions at high (atom-scale) resolution.
"It is an exciting time to do molecular modeling," he said. "The computing power and the methodology have come to the point that we can begin to fully probe biology on timescales very relevant to living things - such as DNA packing."
Virginia Tech's System X supercomputer was critical to this research, he said. "It was the combination of its sheer compute power with the algorithmic advantages that made it possible to run molecular simulations on that scale."
So far, the Virginia Tech research team addressed the question of how flexible the DNA is, which is only a small piece of the "second part of the genetic code" puzzle, Onufriev said. "However, this small piece should pave the way to addressing bigger questions, such as 'Exactly how is the tightly packed genetic content read by cellular machines"'"
"Atomic level simulations can complement experimentation and narrow competing theories," said Onufriev. "For systems as large as the nucleosome, simulations using virtual water may be the only practical way to estimate the stability of various confirmations," he said.
How DNA bends and flexes is critical for many cellular processes including cell differentiation and DNA replication. Although also observed in recent experiments, this unusual DNA flexibility is still unexplained. "Now seeing that DNA is not as hard to bend may lead to radical changes in our perspective," said Onufriev. "We are using these detailed pictures to see exactly how DNA bends and to understand the details of the mechanism behind it, something that is very hard or impossible to do experimentally."
Onufriev and his group of biochemistry, physics, biology, and other computer science researchers received a $1.1 million grant from the National Institutes of Health to develop high performance computing methodology to create molecular models and to probe in atomic detail the mechanisms of biology.
The purpose of the NIH award is to develop the methodology for computer simulations of complex biological processes and address the question of the atomic mechanism of DNA flexibility, Onufriev said. "This research may not only provide fundamental insights into how life works at the molecular level, but also has applications in drug discovery and in particular for rational drug design, which is an important consideration for the NIH."
Contact: Susan Trulove
Virginia Tech
воскресенье, 10 июля 2011 г.
European Network Of Biological Samples Key To Develop New Cures For Complex Diseases
A seminar to explore the challenges and requirements to create a European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) will take place at the EU Parliament on 28 May 2008.
Medical and health research have evolved very quickly in the last decades based on path-breaking advances and discoveries in genomics and molecular biology. Those developments have been proved especially useful in the prevention, diagnose and treatment of complex diseases that arise from a vast array of interacting effects. In this context, human samples such as blood, tissues, cells, DNA and other body fluids are the basic materials that researchers study to uncover the molecular and environmental factors that underlie disease.
Understanding those interactions will depend critically on the study of large sets of samples linked with accurate and up-to-date clinical, biological and molecular information. Europe is without a doubt in a very advantageous position to play a global leading role due to the existence of a long tradition of excellent health systems that have vast collections of samples and data. However, while these important collections already exist in hospital archives, biobanks, and biological resources centres across the EU member states, there is little collaboration and exchange between them. This fragmentation and the limited access by investigators are the main bottleneck impeding progress to the benefit of medical research, European health care, and ultimately, the citizens of the European Union.
This seminar will discuss the importance and the future plans to develop a pan-European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI). Members of the main European research centres and institutes, universities, industry and government representatives will participate in the session to determine the necessary steps to set up an unprecedented network that will enable researchers to interact better, to access larger collections of biological samples and data, and thus to translate already existing potentials into new opportunities. Some of the urgent actions in the agenda are the preparation of an inventory of existing resources, the search for common standards and access rules, the establishment of a data protection system and the definition of the legal, ethical, social and financial governance framework for this initiative.
The planning consortium compromises 51 participants from 21 member states and more than 150 associated organizations. The successful implementation of a pan-European BBMRI will result into increased quality and reduced costs of research, more effective drug discoveries, improved health care and secure industrial competitiveness for the EU.
For a complete program of the seminar please go to bioresource-med/ and check the Forthcoming Events section.
For a complete program of the seminar please go to bioresource-med/ and check the Forthcoming Events section.
bioresource-med/
Medical and health research have evolved very quickly in the last decades based on path-breaking advances and discoveries in genomics and molecular biology. Those developments have been proved especially useful in the prevention, diagnose and treatment of complex diseases that arise from a vast array of interacting effects. In this context, human samples such as blood, tissues, cells, DNA and other body fluids are the basic materials that researchers study to uncover the molecular and environmental factors that underlie disease.
Understanding those interactions will depend critically on the study of large sets of samples linked with accurate and up-to-date clinical, biological and molecular information. Europe is without a doubt in a very advantageous position to play a global leading role due to the existence of a long tradition of excellent health systems that have vast collections of samples and data. However, while these important collections already exist in hospital archives, biobanks, and biological resources centres across the EU member states, there is little collaboration and exchange between them. This fragmentation and the limited access by investigators are the main bottleneck impeding progress to the benefit of medical research, European health care, and ultimately, the citizens of the European Union.
This seminar will discuss the importance and the future plans to develop a pan-European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI). Members of the main European research centres and institutes, universities, industry and government representatives will participate in the session to determine the necessary steps to set up an unprecedented network that will enable researchers to interact better, to access larger collections of biological samples and data, and thus to translate already existing potentials into new opportunities. Some of the urgent actions in the agenda are the preparation of an inventory of existing resources, the search for common standards and access rules, the establishment of a data protection system and the definition of the legal, ethical, social and financial governance framework for this initiative.
The planning consortium compromises 51 participants from 21 member states and more than 150 associated organizations. The successful implementation of a pan-European BBMRI will result into increased quality and reduced costs of research, more effective drug discoveries, improved health care and secure industrial competitiveness for the EU.
For a complete program of the seminar please go to bioresource-med/ and check the Forthcoming Events section.
For a complete program of the seminar please go to bioresource-med/ and check the Forthcoming Events section.
bioresource-med/
четверг, 7 июля 2011 г.
In Vitro And In Vivo Data Show Alfacell's ONCONASE(R) Is Active Against Naive And Chemoresistant Neuroblastoma Cells
Alfacell
Corporation (Nasdaq: ACEL) today announced that new data show ONCONASE, the
company's lead drug candidate, is active against naive and chemoresistant
neuroblastoma cells.
The pre-clinical in vitro and in vivo data published in Cancer Letters
(2007; Vol. 250, Issue 1: 107-116) through a collaboration between Alfacell
and Martin Michaelis, M.D., Ph.D., at the Institute of Medicinal Virology
at Johann Wolfgang University of Frankfurt, were also recently presented in
Germany.
Conclusions from the studies presented indicate that ONCONASE inhibits
neuroblastoma cell growth and induces caspase-independent cell death in
neuroblastoma cells independently of P-gp expression or p53 status, which
has been shown to contribute to multi-drug resistance in neuroblastoma as
well as most other human cancers. Transmission electronic microscope
investigations suggest that ONCONASE induces a process in neuroblastoma
cells called autophagy (the digestion of cellular constituents by enzymes
of the same cell), which leads to apoptosis (programmed cell death).
Anti-tumor activity of ONCONASE against drug-sensitive and chemoresistant
neuroblastoma xenografts was confirmed in animals.
"The data speak to the broad potential application for ONCONASE in
various types of cancer other than the gateway indication for
mesothelioma," said Kuslima Shogen, Alfacell's chairman and chief executive
officer. "We now have an even better understanding of the mechanism of
action that ONCONASE utilizes in overcoming multiple drug resistance in
various tumor types."
Neuroblastoma is a cancer that forms in the nerve tissue. It is the
most common cancer in infants, and the fourth most common type of cancer in
children. Neurons (nerve cells) are the main components of the brain and
spinal cord and of the nerves that connect them to the rest of the body.
Approximately one in 100,000 children develops neuroblastoma in the United
States.
About ONCONASE(R)
ONCONASE is a first-in-class therapeutic product candidate based on
Alfacell's proprietary ribonuclease (RNase) technology. A natural protein
isolated from the leopard frog, ONCONASE has been shown in the laboratory
and clinic to target cancer cells while sparing normal cells. ONCONASE
triggers apoptosis, the natural death of cells, via multiple molecular
mechanisms of action.
About Alfacell Corporation
Alfacell Corporation is the first company to advance a
biopharmaceutical product candidate that works in a manner similar to RNA
interference (RNAi) through late-stage clinical trials. The product
candidate, ONCONASE, is an RNase that overcomes the challenges of targeting
RNA for therapeutic purposes while enabling the development of a new class
of targeted therapies for cancer and other life-threatening diseases. In
addition to an ongoing Phase IIIb study in malignant mesothelioma, Alfacell
is conducting a Phase I/II trial of ONCONASE in non-small cell lung cancer
(NSCLC) and other solid tumors. For more information, visit
alfacell.
Safe Harbor
This press release includes statements that may constitute "forward-
looking" statements, usually containing the words "believe," "estimate,"
"project," "expect" or similar expressions. Forward-looking statements
involve risks and uncertainties that could cause actual results to differ
materially from the forward-looking statements. Factors that would cause or
contribute to such differences include, but are not limited to,
uncertainties involved in transitioning from concept to product,
uncertainties involving the ability of the company to finance research and
development activities, potential challenges to or violations of patents,
uncertainties regarding the outcome of clinical trials, the company's
ability to secure necessary approvals from regulatory agencies, dependence
upon third-party vendors, and other risks discussed in the company's
periodic filings with the Securities and Exchange Commission. By making
these forward-looking statements, the company undertakes no obligation to
update these statements for revisions or changes after the date of this
release.
Alfacell Corporation
alfacell
Corporation (Nasdaq: ACEL) today announced that new data show ONCONASE, the
company's lead drug candidate, is active against naive and chemoresistant
neuroblastoma cells.
The pre-clinical in vitro and in vivo data published in Cancer Letters
(2007; Vol. 250, Issue 1: 107-116) through a collaboration between Alfacell
and Martin Michaelis, M.D., Ph.D., at the Institute of Medicinal Virology
at Johann Wolfgang University of Frankfurt, were also recently presented in
Germany.
Conclusions from the studies presented indicate that ONCONASE inhibits
neuroblastoma cell growth and induces caspase-independent cell death in
neuroblastoma cells independently of P-gp expression or p53 status, which
has been shown to contribute to multi-drug resistance in neuroblastoma as
well as most other human cancers. Transmission electronic microscope
investigations suggest that ONCONASE induces a process in neuroblastoma
cells called autophagy (the digestion of cellular constituents by enzymes
of the same cell), which leads to apoptosis (programmed cell death).
Anti-tumor activity of ONCONASE against drug-sensitive and chemoresistant
neuroblastoma xenografts was confirmed in animals.
"The data speak to the broad potential application for ONCONASE in
various types of cancer other than the gateway indication for
mesothelioma," said Kuslima Shogen, Alfacell's chairman and chief executive
officer. "We now have an even better understanding of the mechanism of
action that ONCONASE utilizes in overcoming multiple drug resistance in
various tumor types."
Neuroblastoma is a cancer that forms in the nerve tissue. It is the
most common cancer in infants, and the fourth most common type of cancer in
children. Neurons (nerve cells) are the main components of the brain and
spinal cord and of the nerves that connect them to the rest of the body.
Approximately one in 100,000 children develops neuroblastoma in the United
States.
About ONCONASE(R)
ONCONASE is a first-in-class therapeutic product candidate based on
Alfacell's proprietary ribonuclease (RNase) technology. A natural protein
isolated from the leopard frog, ONCONASE has been shown in the laboratory
and clinic to target cancer cells while sparing normal cells. ONCONASE
triggers apoptosis, the natural death of cells, via multiple molecular
mechanisms of action.
About Alfacell Corporation
Alfacell Corporation is the first company to advance a
biopharmaceutical product candidate that works in a manner similar to RNA
interference (RNAi) through late-stage clinical trials. The product
candidate, ONCONASE, is an RNase that overcomes the challenges of targeting
RNA for therapeutic purposes while enabling the development of a new class
of targeted therapies for cancer and other life-threatening diseases. In
addition to an ongoing Phase IIIb study in malignant mesothelioma, Alfacell
is conducting a Phase I/II trial of ONCONASE in non-small cell lung cancer
(NSCLC) and other solid tumors. For more information, visit
alfacell.
Safe Harbor
This press release includes statements that may constitute "forward-
looking" statements, usually containing the words "believe," "estimate,"
"project," "expect" or similar expressions. Forward-looking statements
involve risks and uncertainties that could cause actual results to differ
materially from the forward-looking statements. Factors that would cause or
contribute to such differences include, but are not limited to,
uncertainties involved in transitioning from concept to product,
uncertainties involving the ability of the company to finance research and
development activities, potential challenges to or violations of patents,
uncertainties regarding the outcome of clinical trials, the company's
ability to secure necessary approvals from regulatory agencies, dependence
upon third-party vendors, and other risks discussed in the company's
periodic filings with the Securities and Exchange Commission. By making
these forward-looking statements, the company undertakes no obligation to
update these statements for revisions or changes after the date of this
release.
Alfacell Corporation
alfacell
понедельник, 4 июля 2011 г.
Researchers Enlist DNA To Bring Carbon Nanotubes' Promise Closer To Reality
A team of researchers from DuPont and Lehigh University has reported a breakthrough in the quest to produce carbon nanotubes (CNTs) that are suitable for use in electronics, medicine and other applications.
In an article published in the July 9 issue of Nature, the group says it has developed a DNA-based method that sorts and separates specific types of CNTs from a mixture.
CNTs are long, narrow cylinders of graphite with a broad range of electronic, thermal and structural properties that vary according to the tubes' shape and structure. This versatility gives CNTs great promise in electronics, lasers, sensors and biomedicine, and as strengthening elements in composite materials.
Current methods of producing CNTs yield mixtures of tubes with different diameters and symmetry, or "chirality." Before the tubes can be used, however, they must be disentangled from a mixture and "purified" into separate species of CNTs of the same electronic type.
"A systematic method of purifying every single-chirality species of the same electronic type from a synthetic mixture of single-walled nanotubes is highly desirable," the DuPont-Lehigh group wrote in Nature, "but the task has proven to be insurmountable to date."
The Nature article is titled "DNA sequence motifs for structure-specific recognition and separation of carbon nanotubes." Its authors are Ming Zheng, Xiaomin Tu, Anand Jagota and Suresh Manohar. Zheng and Tu are scientists with DuPont Central Research and Development. Jagota is a professor of chemical engineering at Lehigh. Manohar is a graduate student in chemical engineering at Lehigh.
In 2003, a team of scientists from DuPont, MIT and the University of Illinois at Urbana-Champaign developed a new method of separating metallic CNTs from semiconducting CNTs using single-stranded DNA and anion-exchange chromatography. The scientists reported their discovery in Science. The team was led by Zheng and Jagota, who was then a research scientist with DuPont.
The new results improve on the 2003 results by identifying more than 20 DNA short sequences that can recognize individual types, or species, of carbon nanotubes and purify them from a mixture.
The new method utilizes tailored DNA sequences and "allows the purification of all 12 major single-chirality semiconducting species from a synthetic mixture, with sufficient yield for both fundamental studies and application development."
The current experiments were conducted at DuPont by Tu and Zheng, while Manohar and Jagota developed structural models using molecular simulations.
"The interesting discovery made by Tu and Zheng," says Jagota, "is that if you choose the DNA sequence correctly, it recognizes a particular type of CNT and enables us to sort that variety cleanly. This kind of practical improvement brings us closer to manufacturing possibility."
How does DNA recognize and sort types of CNTs? The DuPont-Lehigh team says this could be related to DNA's ability to form a structure different from its usual double helix by wrapping around the CNTs.
An alpha helix, like scotch tape wrapped around a pencil to form a tube, is a common shape seen in proteins, one of the main classes of biological molecules. Another common structure seen in proteins is the beta sheet. If you take a long strand in your palm, stretch it out to the tip of your index finger, loop it to your middle finger, then back to your palm, then out to your ring finger, back to your palm and out to your little finger, you form a type of beta sheet.
"Such a structure is not known for DNA," says Jagota, "but we've shown that it is possible as long as you allow the DNA to adsorb on a surface. If the surface is cylindrical, like a CNT, you get a variant called the beta-barrel."
While the researchers do not have absolute proof, they say circumstantial evidence strongly supports their hypothesis that the DNA is forming this well-organized structure and that it recognizes a specific CNT in the same way that biological molecules recognize each other by structure.
Jagota, who directs Lehigh's bioengineering program, says the biomedical ramifications of the researchers' discovery are particularly exciting. One potential application for CNTs, for example, is to place them on substrates that can be delivered to cells in the body.
"We are very interested in the biomedical applications of this work," says Jagota. "What does this say about how DNA interacts with nanomaterials? Will they be harmful inside the body? Can we take advantage of the interaction for therapeutic applications? It's a big open field."
Source:
Kurt Pfitzer
Lehigh University
In an article published in the July 9 issue of Nature, the group says it has developed a DNA-based method that sorts and separates specific types of CNTs from a mixture.
CNTs are long, narrow cylinders of graphite with a broad range of electronic, thermal and structural properties that vary according to the tubes' shape and structure. This versatility gives CNTs great promise in electronics, lasers, sensors and biomedicine, and as strengthening elements in composite materials.
Current methods of producing CNTs yield mixtures of tubes with different diameters and symmetry, or "chirality." Before the tubes can be used, however, they must be disentangled from a mixture and "purified" into separate species of CNTs of the same electronic type.
"A systematic method of purifying every single-chirality species of the same electronic type from a synthetic mixture of single-walled nanotubes is highly desirable," the DuPont-Lehigh group wrote in Nature, "but the task has proven to be insurmountable to date."
The Nature article is titled "DNA sequence motifs for structure-specific recognition and separation of carbon nanotubes." Its authors are Ming Zheng, Xiaomin Tu, Anand Jagota and Suresh Manohar. Zheng and Tu are scientists with DuPont Central Research and Development. Jagota is a professor of chemical engineering at Lehigh. Manohar is a graduate student in chemical engineering at Lehigh.
In 2003, a team of scientists from DuPont, MIT and the University of Illinois at Urbana-Champaign developed a new method of separating metallic CNTs from semiconducting CNTs using single-stranded DNA and anion-exchange chromatography. The scientists reported their discovery in Science. The team was led by Zheng and Jagota, who was then a research scientist with DuPont.
The new results improve on the 2003 results by identifying more than 20 DNA short sequences that can recognize individual types, or species, of carbon nanotubes and purify them from a mixture.
The new method utilizes tailored DNA sequences and "allows the purification of all 12 major single-chirality semiconducting species from a synthetic mixture, with sufficient yield for both fundamental studies and application development."
The current experiments were conducted at DuPont by Tu and Zheng, while Manohar and Jagota developed structural models using molecular simulations.
"The interesting discovery made by Tu and Zheng," says Jagota, "is that if you choose the DNA sequence correctly, it recognizes a particular type of CNT and enables us to sort that variety cleanly. This kind of practical improvement brings us closer to manufacturing possibility."
How does DNA recognize and sort types of CNTs? The DuPont-Lehigh team says this could be related to DNA's ability to form a structure different from its usual double helix by wrapping around the CNTs.
An alpha helix, like scotch tape wrapped around a pencil to form a tube, is a common shape seen in proteins, one of the main classes of biological molecules. Another common structure seen in proteins is the beta sheet. If you take a long strand in your palm, stretch it out to the tip of your index finger, loop it to your middle finger, then back to your palm, then out to your ring finger, back to your palm and out to your little finger, you form a type of beta sheet.
"Such a structure is not known for DNA," says Jagota, "but we've shown that it is possible as long as you allow the DNA to adsorb on a surface. If the surface is cylindrical, like a CNT, you get a variant called the beta-barrel."
While the researchers do not have absolute proof, they say circumstantial evidence strongly supports their hypothesis that the DNA is forming this well-organized structure and that it recognizes a specific CNT in the same way that biological molecules recognize each other by structure.
Jagota, who directs Lehigh's bioengineering program, says the biomedical ramifications of the researchers' discovery are particularly exciting. One potential application for CNTs, for example, is to place them on substrates that can be delivered to cells in the body.
"We are very interested in the biomedical applications of this work," says Jagota. "What does this say about how DNA interacts with nanomaterials? Will they be harmful inside the body? Can we take advantage of the interaction for therapeutic applications? It's a big open field."
Source:
Kurt Pfitzer
Lehigh University
пятница, 1 июля 2011 г.
Miniature Smart Pump
An innovative micro-pump makes it possible for tiny quantities of liquid - such as medicines - to be dosed accurately and flexibly. Active composites and an electronic control mechanism ensure that the low-maintenance pump works accurately - both forwards and backwards.
Medicines sometimes have to be administered in extremely small quantities. Just a few tenths of a milliliter may be sufficient to give the patient the ideal treatment. Micro-pumps greatly facilitate the dosage of minute quantities. Pumps like these have been built and constantly optimized for over 25 years. They find application in numerous areas - from medical engineering to microproduction technology - wherever tiny volumes have to be variably dosed with extreme accuracy.
However, these micro-pump systems are usually not as flexible as desired: They often work in only one direction, bubbles in the liquid impair their operation, they do not tolerate bothersome particles, they have a fixed pump output and they contain expendable parts such as valves or cogwheels. Together with partners from research institutes and industry, researchers at the Fraunhofer Institute for Mechanics of Materials IWM in Freiburg have developed an innovative pump system that solves all these problems: a controllable peristaltic micro-pump. "The peristaltic pump is a highly complex system," explains IWM project manager Dr. Bärbel Thielicke. "It contracts in waves in a similar way to the human esophagus, and thus propels the liquid along - it changes shape of its own accord. To achieve this, we had to use a whole range of different materials and special material composites." The researchers use lead-zirconate-titanate (PZT) films that are joined in a suitable way with bending elements made of carbon-fiber-reinforced plastic and a flexible tube. "PZT materials change their shape as soon as you apply an electric field to them. This makes it possible to control the pump system electronically," says Thielicke. Special adhesives additionally hold the various components of the pump system together. Thanks to the special control electronics, tiny quantities can be pumped accurately through the system.
The peristaltic pump system has already passed its first functional tests. Now the researchers are working to adapt the peristaltic micro-pump to the various different applications. "We work with special simulation models to do this," says Thielicke. "We calculate in advance how the structure of the pump needs to be modified in order to administer other dosages or other liquids. This helps us save time and money during the development phase."
Source: Baerbel Thielicke
Fraunhofer-Gesellschaft
Medicines sometimes have to be administered in extremely small quantities. Just a few tenths of a milliliter may be sufficient to give the patient the ideal treatment. Micro-pumps greatly facilitate the dosage of minute quantities. Pumps like these have been built and constantly optimized for over 25 years. They find application in numerous areas - from medical engineering to microproduction technology - wherever tiny volumes have to be variably dosed with extreme accuracy.
However, these micro-pump systems are usually not as flexible as desired: They often work in only one direction, bubbles in the liquid impair their operation, they do not tolerate bothersome particles, they have a fixed pump output and they contain expendable parts such as valves or cogwheels. Together with partners from research institutes and industry, researchers at the Fraunhofer Institute for Mechanics of Materials IWM in Freiburg have developed an innovative pump system that solves all these problems: a controllable peristaltic micro-pump. "The peristaltic pump is a highly complex system," explains IWM project manager Dr. Bärbel Thielicke. "It contracts in waves in a similar way to the human esophagus, and thus propels the liquid along - it changes shape of its own accord. To achieve this, we had to use a whole range of different materials and special material composites." The researchers use lead-zirconate-titanate (PZT) films that are joined in a suitable way with bending elements made of carbon-fiber-reinforced plastic and a flexible tube. "PZT materials change their shape as soon as you apply an electric field to them. This makes it possible to control the pump system electronically," says Thielicke. Special adhesives additionally hold the various components of the pump system together. Thanks to the special control electronics, tiny quantities can be pumped accurately through the system.
The peristaltic pump system has already passed its first functional tests. Now the researchers are working to adapt the peristaltic micro-pump to the various different applications. "We work with special simulation models to do this," says Thielicke. "We calculate in advance how the structure of the pump needs to be modified in order to administer other dosages or other liquids. This helps us save time and money during the development phase."
Source: Baerbel Thielicke
Fraunhofer-Gesellschaft
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