The Lasker Foundation awarded Carnegie's Joseph G. Gall the prestigious 2006 Lasker Award for Special Achievement in Medical Science. The citation recognizes that Gall is "a founder of modern cell biology who has made seminal contributions to the field of chromosome structure and function, who invented in situ hybridization, and who has been a long-standing champion of women in science."
Gall has been staff scientist at the Carnegie Institution's Department of Embryology and adjunct professor of The Johns Hopkins University since 1983, and a Professor of Developmental Genetics of the American Cancer Society since 1984. His in situ hybridization technique, developed with graduate students Mary Lou Pardue and Susan Gerbi in 1969, is a powerful method that allows researchers to locate and map genes and specific sequences of DNA on a chromosome. It revolutionized molecular biology and is now used worldwide in gene studies.
"Joe Gall's achievements are a realization of Andrew Carnegie's original dream," remarked Carnegie president Richard Meserve. "Carnegie believed that if exceptional individuals are set free to work in an environment without constraints extraordinary discoveries will result."
Education and Career Path
As a teenager, Gall spent summers on a farm in northern Virginia, where his interest in the natural world flourished. "After much urging, my parents bought me a microscope when I was 14 years old--not one of the toys I had struggled with up to that time, but the real thing," he reflected. Without a local high school to attend, Gall was sent to a boarding school near Charlottesville, Virginia, where after three years the headmaster thought he was ready to go to college.
"How Yale was chosen I am not sure, but I arrived in New Haven in June 1945, just as the Second World War was coming to a close."
Gall received his B.S. from Yale University in zoology in 1949 and his Ph.D. from Yale in 1952. Between 1952 and 1964, he taught at the University of Minnesota in Minneapolis, where he became Professor of Zoology. In 1963 he returned to Yale as part of his sabbatical, but before his year was over he was offered a position as Professor of Molecular Biophysics and Biochemistry. In an unusual twist to an academic career, he decided to leave Yale in 1983 to join Carnegie's Department of Embryology so he could conduct research full time.
Research
Gall's career-long interest is how the structure of the cell, particularly the nucleus, is related to the synthesis and processing of ribonucleic acid, RNA, during gene activity. He specifically looks at changes in the chromosomes and other nuclear components when RNA is synthesized, processed, and transported from the cell's nucleus to the cytoplasm. The in situ hybridization technique takes advantage of the feature that DNA and RNA bond to each other via their complementary sequences. Gall and colleagues developed their technique of labeling RNA with a radioactive label and placing it on cells on a microscope slide. The RNA hybridizes, or binds, with its complement on the DNA and is detected by its radioactivity. This technique allows researchers to see where genes are and determine whether a gene has been turned on in developing embryos. The advent of fluorescent tags have increased the sensitivity and precision.
Gall's development of in situ hybridization was a byproduct of his renowned research on the so-called lampbrush chromosomes--the largest chromosomes in any animal. They reside in amphibian eggs and were named when first viewed in the nineteenth century because they look like brushes then used to clean the narrow chimneys of lamps. Gall looks at the unlaid eggs from the frog Xenopus, which are up to 1.5 millimeters (mm) in diameter, with a nucleus, or germinal vesicle (GV), that is 0.4 mm in diameter. Their large size makes them ideal for understanding chromosome structure and function, Gall's research area since the 1940s. Gall made many discoveries about genes in the lampbrush chromosome including gene amplification in which extra copies of DNA are created at certain times in the oocyte. Similar extra copies of genes are often seen in cancer cells.
Current Interests
Gall has worked with various organisms over the years, from frogs to the fruit fly. It has generally been thought that various factors involved in RNA synthesis travel separately to active genes on the chromosomes for processing.
Using Xenopus eggs, Gall now studies this process. By watching fluorescently tagged molecules, he is able to determine where these factors move. This tracking has led Gall and others to propose that the processing machinery is assembled in structures in the GV, called Cajal bodies, named for the man who described them 100 years ago, Spanish neurobiologist and Nobel laureate Ramуn y Cajal.
Allan Spradling, department director of Carnegie's Department of Embryology commented on Gall's influence: "Joe Gall stands out especially because of the way he has done cutting-edge science throughout a long career. A true scholar of biology, he repeatedly turns his deep knowledge of diverse biological systems and of the forgotten lore of science history into novel experimental approaches that have sometimes spawned whole new fields of study. He shares his unmatched knowledge of microscopy in a unique course combining mathematically rigorous optics with a hands-on examination of historic instruments from every major phase of the field's development. All of these activities are carried out with the highest standards of integrity, respect for others, genuine modesty and with a sheer joy at the pleasures of discovery that seems undiminished from the days when he roamed the Virginia fields with his butterfly net and microscope. In short, Joe Gall's approach to science has long been an inspiration to others and I feel fortunate to count myself among those who have benefited enormously from his example."
Honors and Awards
The Lasker Awards, considered the U.S. Nobels, recognize basic researchers and clinical scientists whose work has been seminal to understanding and treating disease. Since 1962, 71 Lasker Award recipients have gone on to win a Nobel Prize. The Special Achievement Award was created in 1994.
Joe Gall has received numerous other awards over the years for his scientific research, among them the 2004 Society for Developmental Biology Lifetime Achievement Award and the 1996 American Association for the Advancement of Science Mentor Award for Lifetime Achievement. He also received the E. B. Wilson Medal from the American Society for Cell Biology in 1993 and the Wilbur Cross Medal from Yale University in 1988. Gall is a member of the American Academy of Arts and Sciences (1968), the National Academy of Sciences (1972), the American Philosophical Society (1989).
Carnegie geneticists Barbara McClintock and Alfred Hershey, both Nobel laureates, also won Lasker awards for their seminal research.
Andrew Carnegie founded the Carnegie Institution in 1902 as an organization for scientific discovery. The Department of Embryology, founded in 1913 in affiliation with the Anatomy Department of Johns Hopkins University, is one of six departments within the institution. Carnegie scientists are leaders in plant biology, developmental biology, astronomy, materials science, global ecology, and Earth and planetary science.
Contact:
Carnegie Institution
четверг, 26 мая 2011 г.
Student Recognized For Investigations Into The Potential Use Of Bacteriophage Coatings For The Prevention Of Microbial Colonisation On Medical Devices
Oxoid, a world-leading microbiology brand, is pleased to award the Oxoid Prize for the Best Project in Microbiology (2008) at the University of Brighton School of Pharmacy and Biomolecular Sciences to Niamh Kilbride for her investigations into the potential use of bacteriophage coatings for the prevention of microbial colonisation on medical devices.
In her research project, Niamh investigated several different methods for the immobilisation of phage K, with a view to developing a coating that would be effective against Staphylococcus aureus NCTC 10788. She studied the retention of the bacteriophage when dried onto the surface of untreated and silanised glass. She then incorporated the bacteriophage into a hydrogel coating and investigated whether the coating was effective at preventing or inhibiting the growth of bacteria on its surface.
Niamh concluded that it is possible to create a bacteriophage coating that can prevent microbial colonisation at sufficiently high concentrations of bacteriophage. She also concluded that the development of a suitable bacteriophage coating could potentially reduce and prevent the growth of bacteria in vivo.
Alison Smith, pharmaceutical microbiology manager, Oxoid, commented, "We are delighted to recognise this excellent research project. Pharmaceutical microbiologists worldwide are involved in the development and testing of new antimicrobials to fight hospital-acquired infections associated with indwelling medical devices, such as catheters. As a world-leading microbiology brand, we are keen to promote microbiologists like Niamh whose research may hold the answers for the prevention of such infections."
Niamh was presented with a framed certificate and a cheque for ВЈ150 prior to the graduation ceremonies at the University.
For further information about Oxoid products for clinical and industrial use, visit oxoid.
Oxoid is part of Thermo Fisher Scientific Inc., the world leader in serving science.
About Thermo Fisher Scientific
Thermo Fisher Scientific Inc. (NYSE: TMO) is the world leader in serving science, enabling our customers to make the world healthier, cleaner and safer. With annual revenues of $10 billion, we have more than 30,000 employees and serve over 350,000 customers within pharmaceutical and biotech companies, hospitals and clinical diagnostic labs, universities, research institutions and government agencies, as well as environmental and industrial process control settings. Serving customers through two premier brands, Thermo Scientific and Fisher Scientific, we help solve analytical challenges from routine testing to complex research and discovery. Thermo Scientific offers customers a complete range of high-end analytical instruments as well as laboratory equipment, software, services, consumables and reagents to enable integrated laboratory workflow solutions. Fisher Scientific provides a complete portfolio of laboratory equipment, chemicals, supplies and services used in healthcare, scientific research, safety and education. Together, we offer the most convenient purchasing options to customers and continuously advance our technologies to accelerate the pace of scientific discovery, enhance value for customers and fuel growth for shareholders and employees alike.
Thermo Fisher Scientific
In her research project, Niamh investigated several different methods for the immobilisation of phage K, with a view to developing a coating that would be effective against Staphylococcus aureus NCTC 10788. She studied the retention of the bacteriophage when dried onto the surface of untreated and silanised glass. She then incorporated the bacteriophage into a hydrogel coating and investigated whether the coating was effective at preventing or inhibiting the growth of bacteria on its surface.
Niamh concluded that it is possible to create a bacteriophage coating that can prevent microbial colonisation at sufficiently high concentrations of bacteriophage. She also concluded that the development of a suitable bacteriophage coating could potentially reduce and prevent the growth of bacteria in vivo.
Alison Smith, pharmaceutical microbiology manager, Oxoid, commented, "We are delighted to recognise this excellent research project. Pharmaceutical microbiologists worldwide are involved in the development and testing of new antimicrobials to fight hospital-acquired infections associated with indwelling medical devices, such as catheters. As a world-leading microbiology brand, we are keen to promote microbiologists like Niamh whose research may hold the answers for the prevention of such infections."
Niamh was presented with a framed certificate and a cheque for ВЈ150 prior to the graduation ceremonies at the University.
For further information about Oxoid products for clinical and industrial use, visit oxoid.
Oxoid is part of Thermo Fisher Scientific Inc., the world leader in serving science.
About Thermo Fisher Scientific
Thermo Fisher Scientific Inc. (NYSE: TMO) is the world leader in serving science, enabling our customers to make the world healthier, cleaner and safer. With annual revenues of $10 billion, we have more than 30,000 employees and serve over 350,000 customers within pharmaceutical and biotech companies, hospitals and clinical diagnostic labs, universities, research institutions and government agencies, as well as environmental and industrial process control settings. Serving customers through two premier brands, Thermo Scientific and Fisher Scientific, we help solve analytical challenges from routine testing to complex research and discovery. Thermo Scientific offers customers a complete range of high-end analytical instruments as well as laboratory equipment, software, services, consumables and reagents to enable integrated laboratory workflow solutions. Fisher Scientific provides a complete portfolio of laboratory equipment, chemicals, supplies and services used in healthcare, scientific research, safety and education. Together, we offer the most convenient purchasing options to customers and continuously advance our technologies to accelerate the pace of scientific discovery, enhance value for customers and fuel growth for shareholders and employees alike.
Thermo Fisher Scientific
Functional Amino Acids Regulate Key Metabolic Pathways
Functional amino acids play a critical role in the development of both animals and humans, according to a Texas AgriLife Research scientist.
In a journal article appearing in the American Society for Nutrition (Advances in Nutrition 1:31-37, 2010), Dr. Guoyao Wu, AgriLife Research animal nutritionist and senior faculty fellow in the department of animal science at Texas A&M University, calls for scientists to "think out of the box" and place more emphasis on this area of study.
"We need to move forward and capitalize on the potential of functional amino acids in improving health and animal production," he said.
A functional amino acid is an amino acid that can regulate key metabolic pathways to improve health, growth, development and reproduction of animals and humans, Wu said.
"This involves cell signaling through amino acids and their metabolites, and the metabolic pathways may include protein synthesis, antioxidative reactions and oxidation of energy substrates," he said. "A functional amino acid can be either a 'nonessential' or an 'essential' amino acid."
Past research emphasis has focused primarily on essential amino acids. However, Wu says both essential amino acids and non-essential amino acids should be taken into consideration.
"This is important when formulating balanced diets to maximize growth performance in livestock species, poultry and fish," he said. "It is also recommended that nonessential amino acids be provided to humans to prevent growth retardation and chronic diseases."
Wu's previous research discovered that arginine, an amino acid, contributes many positive benefits in growth and embryo development in pigs, sheep and rats. Arginine also aids in fighting obesity. Wu has identified this as an important area for expanded research on new amino acids and health.
"Currently in the U.S., more than 60 percent of adults are overweight or obese," he said. "Globally, more than 300 million adults are obese and more than 1 billion are overweight. Also, a large number of children in the U.S. and other countries are overweight or obese. The most urgent needs of new research in amino acids and health are the roles of functional amino acids in the treatment and prevention of obesity and its associated cardiovascular dysfunction."
Wu also said that dietary supplementation with arginine can help improve meat quality in pigs prior to slaughter.
The two top scientific discoveries in the field of amino acids and health over the past two decades are nitric oxide synthesis from arginine and the role of amino acids in cell signaling.
"An important area of research in the next few years may be to study the molecular and cellular mechanisms whereby some amino acids (e.g., arginine) can regulate metabolic pathways in animals and humans," he said. "An example is how arginine reduces obesity and ameliorates the metabolic syndrome, and how elevated levels of leucine may contribute to mitochondrial dysfunction and insulin resistance (including vascular resistance) in obese subjects."
He said "unquestionably" recent advances in understanding functional amino acids are "expanding our basic knowledge of protein metabolism and transforming practices of nutrition worldwide."
Though nutritional studies conducted on animals have benefited human health, Wu suggests that caution should be taken to "extrapolate animal data to humans" as dietary requirements differ from one species to another.
Wu said that humans need diets with balanced portions of amino acids for cardiovascular and reproductive health.
Source:
Dr. Guoyao Wu
Texas A&M AgriLife Communications
In a journal article appearing in the American Society for Nutrition (Advances in Nutrition 1:31-37, 2010), Dr. Guoyao Wu, AgriLife Research animal nutritionist and senior faculty fellow in the department of animal science at Texas A&M University, calls for scientists to "think out of the box" and place more emphasis on this area of study.
"We need to move forward and capitalize on the potential of functional amino acids in improving health and animal production," he said.
A functional amino acid is an amino acid that can regulate key metabolic pathways to improve health, growth, development and reproduction of animals and humans, Wu said.
"This involves cell signaling through amino acids and their metabolites, and the metabolic pathways may include protein synthesis, antioxidative reactions and oxidation of energy substrates," he said. "A functional amino acid can be either a 'nonessential' or an 'essential' amino acid."
Past research emphasis has focused primarily on essential amino acids. However, Wu says both essential amino acids and non-essential amino acids should be taken into consideration.
"This is important when formulating balanced diets to maximize growth performance in livestock species, poultry and fish," he said. "It is also recommended that nonessential amino acids be provided to humans to prevent growth retardation and chronic diseases."
Wu's previous research discovered that arginine, an amino acid, contributes many positive benefits in growth and embryo development in pigs, sheep and rats. Arginine also aids in fighting obesity. Wu has identified this as an important area for expanded research on new amino acids and health.
"Currently in the U.S., more than 60 percent of adults are overweight or obese," he said. "Globally, more than 300 million adults are obese and more than 1 billion are overweight. Also, a large number of children in the U.S. and other countries are overweight or obese. The most urgent needs of new research in amino acids and health are the roles of functional amino acids in the treatment and prevention of obesity and its associated cardiovascular dysfunction."
Wu also said that dietary supplementation with arginine can help improve meat quality in pigs prior to slaughter.
The two top scientific discoveries in the field of amino acids and health over the past two decades are nitric oxide synthesis from arginine and the role of amino acids in cell signaling.
"An important area of research in the next few years may be to study the molecular and cellular mechanisms whereby some amino acids (e.g., arginine) can regulate metabolic pathways in animals and humans," he said. "An example is how arginine reduces obesity and ameliorates the metabolic syndrome, and how elevated levels of leucine may contribute to mitochondrial dysfunction and insulin resistance (including vascular resistance) in obese subjects."
He said "unquestionably" recent advances in understanding functional amino acids are "expanding our basic knowledge of protein metabolism and transforming practices of nutrition worldwide."
Though nutritional studies conducted on animals have benefited human health, Wu suggests that caution should be taken to "extrapolate animal data to humans" as dietary requirements differ from one species to another.
Wu said that humans need diets with balanced portions of amino acids for cardiovascular and reproductive health.
Source:
Dr. Guoyao Wu
Texas A&M AgriLife Communications
Tweaking Taxol Points Way To A Greener, More Productive Future
As the effective cancer-treatment drug Taxol enters its next generation, Michigan State University announces discoveries which point to both environmentally friendly ways to produce more Taxol, and ultimately innovations to produce a more potent second-generation drug.
Kevin Walker, a chemistry and biochemistry and molecular biology assistant professor, in the March issue of Chemistry & Biology, reports a step toward manufacturing more-potent Taxol molecules that could potentially reduce treatment dosages. The methods described minimize dangerous chemical usage, and put E.coli to work in the production process.
"We're trying to develop a biosynthetic process for the drugs that circumvents the use of organic solvent-based methods requiring costly waste management," Walker said. "This attempt is a green chemistry approach to produce more potent versions of Taxol."
Taxol - generically known as paclitaxel - is a top-selling cancer-fighting drug. It's most commonly used against ovarian and breast cancers, but currently is used in certain aspects of heart disease treatment, and is showing promise in Alzheimer's therapy.
Taxol is derived in small quantities from the Pacific yew tree. To fulfill large-scale production, pharmaceutical companies isolate, from the tree, an abundant natural product that is synthetically converted to Taxol in the laboratory.
Now, as abundant molecules from the yew are being synthetically modified for new, more potent versions of Taxol, Walker, along with Catherine Loncaric, a visiting research associate, and undergraduate Erin Merriweather, is looking for alternative, biological routes to introduce the modifications. Walker's laboratory makes use of recently identified genes of the yew that produce enzymes that craft the pathway to Taxol. The targets: five enzymes that biosynthetically decorate the core of the Taxol molecule.
The enzymes in natural and, potentially, genetically modified form can be used to produce second-generation versions of the drug. Walker said the added advantage is that water-based chemicals rather than chlorinated solvents can be used with his methods.
For reasons ranging from competitive advantage to corporate culture, or to a desire to be a good corporate citizen, pharmaceutical companies are drawn to finding ways to minimize their environmental footprint as they make life-saving drugs.
"In fighting one pathological system, it makes sense to not create another problem that can have a global effect," Walker said.
Plus, Walker said assessing the Taxol pathway enzymes opens doors to new, more natural ways to make Taxol. He said that learning to genetically modify the qualities of the Pacific yew organism to make tomorrow's versions of Taxol could mean transferring all the genes - the entire pathway - into a bacterium for large-scale production of the new and improved Taxol, without further depleting the yew plant.
"Eventually, it will be cool when we're able potentially to have bacteria make all of the necessary plant enzymes, and we can sit back and watch E. coli make first- and second-generation Taxol molecules," Walker said.
The research was funded by MSU College of Natural Science. Walker's laboratory also is funded by the Michigan Agricultural Experiment Station.
Contact: Kevin Walker
walke284msu
Sue Nichols
University Relations
nicholsmsu
Michigan State University
View drug information on Taxol.
Kevin Walker, a chemistry and biochemistry and molecular biology assistant professor, in the March issue of Chemistry & Biology, reports a step toward manufacturing more-potent Taxol molecules that could potentially reduce treatment dosages. The methods described minimize dangerous chemical usage, and put E.coli to work in the production process.
"We're trying to develop a biosynthetic process for the drugs that circumvents the use of organic solvent-based methods requiring costly waste management," Walker said. "This attempt is a green chemistry approach to produce more potent versions of Taxol."
Taxol - generically known as paclitaxel - is a top-selling cancer-fighting drug. It's most commonly used against ovarian and breast cancers, but currently is used in certain aspects of heart disease treatment, and is showing promise in Alzheimer's therapy.
Taxol is derived in small quantities from the Pacific yew tree. To fulfill large-scale production, pharmaceutical companies isolate, from the tree, an abundant natural product that is synthetically converted to Taxol in the laboratory.
Now, as abundant molecules from the yew are being synthetically modified for new, more potent versions of Taxol, Walker, along with Catherine Loncaric, a visiting research associate, and undergraduate Erin Merriweather, is looking for alternative, biological routes to introduce the modifications. Walker's laboratory makes use of recently identified genes of the yew that produce enzymes that craft the pathway to Taxol. The targets: five enzymes that biosynthetically decorate the core of the Taxol molecule.
The enzymes in natural and, potentially, genetically modified form can be used to produce second-generation versions of the drug. Walker said the added advantage is that water-based chemicals rather than chlorinated solvents can be used with his methods.
For reasons ranging from competitive advantage to corporate culture, or to a desire to be a good corporate citizen, pharmaceutical companies are drawn to finding ways to minimize their environmental footprint as they make life-saving drugs.
"In fighting one pathological system, it makes sense to not create another problem that can have a global effect," Walker said.
Plus, Walker said assessing the Taxol pathway enzymes opens doors to new, more natural ways to make Taxol. He said that learning to genetically modify the qualities of the Pacific yew organism to make tomorrow's versions of Taxol could mean transferring all the genes - the entire pathway - into a bacterium for large-scale production of the new and improved Taxol, without further depleting the yew plant.
"Eventually, it will be cool when we're able potentially to have bacteria make all of the necessary plant enzymes, and we can sit back and watch E. coli make first- and second-generation Taxol molecules," Walker said.
The research was funded by MSU College of Natural Science. Walker's laboratory also is funded by the Michigan Agricultural Experiment Station.
Contact: Kevin Walker
walke284msu
Sue Nichols
University Relations
nicholsmsu
Michigan State University
View drug information on Taxol.
Gene Fusion Subtypes In Prostate Carcinoma Have Clinical Implications
Building on an earlier study
that used Oncomine(TM) to identify ETS-fusion proteins in prostate cancer
(Science, Oct 28 2005), Tomlins et al. today report the identification of
four additional classes of ETS rearrangements in prostate cancer, each of
which activates ETV1 by a different genetic mechanism (Nature, Aug 2 2007).
Tomlins et al. queried the Oncomine database to determine the tissue
specificity of three of the new fusion gene partners, demonstrating that
two new partners are prostate cancer specific while the third partner is a
generally over-expressed 'house-keeping' gene. In addition, Oncomine
Concepts Map was applied to test for similarities between the set of genes
regulated by ETV1 with sets of genes related to other biological concepts.
This analysis revealed a clear association between ETV1 activation and
cellular invasion, a hallmark of cancer.
Oncomine, a dynamic repository that combines rich data, sophisticated
analysis, and responsive user interface, empowers oncology research by
bringing data analysis tools to a large cancer gene expression database,
which includes data from 20,000+ microarray experiments curated from 300+
independent studies. Oncomine Concepts Map, an extension of Oncomine, is a
compilation of nearly 8,000 Oncomine cancer gene signatures together with
11,500 gene, protein, drug, and pathway signatures collected from the
literature and other public sources.
"This study marks an important advance in our understanding of the
molecular basis of prostate cancer. Oncomine again proved invaluable in
examining the expression of genes in cancer, and in this case aided in the
characterization of new sub-types of prostate cancer," said Dan Rhodes,
Ph.D., co-founder and Chief Science Officer of Compendia Bioscience. "The
authors went on to show that one of the new subtypes is unlikely to respond
to conventional anti-androgen therapy, and another may be adversely
affected by standard therapies. This strongly suggests that using this type
of molecular information to distinguish patient populations will have
important clinical implications."
About Compendia Bioscience, Inc.
Compendia Bioscience is dedicated to harnessing the global collection
of high throughput molecular data to provide researchers with the data and
analysis tools necessary to validate biomarker and gene target discoveries,
better understand mechanisms of disease, and optimize clinical outcomes.
About Oncomine(TM)
Oncomine(TM) combines a rapidly growing compendium of 20,000+ cancer
transcriptome profiles with a sophisticated analysis engine and a powerful
web application for data mining and visualization. Oncomine facilitates
rapid and reliable biomarker and therapeutic target discovery, validation,
and prioritization.
About Oncomine(TM) Concepts Map
Oncomine Concepts Map is licensed to commercial users as part of the
Oncomine Concepts Edition and the Oncomine Enterprise Edition. Visit
compendiabio for more information. An academic preview
edition is available to academic and non-profit researchers at
oncomine.
Compendia Bioscience, Inc.
compendiabio
that used Oncomine(TM) to identify ETS-fusion proteins in prostate cancer
(Science, Oct 28 2005), Tomlins et al. today report the identification of
four additional classes of ETS rearrangements in prostate cancer, each of
which activates ETV1 by a different genetic mechanism (Nature, Aug 2 2007).
Tomlins et al. queried the Oncomine database to determine the tissue
specificity of three of the new fusion gene partners, demonstrating that
two new partners are prostate cancer specific while the third partner is a
generally over-expressed 'house-keeping' gene. In addition, Oncomine
Concepts Map was applied to test for similarities between the set of genes
regulated by ETV1 with sets of genes related to other biological concepts.
This analysis revealed a clear association between ETV1 activation and
cellular invasion, a hallmark of cancer.
Oncomine, a dynamic repository that combines rich data, sophisticated
analysis, and responsive user interface, empowers oncology research by
bringing data analysis tools to a large cancer gene expression database,
which includes data from 20,000+ microarray experiments curated from 300+
independent studies. Oncomine Concepts Map, an extension of Oncomine, is a
compilation of nearly 8,000 Oncomine cancer gene signatures together with
11,500 gene, protein, drug, and pathway signatures collected from the
literature and other public sources.
"This study marks an important advance in our understanding of the
molecular basis of prostate cancer. Oncomine again proved invaluable in
examining the expression of genes in cancer, and in this case aided in the
characterization of new sub-types of prostate cancer," said Dan Rhodes,
Ph.D., co-founder and Chief Science Officer of Compendia Bioscience. "The
authors went on to show that one of the new subtypes is unlikely to respond
to conventional anti-androgen therapy, and another may be adversely
affected by standard therapies. This strongly suggests that using this type
of molecular information to distinguish patient populations will have
important clinical implications."
About Compendia Bioscience, Inc.
Compendia Bioscience is dedicated to harnessing the global collection
of high throughput molecular data to provide researchers with the data and
analysis tools necessary to validate biomarker and gene target discoveries,
better understand mechanisms of disease, and optimize clinical outcomes.
About Oncomine(TM)
Oncomine(TM) combines a rapidly growing compendium of 20,000+ cancer
transcriptome profiles with a sophisticated analysis engine and a powerful
web application for data mining and visualization. Oncomine facilitates
rapid and reliable biomarker and therapeutic target discovery, validation,
and prioritization.
About Oncomine(TM) Concepts Map
Oncomine Concepts Map is licensed to commercial users as part of the
Oncomine Concepts Edition and the Oncomine Enterprise Edition. Visit
compendiabio for more information. An academic preview
edition is available to academic and non-profit researchers at
oncomine.
Compendia Bioscience, Inc.
compendiabio
Seizure Generation In Brain Is Isolated From Surrounding Brain Regions
Mayo Clinic researchers found that the part of the brain generating seizures in individuals with epilepsy is functionally isolated from surrounding brain regions. The researchers hope this finding could be a clinical biomarker to help identify individuals with abnormal brain function. This study was presented at the American Epilepsy Society's annual meeting in San Antonio on Dec. 4.
Epilepsy is a disorder characterized by the occurrence of two or more seizures. It affects almost 3 million Americans.
"The synchronization of local and distributed neuronal assemblies underlies fundamental brain processes like perception, learning and cognition," says Gregory Worrell, M.D., Ph.D., a Mayo Clinic epileptologist and an author of this study. "In neurological disease, neuronal synchrony can be altered, and in epilepsy the synchrony plays an important role in the generation of seizures."
Mayo Clinic researchers investigated neuronal synchrony by studying intracranial EEG (electroencephalogram) recordings from patients with epilepsy and control subjects with facial pain. Researchers discovered that the control patients had greater average synchrony than patients with focal epilepsy (when seizures are produced in a small part of the brain, not the entire brain). When implanted electrode pairs bridged seizure-generating brain and other brain regions, the synchrony was significantly less than between other electrode pairs in the epileptic brain and the control brain. The team also found that with greater activity in the seizure-generating region, there was less synchrony with neighboring tissue outside that region.
"Our study shows us that the part of the brain generating seizures is isolated from the surrounding brain regions," says Dr. Worrell. "This finding could serve as a clinical biomarker of an abnormal brain, and it can also be useful in epilepsy surgery and brain stimulation treatments, as well as helping us understand how seizures are generated."
Other scientists involved in this research include C. Warren, Ph.D.; S. Hu; S. Stead, M.D., Ph.D.; B. Brinkmann, and M. Bower, Ph.D.
Source: Mayo Clinic
Epilepsy is a disorder characterized by the occurrence of two or more seizures. It affects almost 3 million Americans.
"The synchronization of local and distributed neuronal assemblies underlies fundamental brain processes like perception, learning and cognition," says Gregory Worrell, M.D., Ph.D., a Mayo Clinic epileptologist and an author of this study. "In neurological disease, neuronal synchrony can be altered, and in epilepsy the synchrony plays an important role in the generation of seizures."
Mayo Clinic researchers investigated neuronal synchrony by studying intracranial EEG (electroencephalogram) recordings from patients with epilepsy and control subjects with facial pain. Researchers discovered that the control patients had greater average synchrony than patients with focal epilepsy (when seizures are produced in a small part of the brain, not the entire brain). When implanted electrode pairs bridged seizure-generating brain and other brain regions, the synchrony was significantly less than between other electrode pairs in the epileptic brain and the control brain. The team also found that with greater activity in the seizure-generating region, there was less synchrony with neighboring tissue outside that region.
"Our study shows us that the part of the brain generating seizures is isolated from the surrounding brain regions," says Dr. Worrell. "This finding could serve as a clinical biomarker of an abnormal brain, and it can also be useful in epilepsy surgery and brain stimulation treatments, as well as helping us understand how seizures are generated."
Other scientists involved in this research include C. Warren, Ph.D.; S. Hu; S. Stead, M.D., Ph.D.; B. Brinkmann, and M. Bower, Ph.D.
Source: Mayo Clinic
Award Received By Boston Medical Center/Boston University School Of Medicine Researcher
M. Michael Wolfe, M.D., professor of medicine and research professor of physiology and biophysics at Boston University School of Medicine and chief of the Gastroenterology Section at Boston Medical Center, was awarded an Individual Biomedical Research Award by The Hartwell Foundation. Wolfe, considered a premier authority on the biology of GI regulatory peptides, will receive $300,000 direct cost over three years as a Hartwell Investigator for his project, "Peptide Replacement Therapy Using Transgenic Stem Cells Delivered to the Small Intestinal Mucosa".
Wolfe and his colleagues are developing a technique to redress hormone and enzyme deficiencies that cause diseases such as type 1 diabetes. The technique relies on engineering stem cells that produce the missing peptides and implanting them in the small intestine.
Because of their molecular size and susceptibility to degradation by stomach acid and digestive enzymes, insulin and other hormones must currently be administered by injection. The discomfort and inconvenience associated with injections often diminish patient compliance, particularly in children, which increases the risk of long-term complications. This concern is of particular importance for patients with type 1 diabetes, who often require multiple daily insulin injections to maintain stable blood sugar. Type I diabetes is one of the most common severe chronic diseases in children (1/300 in the US) and a major cause of end-stage renal disease, blindness, cardiovascular disease and premature death in the general population.
In a manuscript published in Science in 2000, Wolfe and his collaborators reported that intestinal K-cells of transgenic mice, which normally manufacture a hormone called GIP, could be engineered to express insulin and maintain normal blood glucose levels, even after pancreatic insulin-producing ("islet-beta") cells were destroyed. Employing the same genetic approach, Wolfe plans to transform stem cells that, like pancreatic islet-beta cells, will produce insulin in response to food ingestion. Using endoscopy, he plans to introduce transformed cells into the intestinal lining, where they will be programmed to become K-cells and produce insulin as well as GIP. The relocation of insulin production to the upper small intestine will "hide" it from the autoimmune response that destroys beta-cells in type 1 diabetes. Moreover, because K- and beta-cells are functionally similar, the K-cell appears to represent the ideal candidate for "hosting" the "foreign" insulin gene.
Wolfe is recognized as one of the world's leading authorities on GIP, and he initially cloned the GIP cDNA and ascertained its central role as principal mediator of the "enteroinsular axis". This axis functions as the hormonal connection between the intestine and pancreas following the ingestion of food. He established GIP as the likely mediator of the glycemic index and has theorized that low carbohydrate diets and gastric bypass surgery mediate their beneficial effects in part by suppressing GIP expression. He proved its importance in obesity by demonstrating functional receptors on adipocytes and by showing that GIP, like insulin, suppresses the breakdown of fat, which in essence results in an increase in fat storage.
"Boston University is delighted to have been invited by The Hartwell Foundation to participate in this year's competition and is deeply proud of Dr. Wolfe's selection for this exceptionally competitive Individual Biomedical Research Award," said Karen Antman, MD, dean of Boston University School of Medicine and provost of Boston University Medical Campus. "The award provides strategic funding for remarkably original research that combines genetic engineering, stem cell therapeutics, and gastroenterology, with exciting potential clinical implications. Private funding is vital to advancing such high-risk, high-gain work, and we are very grateful to The Hartwell Foundation for playing that role at BU."
Wolfe is highly regarded for his ability to translate his own research and others' observations into the clinical arena. He has been funded nearly continuously by the National Institutes of Health since the early 1980s and is one of only a very few American academicians with an invention that culminated with a drug currently on the market (Pepcid Complete®).
"The Hartwell Foundation is honored to provide financial support to Dr. Wolfe," said Foundation President Frederick Dombrose, Ph.D. "Participating institutions nominated exceptional individuals, making this year's competition for Investigator awards very tough."
Each year, The Hartwell Foundation announces its Top Ten Centers of Biomedical Research, inviting each center to hold an internal competition to nominate four candidates for a Hartwell Individual Biomedical Research Award. In August, Boston University was invited to participate as an extraordinary 11th institution and to submit two nominees for consideration.
The Hartwell Foundation seeks to inspire innovation and achievement by providing financial support to individual researchers in the United States for innovative and cutting-edge applied biomedical research that has the potential to benefit children. The general aim is to provide funds for early stage research projects that have not yet qualified for funding from traditional sources.
More information about The Hartwell Foundation is available on their web site, at thehartwellfoundation/.
Source: Michelle Roberts
Boston University
View drug information on Pepcid Complete.
Wolfe and his colleagues are developing a technique to redress hormone and enzyme deficiencies that cause diseases such as type 1 diabetes. The technique relies on engineering stem cells that produce the missing peptides and implanting them in the small intestine.
Because of their molecular size and susceptibility to degradation by stomach acid and digestive enzymes, insulin and other hormones must currently be administered by injection. The discomfort and inconvenience associated with injections often diminish patient compliance, particularly in children, which increases the risk of long-term complications. This concern is of particular importance for patients with type 1 diabetes, who often require multiple daily insulin injections to maintain stable blood sugar. Type I diabetes is one of the most common severe chronic diseases in children (1/300 in the US) and a major cause of end-stage renal disease, blindness, cardiovascular disease and premature death in the general population.
In a manuscript published in Science in 2000, Wolfe and his collaborators reported that intestinal K-cells of transgenic mice, which normally manufacture a hormone called GIP, could be engineered to express insulin and maintain normal blood glucose levels, even after pancreatic insulin-producing ("islet-beta") cells were destroyed. Employing the same genetic approach, Wolfe plans to transform stem cells that, like pancreatic islet-beta cells, will produce insulin in response to food ingestion. Using endoscopy, he plans to introduce transformed cells into the intestinal lining, where they will be programmed to become K-cells and produce insulin as well as GIP. The relocation of insulin production to the upper small intestine will "hide" it from the autoimmune response that destroys beta-cells in type 1 diabetes. Moreover, because K- and beta-cells are functionally similar, the K-cell appears to represent the ideal candidate for "hosting" the "foreign" insulin gene.
Wolfe is recognized as one of the world's leading authorities on GIP, and he initially cloned the GIP cDNA and ascertained its central role as principal mediator of the "enteroinsular axis". This axis functions as the hormonal connection between the intestine and pancreas following the ingestion of food. He established GIP as the likely mediator of the glycemic index and has theorized that low carbohydrate diets and gastric bypass surgery mediate their beneficial effects in part by suppressing GIP expression. He proved its importance in obesity by demonstrating functional receptors on adipocytes and by showing that GIP, like insulin, suppresses the breakdown of fat, which in essence results in an increase in fat storage.
"Boston University is delighted to have been invited by The Hartwell Foundation to participate in this year's competition and is deeply proud of Dr. Wolfe's selection for this exceptionally competitive Individual Biomedical Research Award," said Karen Antman, MD, dean of Boston University School of Medicine and provost of Boston University Medical Campus. "The award provides strategic funding for remarkably original research that combines genetic engineering, stem cell therapeutics, and gastroenterology, with exciting potential clinical implications. Private funding is vital to advancing such high-risk, high-gain work, and we are very grateful to The Hartwell Foundation for playing that role at BU."
Wolfe is highly regarded for his ability to translate his own research and others' observations into the clinical arena. He has been funded nearly continuously by the National Institutes of Health since the early 1980s and is one of only a very few American academicians with an invention that culminated with a drug currently on the market (Pepcid Complete®).
"The Hartwell Foundation is honored to provide financial support to Dr. Wolfe," said Foundation President Frederick Dombrose, Ph.D. "Participating institutions nominated exceptional individuals, making this year's competition for Investigator awards very tough."
Each year, The Hartwell Foundation announces its Top Ten Centers of Biomedical Research, inviting each center to hold an internal competition to nominate four candidates for a Hartwell Individual Biomedical Research Award. In August, Boston University was invited to participate as an extraordinary 11th institution and to submit two nominees for consideration.
The Hartwell Foundation seeks to inspire innovation and achievement by providing financial support to individual researchers in the United States for innovative and cutting-edge applied biomedical research that has the potential to benefit children. The general aim is to provide funds for early stage research projects that have not yet qualified for funding from traditional sources.
More information about The Hartwell Foundation is available on their web site, at thehartwellfoundation/.
Source: Michelle Roberts
Boston University
View drug information on Pepcid Complete.
Corn Genetics May Lead To Next Generation Of Plant-Based Biofuels
Identifying the corn genes involved with plant cell wall generation and learning their function will help develop new, more productive sources of transportation biofuel, according to two Purdue University researchers.
Nick Carpita and Maureen McCann will study genes involved in the formation of cell walls in the group of plants known as grasses, which includes corn. The goal is to find ways to produce more biomass containing more sugars that can be efficiently processed into biofuel.
"The close evolutionary and genomic relationships of maize or corn to other grasses will take us one step closer to some new, good sources of bioenergy," said Carpita, a geneticist in the Department of Botany and Plant Pathology. "Maize cell walls and the genes responsible for wall formation are characteristic of all grasses."
The research team will analyze the genes in both maize and switchgrass. Switchgrass is another plant investigated for biofuel production, but it also needs modification to increase yields.
Researchers already know that most plants use about 10 percent of their entire genome for cell wall construction, but very little is known about the specific functions of those genes.
"Maize has the same genes arranged in the same order and on the same chromosomes as the other grasses," said McCann, an associate professor of biological science. "We'll switch genes on and off as we identify them to see what they do. Once we know the genes and their functions, then we can assess which ones might make good targets for modification for enhanced biomass and sugars for processing into biofuel."
In the United States, ethanol is mainly made from corn because starch in the kernels is easily converted to sugar for fermentation to the alternative fuel. Scientists are studying ways to more easily produce fuel from plant biomass, which is composed of cell walls.
Identifying and classifying the genes for cell wall building and regulation in maize also will help determine how grasses grow and develop.
A U.S. Department of Energy/U.S. Department of Agriculture research program to accelerate development of biofuels from plants funds Carpita and McCann's genomic plant cell wall construction study with a $1.2 million grant.
Written by: Susan A. Steeves
purdue
Nick Carpita and Maureen McCann will study genes involved in the formation of cell walls in the group of plants known as grasses, which includes corn. The goal is to find ways to produce more biomass containing more sugars that can be efficiently processed into biofuel.
"The close evolutionary and genomic relationships of maize or corn to other grasses will take us one step closer to some new, good sources of bioenergy," said Carpita, a geneticist in the Department of Botany and Plant Pathology. "Maize cell walls and the genes responsible for wall formation are characteristic of all grasses."
The research team will analyze the genes in both maize and switchgrass. Switchgrass is another plant investigated for biofuel production, but it also needs modification to increase yields.
Researchers already know that most plants use about 10 percent of their entire genome for cell wall construction, but very little is known about the specific functions of those genes.
"Maize has the same genes arranged in the same order and on the same chromosomes as the other grasses," said McCann, an associate professor of biological science. "We'll switch genes on and off as we identify them to see what they do. Once we know the genes and their functions, then we can assess which ones might make good targets for modification for enhanced biomass and sugars for processing into biofuel."
In the United States, ethanol is mainly made from corn because starch in the kernels is easily converted to sugar for fermentation to the alternative fuel. Scientists are studying ways to more easily produce fuel from plant biomass, which is composed of cell walls.
Identifying and classifying the genes for cell wall building and regulation in maize also will help determine how grasses grow and develop.
A U.S. Department of Energy/U.S. Department of Agriculture research program to accelerate development of biofuels from plants funds Carpita and McCann's genomic plant cell wall construction study with a $1.2 million grant.
Written by: Susan A. Steeves
purdue
How A Statin Drug Reduces Cholesterol And Fat In Blood Vessels
Scientists have provided new details about how a drug used against heart disease helps to unclog blood vessels from an excess of cholesterol and fats. The results help explain how the drug works and may provide ways to improve similar drugs in the future.
A type of white blood cell called macrophage is responsible for the accumulation of fat in blood vessels, leading to inflammation and plaque formation on the inner linings of the vessel. Macrophages produce enzymes called lipases that have been shown to promote fat accumulation in blood vessels. Drugs called statins reduce the accumulation of fat in macrophages but their effects on lipases have not been explored yet.
John S. Hill and colleagues studied the effect of a statin drug called atorvastatin on two lipases, called lipoprotein lipase and endothelial lipase, which break down different types of fats. The researchers showed that the statin significantly reduced the levels of both lipases in macrophages and described in detail the proteins that are affected within the macrophages. These results may help to understand how other statin drugs work and could help design better drugs against heart disease in the future, the scientists conclude.
Article: "Atorvastatin Decreases Lipoprotein Lipase and Endothelial Lipase Expression in Human THP-1 Macrophages," by Guosong Qiu and John S. Hill
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
American Society for Biochemistry and Molecular Biology
A type of white blood cell called macrophage is responsible for the accumulation of fat in blood vessels, leading to inflammation and plaque formation on the inner linings of the vessel. Macrophages produce enzymes called lipases that have been shown to promote fat accumulation in blood vessels. Drugs called statins reduce the accumulation of fat in macrophages but their effects on lipases have not been explored yet.
John S. Hill and colleagues studied the effect of a statin drug called atorvastatin on two lipases, called lipoprotein lipase and endothelial lipase, which break down different types of fats. The researchers showed that the statin significantly reduced the levels of both lipases in macrophages and described in detail the proteins that are affected within the macrophages. These results may help to understand how other statin drugs work and could help design better drugs against heart disease in the future, the scientists conclude.
Article: "Atorvastatin Decreases Lipoprotein Lipase and Endothelial Lipase Expression in Human THP-1 Macrophages," by Guosong Qiu and John S. Hill
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
American Society for Biochemistry and Molecular Biology
Infections Of Parasitic Roundworms Could Be Stemmed By Discovery
Working with researchers in China, biologists at UC San Diego have discovered how a Chinese drug, effective in killing parasitic roundworms, works.
Their discovery of the drug's biological mechanism provides important new information about how to combat parasitic roundworms, which infect more than a billion people in tropical regions and are one of the leading causes of debilitation in underdeveloped countries. The researchers detail their findings in the current issue of the open-access journal PLoS Neglected Tropical Diseases.
Parasitic intestinal roundworms, such as hookworms - estimated to affect as many as 740 million people worldwide - and whipworms, which infect an estimated 795 million people, are considered by public-health officials to have a combined debilitating impact on human populations that is equal to or great than malaria or tuberculosis. But few drugs have been developed to effectively combat their infection.
"For practical reasons, only one drug, albendazole, is now widely used in administering single-dose treatments to large populations," said Raffi Aroian, a professor of biology at UCSD who headed the research effort. "But because of the enormous numbers of people that need to be treated and the necessity of repeated treatments due to high re-infection rates, the development of resistance to albendazole is a serious threat to large-scale de-worming efforts."
"We are studying this Chinese drug, tribendimidine, that clinically appears to be as good as albendazole," he added.
Developed by the Chinese Center for Disease Control and Prevention in Shanghai, tribendimidine has not yet been approved for human use. Recent clinical trials in China and Africa have found the drug to be effective in humans against some roundworm parasites, such as hookworms. But not much is known about the biological mechanisms by which the drug kills roundworms or the biochemical pathways through which roundworms can develop resistance to tribendimidine.
"This information is important for preventing, detecting and managing the resistance that some organisms can evolve to drugs," said Aroian. "It's also important in order to safely administer the drug to large populations and for knowing how to combine tribendimidine with other drugs."
Yan Hu, a postdoctoral fellow from China working in Aroian's laboratory, contacted Shu-Hua Xiao, a professor at the Chinese CDC in Shanghai, and began a two-year series of studies with the laboratory roundworm C. elegans that allowed her to determine tribendimidine's mechanism of action.
She did this by first developing genetic mutants resistant to tribendimidine and later analyzing another set of mutants to two other drugs used to treat roundworms - levamisole and pyrantel. Hu then determined that all of the mutants had the same genetic abnormalities, meaning that the biochemical pathways used to develop drug resistance in the animals were similar in all three. Mutants that develop resistance to albendazole, meanwhile, have a totally different set of genetic abnormalities.
Because levamisole and pyrantel are substantially less effective as albendazole in killing roundworms, these drugs are not the first choice for mass administration of drugs. But the results from Hu and her collaborators suggest that tribendimidine could be effectively used in areas instead of albendazole where parasites are likely to or have already developed a resistance to albendazole. Tribendimidine could also be combined with albendazole, the researchers said, to increase the effectiveness of killing parasitic roundworms, since both drugs have different biological killing mechanisms.
"Tribendimidine is not just a little bit different from albendazole," said Aroian. "It's in an entirely different class of drugs. The fact that tribendimidine is different from albendazole, but has the same level of effectiveness, and is in the same class as pyrantel and levamisole should increase people's comfort level in using this new drug."
A video of Aroian and Hu describing their results can be found at: wormfreeworld/worms.mp4. The researchers were supported in their study by grants from the National Institutes of Health.
Source:
Kim McDonald
University of California - San Diego
Their discovery of the drug's biological mechanism provides important new information about how to combat parasitic roundworms, which infect more than a billion people in tropical regions and are one of the leading causes of debilitation in underdeveloped countries. The researchers detail their findings in the current issue of the open-access journal PLoS Neglected Tropical Diseases.
Parasitic intestinal roundworms, such as hookworms - estimated to affect as many as 740 million people worldwide - and whipworms, which infect an estimated 795 million people, are considered by public-health officials to have a combined debilitating impact on human populations that is equal to or great than malaria or tuberculosis. But few drugs have been developed to effectively combat their infection.
"For practical reasons, only one drug, albendazole, is now widely used in administering single-dose treatments to large populations," said Raffi Aroian, a professor of biology at UCSD who headed the research effort. "But because of the enormous numbers of people that need to be treated and the necessity of repeated treatments due to high re-infection rates, the development of resistance to albendazole is a serious threat to large-scale de-worming efforts."
"We are studying this Chinese drug, tribendimidine, that clinically appears to be as good as albendazole," he added.
Developed by the Chinese Center for Disease Control and Prevention in Shanghai, tribendimidine has not yet been approved for human use. Recent clinical trials in China and Africa have found the drug to be effective in humans against some roundworm parasites, such as hookworms. But not much is known about the biological mechanisms by which the drug kills roundworms or the biochemical pathways through which roundworms can develop resistance to tribendimidine.
"This information is important for preventing, detecting and managing the resistance that some organisms can evolve to drugs," said Aroian. "It's also important in order to safely administer the drug to large populations and for knowing how to combine tribendimidine with other drugs."
Yan Hu, a postdoctoral fellow from China working in Aroian's laboratory, contacted Shu-Hua Xiao, a professor at the Chinese CDC in Shanghai, and began a two-year series of studies with the laboratory roundworm C. elegans that allowed her to determine tribendimidine's mechanism of action.
She did this by first developing genetic mutants resistant to tribendimidine and later analyzing another set of mutants to two other drugs used to treat roundworms - levamisole and pyrantel. Hu then determined that all of the mutants had the same genetic abnormalities, meaning that the biochemical pathways used to develop drug resistance in the animals were similar in all three. Mutants that develop resistance to albendazole, meanwhile, have a totally different set of genetic abnormalities.
Because levamisole and pyrantel are substantially less effective as albendazole in killing roundworms, these drugs are not the first choice for mass administration of drugs. But the results from Hu and her collaborators suggest that tribendimidine could be effectively used in areas instead of albendazole where parasites are likely to or have already developed a resistance to albendazole. Tribendimidine could also be combined with albendazole, the researchers said, to increase the effectiveness of killing parasitic roundworms, since both drugs have different biological killing mechanisms.
"Tribendimidine is not just a little bit different from albendazole," said Aroian. "It's in an entirely different class of drugs. The fact that tribendimidine is different from albendazole, but has the same level of effectiveness, and is in the same class as pyrantel and levamisole should increase people's comfort level in using this new drug."
A video of Aroian and Hu describing their results can be found at: wormfreeworld/worms.mp4. The researchers were supported in their study by grants from the National Institutes of Health.
Source:
Kim McDonald
University of California - San Diego
New Focus On Women In Evolution From Anthropologist's Studies Of Childbirth
Contrary to the TV sitcom where the wife experiencing strong labor pains screams at her husband to stay away from her, women rarely give birth alone. There are typically doctors, nurses and husbands in hospital delivery rooms, and sometimes even other relatives and friends. Midwives often are called on to help with births at home.
Assisted birth has likely been around for millennia, possibly dating as far back as 5 million years ago when our ancestors first began walking upright, according to University of Delaware paleoanthropologist Karen Rosenberg.
She says that social assistance during childbirth is just one aspect of our evolutionary heritage that makes us distinctive as humans.
Rosenberg, who is a professor and chairperson of the Department of Anthropology at the University of Delaware, presented a talk on natural selection and childbirth on Feb. 13 at the annual meeting of the American Association for the Advancement of Science in Chicago. It was part of the symposium "The Invisible Woman in Evolution: Natural Cycle and Life-Cycle Events," which Rosenberg co-organized.
The meeting's theme, "Our Planet and Its Life: Origins and Futures," commemorated the 200th anniversary of Charles Darwin's birth and the 150th anniversary of the publication of his book On the Origin of Species by Means of Natural Selection.
"Humans need helpers in childbirth because it is difficult and potentially dangerous," Rosenberg says. "While it's not so risky today -- maternal mortality is low -- as recently as two generations ago, it was not uncommon to hear of women dying in childbirth."
Through fossil records and comparisons of humans with other primates, Rosenberg says that anthropologists can now show how the uniquely human traits of bipedalism, large brains, infant helplessness and social assistance all came together, resulting in the challenging and somewhat dangerous manner in which humans give birth.
When our ancestors evolved to begin walking on two legs, Rosenberg says, this upright posture created a wide but short opening in the pelvis in which the baby must travel, requiring a new form of birth so that the baby could find its way through a now tight birth canal.
According to Rosenberg, the average pelvic opening in women today is 13 centimeters at its largest diameter and 10 centimeters at its smallest. The average infant head is 10 centimeters from front to back, and the shoulders are 12 centimeters across. And today the birth canal is a twisty tunnel subjecting the infant to a series of complex twists and turns on its way out.
"Until recently, there was a sexism in the study of evolution," Rosenberg says. "Researchers focused on men and the tools they used in hunting, and these things were more difficult to connect to reproductive success and hence to natural selection," she notes.
"With childbirth, as well as many of the other things that happen to women -- pregnancy, nursing, menopause -- it's really easy to see how natural selection works," Rosenberg notes.
Childbirth is just one of a series of examples throughout a woman's life cycle, in which enlisting the help of other women significantly improves reproductive outcomes, according to Rosenberg.
"Women take up the slack for other women when they are pregnant and nursing so that they have the energy to devote to their infants. Cooperative childcare is something in which women help each other out. Often, but not always, these helpers are post-reproductive women who have fewer of those responsibilities of their own, but may be helping out their daughters. All of this puts a great selective premium on a kind of social intelligence that many scientists think partly accounts for the increase in brain size that happened over the last two million years," she notes.
How will women and childbirth continue to evolve? Will the birth canal grow narrower, or wider? Will childbirth become more painful, or easier? Will more helpers be needed in future births? It's really anybody's guess.
"Evolution doesn't have a direction," Rosenberg says. "Knowing where we've been doesn't give us any help in where we're going. But it does help us understand what makes us human, as well as how we're connected to the natural world. "
A graduate of the University of Chicago, Rosenberg received her doctorate in biological anthropology from the University of Michigan and joined the University of Delaware faculty in 1987.
She says she began focusing on the evolution of women and childbirth around the time she had her first child, although she doesn't think there was a connection between the two.
Ironically, her brother is an obstetrician although she and he have never conducted research together.
Article by Tracey Bryant
Source: Tracey Bryant
University of Delaware
Assisted birth has likely been around for millennia, possibly dating as far back as 5 million years ago when our ancestors first began walking upright, according to University of Delaware paleoanthropologist Karen Rosenberg.
She says that social assistance during childbirth is just one aspect of our evolutionary heritage that makes us distinctive as humans.
Rosenberg, who is a professor and chairperson of the Department of Anthropology at the University of Delaware, presented a talk on natural selection and childbirth on Feb. 13 at the annual meeting of the American Association for the Advancement of Science in Chicago. It was part of the symposium "The Invisible Woman in Evolution: Natural Cycle and Life-Cycle Events," which Rosenberg co-organized.
The meeting's theme, "Our Planet and Its Life: Origins and Futures," commemorated the 200th anniversary of Charles Darwin's birth and the 150th anniversary of the publication of his book On the Origin of Species by Means of Natural Selection.
"Humans need helpers in childbirth because it is difficult and potentially dangerous," Rosenberg says. "While it's not so risky today -- maternal mortality is low -- as recently as two generations ago, it was not uncommon to hear of women dying in childbirth."
Through fossil records and comparisons of humans with other primates, Rosenberg says that anthropologists can now show how the uniquely human traits of bipedalism, large brains, infant helplessness and social assistance all came together, resulting in the challenging and somewhat dangerous manner in which humans give birth.
When our ancestors evolved to begin walking on two legs, Rosenberg says, this upright posture created a wide but short opening in the pelvis in which the baby must travel, requiring a new form of birth so that the baby could find its way through a now tight birth canal.
According to Rosenberg, the average pelvic opening in women today is 13 centimeters at its largest diameter and 10 centimeters at its smallest. The average infant head is 10 centimeters from front to back, and the shoulders are 12 centimeters across. And today the birth canal is a twisty tunnel subjecting the infant to a series of complex twists and turns on its way out.
"Until recently, there was a sexism in the study of evolution," Rosenberg says. "Researchers focused on men and the tools they used in hunting, and these things were more difficult to connect to reproductive success and hence to natural selection," she notes.
"With childbirth, as well as many of the other things that happen to women -- pregnancy, nursing, menopause -- it's really easy to see how natural selection works," Rosenberg notes.
Childbirth is just one of a series of examples throughout a woman's life cycle, in which enlisting the help of other women significantly improves reproductive outcomes, according to Rosenberg.
"Women take up the slack for other women when they are pregnant and nursing so that they have the energy to devote to their infants. Cooperative childcare is something in which women help each other out. Often, but not always, these helpers are post-reproductive women who have fewer of those responsibilities of their own, but may be helping out their daughters. All of this puts a great selective premium on a kind of social intelligence that many scientists think partly accounts for the increase in brain size that happened over the last two million years," she notes.
How will women and childbirth continue to evolve? Will the birth canal grow narrower, or wider? Will childbirth become more painful, or easier? Will more helpers be needed in future births? It's really anybody's guess.
"Evolution doesn't have a direction," Rosenberg says. "Knowing where we've been doesn't give us any help in where we're going. But it does help us understand what makes us human, as well as how we're connected to the natural world. "
A graduate of the University of Chicago, Rosenberg received her doctorate in biological anthropology from the University of Michigan and joined the University of Delaware faculty in 1987.
She says she began focusing on the evolution of women and childbirth around the time she had her first child, although she doesn't think there was a connection between the two.
Ironically, her brother is an obstetrician although she and he have never conducted research together.
Article by Tracey Bryant
Source: Tracey Bryant
University of Delaware
Immune Damage To Harbor Seals Caused By Mercury Pollution
Methylmercury (MeHg), the predominant form of mercury found in the blood of marine mammals and fish-eating communities, could be more damaging to seals than has previously been thought. Research published in BioMed Central's open access journal Environmental Health shows that MeHg harms T-lymphocytes, key cells in a seal's immune system. Similar results were also found for human lymphocytes.
Mercury exposure is known to occur as a result of man-made pollution and natural events such as volcanic eruptions. According to the lead author of this study, Krishna Das of the UniversitГ© de LiГЁge, Belgium, "Mercury is known to bioaccumulate and to magnify in marine mammals, which is a cause of great concern in terms of their general health. In particular, the immune system is known to be susceptible to long-term mercury exposure". In order to determine the scale of this problem, the authors carried out analysis of the blood mercury levels of harbour seals caught in the North Sea and tested the effects of MeHg in lab experiments.
By applying increasing doses of MeHg to lymphocytes, a type of white blood cell, the authors determined that the amount of mercury found in the blood of the seals studied was enough to cause damage to the important immune system cells. They said, "Although the in vitro approach utilised in this investigation represents an extreme reductionism relative to the complex situation in the intact organism, it provides an insight into the specific effects of mercury pollution."
Immune system damage may already have taken a toll on the population of harbour seals. The 1998 and 2002 outbreaks of phocine distemper virus, known to have killed thousands of seals, were linked to the deleterious effects of pollution on the seals' ability to fight the infection.
Notes:
1. Mercury immune toxicity in harbour seals: links to in vitro toxicity
Krishna Das, Ursula Siebert, Audrey Gillet, AurГ©lie Dupont, Carole Di-Poi, Sonja Fonfara, Gabriel Mazzucchelli, Edwin De Pauw and Marie-Claire De Pauw-Gillet
Environmental Health (in press)
Article available at journal website: ehjournal/
All articles are available free of charge, according to BioMed Central's open access policy.
2. Environmental Health is an Open Access, peer-reviewed, online journal that considers manuscripts on all aspects of environmental and occupational medicine, and related studies in toxicology and epidemiology. Environmental Health is aimed at scientists and practitioners in all areas of environmental science where human health and well-being are involved, either directly or indirectly. Environmental Health is a public health journal serving the public health community and scientists working on matters of public health interest and importance pertaining to the environment.
3. BioMed Central (biomedcentral/) is an independent online publishing house committed to providing immediate access without charge to the peer-reviewed biological and medical research it publishes. This commitment is based on the view that open access to research is essential to the rapid and efficient communication of science.
Source: Graeme Baldwin
BioMed Central
Mercury exposure is known to occur as a result of man-made pollution and natural events such as volcanic eruptions. According to the lead author of this study, Krishna Das of the UniversitГ© de LiГЁge, Belgium, "Mercury is known to bioaccumulate and to magnify in marine mammals, which is a cause of great concern in terms of their general health. In particular, the immune system is known to be susceptible to long-term mercury exposure". In order to determine the scale of this problem, the authors carried out analysis of the blood mercury levels of harbour seals caught in the North Sea and tested the effects of MeHg in lab experiments.
By applying increasing doses of MeHg to lymphocytes, a type of white blood cell, the authors determined that the amount of mercury found in the blood of the seals studied was enough to cause damage to the important immune system cells. They said, "Although the in vitro approach utilised in this investigation represents an extreme reductionism relative to the complex situation in the intact organism, it provides an insight into the specific effects of mercury pollution."
Immune system damage may already have taken a toll on the population of harbour seals. The 1998 and 2002 outbreaks of phocine distemper virus, known to have killed thousands of seals, were linked to the deleterious effects of pollution on the seals' ability to fight the infection.
Notes:
1. Mercury immune toxicity in harbour seals: links to in vitro toxicity
Krishna Das, Ursula Siebert, Audrey Gillet, AurГ©lie Dupont, Carole Di-Poi, Sonja Fonfara, Gabriel Mazzucchelli, Edwin De Pauw and Marie-Claire De Pauw-Gillet
Environmental Health (in press)
Article available at journal website: ehjournal/
All articles are available free of charge, according to BioMed Central's open access policy.
2. Environmental Health is an Open Access, peer-reviewed, online journal that considers manuscripts on all aspects of environmental and occupational medicine, and related studies in toxicology and epidemiology. Environmental Health is aimed at scientists and practitioners in all areas of environmental science where human health and well-being are involved, either directly or indirectly. Environmental Health is a public health journal serving the public health community and scientists working on matters of public health interest and importance pertaining to the environment.
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Source: Graeme Baldwin
BioMed Central
Misdiagnosis Of Monkey Malaria In Humans Can Be Fatal
A potentially fatal species of malaria is being commonly misdiagnosed as a more benign form of the disease, thereby putting lives at risk, according to research funded by the Wellcome Trust and the University Malaysia Sarawak.
Researchers in Malaysia studied more than 1,000 samples from malaria patients across the country. Using DNA-based technology they found that more than one in four patients in Sarawak, Malaysian Borneo, were infected with Plasmodium knowlesi, a malaria parasite of macaque monkeys, and that the disease was more widespread in Malaysia than previously thought. Infections were most often misdiagnosed as the normally uncomplicated human malaria caused by P. malariae.
Malaria, which kills more than one million people each year, is caused when Plasmodium parasites are passed into the bloodstream from the salivary glands of mosquitoes. Some types, such as P. falciparum, found most commonly in Africa, are more deadly than others. P. malariae, found in tropical and sub-tropical regions across the globe, is often known as "benign malaria" as its symptoms are usually less serious than other types of malaria.
Until recently, P. knowlesi, was thought to infect only monkeys, in particular long-tailed macaques found in the rainforests of South East Asia. Natural infections of man were thought to be rare until human infections were described in one area in Sarawak, Malaysian Borneo. However, in a study published in the journal Clinical Infectious Diseases, Professors Janet Cox-Singh and Balbir Singh with colleagues at the University Malaysia Sarawak and three State Departments of Health in Malaysia have shown that knowlesi malaria is widespread in Malaysia.
Under the microscope, the early parasite stages of P. knowlesi look very similar to P. falciparum, the most severe form of human malaria, while the later parasite stages are indistinguishable from the more benign P. malariae. Misdiagnosis as P. falciparum is clinically less important as P. falciparum infections are treated with a degree of urgency and P. knowlesi responds to the same treatment. However, misdiagnosis as the more benign slower growing parasite P. malariae is a problem.
P. knowlesi is unprecedented among the malaria parasites of humans and non-human primates as it reproduces every 24 hours, and one of the features of fatal P. knowlesi infections is the high number of infected red blood cells in these patients. Therefore, even a short delay in accurate diagnosis and treatment could lead to the rapid onset of complications, including liver and kidney failure, and death.
Using DNA detection methods, Professor Cox-Singh and colleagues found malaria infection with P. knowlesi to be widely distributed in Malaysian Borneo and mainland Malaysia, sometimes proving fatal. In addition, single human infections have been reported in Thailand and Myanmar.
"I believe that if we look at malaria infections in South East Asia more carefully, we will find that this potentially fatal type of the disease is more widespread than is currently thought," says Professor Cox-Singh. "Given the evident severity of the illness that it causes, I would recommend that doctors treating patients with a laboratory diagnosis of P. malariae remain alert to the possibility that they may be dealing with the potentially more aggressive P. knowlesi. This would be particularly important in patients who have spent time in the forest fringe areas of South East Asia where the non-human primate host exists."
Source: Craig Brierley
Wellcome Trust
Researchers in Malaysia studied more than 1,000 samples from malaria patients across the country. Using DNA-based technology they found that more than one in four patients in Sarawak, Malaysian Borneo, were infected with Plasmodium knowlesi, a malaria parasite of macaque monkeys, and that the disease was more widespread in Malaysia than previously thought. Infections were most often misdiagnosed as the normally uncomplicated human malaria caused by P. malariae.
Malaria, which kills more than one million people each year, is caused when Plasmodium parasites are passed into the bloodstream from the salivary glands of mosquitoes. Some types, such as P. falciparum, found most commonly in Africa, are more deadly than others. P. malariae, found in tropical and sub-tropical regions across the globe, is often known as "benign malaria" as its symptoms are usually less serious than other types of malaria.
Until recently, P. knowlesi, was thought to infect only monkeys, in particular long-tailed macaques found in the rainforests of South East Asia. Natural infections of man were thought to be rare until human infections were described in one area in Sarawak, Malaysian Borneo. However, in a study published in the journal Clinical Infectious Diseases, Professors Janet Cox-Singh and Balbir Singh with colleagues at the University Malaysia Sarawak and three State Departments of Health in Malaysia have shown that knowlesi malaria is widespread in Malaysia.
Under the microscope, the early parasite stages of P. knowlesi look very similar to P. falciparum, the most severe form of human malaria, while the later parasite stages are indistinguishable from the more benign P. malariae. Misdiagnosis as P. falciparum is clinically less important as P. falciparum infections are treated with a degree of urgency and P. knowlesi responds to the same treatment. However, misdiagnosis as the more benign slower growing parasite P. malariae is a problem.
P. knowlesi is unprecedented among the malaria parasites of humans and non-human primates as it reproduces every 24 hours, and one of the features of fatal P. knowlesi infections is the high number of infected red blood cells in these patients. Therefore, even a short delay in accurate diagnosis and treatment could lead to the rapid onset of complications, including liver and kidney failure, and death.
Using DNA detection methods, Professor Cox-Singh and colleagues found malaria infection with P. knowlesi to be widely distributed in Malaysian Borneo and mainland Malaysia, sometimes proving fatal. In addition, single human infections have been reported in Thailand and Myanmar.
"I believe that if we look at malaria infections in South East Asia more carefully, we will find that this potentially fatal type of the disease is more widespread than is currently thought," says Professor Cox-Singh. "Given the evident severity of the illness that it causes, I would recommend that doctors treating patients with a laboratory diagnosis of P. malariae remain alert to the possibility that they may be dealing with the potentially more aggressive P. knowlesi. This would be particularly important in patients who have spent time in the forest fringe areas of South East Asia where the non-human primate host exists."
Source: Craig Brierley
Wellcome Trust
Tinkering With The Circadian Clock Can Suppress Cancer Growth: UNC Study
Researchers at the University of North Carolina at Chapel Hill have shown that disruption of the circadian clock - the internal time-keeping mechanism that keeps the body running on a 24-hour cycle - can slow the progression of cancer.
The study disputes some of the most recent research in the field indicating that alteration of this daily cycle predisposes humans and mice to cancer. The UNC researchers found that genetically altering one of four essential "clock" genes actually suppressed cancer growth in a mouse model commonly used to investigate cancer. The findings could enable clinicians to reset the internal clock of each cancer cell to render it more vulnerable to attack with chemotherapeutic drugs.
"Adjusting the clock in this way could certainly be a new target for cancer treatment," said senior study author Aziz Sancar, M.D., Ph.D., a member of the UNC Lineberger Comprehensive Cancer Center and Sarah Graham Kenan Professor of Biochemistry and Biophysics in the UNC School of Medicine. Sancar is also a member of the National Academy of Sciences, the Turkish Academy of Sciences and the American Academy of Arts and Sciences.
"Our study indicates that interfering with the function of these clock genes in cancer tissue may be an effective way to kill cancer cells and could be a way to improve upon traditional chemotherapy," Sancar said. His findings appear February 2, 2009 in the online early edition of the Proceedings of the National Academy of Sciences.
Previous research has shown that the disruption of the body's natural circadian rhythms affects people's health. One of the largest epidemiological studies ever performed, the Nurses' Health Study, found that nurses who worked the night shift had a higher incidence of breast cancer than those who worked days. Another study of flight attendants whose internal biological clocks had been wrecked by travel on transatlantic flights produced similar findings.
Yet when scientists, including Sancar, began to tinker with the molecular mechanisms within the internal clocks of animal models, they did not always see such an effect. Circadian rhythms in humans and in mice are controlled by "clock genes," four of which are absolutely essential. In a study four years ago, Sancar found that deleting the clock gene cryptochrome in mice did not increase the incidence of cancer as had previously been expected.
While altering the clock gene did not cause cancer in otherwise normal mice, Sancar and his colleagues wanted to see if it would accelerate the development of tumors in a mouse model that is already predisposed to cancer. Therefore, in this study they modified the cryptochrome gene in mice that also had defects in a gene called P53, which is mutated in nearly half of human cancers. The researchers found that disturbing the internal clock in these mice did not speed up the onset of cancer, but instead had the opposite effect - it extended their lives by 50 percent.
The researchers then wanted to know how interfering with the cryptochrome gene had reduced the incidence of cancer. By closely examining the series of biological events in the disease's development, they determined that the mutation of this clock gene reactivates the intracellular signals that can eliminate cancerous cells. Sancar said this tactic essentially makes cancer cells more likely to commit cell suicide - through a process known as apoptosis - in response to the stresses of UV radiation or chemotherapy.
"These results suggest that altering the function of this clock gene, at least in the 50 percent of human cancers associated with p53 mutations, may slow the progression of cancer," Sancar said. "In combination with other approaches to cancer treatment, this method may one day be used to increase the success rate of remission."
The research was supported by the National Institutes of Health. Study co-authors from Sancar's UNC laboratory include the lead author and postdoctoral fellow Nuri Ozturk, Ph.D.; Jin Hyup Lee, a graduate student; and postdoctoral fellow Shobhan Gaddemeedhi, Ph.D.
The study follows the recent publication earlier this month of another paper from Sancar's laboratory in the Proceedings of the National Academy of Sciences. It suggested that chemotherapy treatment for cancer is most effective at certain times of day because that is when a particular enzyme system - one that can reverse the actions of chemotherapeutic drugs - is at its lowest levels in the body.
Click here to read the news release about the previous study.
Source: Leslie Lang
University of North Carolina School of Medicine
The study disputes some of the most recent research in the field indicating that alteration of this daily cycle predisposes humans and mice to cancer. The UNC researchers found that genetically altering one of four essential "clock" genes actually suppressed cancer growth in a mouse model commonly used to investigate cancer. The findings could enable clinicians to reset the internal clock of each cancer cell to render it more vulnerable to attack with chemotherapeutic drugs.
"Adjusting the clock in this way could certainly be a new target for cancer treatment," said senior study author Aziz Sancar, M.D., Ph.D., a member of the UNC Lineberger Comprehensive Cancer Center and Sarah Graham Kenan Professor of Biochemistry and Biophysics in the UNC School of Medicine. Sancar is also a member of the National Academy of Sciences, the Turkish Academy of Sciences and the American Academy of Arts and Sciences.
"Our study indicates that interfering with the function of these clock genes in cancer tissue may be an effective way to kill cancer cells and could be a way to improve upon traditional chemotherapy," Sancar said. His findings appear February 2, 2009 in the online early edition of the Proceedings of the National Academy of Sciences.
Previous research has shown that the disruption of the body's natural circadian rhythms affects people's health. One of the largest epidemiological studies ever performed, the Nurses' Health Study, found that nurses who worked the night shift had a higher incidence of breast cancer than those who worked days. Another study of flight attendants whose internal biological clocks had been wrecked by travel on transatlantic flights produced similar findings.
Yet when scientists, including Sancar, began to tinker with the molecular mechanisms within the internal clocks of animal models, they did not always see such an effect. Circadian rhythms in humans and in mice are controlled by "clock genes," four of which are absolutely essential. In a study four years ago, Sancar found that deleting the clock gene cryptochrome in mice did not increase the incidence of cancer as had previously been expected.
While altering the clock gene did not cause cancer in otherwise normal mice, Sancar and his colleagues wanted to see if it would accelerate the development of tumors in a mouse model that is already predisposed to cancer. Therefore, in this study they modified the cryptochrome gene in mice that also had defects in a gene called P53, which is mutated in nearly half of human cancers. The researchers found that disturbing the internal clock in these mice did not speed up the onset of cancer, but instead had the opposite effect - it extended their lives by 50 percent.
The researchers then wanted to know how interfering with the cryptochrome gene had reduced the incidence of cancer. By closely examining the series of biological events in the disease's development, they determined that the mutation of this clock gene reactivates the intracellular signals that can eliminate cancerous cells. Sancar said this tactic essentially makes cancer cells more likely to commit cell suicide - through a process known as apoptosis - in response to the stresses of UV radiation or chemotherapy.
"These results suggest that altering the function of this clock gene, at least in the 50 percent of human cancers associated with p53 mutations, may slow the progression of cancer," Sancar said. "In combination with other approaches to cancer treatment, this method may one day be used to increase the success rate of remission."
The research was supported by the National Institutes of Health. Study co-authors from Sancar's UNC laboratory include the lead author and postdoctoral fellow Nuri Ozturk, Ph.D.; Jin Hyup Lee, a graduate student; and postdoctoral fellow Shobhan Gaddemeedhi, Ph.D.
The study follows the recent publication earlier this month of another paper from Sancar's laboratory in the Proceedings of the National Academy of Sciences. It suggested that chemotherapy treatment for cancer is most effective at certain times of day because that is when a particular enzyme system - one that can reverse the actions of chemotherapeutic drugs - is at its lowest levels in the body.
Click here to read the news release about the previous study.
Source: Leslie Lang
University of North Carolina School of Medicine
Researchers Find Red Wine And Grape Juice Help Defend Against Food-borne Diseases
Red wine is known to have multiple health benefits. Researchers at the University of Missouri-Columbia have found that red wine may also protect humans from common food-borne diseases.
Researchers Azlin Mustapha, associate professor of food science in the College of Agriculture, Food and Natural Resources, and Atreyee Das, a doctoral student in the food science program, are conducting on-going studies examining the inhibitory effects of numerous types of red wines, as well as grape juice, against pathogens and probiotic bacteria, which naturally reside in the intestinal tract and can be beneficial in combating, among other things, high cholesterol and tumors.
They found that red wines -- Cabernet, Zinfandel and Merlot in particular -- have anti-microbial properties that defend against food-borne pathogens and don't harm naturally useful bacteria like probiotic bacteria.
E. coli, Salmonella Typhimurium, Listeria monocytogenes and H. pylori were among the pathogens examined. E. coli and Listeria can be fatal. Mustapha said the most promising results involved Helicobacter pylori, which can be transmitted via food and water and is the main cause of stomach ulcers.
"Our study is a little different than those previously reported in the media. Those studies promote moderate red wine consumption for cardiovascular diseases," she said. "We went a step farther and asked: If red wine is already good for cardiovascular diseases, what about food-borne pathogens? If you get a food-borne illness and drink red wine, will that help decrease the symptoms a little bit? This study showed that the four probiotics tested weren't inhibited by red wines; the pathogens were."
In lab tests, Mustapha and Das focused on ethanol, pH levels and reseveratrol, which is a phytochemical found in grape vines and the skin of grapes. It also is responsible for the red coloring in red wines. They found that in addition to ethanol, pH and reseveratrol also may inhibit food-borne pathogens.
Numerous white wines also were tested, but yielded no positive results, the researchers said.
"It's not just ethanol in the red wine that is inhibitory toward food-borne pathogens, but other factors which include the pH of the wine -- because wines are a little acidic, and possibly the phytochemicals may have an effect," said Mustapha, noting that grape juice produces similar results. "We hypothesize that these phytochemicals, reseveratrol being the main one, also play a role not just as antioxidants but also may have some inhibitions against food-borne pathogens. Now, we're concentrating mainly on the reseveratrol effects on these pathogens."
The findings were recently presented at the Institute of Food Technologists annual conference in Chicago.
Source: Bryan Daniels
University of Missouri-Columbia
Researchers Azlin Mustapha, associate professor of food science in the College of Agriculture, Food and Natural Resources, and Atreyee Das, a doctoral student in the food science program, are conducting on-going studies examining the inhibitory effects of numerous types of red wines, as well as grape juice, against pathogens and probiotic bacteria, which naturally reside in the intestinal tract and can be beneficial in combating, among other things, high cholesterol and tumors.
They found that red wines -- Cabernet, Zinfandel and Merlot in particular -- have anti-microbial properties that defend against food-borne pathogens and don't harm naturally useful bacteria like probiotic bacteria.
E. coli, Salmonella Typhimurium, Listeria monocytogenes and H. pylori were among the pathogens examined. E. coli and Listeria can be fatal. Mustapha said the most promising results involved Helicobacter pylori, which can be transmitted via food and water and is the main cause of stomach ulcers.
"Our study is a little different than those previously reported in the media. Those studies promote moderate red wine consumption for cardiovascular diseases," she said. "We went a step farther and asked: If red wine is already good for cardiovascular diseases, what about food-borne pathogens? If you get a food-borne illness and drink red wine, will that help decrease the symptoms a little bit? This study showed that the four probiotics tested weren't inhibited by red wines; the pathogens were."
In lab tests, Mustapha and Das focused on ethanol, pH levels and reseveratrol, which is a phytochemical found in grape vines and the skin of grapes. It also is responsible for the red coloring in red wines. They found that in addition to ethanol, pH and reseveratrol also may inhibit food-borne pathogens.
Numerous white wines also were tested, but yielded no positive results, the researchers said.
"It's not just ethanol in the red wine that is inhibitory toward food-borne pathogens, but other factors which include the pH of the wine -- because wines are a little acidic, and possibly the phytochemicals may have an effect," said Mustapha, noting that grape juice produces similar results. "We hypothesize that these phytochemicals, reseveratrol being the main one, also play a role not just as antioxidants but also may have some inhibitions against food-borne pathogens. Now, we're concentrating mainly on the reseveratrol effects on these pathogens."
The findings were recently presented at the Institute of Food Technologists annual conference in Chicago.
Source: Bryan Daniels
University of Missouri-Columbia
Study First To Combine 2 Chemotherapies And 2 Targeted Therapies
The four drug-combination of carboplatin and paclitaxel, with the targeted therapies bevacizumab (Avastin) and cetuximab (Erbitux), is safe and may improve survival for patients with advanced lung cancer, according to a cooperative group study led by The University of Texas M. D. Anderson Cancer Center.
Presented on the press program of the 2008 Chicago Multidisciplinary Symposium in Thoracic Oncology, sponsored by ASTRO, ASCO, IASLC and the University of Chicago, the study is the first to investigate in lung cancer a four-drug regimen of two standard chemotherapies and targeted therapies.
The Southwest Oncology Group (SWOG) Phase II study was led by Edward S. Kim, M.D., assistant professor in M. D. Anderson's Department of Thoracic Head and Neck Medical Oncology. Until now, the SWOG standard regimen for lung cancer has been carboplatin, paclitaxel and Erbitux, explained Kim; with the addition of Avastin, this study looked to increase efficacy without compromising safety.
"We could not conduct a study with four chemotherapeutic agents in patients due to toxicity concerns," said Kim, the study's principal investigator. "The rationale behind the study was the finding that Avastin enhances the efficacy of existing therapy, thereby possibly improving the carboplatin-paclitaxel-Erbitux regimen."
Data in lung cancer has also suggested there's a "synergistic effect" of pairing the epidermal growth factor (EGFR) inhibitor compounds with the vascular endothelial growth factor (VEGF) inhibitor, explained Kim.
Interestingly, explained Kim, the SWOG's study came at a crossroads for lung cancer - soon after a study was presented showing the benefits of adding Avastin to standard chemotherapy, and prior to a study showing a modest survival benefit when Erbitux is combined with chemotherapy.
Between August 2006 and September 2007, the large Phase II study enrolled 110 Stage IIIB or IV non-small cell lung cancer patients, 99 of whom were able to be evaluated. Patients received six cycles of the four-drug regimen, and as maintenance, continued receiving both Avastin and Erbitux. It's unique for a trial to feature a two-drug maintenance biologic therapy combination, explained Kim.
The study met its primary endpoint, safety, defined by frequency of pulmonary hemorrhage, or bleeding, a concern related to Avastin. There were four treatment-related deaths and two due to bleeding, which is consistent with prior Avastin studies, explained Kim. Adverse events such as low blood counts and neuropathy were reported in 40 patients, also consistent with standard chemotherapy.
Secondary endpoints included response rate, progression-free survival and overall survival. Of patients enrolled, 53 percent had shrinkage of their tumors and 24 percent had stable disease. The median progression-free survival rate was seven months and overall survival was 14 months. In contrast, previous SWOG studies showed an average progression-free survival rate of five-and-a-half months and overall survival of 12 months.
"These findings were certainly compelling, and are the best results ever for a SWOG-based study for advanced lung cancer. While early, this four-drug combination seems to show promising, yet modest improvement in efficacy without compromising patients' safety," said Kim. "Our next priority will be to analyze the tissue from this to study to help find appropriate biomarkers for the disease to best understand who might benefit from this drug regimen."
A biomarker analysis of this study is ongoing and a randomized Phase III study is planned, with the trial scheduled to open in 2009.
Lung cancer is the leading cause of cancer death in the United States, according to the American Cancer Society. In 2008, approximately 215,000 people will be diagnosed with lung cancer and approximately 114,000 people will die from the disease.
Source: Laura Sussman
University of Texas M. D. Anderson Cancer Center
View drug information on Avastin; Erbitux.
Presented on the press program of the 2008 Chicago Multidisciplinary Symposium in Thoracic Oncology, sponsored by ASTRO, ASCO, IASLC and the University of Chicago, the study is the first to investigate in lung cancer a four-drug regimen of two standard chemotherapies and targeted therapies.
The Southwest Oncology Group (SWOG) Phase II study was led by Edward S. Kim, M.D., assistant professor in M. D. Anderson's Department of Thoracic Head and Neck Medical Oncology. Until now, the SWOG standard regimen for lung cancer has been carboplatin, paclitaxel and Erbitux, explained Kim; with the addition of Avastin, this study looked to increase efficacy without compromising safety.
"We could not conduct a study with four chemotherapeutic agents in patients due to toxicity concerns," said Kim, the study's principal investigator. "The rationale behind the study was the finding that Avastin enhances the efficacy of existing therapy, thereby possibly improving the carboplatin-paclitaxel-Erbitux regimen."
Data in lung cancer has also suggested there's a "synergistic effect" of pairing the epidermal growth factor (EGFR) inhibitor compounds with the vascular endothelial growth factor (VEGF) inhibitor, explained Kim.
Interestingly, explained Kim, the SWOG's study came at a crossroads for lung cancer - soon after a study was presented showing the benefits of adding Avastin to standard chemotherapy, and prior to a study showing a modest survival benefit when Erbitux is combined with chemotherapy.
Between August 2006 and September 2007, the large Phase II study enrolled 110 Stage IIIB or IV non-small cell lung cancer patients, 99 of whom were able to be evaluated. Patients received six cycles of the four-drug regimen, and as maintenance, continued receiving both Avastin and Erbitux. It's unique for a trial to feature a two-drug maintenance biologic therapy combination, explained Kim.
The study met its primary endpoint, safety, defined by frequency of pulmonary hemorrhage, or bleeding, a concern related to Avastin. There were four treatment-related deaths and two due to bleeding, which is consistent with prior Avastin studies, explained Kim. Adverse events such as low blood counts and neuropathy were reported in 40 patients, also consistent with standard chemotherapy.
Secondary endpoints included response rate, progression-free survival and overall survival. Of patients enrolled, 53 percent had shrinkage of their tumors and 24 percent had stable disease. The median progression-free survival rate was seven months and overall survival was 14 months. In contrast, previous SWOG studies showed an average progression-free survival rate of five-and-a-half months and overall survival of 12 months.
"These findings were certainly compelling, and are the best results ever for a SWOG-based study for advanced lung cancer. While early, this four-drug combination seems to show promising, yet modest improvement in efficacy without compromising patients' safety," said Kim. "Our next priority will be to analyze the tissue from this to study to help find appropriate biomarkers for the disease to best understand who might benefit from this drug regimen."
A biomarker analysis of this study is ongoing and a randomized Phase III study is planned, with the trial scheduled to open in 2009.
Lung cancer is the leading cause of cancer death in the United States, according to the American Cancer Society. In 2008, approximately 215,000 people will be diagnosed with lung cancer and approximately 114,000 people will die from the disease.
Source: Laura Sussman
University of Texas M. D. Anderson Cancer Center
View drug information on Avastin; Erbitux.
How cells use biological flows to signal and organize
An EPFL (Ecole Polytechnique Federale de Lausanne) team led by professor Melody Swartz has demonstrated for the first time that the presence of very slow biological flows affects the extracellular environment in ways that are critical for tissue formation and cell migration. Their results will appear online the week of October 24 in Proceedings of the National Academy of Sciences.
A major challenge for tissue engineering is to identify the essential environmental ingredients that cells need in order to communicate, migrate, and organize into living tissues. One of these ingredients is the presence, outside the cell, of minute changes in the concentration of special proteins called morphogens. Cells can sense even the tiniest differences in morphogen concentration and will alter their functions accordingly. In embryonic development, stem cells differentiate into organs by means of the actions of morphogens. And even cancer cells can use morphogens to grow, induce a blood supply, and metastasize.
Although the concept of cell organization in response to these morphogen gradients is well documented, little is known about how these subtle concentration changes get established the first place, particularly within the dynamic environment of a real tissue. This research provides evidence that tiny biophysical forces in the extracellular environment may play an important role.
Swartz and her colleagues have found that slow biophysical flows, such as the slow-moving flows that exist between the lymphatic and blood capillaries to help transport macromolecules from blood to tissues, play an important role in the formation of these gradients. They used a computational model developed by PhD student Mark Fleury to demonstrate that in the presence of a slow moving flow, cells can set up and even amplify their own morphogen gradients. "This exquisite system may have evolved as a way for cells to gain better control of their local extracellular surroundings, where they can use the fluid forces that exist in tissues to direct and amplify communication and organization," explains Swartz.
First author Cara-Lynn Helm (a PhD student at Northwestern University) used an in vitro model of capillary formation to demonstrate proof-of-concept that small biophysical flows play a critical role in tissue formation. She placed human blood and lymphatic endothelial cells in an environment containing matrix-bound vascular endothelial growth factor (VEGF) and subjected the system to a very slow externally-induced flow.
Without the flow, very little cell organization took place. With the combination of flow and VEGF, the endothelial cells networked and organized, quickly forming capillaries. "We gave our cells the right environment and a physical impetus and the two conditions combined synergistically, driving the cells to organize into functional structures," says Swartz.
This research shows clearly and for the first time that small biophysical forces are among the critical environmental ingredients that cells need to migrate and organize into functional tissues. This new knowledge could be immediately used in tissue engineering applications. It could also be used to improve our understanding of basic cellular signaling and organization processes.
"This result can be generalized to any system that is driven by protein gradients that bind to the extracellular matrix," notes Swartz. "This includes proteins that drive immune cells into the lymphatic system, an important part of the immune response, and others that drive tumor cells into the lymphatic system, where they spread and become deadly. We need to understand these basic processes if we want to design strategies to enhance or inhibit them."
On the web: lmbm.epfl.ch
Melody Swartz
melody.swartzepfl.ch
Ecole Polytechnique Fйdйrale de Lausanne
epfl.ch
A major challenge for tissue engineering is to identify the essential environmental ingredients that cells need in order to communicate, migrate, and organize into living tissues. One of these ingredients is the presence, outside the cell, of minute changes in the concentration of special proteins called morphogens. Cells can sense even the tiniest differences in morphogen concentration and will alter their functions accordingly. In embryonic development, stem cells differentiate into organs by means of the actions of morphogens. And even cancer cells can use morphogens to grow, induce a blood supply, and metastasize.
Although the concept of cell organization in response to these morphogen gradients is well documented, little is known about how these subtle concentration changes get established the first place, particularly within the dynamic environment of a real tissue. This research provides evidence that tiny biophysical forces in the extracellular environment may play an important role.
Swartz and her colleagues have found that slow biophysical flows, such as the slow-moving flows that exist between the lymphatic and blood capillaries to help transport macromolecules from blood to tissues, play an important role in the formation of these gradients. They used a computational model developed by PhD student Mark Fleury to demonstrate that in the presence of a slow moving flow, cells can set up and even amplify their own morphogen gradients. "This exquisite system may have evolved as a way for cells to gain better control of their local extracellular surroundings, where they can use the fluid forces that exist in tissues to direct and amplify communication and organization," explains Swartz.
First author Cara-Lynn Helm (a PhD student at Northwestern University) used an in vitro model of capillary formation to demonstrate proof-of-concept that small biophysical flows play a critical role in tissue formation. She placed human blood and lymphatic endothelial cells in an environment containing matrix-bound vascular endothelial growth factor (VEGF) and subjected the system to a very slow externally-induced flow.
Without the flow, very little cell organization took place. With the combination of flow and VEGF, the endothelial cells networked and organized, quickly forming capillaries. "We gave our cells the right environment and a physical impetus and the two conditions combined synergistically, driving the cells to organize into functional structures," says Swartz.
This research shows clearly and for the first time that small biophysical forces are among the critical environmental ingredients that cells need to migrate and organize into functional tissues. This new knowledge could be immediately used in tissue engineering applications. It could also be used to improve our understanding of basic cellular signaling and organization processes.
"This result can be generalized to any system that is driven by protein gradients that bind to the extracellular matrix," notes Swartz. "This includes proteins that drive immune cells into the lymphatic system, an important part of the immune response, and others that drive tumor cells into the lymphatic system, where they spread and become deadly. We need to understand these basic processes if we want to design strategies to enhance or inhibit them."
On the web: lmbm.epfl.ch
Melody Swartz
melody.swartzepfl.ch
Ecole Polytechnique Fйdйrale de Lausanne
epfl.ch
Stored Ovarian Tissue Should Undergo Adequate Testing Before Re-Implantation To Avoid Return Of Cancer
Cancer patients who have been successfully treated for their disease face the prospect of its return if stored ovarian (or testicular) tissue is transplanted back into their bodies without adequate checks, according to researchers at two university hospitals in Israel.
Writing in Europe's leading reproductive medicine journal, Human Reproduction, the researchers say that hundreds of cancer patients worldwide have ovarian tissue and, in some cases, testicular tissue frozen in the hope of being able to have children after their cancer treatment has finished; but they warn that few fertility centres have the skills and use the technology needed to check the tissue for residual cancer cells, making it possible for the original cancer to re-infect the body when the tissue is re-implanted to restore the patients' fertility. [1]
"The interest in ovarian tissue storage as a real option for preserving fertility in cancer patients has increased. However, genuine concerns regarding the possible recrudescence [re-appearance] of the primary disease following re-implantation of stored ovarian tissue with malignant cells exist," write the authors.
The first author of the report, Dr Dror Meirow, said: "We think it's vitally important to raise awareness amongst cancer patients, fertility specialists, oncologists and haematologists. There are few fertility centres in the world with the expertise and the technology to run the types of tests on tissue that are needed to detect residual cancer.
"However, not every reproductive service that has surgical skills and freezing facilities can be safely responsible for ovarian tissue cryopreservation. We suggest that these centres should store tissue for future investigation, and samples can be shipped to specialist centres for analysis."
Dr Meirow, who leads the fertility preservation programme in the IVF Unit at Chaim Sheba Medical Center, Tel Hashomer (headed by Professor Jehoshua Dor), carried out the research with Professor Dina Ben Yehuda, director of the Hematology Division at Hadassah University Hospital, Jerusalem. Dr Meirow said that fertility centres with close connections to cancer and haematological centres should be able to work together in order to adopt the correct methods for checking stored tissue.
Before collecting tissue from the 58 young women in this study, Dr Meirow and his colleagues used various imaging methods (sonography, CT and PET scans) to look for cancer in the pelvis and ovaries of the patients; the women were about to receive chemotherapy for haematological cancers such as Hodgkin's lymphoma, non-Hodgkin's lymphoma and leukaemia, between 1997 and 2007. They found cancer in the pelvic area of two patients, and therefore ovarian tissue was not harvested. They collected tissue from the other 56 patients and, in addition to freezing strips for future transplantation; they also froze a smaller piece of ovarian tissue separately for each patient. They planned to use these extra strips for future checks for the presence of cancer cells, using the most modern methods that would be available at the time the tissue was thawed and prepared for transplantation.
When the ovarian tissue was thawed, they used several different methods to detect minimal residual disease:
Histological evaluation (close examination of thin strips of tissue)
Immunohistochemical staining (using antibodies to detect abnormal cells)
PCR (polymerase chain reaction, which amplifies sections of DNA) and real-time PCR to detect molecular markers that would indicate the presence of cancer cells.
The results were compared with the same tests carried out on the patients' diseased tissue to check that the tests were capable of detecting cancer when it was known to be present.
None of the tests detected minimal residual disease in ovarian tissue for any of the patients, with one exception: modern highly sensitive real-time PCR detected cells in one CML patient where previous tests had not detected any sign of cancer, and so ovarian tissue transplantation was not carried out.
Dr Meirow said: "For this research we concentrated on haematological malignancies, which are common in young patients, but we are working also on solid tumours. Tumour cells of haematological cancers do not often form clumps of cells, which are easier to detect. Therefore, it is highly important to identify single cancer cells among hundreds of thousands of normal cells.
"It is important to use the method and the specific probe that is suitable for each patient, and with this research we had a positive control test from the tumour itself."
The authors suggest that, as methods for detecting cancer cells are improving all the time and ovarian tissue can be stored for more than ten years, tests to detect residual disease should be carried out just before transplantation rather than at the time of collection. To do this, it is necessary to freeze smaller piece of ovarian tissue separately for minimal residual disease investigation.
Dr Meirow said: "Following our pioneer report in 2005 on pregnancy and delivery post transplantation of ovarian tissue, the next step is to inform patients about the increasing success of ovarian tissue transplantation, to continue to improve the success of ovarian tissue transplantation, but also to call on fertility centres that store ovarian tissue to look for minimal residual disease and to start freezing tissue now for future investigation. All of this holds true for testicular tissue too, although we are not so advanced in successfully removing, storing and transplanting testicular tissue as we are with ovarian tissue."
[1] Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients. Human Reproduction Vol.23, Issue 5. doi:10.1093/humrep/den055.
Source: Emma Mason
European Society for Human Reproduction and Embryology
Writing in Europe's leading reproductive medicine journal, Human Reproduction, the researchers say that hundreds of cancer patients worldwide have ovarian tissue and, in some cases, testicular tissue frozen in the hope of being able to have children after their cancer treatment has finished; but they warn that few fertility centres have the skills and use the technology needed to check the tissue for residual cancer cells, making it possible for the original cancer to re-infect the body when the tissue is re-implanted to restore the patients' fertility. [1]
"The interest in ovarian tissue storage as a real option for preserving fertility in cancer patients has increased. However, genuine concerns regarding the possible recrudescence [re-appearance] of the primary disease following re-implantation of stored ovarian tissue with malignant cells exist," write the authors.
The first author of the report, Dr Dror Meirow, said: "We think it's vitally important to raise awareness amongst cancer patients, fertility specialists, oncologists and haematologists. There are few fertility centres in the world with the expertise and the technology to run the types of tests on tissue that are needed to detect residual cancer.
"However, not every reproductive service that has surgical skills and freezing facilities can be safely responsible for ovarian tissue cryopreservation. We suggest that these centres should store tissue for future investigation, and samples can be shipped to specialist centres for analysis."
Dr Meirow, who leads the fertility preservation programme in the IVF Unit at Chaim Sheba Medical Center, Tel Hashomer (headed by Professor Jehoshua Dor), carried out the research with Professor Dina Ben Yehuda, director of the Hematology Division at Hadassah University Hospital, Jerusalem. Dr Meirow said that fertility centres with close connections to cancer and haematological centres should be able to work together in order to adopt the correct methods for checking stored tissue.
Before collecting tissue from the 58 young women in this study, Dr Meirow and his colleagues used various imaging methods (sonography, CT and PET scans) to look for cancer in the pelvis and ovaries of the patients; the women were about to receive chemotherapy for haematological cancers such as Hodgkin's lymphoma, non-Hodgkin's lymphoma and leukaemia, between 1997 and 2007. They found cancer in the pelvic area of two patients, and therefore ovarian tissue was not harvested. They collected tissue from the other 56 patients and, in addition to freezing strips for future transplantation; they also froze a smaller piece of ovarian tissue separately for each patient. They planned to use these extra strips for future checks for the presence of cancer cells, using the most modern methods that would be available at the time the tissue was thawed and prepared for transplantation.
When the ovarian tissue was thawed, they used several different methods to detect minimal residual disease:
Histological evaluation (close examination of thin strips of tissue)
Immunohistochemical staining (using antibodies to detect abnormal cells)
PCR (polymerase chain reaction, which amplifies sections of DNA) and real-time PCR to detect molecular markers that would indicate the presence of cancer cells.
The results were compared with the same tests carried out on the patients' diseased tissue to check that the tests were capable of detecting cancer when it was known to be present.
None of the tests detected minimal residual disease in ovarian tissue for any of the patients, with one exception: modern highly sensitive real-time PCR detected cells in one CML patient where previous tests had not detected any sign of cancer, and so ovarian tissue transplantation was not carried out.
Dr Meirow said: "For this research we concentrated on haematological malignancies, which are common in young patients, but we are working also on solid tumours. Tumour cells of haematological cancers do not often form clumps of cells, which are easier to detect. Therefore, it is highly important to identify single cancer cells among hundreds of thousands of normal cells.
"It is important to use the method and the specific probe that is suitable for each patient, and with this research we had a positive control test from the tumour itself."
The authors suggest that, as methods for detecting cancer cells are improving all the time and ovarian tissue can be stored for more than ten years, tests to detect residual disease should be carried out just before transplantation rather than at the time of collection. To do this, it is necessary to freeze smaller piece of ovarian tissue separately for minimal residual disease investigation.
Dr Meirow said: "Following our pioneer report in 2005 on pregnancy and delivery post transplantation of ovarian tissue, the next step is to inform patients about the increasing success of ovarian tissue transplantation, to continue to improve the success of ovarian tissue transplantation, but also to call on fertility centres that store ovarian tissue to look for minimal residual disease and to start freezing tissue now for future investigation. All of this holds true for testicular tissue too, although we are not so advanced in successfully removing, storing and transplanting testicular tissue as we are with ovarian tissue."
[1] Searching for evidence of disease and malignant cell contamination in ovarian tissue stored from hematologic cancer patients. Human Reproduction Vol.23, Issue 5. doi:10.1093/humrep/den055.
Source: Emma Mason
European Society for Human Reproduction and Embryology
Nanotube Production: From Sooty Mess In Test Tube To Ready Formed Chemical Microsensors
Carbon nanotubes' potential as a super material is blighted by the fact that when first made they often take the form of an unprepossessing pile of sooty black mess in the bottom of a test tube. Now researchers in the University of Warwick's Department of Chemistry have found a way of producing carbon nanotubes in which they instantly form a highly sensitive ready made electric circuit.
The research has just been published in a paper entitled "Single-Walled Carbon Nanotube Network Ultramicroelectrodes" by University of Warwick researchers Ioana Dumitrescu, Professor Julie Macpherson, Professor Patrick Unwin, and Neil Wilson in Analytical Chemistry, 2008, 10.1021/ac702518g
The researchers used a form of chemical vapour deposition and lithography to create the ready made disc shaped single walled carbon nanotube based ultramicroelectrodes. The nanotubes deposit themselves flat on a surface in a random but relatively even manner. They also all overlap sufficiently to create a single complete metallic micro-circuit right across the final disc. What is even more impressive is that they take up less than one per cent of the surface area of the disc.
This final property makes these instant ultramicroelecrodes particular useful for the creation of ultra sensitive sensors. The low surface area of the conducting part of the disc means that they can be used to screen out background "noise" and cope with low signal to noise ratios making them up to 1000 times more sensitive than conventional ultramicroelecrodes sensors. This property also produces very fast response times allowing them to respond ten times faster than conventional ultramicroelecrodes.
As these ready made ultramicroelecrodes are carbon based they also open up a range of new possibilities for use in living systems. The biocompatibility of carbon is in stark contrast with the obvious problems that platinum and other metal based probes can pose for living tissue. The Warwick research team are already beginning to explore how their single walled carbon nanotube based ultramicroelecrodes can be used to measure levels of neurotransmitters.
The new ultramicroelecrodes also open up interesting possibilities for catalysis in fuel cells. Up till now researchers had been aware that this form of carbon nanotubes appeared to be particularly useful in the area of catalysis but there was uncertainty as to whether it was the properties of the carbon nanotubes per se that provide this benefit or whether it was due to impurities in their production. The researchers have been able to use this new method of single walled carbon nanotube assembly to prove that it is actually the properties of the carbon nanotubes themselves that are useful for catalysis. The new carbon nanotube assembly technique brings a further benefit to catalysis applications as the Warwick researchers have been able to use electrodepoistion to quickly and easily apply specific metal coatings to the ready formed single walled carbon nanotube microelectrode networks. This will be of significant benefit to anyone wanting to use single walled carbon nanotube for catalysis in fuel cell technology.
PR35 6th May 2008
Source: Peter Dunn
University of Warwick
The research has just been published in a paper entitled "Single-Walled Carbon Nanotube Network Ultramicroelectrodes" by University of Warwick researchers Ioana Dumitrescu, Professor Julie Macpherson, Professor Patrick Unwin, and Neil Wilson in Analytical Chemistry, 2008, 10.1021/ac702518g
The researchers used a form of chemical vapour deposition and lithography to create the ready made disc shaped single walled carbon nanotube based ultramicroelectrodes. The nanotubes deposit themselves flat on a surface in a random but relatively even manner. They also all overlap sufficiently to create a single complete metallic micro-circuit right across the final disc. What is even more impressive is that they take up less than one per cent of the surface area of the disc.
This final property makes these instant ultramicroelecrodes particular useful for the creation of ultra sensitive sensors. The low surface area of the conducting part of the disc means that they can be used to screen out background "noise" and cope with low signal to noise ratios making them up to 1000 times more sensitive than conventional ultramicroelecrodes sensors. This property also produces very fast response times allowing them to respond ten times faster than conventional ultramicroelecrodes.
As these ready made ultramicroelecrodes are carbon based they also open up a range of new possibilities for use in living systems. The biocompatibility of carbon is in stark contrast with the obvious problems that platinum and other metal based probes can pose for living tissue. The Warwick research team are already beginning to explore how their single walled carbon nanotube based ultramicroelecrodes can be used to measure levels of neurotransmitters.
The new ultramicroelecrodes also open up interesting possibilities for catalysis in fuel cells. Up till now researchers had been aware that this form of carbon nanotubes appeared to be particularly useful in the area of catalysis but there was uncertainty as to whether it was the properties of the carbon nanotubes per se that provide this benefit or whether it was due to impurities in their production. The researchers have been able to use this new method of single walled carbon nanotube assembly to prove that it is actually the properties of the carbon nanotubes themselves that are useful for catalysis. The new carbon nanotube assembly technique brings a further benefit to catalysis applications as the Warwick researchers have been able to use electrodepoistion to quickly and easily apply specific metal coatings to the ready formed single walled carbon nanotube microelectrode networks. This will be of significant benefit to anyone wanting to use single walled carbon nanotube for catalysis in fuel cell technology.
PR35 6th May 2008
Source: Peter Dunn
University of Warwick
Developing A Short And Sweet Diagnosis For Cancer
In order to provide the most effective treatments for cancer patients, it is essential to develop methods of sensitive and specific early detection of the disease. A team of scientists from the NIBRT Dublin-Oxford Glycobiology Laboratory at UCD has developed a system which aims to pinpoint potential "biomarkers" of early forms of the disease. They do this by looking at the structures of specific sugar molecules which are attached either to proteins made by cancerous cells or to proteins involved in the host response. It is hoped that the availability of such cancer biomarkers would also allow disease progression and response to therapy to be monitored more accurately than is currently possible. Professor Pauline Rudd, who is leading the team, presented some of their results at the Society for Experimental Biology's Annual Meeting in Marseille [Session C4].
It is known that cancer cells not only have different sets of proteins from normal human cells, but that their proteins have changes in the types and numbers of sugar molecules that are attached to them. Dr Rudd and her colleagues believe that being able to detect these changes holds the key to developing a new approach for diagnosing cancer. "We have found that there are alterations in sugars attached to proteins in blood serum from all cancers we have looked at, and some of these appear to be early markers of the disease processes. What is more, we have been able to isolate several sugar-linked variants of particular proteins which are associated with different types of cancer, including prostate, pancreatic and ovarian and breast cancers," she reveals. "In the long term, we envisage that by finding more specific sugar variants, we will be able to use combinations of these as biomarkers to allow very accurate early diagnosis of particular cancers". These techniques could act alongside or even replace physical methods, such as scanning, which are less dependable for early diagnosis.
In order to detect differences between cancerous and normal cells, the scientists are developing a robotic technique to analyse the sugars. "Sugars are removed from the proteins and then broken down into very small components using enzymes. These fragments can be individually characterised leading to the formation of a 'fingerprint' for each sugar we analyse," Professor Rudd explains. "By comparing the fingerprints of sugars from serum or individual proteins from cancer patients with those of disease-free people, we can find sugars which differ slightly between the two - these are the ones that are being tested as potential biomarkers. We are also refining a statistical analysis program which will enable more detailed examination of the data. As our method is high-throughput, we hope to be able to identify a large number of markers which can be taken forward for further testing and then clinical trials, leading to their potential use in both diagnosis and monitoring of cancer progression."
* Results have been published, see PubMed and for example:
Royle L, Campbell MP, Radcliffe CM, White DM, Harvey DJ, Abrahams JL, Kim YG, Henry GW, Shadick NA, Weinblatt ME, Lee DM, Rudd PM, Dwek RA: HPLC-based analysis of serum N-glycans on a 96-well plate platform with dedicated database software-Analytical Biochem 2008, vol. 376, pp. 1-12.
TabarГ©s G, Radcliffe CM, BarrabГ©s S, RamГrez M, Aleixandre RN, Hoesel W, Dwek RA, Rudd PM, Peracaula R, de Llorens R. Different glycan structures in prostate-specific antigen from prostate cancer sera in relation to seminal plasma PSA. Glycobiology. 2006 Feb;16(2):132-45. Epub 2005 Sep 21.
Saldova R, Royle L, Radcliffe CM, Abd Hamid UM, Evans R, Arnold JN, Banks RE, Hutson R, Harvey DJ, Antrobus R, Petrescu SM., Dwek RA, Rudd PM: Ovarian cancer is associated with changes in glycosylation in both acute-phase proteins and IgG -ycobiology. 2007, vol. 17, no.12, pp.1344-1356.
This work was presented at the Society for Experimental Biology's Annual Meeting (6th - 10th July 2008) at Parc Chanot, Marseille, France.
Source: Holly Astley
Society for Experimental Biology
It is known that cancer cells not only have different sets of proteins from normal human cells, but that their proteins have changes in the types and numbers of sugar molecules that are attached to them. Dr Rudd and her colleagues believe that being able to detect these changes holds the key to developing a new approach for diagnosing cancer. "We have found that there are alterations in sugars attached to proteins in blood serum from all cancers we have looked at, and some of these appear to be early markers of the disease processes. What is more, we have been able to isolate several sugar-linked variants of particular proteins which are associated with different types of cancer, including prostate, pancreatic and ovarian and breast cancers," she reveals. "In the long term, we envisage that by finding more specific sugar variants, we will be able to use combinations of these as biomarkers to allow very accurate early diagnosis of particular cancers". These techniques could act alongside or even replace physical methods, such as scanning, which are less dependable for early diagnosis.
In order to detect differences between cancerous and normal cells, the scientists are developing a robotic technique to analyse the sugars. "Sugars are removed from the proteins and then broken down into very small components using enzymes. These fragments can be individually characterised leading to the formation of a 'fingerprint' for each sugar we analyse," Professor Rudd explains. "By comparing the fingerprints of sugars from serum or individual proteins from cancer patients with those of disease-free people, we can find sugars which differ slightly between the two - these are the ones that are being tested as potential biomarkers. We are also refining a statistical analysis program which will enable more detailed examination of the data. As our method is high-throughput, we hope to be able to identify a large number of markers which can be taken forward for further testing and then clinical trials, leading to their potential use in both diagnosis and monitoring of cancer progression."
* Results have been published, see PubMed and for example:
Royle L, Campbell MP, Radcliffe CM, White DM, Harvey DJ, Abrahams JL, Kim YG, Henry GW, Shadick NA, Weinblatt ME, Lee DM, Rudd PM, Dwek RA: HPLC-based analysis of serum N-glycans on a 96-well plate platform with dedicated database software-Analytical Biochem 2008, vol. 376, pp. 1-12.
TabarГ©s G, Radcliffe CM, BarrabГ©s S, RamГrez M, Aleixandre RN, Hoesel W, Dwek RA, Rudd PM, Peracaula R, de Llorens R. Different glycan structures in prostate-specific antigen from prostate cancer sera in relation to seminal plasma PSA. Glycobiology. 2006 Feb;16(2):132-45. Epub 2005 Sep 21.
Saldova R, Royle L, Radcliffe CM, Abd Hamid UM, Evans R, Arnold JN, Banks RE, Hutson R, Harvey DJ, Antrobus R, Petrescu SM., Dwek RA, Rudd PM: Ovarian cancer is associated with changes in glycosylation in both acute-phase proteins and IgG -ycobiology. 2007, vol. 17, no.12, pp.1344-1356.
This work was presented at the Society for Experimental Biology's Annual Meeting (6th - 10th July 2008) at Parc Chanot, Marseille, France.
Source: Holly Astley
Society for Experimental Biology
Hormone Disorder Drug Could Help Drinkers Stay Sober
A drug prescribed for male and female infertility and menstrual disorders could hold the key to a more effective treatment for alcoholism, according to a study by researchers at the UCSF-affiliated Ernest Gallo Clinic and Research Center.
The study showed that "alcoholic" rodents, when injected with the drug cabergoline, decreased their alcohol consumption and alcohol-seeking behavior and were less likely to relapse.
Cabergoline, which is marketed under the trade name Dostinex, is approved by the Food and Drug Administration in pill form to treat conditions caused by excess of the hormone prolactin.
The study, led by Dorit Ron, PhD, a principal investigator at the Gallo Center and associate professor of neurology at UCSF, is now on line (February 20, 2009), in the journal Biological Psychiatry. (See end of news release for link to paper.)
Notably, cabergoline did not impact the rats' consumption of sucrose and, in a subgroup of binge-drinking mice, the drug did not appear to significantly affect intake of water or saccharin.
"This is encouraging," says Ron, "because it demonstrates that cabergoline is specific for alcohol, but does not affect general reward or pleasure. One of the problems with some existing drugs to treat alcoholism is a side effect that decreases pleasure, making compliance an obstacle to sobriety."
The research builds on an earlier, provocative finding by Ron and her colleagues regarding the protein GDNF (glial cell line-derived neurotrophic factor), which they had injected into rats' VTA (ventral tegmental area) brain region, associated with drug-seeking behavior.
In this earlier study, the scientists had trained rats to consume alcohol. Some, like humans, drank in moderation, while others binged. But when GDNF was administered, both heavy and light drinkers lost at least some of their craving for alcohol. This effect became apparent within 10 minutes and lasted at least 24 hours, the scientists discovered. Importantly, administration of GDNF into the brain prevented the rats from relapsing after a period of abstinence.
While the discovery broke new ground, the scientists knew that GDNF could not be used to treat alcoholic humans because its molecule is too large to cross the blood-brain barrier. So, in the present study, Ron and her colleagues looked at cabergoline, a compound that has been shown in cells to increase the expression of GDNF.
After establishing that cabergoline treatment resulted in an increase of the level of GDNF and activation of the GDNF pathway in the rats' VTA, the researchers sought to test its impact on rodents' drinking habits.
Rats underwent a two-month training program in which they learned to press a lever to obtain alcohol. Researchers found that when rats were injected with cabergoline, they were less likely to press the lever. The higher the dose of cabergoline, the lower the number of lever presses reported. The researchers also found that binge-drinking mice consumed less alcohol after cabergoline administration.
In further study, the researchers found that cabergoline was effective in reducing both craving for alcohol and relapse to drinking. Relapse is a critical issue for alcoholic patients trying to stay abstinent.
As further evidence of the interplay between cabergoline and GDNF, alcohol intake was tested on mice that had been genetically engineered to have a single copy of the GDNF gene, and therefore less GDNF in the brain. As expected, the scientists found that the drinking habits of these genetically modified mice were not affected by cabergoline.
Although the results of the study offer fresh hope to problem drinkers, Ron cautions that human clinical trials are needed before cabergoline can be safely prescribed. Higher doses of cabergoline have been used to treat Parkinson's disease and have been linked to heart valve problems.
"However," notes Ron, "we show that in mice and rats, a low dose of the drug is enough to reduce excessive alcohol consumption, alcohol seeking and relapse. The dose is similar to what is given to humans for the treatment of hyperprolactinemia."
Cabergoline may eventually be prescribed for other addictions. A pilot study conducted on cocaine addicts, cited in Ron's paper, reported a substantial reduction in cocaine use.
In the United States, 17.6 million people - approximately one in every 12 adults - abuses alcohol or is alcohol-dependent, according to the National Institutes of Health. But there are just three medications approved to treat alcohol dependence - disulfiram (Antabuse), naltrexone (Depade, ReVia), and acamprosate (Campral).
Lead author of the study is Sebastien Carnicella, PhD, postdoctoral fellow at the Gallo Center. Co-authors are Dao-Yao He, PhD, senior research scientist; Patricia Janak, PhD, associate professor of neurology at UCSF; Selena Bartlett, PhD, director of the center's preclinical development group; Carsten Nielsen, PhD, associate research scientist; and Somayeh Ahmadiantehrani, graduate student.
Research was funded by the National Institutes of Health and the State of California for medical research on alcohol and substance abuse through UCSF.
The Ernest Gallo Clinic and Research Center at UCSF is one of the world's preeminent academic centers for the study of the biological basis of alcohol and substance use disorders. It is the only center studying alcoholism in the United States that is based in a department of neurology. Gallo Center discoveries of potential molecular targets for the development of therapeutic medications are extended through preclinical and proof-of-concept clinical studies.
UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions and excellence in patient care.
Link to paper: Cabergoline Decreases Alcohol Drinking and Seeking Behaviors Via Glial Cell Line-Derived Neurotrophic Factor
Source: Jennifer O'Brien
University of California - San Francisco
View drug information on Campral; Dostinex Tablets; Naltrexone Hydrochloride Tablets.
The study showed that "alcoholic" rodents, when injected with the drug cabergoline, decreased their alcohol consumption and alcohol-seeking behavior and were less likely to relapse.
Cabergoline, which is marketed under the trade name Dostinex, is approved by the Food and Drug Administration in pill form to treat conditions caused by excess of the hormone prolactin.
The study, led by Dorit Ron, PhD, a principal investigator at the Gallo Center and associate professor of neurology at UCSF, is now on line (February 20, 2009), in the journal Biological Psychiatry. (See end of news release for link to paper.)
Notably, cabergoline did not impact the rats' consumption of sucrose and, in a subgroup of binge-drinking mice, the drug did not appear to significantly affect intake of water or saccharin.
"This is encouraging," says Ron, "because it demonstrates that cabergoline is specific for alcohol, but does not affect general reward or pleasure. One of the problems with some existing drugs to treat alcoholism is a side effect that decreases pleasure, making compliance an obstacle to sobriety."
The research builds on an earlier, provocative finding by Ron and her colleagues regarding the protein GDNF (glial cell line-derived neurotrophic factor), which they had injected into rats' VTA (ventral tegmental area) brain region, associated with drug-seeking behavior.
In this earlier study, the scientists had trained rats to consume alcohol. Some, like humans, drank in moderation, while others binged. But when GDNF was administered, both heavy and light drinkers lost at least some of their craving for alcohol. This effect became apparent within 10 minutes and lasted at least 24 hours, the scientists discovered. Importantly, administration of GDNF into the brain prevented the rats from relapsing after a period of abstinence.
While the discovery broke new ground, the scientists knew that GDNF could not be used to treat alcoholic humans because its molecule is too large to cross the blood-brain barrier. So, in the present study, Ron and her colleagues looked at cabergoline, a compound that has been shown in cells to increase the expression of GDNF.
After establishing that cabergoline treatment resulted in an increase of the level of GDNF and activation of the GDNF pathway in the rats' VTA, the researchers sought to test its impact on rodents' drinking habits.
Rats underwent a two-month training program in which they learned to press a lever to obtain alcohol. Researchers found that when rats were injected with cabergoline, they were less likely to press the lever. The higher the dose of cabergoline, the lower the number of lever presses reported. The researchers also found that binge-drinking mice consumed less alcohol after cabergoline administration.
In further study, the researchers found that cabergoline was effective in reducing both craving for alcohol and relapse to drinking. Relapse is a critical issue for alcoholic patients trying to stay abstinent.
As further evidence of the interplay between cabergoline and GDNF, alcohol intake was tested on mice that had been genetically engineered to have a single copy of the GDNF gene, and therefore less GDNF in the brain. As expected, the scientists found that the drinking habits of these genetically modified mice were not affected by cabergoline.
Although the results of the study offer fresh hope to problem drinkers, Ron cautions that human clinical trials are needed before cabergoline can be safely prescribed. Higher doses of cabergoline have been used to treat Parkinson's disease and have been linked to heart valve problems.
"However," notes Ron, "we show that in mice and rats, a low dose of the drug is enough to reduce excessive alcohol consumption, alcohol seeking and relapse. The dose is similar to what is given to humans for the treatment of hyperprolactinemia."
Cabergoline may eventually be prescribed for other addictions. A pilot study conducted on cocaine addicts, cited in Ron's paper, reported a substantial reduction in cocaine use.
In the United States, 17.6 million people - approximately one in every 12 adults - abuses alcohol or is alcohol-dependent, according to the National Institutes of Health. But there are just three medications approved to treat alcohol dependence - disulfiram (Antabuse), naltrexone (Depade, ReVia), and acamprosate (Campral).
Lead author of the study is Sebastien Carnicella, PhD, postdoctoral fellow at the Gallo Center. Co-authors are Dao-Yao He, PhD, senior research scientist; Patricia Janak, PhD, associate professor of neurology at UCSF; Selena Bartlett, PhD, director of the center's preclinical development group; Carsten Nielsen, PhD, associate research scientist; and Somayeh Ahmadiantehrani, graduate student.
Research was funded by the National Institutes of Health and the State of California for medical research on alcohol and substance abuse through UCSF.
The Ernest Gallo Clinic and Research Center at UCSF is one of the world's preeminent academic centers for the study of the biological basis of alcohol and substance use disorders. It is the only center studying alcoholism in the United States that is based in a department of neurology. Gallo Center discoveries of potential molecular targets for the development of therapeutic medications are extended through preclinical and proof-of-concept clinical studies.
UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions and excellence in patient care.
Link to paper: Cabergoline Decreases Alcohol Drinking and Seeking Behaviors Via Glial Cell Line-Derived Neurotrophic Factor
Source: Jennifer O'Brien
University of California - San Francisco
View drug information on Campral; Dostinex Tablets; Naltrexone Hydrochloride Tablets.
Pepscan Achieves A Breakthrough With CLIPS Immunogen Technology
Pepscan reports that it has achieved a major scientific breakthrough through the use of its CLIPS-based synthetic peptide immunogen technology. By constructing synthetic 3D mimics of the ligand binding-site on CXCR7 it has induced functional antibodies against the formerly intractable GPCR target CXCR7. CXCR7 is novel therapeutic target thought to be involved in tumor angiogenesis.
"We are proud and confident with achieving this major breakthrough!" says Professor Rob H. Meloen, Pepscan's founder and Chief Scientific officer. "Since a number of years we have been working on developing our CLIPS technology through which we can synthesize 3D conformational mimics of protein active sites , allowing us to do site-specific immunization to come up with functional antibodies against very difficult targets such as G-protein coupled receptors, as we have now proven with CXCR7." Meloen states that the CLIPS-technology is not limited to application in the GPCR field but also offers possibilities with other therapeutically interesting target such as for instance ion-channels.
Pepscan's Chief Commercial Officer Dr. Peter van Dijken thinks that this technology might unlock a whole new area of interesting therapeutic targets that could so far not be addressed: "One-third of the interesting GPCR targets have proven to be "undrugable" until now. Our CLIPS technology provides a systematic and efficient way to unlock these targets and make them available to antibody therapy, that is a multi-billion dollar playing field to which Pepscan now holds the unique technological key!"
Pepscan indicated that over the coming period, it will continue to technically and commercially develop its clips-based technology for additional targets and indications.
Therapeutic antibody therapy is well established. Monoclonal antibodies are produced outside the body and administered by infusion (passive immunization). A major stumbling block for immunization is often the inability to generate potent antibodies, especially when the target antigen is complex in nature (GPCR's, ion-channels) or blocked by patents. Pepscan's new and now proven technologies provide an elegant and effective way to arrive at superior immunogens for monoclonals and therapeutic vaccines. Intractable targets are drug targets that would be desirable to address with monoclonal antibodies but are inaccessible with alternative commercially available technologies. This can be due to either it being unavailable as recombinant product (e.g. membrane proteins like GPCRs and ion channels) or the target proteins already being patented. The CLIPS technology makes it possible to derive immunogens from intractable targets that induce antibodies against the native antigen. Ordinary peptides are poor mimics of complex protein structures due to their lack of structure. Pepscan's CLIPSTM technology makes it possible to mimic complex protein domains by presenting one or more amino peptides in a spatially defined conformation. These molecules have proven to be superior in defining discontinuous epitopes. More importantly, CLIPS antigens have now proven to yield antibodies that recognize the protein they are derived from.
Pepscan Therapeutics is a privately owned company based in Lelystad, The Netherlands. Pepscan Therapeutics is wholly owned subsidiary of Pepscan Holding. All fee-for-service activities using Pepscan's technology are handled by Pepscan PRESTO.
Source: Pepscan Therapeutics B.V
"We are proud and confident with achieving this major breakthrough!" says Professor Rob H. Meloen, Pepscan's founder and Chief Scientific officer. "Since a number of years we have been working on developing our CLIPS technology through which we can synthesize 3D conformational mimics of protein active sites , allowing us to do site-specific immunization to come up with functional antibodies against very difficult targets such as G-protein coupled receptors, as we have now proven with CXCR7." Meloen states that the CLIPS-technology is not limited to application in the GPCR field but also offers possibilities with other therapeutically interesting target such as for instance ion-channels.
Pepscan's Chief Commercial Officer Dr. Peter van Dijken thinks that this technology might unlock a whole new area of interesting therapeutic targets that could so far not be addressed: "One-third of the interesting GPCR targets have proven to be "undrugable" until now. Our CLIPS technology provides a systematic and efficient way to unlock these targets and make them available to antibody therapy, that is a multi-billion dollar playing field to which Pepscan now holds the unique technological key!"
Pepscan indicated that over the coming period, it will continue to technically and commercially develop its clips-based technology for additional targets and indications.
Therapeutic antibody therapy is well established. Monoclonal antibodies are produced outside the body and administered by infusion (passive immunization). A major stumbling block for immunization is often the inability to generate potent antibodies, especially when the target antigen is complex in nature (GPCR's, ion-channels) or blocked by patents. Pepscan's new and now proven technologies provide an elegant and effective way to arrive at superior immunogens for monoclonals and therapeutic vaccines. Intractable targets are drug targets that would be desirable to address with monoclonal antibodies but are inaccessible with alternative commercially available technologies. This can be due to either it being unavailable as recombinant product (e.g. membrane proteins like GPCRs and ion channels) or the target proteins already being patented. The CLIPS technology makes it possible to derive immunogens from intractable targets that induce antibodies against the native antigen. Ordinary peptides are poor mimics of complex protein structures due to their lack of structure. Pepscan's CLIPSTM technology makes it possible to mimic complex protein domains by presenting one or more amino peptides in a spatially defined conformation. These molecules have proven to be superior in defining discontinuous epitopes. More importantly, CLIPS antigens have now proven to yield antibodies that recognize the protein they are derived from.
Pepscan Therapeutics is a privately owned company based in Lelystad, The Netherlands. Pepscan Therapeutics is wholly owned subsidiary of Pepscan Holding. All fee-for-service activities using Pepscan's technology are handled by Pepscan PRESTO.
Source: Pepscan Therapeutics B.V
Shire Expands Pipeline To Treat Orphan Muscle Diseases Through Collaboration With Acceleron Pharma
Shire plc (LSE: SHP, NASDAQ: SHPGY), the global specialty biopharmaceutical company, announced the expansion of its Human Genetic Therapies pipeline through the exclusive license, in markets outside of North America, for the activin receptor type IIB (ActRIIB) class of molecules being developed by Acceleron Pharma Inc., a private biotechnology company based in Cambridge, Massachusetts. The collaboration will initially investigate ACE-031, Acceleron's lead ActRIIB drug candidate, currently in a Phase 2a trial for the treatment of patients with Duchenne Muscular Dystrophy (DMD). DMD is a fatal orphan muscle disease with no current treatment. ACE-031 and other ActRIIB molecules have the potential to be used in other muscular and neuromuscular disorders with high unmet medical need.
Shire and Acceleron will jointly collaborate on a worldwide development program to advance ACE-031 into a global Phase 2/3 clinical program designed to demonstrate disease modification in DMD patients. Shire will utilize its Lexington, Massachusetts manufacturing facility to produce commercial supplies of the product for both parties. If marketing authorization is received, Acceleron will commercialize ACE-031 in the U.S. and Canada, and Shire has the exclusive right to commercialize the therapy in the rest of the world.
Under the terms of the agreement, Shire will make an upfront payment to Acceleron of $45 million. Acceleron is eligible to receive additional development, regulatory and sales milestone payments of up to $165 million for the successful commercialization of ACE-031 in DMD, up to an additional $288 million for successful commercialization of other indications and molecules, and royalties on product sales. Shire will also make a contribution to global development costs. Shire's 2010 outlook of Non GAAP earnings trending towards $4.00 per ADS which was recently announced in its second quarter earnings press release is unchanged.
"This collaboration is an excellent strategic fit to the work that Shire is already doing on behalf of patients with rare diseases," said Sylvie Gregoire, President of Shire Human Genetic Therapies. "Working with Acceleron on the development of ACE-031 for DMD allows us to use our expertise to help patients suffering from this devastating disease, as well as expand our pipeline into a new therapeutic area."
"The structure of this collaboration allows Acceleron to retain commercial rights in North America with the opportunity to build a highly valuable business while collaborating with an ideal partner for ACE-031," said John Knopf, Ph.D., Chief Executive Officer of Acceleron. "Shire's international presence and their proven leadership and dedicated focus on orphan diseases forms the basis for successful collaboration to bring innovative therapies to patients with enormous unmet medical need."
About Duchenne Muscular Dystrophy (DMD)
DMD is a debilitating and fatal genetic disorder characterized by the progressive loss of muscle strength and function. It primarily affects boys and occurs in approximately 1 in every 3,500 live male births. DMD is caused by genetic mutations that result in the absence of dystrophin, a protein necessary to maintain the structural integrity of muscle fibers. This condition leads to damage and deterioration of skeletal and cardiac muscles, which eventually become infiltrated by non-functional scar and fatty tissue. As a result, patients experience a relentless decline in muscle strength that impairs their ability to walk, breathe and live independently. Many patients spend the majority of their lives using wheelchairs and eventually lose upper body function as well. Few patients survive beyond their late-20s when their heart and respiratory muscles weaken and eventually fail.
About ACE-031
ACE-031 is an investigational protein therapeutic designed to build muscle and increase strength by inhibiting signaling through a cell surface receptor called activin receptor type IIB (ActRIIB). ACE-031 is a recombinant fusion protein that is produced by joining a portion of the human ActRIIB receptor to a portion of a human antibody. This creates a freely circulating, decoy version of ActRIIB which interferes with proteins, such as GDF-8 (myostatin), that normally limit the growth and regeneration of muscle by binding to and activating endogenous ActRIIB. Recent studies with ACE-031 suggest that blocking signaling through ActRIIB may be a way to increase muscle mass and improve physical function. In a range of animal models of muscle disease, including models of muscular dystrophy, and muscle loss related to corticosteroid treatment, androgen deprivation or advanced age, ACE-031 increased muscle mass, strength and physical function. Unlike the mutation specific RNA based therapeutics in clinical development for DMD, ACE-031 could potentially benefit all patients with DMD, irrespective of the underlying genetic mutation. Moreover, given its novel mechanism of action, ACE-031 could be used in combination with many of the therapies currently in development.
"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
Statements included herein that are not historical facts are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, the Company's results could be materially adversely affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of research, development, approval, reimbursement, manufacturing and commercialization of the Company's Specialty Pharmaceutical and Human Genetic Therapies products, as well as the ability to secure and integrate new products for commercialization and/or development; government regulation of the Company's products; the Company's ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on the Company's products; the Company's ability to register, maintain and enforce patents and other intellectual property rights relating to its products; the Company's ability to obtain and maintain government and other third-party reimbursement for its products; and other risks and uncertainties detailed from time to time in the Company's filings with the Securities and Exchange Commission.
Source: Shire plc
Shire and Acceleron will jointly collaborate on a worldwide development program to advance ACE-031 into a global Phase 2/3 clinical program designed to demonstrate disease modification in DMD patients. Shire will utilize its Lexington, Massachusetts manufacturing facility to produce commercial supplies of the product for both parties. If marketing authorization is received, Acceleron will commercialize ACE-031 in the U.S. and Canada, and Shire has the exclusive right to commercialize the therapy in the rest of the world.
Under the terms of the agreement, Shire will make an upfront payment to Acceleron of $45 million. Acceleron is eligible to receive additional development, regulatory and sales milestone payments of up to $165 million for the successful commercialization of ACE-031 in DMD, up to an additional $288 million for successful commercialization of other indications and molecules, and royalties on product sales. Shire will also make a contribution to global development costs. Shire's 2010 outlook of Non GAAP earnings trending towards $4.00 per ADS which was recently announced in its second quarter earnings press release is unchanged.
"This collaboration is an excellent strategic fit to the work that Shire is already doing on behalf of patients with rare diseases," said Sylvie Gregoire, President of Shire Human Genetic Therapies. "Working with Acceleron on the development of ACE-031 for DMD allows us to use our expertise to help patients suffering from this devastating disease, as well as expand our pipeline into a new therapeutic area."
"The structure of this collaboration allows Acceleron to retain commercial rights in North America with the opportunity to build a highly valuable business while collaborating with an ideal partner for ACE-031," said John Knopf, Ph.D., Chief Executive Officer of Acceleron. "Shire's international presence and their proven leadership and dedicated focus on orphan diseases forms the basis for successful collaboration to bring innovative therapies to patients with enormous unmet medical need."
About Duchenne Muscular Dystrophy (DMD)
DMD is a debilitating and fatal genetic disorder characterized by the progressive loss of muscle strength and function. It primarily affects boys and occurs in approximately 1 in every 3,500 live male births. DMD is caused by genetic mutations that result in the absence of dystrophin, a protein necessary to maintain the structural integrity of muscle fibers. This condition leads to damage and deterioration of skeletal and cardiac muscles, which eventually become infiltrated by non-functional scar and fatty tissue. As a result, patients experience a relentless decline in muscle strength that impairs their ability to walk, breathe and live independently. Many patients spend the majority of their lives using wheelchairs and eventually lose upper body function as well. Few patients survive beyond their late-20s when their heart and respiratory muscles weaken and eventually fail.
About ACE-031
ACE-031 is an investigational protein therapeutic designed to build muscle and increase strength by inhibiting signaling through a cell surface receptor called activin receptor type IIB (ActRIIB). ACE-031 is a recombinant fusion protein that is produced by joining a portion of the human ActRIIB receptor to a portion of a human antibody. This creates a freely circulating, decoy version of ActRIIB which interferes with proteins, such as GDF-8 (myostatin), that normally limit the growth and regeneration of muscle by binding to and activating endogenous ActRIIB. Recent studies with ACE-031 suggest that blocking signaling through ActRIIB may be a way to increase muscle mass and improve physical function. In a range of animal models of muscle disease, including models of muscular dystrophy, and muscle loss related to corticosteroid treatment, androgen deprivation or advanced age, ACE-031 increased muscle mass, strength and physical function. Unlike the mutation specific RNA based therapeutics in clinical development for DMD, ACE-031 could potentially benefit all patients with DMD, irrespective of the underlying genetic mutation. Moreover, given its novel mechanism of action, ACE-031 could be used in combination with many of the therapies currently in development.
"SAFE HARBOR" STATEMENT UNDER THE PRIVATE SECURITIES LITIGATION REFORM ACT OF 1995
Statements included herein that are not historical facts are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, the Company's results could be materially adversely affected. The risks and uncertainties include, but are not limited to, risks associated with: the inherent uncertainty of research, development, approval, reimbursement, manufacturing and commercialization of the Company's Specialty Pharmaceutical and Human Genetic Therapies products, as well as the ability to secure and integrate new products for commercialization and/or development; government regulation of the Company's products; the Company's ability to manufacture its products in sufficient quantities to meet demand; the impact of competitive therapies on the Company's products; the Company's ability to register, maintain and enforce patents and other intellectual property rights relating to its products; the Company's ability to obtain and maintain government and other third-party reimbursement for its products; and other risks and uncertainties detailed from time to time in the Company's filings with the Securities and Exchange Commission.
Source: Shire plc
New Paradigms In The Research Of The Biomolecular Composition Of Water
Water nurtures life in all its forms, but not all water in our life systems is equal. Water in a lake, in the sea or in a cup of tea is different from the water in our bodies. This much we do know. Yet science does not yet have a complete understanding as to why intracellular water is different to other water forms. The science of water is subject to conflicting theories. The very structure of water, as an open system and out of equilibrium, makes it an extremely controversial field.
The tools that have been used in the study of other materials no longer comply with the study of water if we wish to make real progress in the research. Do-Coop Technologies Ltd wishes to engage with colleagues and interested parties in a discussion of new, progressive research methods that meet the current needs in the field.
Do-Coop's own research has led to the development of water-based nanotechnology termed Neowater®. Neowater® is water that displays a clear shift in its physical properties due to the unique organization and interaction between the water, surface and Carbon Dioxide. This stable proprietary structure allows solubility of hydrophobic drugs, stability of proteins and cell cultures, enhancement of biological in vitro and in vivo applications and reduced need for stabilizers and detergents, by solid surface and Carbon Dioxide repackaging in the liquid phase of water in standard conditions (STP). Neowater® uses the surface effect produced by the minute amount of 1015 particles per liter and elevated amount of insoluble Carbon Dioxide to compete on the free bulk water, reducing the entropy of the bulk and producing a colloidal structure within the water, as proven by ITC measurements, ultrasound propagations and Zeta potential.
This new and original approach has far-reaching implications for both the study of the science of water, and in its practical applications. Neowater® gives the industry and the scientific community a stable and unique water-based environment that is more similar to the water that supports life. This enables an improved balance between toxicity and efficacy, ensuring cost-effective and efficient drug development, as well as extended shelf life, IP extension and superior drug delivery.
Nature uses the unique properties of water, earth and air in forming life-supporting niche environments. The chemicals extracted from nature for use in pharmaceuticals are packaged perfectly in the environment. What if technology could replicate these circumstances, creating an environment as close to the natural ideal as possible?
The Do-Coop Technologies team looks forward to the opportunity of an open dialogue of the future directions in the study of the biochemical composition of water with co-participants at the upcoming Scientific Water Meeting in Vermont.
Source: Irit Gabbai
Do-Coop Technologies Ltd.
The tools that have been used in the study of other materials no longer comply with the study of water if we wish to make real progress in the research. Do-Coop Technologies Ltd wishes to engage with colleagues and interested parties in a discussion of new, progressive research methods that meet the current needs in the field.
Do-Coop's own research has led to the development of water-based nanotechnology termed Neowater®. Neowater® is water that displays a clear shift in its physical properties due to the unique organization and interaction between the water, surface and Carbon Dioxide. This stable proprietary structure allows solubility of hydrophobic drugs, stability of proteins and cell cultures, enhancement of biological in vitro and in vivo applications and reduced need for stabilizers and detergents, by solid surface and Carbon Dioxide repackaging in the liquid phase of water in standard conditions (STP). Neowater® uses the surface effect produced by the minute amount of 1015 particles per liter and elevated amount of insoluble Carbon Dioxide to compete on the free bulk water, reducing the entropy of the bulk and producing a colloidal structure within the water, as proven by ITC measurements, ultrasound propagations and Zeta potential.
This new and original approach has far-reaching implications for both the study of the science of water, and in its practical applications. Neowater® gives the industry and the scientific community a stable and unique water-based environment that is more similar to the water that supports life. This enables an improved balance between toxicity and efficacy, ensuring cost-effective and efficient drug development, as well as extended shelf life, IP extension and superior drug delivery.
Nature uses the unique properties of water, earth and air in forming life-supporting niche environments. The chemicals extracted from nature for use in pharmaceuticals are packaged perfectly in the environment. What if technology could replicate these circumstances, creating an environment as close to the natural ideal as possible?
The Do-Coop Technologies team looks forward to the opportunity of an open dialogue of the future directions in the study of the biochemical composition of water with co-participants at the upcoming Scientific Water Meeting in Vermont.
Source: Irit Gabbai
Do-Coop Technologies Ltd.
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