|  Author | Topic: MedTech IV: R & D (Read 7,617 times) |
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|  | Re: MedTech IV: R & D
« Reply #285 on Oct 29, 2011, 2:04am » | |
Building Better HIV Antibodies: Biologists Create Neutralizing Antibody That Shows Increased Potency
![[image]](http://img84.imageshack.us/img84/5074/1110271458551691899.jpg "[image]")
The increased potency of a new HIV antibody (green and blue), is explained by an insertion (pink) that contacts the inner domain of the HIV gp120 spike protein (yellow). (Credit: Ron Diskin/Caltech)
ScienceDaily (Oct. 27, 2011) — Using highly potent antibodies isolated from HIV-positive people, researchers have recently begun to identify ways to broadly neutralize the many possible subtypes of HIV. Now, a team led by biologists at the California Institute of Technology (Caltech) has built upon one of these naturally occurring antibodies to create a stronger version they believe is a better candidate for clinical applications.
Current advances in isolating antibodies from HIV-infected individuals have allowed for the discovery of a large number of new, broadly neutralizing anti-HIV antibodies directed against the host receptor (CD4) binding site -- a functional site on the surface of the virus that allows for cell entry and infection. Using a technique known as structure-based rational design, the team modified one already-known and particularly potent antibody -- NIH45-46 -- so that it can target the binding site in a different and more powerful way. A study outlining their process was published in the Oct. 27 issue of Science Express.
"NIH45-46 was already one of the most broad and potent of the known anti-HIV antibodies," says Pamela Bjorkman, Max Delbrück Professor of Biology at Caltech and senior author on the study. "Our new antibody is now arguably the best of the currently available, broadly neutralizing anti-HIV antibodies."
By conducting structural studies, the researchers were able to identify how NIH45-46 interacted with gp120 -- a protein on the surface of the virus that's required for the successful entry of HIV into cells -- to neutralize the virus. Using this information, they were able to create a new antibody (dubbed NIH45-46G54W) that is better able to grab onto and interfere with gp120. This improves the antibody's breadth -- or extent to which it effectively targets many subtypes of HIV -- and potency by an order of magnitude, according to Ron Diskin, a postdoctoral scholar in Bjorkman's lab at Caltech and the paper's lead author.
"Not only did we design an improved version of NIH45-46, our structural data are calling into question previous assumptions about how to make a vaccine in order to elicit such antibodies," says Diskin. "We hope that these observations will help to guide and improve future immunogen design."
By improving the efficacy of antibodies that can neutralize HIV, the researchers point to the possibility of clinical testing for NIH45-46G54W and other antibodies as therapeutic agents. It's also plausible that understanding effective neutralization by powerful antibodies may be useful in vaccine development.
"The results uncover the structural underpinnings of anti-HIV antibody breadth and potency, offer a new view of neutralization by CD4-binding site anti-HIV antibodies, and establish principles that may enable the creation of a new group of HIV therapeutics," says Bjorkman, who is also a Howard Hughes Medical Institute investigator.
Other Caltech authors on the study, "Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design," include Paola M. Marcovecchio, Anthony P. West, Jr., Han Gao, and Priyanthi N.P. Gnanapragasm. Johannes Scheid, Florian Klein, Alexander Abadir, and Michel Nussenweig from Rockefeller University, and Michael Seaman from Beth Israel Deaconess Medical Center in Boston also contributed to the paper. The research was funded by the Bill & Melinda Gates Foundation, the National Institutes of Health, the Gordon and Betty Moore Foundation, and the German Research Foundation.
Story Source:
The above story is reprinted from materials provided by California Institute of Technology. The original article was written by Katie Neith.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
1. Ron Diskin, Johannes F. Scheid, Paola M. Marcovecchio, Anthony P. West, Jr., Florian Klein, Han Gao, Priyanthi N. P. Gnanapragasam, Alexander Abadir, Michael S. Seaman, Michel C. Nussenzweig, Pamela J. Bjorkman. Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design. Science, Published online Oct. 27, 2011 DOI: 10.1126/science.1213782
http://www.sciencedaily.com/releases/2011/10/111027145855.htm
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
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Big Bunny
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| | Re: MedTech IV: R & D
« Reply #286 on Oct 30, 2011, 10:45pm » | |
Novel Strategy Stymies SARS and Other Viruses: Versatile Inhibitor Prevents Viral Replication
ScienceDaily (Oct. 28, 2011) — Broad-spectrum antibiotics, which are active against a whole range of bacterial pathogens, have been on the market for a long time. Comparably versatile drugs to treat viral diseases, on the other hand, have remained elusive. Using a new approach, research teams led by Dr. Albrecht von Brunn of LMU Munich and Professor Christian Drosten from the University of Bonn have identified a compound that inhibits the replication of several different viruses, including the highly aggressive SARS virus that is responsible for severe acute respiratory syndrome.
The new method exploits the fact that interactions between certain host proteins and specific viral proteins are essential for viral replication. One of these host proteins is part of a signaling relay in the cell. The broad-spectrum antiviral compound used by the researchers blocks this signal pathway without having a deleterious effect on the host. "We have shown in this study that a broadly based search for new cellular targets can uncover new functional principles that have a demonstrable impact on virus replication," says von Brunn. "We have confirmed that the approach works in cell culture. We now hope that these laboratory results can be translated into clinically effective therapies. At the very least, our high-throughput procedure can be utilized to systematically screen various protein-virus interactions as potential targets for inhibitory compounds."
The new study was carried out under the auspices of the SARS Research Network, which is supported by the Federal Ministry for Education and Research (BMBF).
Broad-spectrum antibiotics that inhibit the growth of various species of bacterial pathogens are well known. Virologists, unfortunately, have no comparably versatile weapons in their armory. Individual drugs that are active against different types of viral pathogens are simply not available. "All of the antiviral agents we have are directed specifically at the virus itself," explains Professor Christian Drosten, Director of the Institute of Virology at Bonn University Hospital. "And since viral pathogens are highly diverse, each of these agents can attack only certain viruses." Moreover, viruses are also highly mutable, making the weaponry they can deploy against us even more powerful. What works against one viral strain may be essentially useless against another.
The SARS virus, a previously unknown pathogen which threatened to cause a worldwide pandemic in 2003, has spurred on the search for new antiviral substances. Only recently, it was shown that not only Chinese, but also European, bats carry the SARS virus. "But in contrast to the situation with bird influenza, one cannot simply kill these free-living animals in order to eradicate the pathogen," says Drosten. "That would have catastrophic ecological consequences and, apart from that, bats are retiring and secretive in their habits." If one wishes to develop drugs against viruses that can "hide" in animal species, one must explore other alternatives.
The research teams assembled by von Brunn and Drosten have now discovered a way to prevent the replication of a whole family of viruses by depriving them of an essential host factor. They first identified host proteins with which SARS viral proteins interact. This strategy led to the finding that a cellular signaling pathway is essential for the replication not only of the SARS virus, but also of a whole set of related viruses that are pathogenic to humans and animals.
"This signal pathway is normally involved in regulating the immune system," says Drosten. "We used a substance that inhibits the function of one of the proteins in the pathway, and found that it suppresses viral replication." In other words, drugs that block this pathway inhibit the replication of many different viruses, and therefore act as broad-spectrum antivirals. This opens a route to the treatment of conditions caused by the SARS virus, but also a whole variety of human coronaviruses, and pathogens that infect the internal organs of chickens, pigs and cats. Inhibition of this pathway does not damage the host, because parallel pathways can compensate for its normal role in the cell.
The successful inhibition of virus replication was not a result of serendipity. The researchers in Munich have developed a technique that allows them to systematically probe different proteins for the ability to interact with defined targets. "In order to replicate in the body of its host, a virus must first gain entry to a suitable cell type by binding to a specific receptor protein on its surface," says von Brunn, who works in the Max von Pettenkofer Institute at LMU Munich. "We have used an automated, high-throughput process to systematically test various protein-virus combinations as potential targets for possible inhibitors. The success of this strategy proves that a broadly based search for cellular targets can uncover new functional principles that have a demonstrable impact on virus replication," says von Brunn.
The investigators have shown in cell cultures that their approach actually works. "However, it will be years before we know whether or not these results can be translated into effective treatments," Drosten says. The study also underlines the importance of research collaborations. Drosten is convinced that "neither group could have done this on its own." The SARS Research Network, which is coordinated by Drosten, brings together virological expertise from six university institutes, two veterinary and four medical, located in Hannover, Gießen, Marburg, Bonn, Munich and St. Gallen (Switzerland).
Story Source:
The above story is reprinted from materials provided by Ludwig-Maximilians-Universitaet Muenchen (LMU).
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
1. Susanne Pfefferle, Julia Schöpf, Manfred Kögl, Caroline C. Friedel, Marcel A. Müller, Javier Carbajo-Lozoya, Thorsten Stellberger, Ekatarina von Dall’Armi, Petra Herzog, Stefan Kallies, Daniela Niemeyer, Vanessa Ditt, Thomas Kuri, Roland Züst, Ksenia Pumpor, Rolf Hilgenfeld, Frank Schwarz, Ralf Zimmer, Imke Steffen, Friedemann Weber, Volker Thiel, Georg Herrler, Heinz-Jürgen Thiel, Christel Schwegmann-Weßels, Stefan Pöhlmann, Jürgen Haas, Christian Drosten, Albrecht von Brunn. The SARS-Coronavirus-Host Interactome: Identification of Cyclophilins as Target for Pan-Coronavirus Inhibitors. PLoS Pathogens, 2011; 7 (10): e1002331 DOI: 10.1371/journal.ppat.1002331
http://www.sciencedaily.com/releases/2011/10/111028103225.htm
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
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Big Bunny
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| | Re: MedTech IV: R & D
« Reply #287 on Oct 30, 2011, 10:47pm » | |
New Drug Targets Revealed from Giant Parasitic Worm Genome Sequence
ScienceDaily (Oct. 26, 2011) — Scientists have identified the genetic blueprint of the giant intestinal roundworm, Ascaris suum, revealing potential targets to control the devastating parasitic disease, ascariasis which affects more than one billion people in China, South East Asia, South America and parts of Africa, killing thousands of people annually and causing chronic effects in young children.
Dr Aaron Jex and Professor Robin Gasser from the University of Melbourne's Faculty of Veterinary Science led the international research project which was published in the journal Nature.
The work has provided new insights to treat the condition ascariasis, identified by the World Health Organization as a key, neglected disease in urgent need of extensive research and significantly improved control.
"Sequencing the genome of Ascaris suum is a major step towards controlling the infection it causes because the more we know about the genetics of the parasite and how it works, the better we can fight it with novel treatments," Dr Jex said.
"From the genome sequence we have identified five high priority drug targets that are likely to be relevant for many other parasitic worms. New treatments are urgently needed and genome-guided drug target discovery is ideal for identifying targets that selectively kill the parasite and not the host.
"We also identified key information on how the parasite hides from the immune system, which is essential for any future vaccine development."
The team sequenced the nuclear genome of Ascaris suum which is an easier worm to study in the laboratory and mainly only infects pigs, but is very closely related to Ascaris lumbricoides which causes ascariasis in humans. The worms range from 15-30cm in length and are spread via eggs in contaminated food.
Ascaris lumbricoides is one of the most common parasites of humans, affecting more than one billion people in developing countries, particularly children, causing impaired physical and cognitive development, and in severe cases death, due to lack of nutrient absorption and intestinal blockage.
Ascaris suum also causes major production losses in swine farming due to reduced growth, failure to thrive and mortality.
The research was conducted in collaboration with BGI-Shenzhen, China, the University of Ghent, Belgium, the University of Copenhagen, Denmark, California Institute of Technology, USA, the Ontario Institute for Cancer Research, Canada, and Macquarie University, Sydney.
Story Source:
The above story is reprinted from materials provided by University of Melbourne.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
1. Aaron R. Jex, Shiping Liu, Bo Li, Neil D. Young, Ross S. Hall, Yingrui Li, Linfeng Yang, Na Zeng, Xun Xu, Zijun Xiong, Fangyuan Chen, Xuan Wu, Guojie Zhang, Xiaodong Fang, Yi Kang, Garry A. Anderson, Todd W. Harris, Bronwyn E. Campbell, Johnny Vlaminck, Tao Wang, Cinzia Cantacessi, Erich M. Schwarz, Shoba Ranganathan, Peter Geldhof, Peter Nejsum, Paul W. Sternberg, Huanming Yang, Jun Wang, Jian Wang, Robin B. Gasser. Ascaris suum draft genome. Nature, 2011; DOI: 10.1038/nature10553
http://www.sciencedaily.com/releases/2011/10/111026143725.htm
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
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Big Bunny
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| | Re: MedTech IV: R & D
« Reply #288 on Nov 7, 2011, 7:36pm » | |
7 November 2011 Last updated at 07:54 GMT
Light 'promising' in cancer fight
By James Gallagher Health reporter, BBC News
Light is a "promising" tool in the fight against cancer, say researchers in the US.
A study, published in Nature Medicine, showed how a drug could be created which sticks to tumours, but is then only activated when hit by specific waves of light.
It means a treatment can be highly targeted and not damage the surrounding tissue.
A cancer charity said the treatment showed early promise.
Currently, treatments for cancer can be separated into three categories: blasting it with radiation, surgically removing a tumour or using drugs to kill the cancerous cells. All have side effects and scientists are trying to come up with more precise therapies.
In this study, researchers at the National Cancer Institute, Maryland, used an antibody which targets proteins on the surface of cancerous cells.
They then attached a chemical, IR700, to the antibody. IR700 is activated when it is hit by near infrared light. This wavelength of light can penetrate several centimetres into the skin.
To test the antibody-chemical combination, researchers implanted tumours, squamous cell carcinoma, into the backs of mice. They were given the drug and exposed to near infrared light.
Shrinking tumour
The study said: "Tumour volume was significantly reduced... compared to untreated control mice and survival was significantly prolonged.
"This selective killing minimises damage to normal cells."
The authors said the combination was "a promising therapeutic and diagnostic agent for the treatment of cancer".
"Although we observed no toxicity in our experiments, clinical translation of this method will require formal toxicity studies," they added.
Dr Laura McCallum, Cancer Research UK's science communications officer, said the research was promising.
"Using antibodies or photodynamic therapy to specifically target cancer cells have both been successful for treating some cancers, so combining the two together is certainly an exciting plan.
"But it's important to remember that this work was done in mice, so it's much too early to tell if it will work in people with cancer.
"This potential treatment has promise as scientists - including our own - are also looking at using antibodies to deliver other knockout punches, such as radiation, directly to cancer cells."
http://www.bbc.co.uk/news/health-15571711
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
|
Big Bunny
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| | Re: MedTech IV: R & D
« Reply #289 on Nov 10, 2011, 11:38am » | |
10 November 2011 Last updated at 01:48 GMT
New hope for head injury patients
By Fergus Walsh Medical correspondent, BBC News
A method of communicating with brain damaged patients who appear to be in a vegetative state has been discovered by scientists in the UK and Belgium.
Writing in The Lancet medical journal they describe how they measured electrical activity in the brain to detect consciousness.
The technique, known as EEG, is painless and involves attaching electrodes to the head.
Doctors hope it can be used as a diagnostic tool in homes and hospitals.
The trial involved 16 patients at Addenbrooke's Hospital in Cambridge and the University Hospital of Liege in Belgium.
All had been diagnosed as being in a vegetative state - a condition where a person is awake, but has no sense of awareness of themselves or their surroundings.
The patients were asked to imagine wiggling their toes or squeezing their right hand. The brain activity of three of the 16 patients showed they were repeatedly able to follow commands.
The report author, Professor Adrian Owen, from the Centre for Brain and Mind, University of Western Ontario, Canada said: "Many areas of the brain that activate when you perform a movement also activate when you imagine doing it.
"We know these three patients were conscious as they were able to respond repeatedly to the instructions we had given them. One of the patients was able to do it more than 100 times."
'Wrong' diagnosis
Professor Owen's team at the MRC Cognition and Brain Sciences Unit in Cambridge previously showed that it was possible to communicate with some vegetative patients using functional magnetic resonance imaging (fMRI).
But many brain injured patients cannot be assessed in these scanners because they have metal plates or pins, or they are unable to remain still.
The EEG device is comparatively cheap and portable. Professor Owen said: "This is exciting because it means we can get out into the community, take it to patients in nursing and care homes, and assess many more patients at the bedside to see if we can detect covert awareness."
Helen Gill-Thwaites, a consultant in the diagnosis of low awareness states at the Royal Hospital for Neuro-disability (RHN) in Putney said: "For a small proportion of patients EEG could be a very useful tool in the diagnostic process.
"It would however be a useful addition and not a replacement, to current methods of assessing severely brain-injured patients.
"Sadly, in my work outside of the RHN I meet many patients who have never had a proper assessment and have been wrongly diagnosed as being in a vegetative state."
Paul Matthews, Professor of Clinical Neurosciences, Department of Medicine, Imperial College, London said: "The approach suggests a simple, practical way in which some of these patients might be helped to communicate.
"This innovative work has taken fundamental brain science right to the bedside. Efforts to further evaluate this and related approach in the clinic should be prioritised."
http://www.bbc.co.uk/news/health-15661977
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
|
Big Bunny
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| | Re: MedTech IV: R & D
« Reply #290 on Nov 10, 2011, 8:10pm » | |
First Large-Scale Study of Pain Reveals Risk Factors
ScienceDaily (Nov. 10, 2011) — Millions of Americans are affected by painful jaw problems known as TMD, temporomandibular disorders, but predicting who is at risk has been extremely difficult.
Now, for the first time, researchers in the University at Buffalo School of Dental Medicine are publishing a comprehensive set of clinical characteristics that they say will lead to the ability to identify individuals at risk for developing the painful conditions.
Their new clinical assessments will help researchers and clinicians better understand TMD and other pain conditions, so as to find ways to better manage and treat them.
Published in the November issue of the Journal of Pain, the UB research results are part of the Orofacial Pain Prospective Evaluation and Risk Assessment (OPPERA) study.
It is the largest clinical study of pain conditions and how they develop that has ever been done.
The UB researchers, led by Richard Ohrbach, DDS, PhD, associate professor of oral diagnostic sciences in the UB School of Dental Medicine, have been studying pain and TMD for several decades. Ohrbach is the lead author on the paper.
"The UB role in the project was to develop well-designed examination procedures to help dentists and other health care providers identify risk factors for TMD," says Ohrbach.
Ohrbach and his co-authors studied 71 different clinical variables in 1,633 controls -- individuals who never had TMD -- and in 185 people with chronic painful TMD.
They assessed the individuals through lengthy questionnaires about health histories and current symptoms and through clinical exams. Participants were from Western New York, Maryland, North Carolina and Florida.
The UB researchers found that a very high rate of the variables they assessed, 59 out of 71, were significantly associated with painful TMD.
"Our results indicate that individuals with TMD differ substantially from the controls across almost all of the variables we assessed," says Ohrbach.
TMD sufferers tended to have significantly higher levels of the following variables: trauma to the jaw, non-pain symptoms in the facial area, jaw locking and noises, and pain during such jaw movements as chewing, smiling or talking. Ohrbach notes that while the last two findings were clearly expected, very little has been known about the first two findings.
In particular, the UB researchers found that TMD sufferers reported a much higher rate of neural and sensory medical conditions, such as earaches, tinnitus or hearing loss, fainting and dizziness, as well as seizures due to epilepsy and other conditions.
Ohrbach said that the study also confirmed many findings that long have been associated with TMD but which have not, until now, been proven in a comprehensive, large-scale study.
Among these is the finding that any pain disorder, such as headache, backache and abdominal pain, is more likely to occur in TMD patients than in people who do not have TMD.
"Why are other pain disorders more common in people with TMD?" asks Ohrbach. "Is it because those pain conditions predispose them to develop TMD or do they develop TMD first and does TMD lead them to then develop other pain disorders?"
To answer these and other related questions, Ohrbach says he and his colleagues will next look at comorbidity.
"We'll be tracking these multiple pain disorders over time with particular variables," he says.
Ultimately, the findings of the UB researchers and their colleagues on the OPPERA study will be geared toward a better understanding of pain conditions in general.
"How do we understand the pain? How do we establish a reliable and clinically useful marker of pain so that significant pain can be more readily diagnosed?" asks Ohrbach. "To answer these questions, we need to have a model that puts all of the pieces together, that takes the findings from a clinical exam, puts it into a rigorous framework using the right assessment and diagnosis tools in order to chart the nature of multiple physical disorders so that we can ultimately understand how the pain is affecting the individual."
The OPPERA study was funded by the National Institute of Dental and Craniofacial Research.
Co-authors with Ohrbach on the paper are: Yoly Gonzalez of the UB Department of Oral Diagnostic Sciences; Roger B. Fillingim, University of Florida, College of Dentistry, North Florida/South Georgia Veterans Health System; Sharon Gordon, Department of Oral-Maxillofacial Surgery and Brotman Facial Pain Center, University of Maryland-Baltimore, Dental School; Henry Gremillion, Louisiana State University Health Sciences Center School of Dentistry; Margarete Ribeiro-Dasilva, Department of Community Dentistry and Behavioral Science, University of Florida, College of Dentistry; Joel D. Greenspan, Department of Neural and Pain Sciences, and Brotman Facial Pain Center; Charles Knott, Battelle Memorial Institute; and Pei-Feng Lim, William Maixner, Flora Mulkey and Gary Slade, all of the University of North Carolina-Chapel Hill.
Story Source:
The above story is reprinted from materials provided by University at Buffalo.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
1. Richard Ohrbach, Roger B. Fillingim, Flora Mulkey, Yoly Gonzalez, Sharon Gordon, Henry Gremillion, Pei-Feng Lim, Margarete Ribeiro-Dasilva, Joel D. Greenspan, Charles Knott, William Maixner, Gary Slade. Clinical Findings and Pain Symptoms as Potential Risk Factors for Chronic TMD: Descriptive Data and Empirically Identified Domains from the OPPERA Case-Control Study. The Journal of Pain, 2011; 12 (11): T27 DOI: 10.1016/j.jpain.2011.09.001
http://www.sciencedaily.com/releases/2011/11/111110125957.htm
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
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Big Bunny
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| | Re: MedTech IV: R & D
« Reply #291 on Nov 10, 2011, 9:43pm » | |
Easily 'Re-Programmable Cells' Could Be Key in Creation of New Life Forms
![[image]](http://img715.imageshack.us/img715/7960/1111071622239261336.jpg "[image]")
Illustration of cells. (Credit: © Jezper / Fotolia)
ScienceDaily (Nov. 7, 2011) — Scientists at The University of Nottingham are leading an ambitious research project to develop an in vivo biological cell-equivalent of a computer operating system.
The success of the project to create a 're-programmable cell' could revolutionise synthetic biology and would pave the way for scientists to create completely new and useful forms of life using a relatively hassle-free approach.
Professor Natalio Krasnogor of the University's School of Computer Science, who leads the Interdisciplinary Computing and Complex Systems Research Group, said: "We are looking at creating a cell's equivalent to a computer operating system in such a way that a given group of cells could be seamlessly re-programmed to perform any function without needing to modifying its hardware."
"We are talking about a highly ambitious goal leading to a fundamental breakthrough that will, -- ultimately, allow us to rapidly prototype, implement and deploy living entities that are completely new and do not appear in nature, adapting them so they perform new useful functions."
The game-changing technology could substantially accelerate Synthetic Biology research and development, which has been linked to myriad applications -- from the creation of new sources of food and environmental solutions to a host of new medical breakthroughs such as drugs tailored to individual patients and the growth of new organs for transplant patients.
The multi-disciplinary project, funded with a leadership fellowship for Professor Krasnogor worth more than £1 million from the Engineering and Physical Sciences Research Council (EPSRC), involves computer scientists, biologists and chemists from Nottingham as well as academic colleagues at other universities in Scotland, the US, Spain and Israel.
The project -- Towards a Biological Cell Operating System (AUdACiOuS) -- is attempting to go beyond systems biology -- the science behind understanding how living organisms work -- to give scientists the power to create biological systems. The scientists will start the work by attempting to make e.coli bacteria much more easy to program.
Professor Krasnogor added: "This EPSRC Leadership Fellowship will allow me to transfer my expertise in Computer Science and informatics into the wet lab.
"Currently, each time we need a cell that will perform a certain new function we have to recreate it from scratch which is a long and laborious process. Most people think all we have to do to modify behaviour is to modify a cell's DNA but it's not as simple as that -- we usually find we get the wrong behaviour and then we are back to square one. If we succeed with this AUdACiOuS project, in five years time, we will be programming bacterial cells in the computer and compiling and storing its program into these new cells so they can readily execute them.
"Like for a computer, we are trying to create a basic operating system for a biological cell."
Among the most fundamental challenges facing the scientists will be developing new computer models that more accurately predict the behaviour of cells in the laboratory.
Scientists can already programme individual cells to complete certain tasks but scaling up to create a larger organism is trickier.
The creation of more sophisticated computer modelling programmes and a cell that could be re-programmed to fulfil any function without having to go back to the drawing board each time could largely remove the trial and error approach currently taken and allow synthetic biology research to take a significant leap forward.
The technology could be used in a whole range of applications where being able to modify the behaviour of organisms could be advantageous. In the long run, this includes the creation of new microorganisms that could help to clean the environment for example by capturing carbon from the burning of fossil fuel or removing contaminants, e.g. arsenic from water sources. Alternatively, the efficacy of medicine could be improved by tailoring it to specific patients to maximise the effect of the drugs and to reduce any harmful side effects.
The partners in the project are The University of Nottingham and The University of Edinburgh in the UK; Arizona State University, Massachusetts Institute of Technology, Michigan State University, New York University, University of California Santa Barbara, University of California, San Francisco in the US; Centro Nacional de Biotecnologia in Spain; and the Weizmann Institute of Science in Israel.
Story Source:
The above story is reprinted from materials provided by University of Nottingham.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
http://www.sciencedaily.com/releases/2011/11/111107162223.htm
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
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Big Bunny
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| | Re: MedTech IV: R & D
« Reply #292 on Nov 12, 2011, 11:30pm » | |
Chemists Reveal the Force Within You: New Method for Visualizing Mechanical Forces On Cell Surface
![[image]](http://img442.imageshack.us/img442/9486/111109115818large842608.jpg "[image]")
"Once a force is applied to the polymer, it stretches out,” Salaita explains. “And as it extends, the distance from the quencher increases and the fluorescent signal turns on and grows brighter." (Credit: Graphic by Daniel Stabley.)
ScienceDaily (Nov. 9, 2011) — A new method for visualizing mechanical forces on the surface of a cell, reported in Nature Methods, provides the first detailed view of those forces, as they occur in real-time.
"Now we're able to measure something that's never been measured before: The force that one molecule applies to another molecule across the entire surface of a living cell, and as this cell moves and goes about its normal processes," says Khalid Salaita, assistant professor of biomolecular chemistry at Emory University. "And we can visualize these forces in a time-lapsed movie."
Salaita developed the florescent-sensor technique with chemistry graduate students Daniel Stabley and Carol Jurchenko, and undergraduate senior Stephen Marshall.
"Cells are constantly tugging and pushing on their surroundings, and they can even communicate with one another using mechanics," Salaita says. "One way that cells use forces is evident from the characteristic architecture of tissue, like a lung or a heart. If we want to really understand cells and how they work, we have to understand cell mechanics at a molecular level. The first step is to measure the tension applied to specific receptors on the cell surface."
The researchers demonstrated their technique on the epidermal growth factor receptor (EGFR), one of the most studied cellular signaling pathways. They mapped the mechanical strain exerted by EGFR during the early stages of endocytosis, when the protein receptor of a cell takes in a ligand, or binding molecule. The results showed that the cell does not passively absorb the ligand, but physically pulls it inside during the process. Their experiments provide the first direct evidence that force is exerted during endocytosis.
Mapping such forces may help to diagnose and treat diseases related to cellular mechanics. Cancer cells, for instance, move differently from normal cells, and it is unclear whether that difference is a cause or an effect of the disease.
"It's known that if EGFR is over-active, that can lead to cancer," Salaita says. "And one of the ways that EGFR is activated is by binding its ligand and taking it in. So if we can understand how tugging on EGFR force changes the pathway, and whether it plays a role in cancer, it might be possible to design drugs that target this pulling process."
Several methods have been developed in recent years to try to study the mechanics of cellular forces, but they have major limitations.
One genetic engineering approach requires splitting open and modifying proteins of a cell. This invasive technique may change the behavior of the cell, skewing the results.
The technique developed at Emory is non-invasive, does not modify the cell, and can be done with a standard fluorescence microscope. A flexible polymer is chemically modified at both ends. One end gets a fluorescence-based turn-on sensor that will bind to a receptor on the cell surface. The other end is chemically anchored to a microscope slide and a molecule that quenches fluorescence.
"Once a force is applied to the polymer, it stretches out," Salaita explains. "And as it extends, the distance from the quencher increases and the fluorescent signal turns on and grows brighter. We can determine the force being exerted by measuring the amount of fluorescent light emitted."
The forces of any individual protein or molecule on the cell surface can be measured using the technique, at far higher spatial and temporal resolutions than was previously possible.
Many mysteries beyond the biology and chemistry of cells may be explained through measuring cellular forces. How does a cancer cell crawl when a tumor spreads? What are the forces involved in cell division and immune response? What are the mechanics that allow groups of cardiac cells to beat in unison?
"Our method can be applied to nearly any receptor, opening the door to rapidly studying chemical and mechanical interactions across the thousands of membrane-bound receptors on the surface of virtually any cell type," Salaita says. "We hope that measuring cellular forces could then become part of the standard repertoire of biochemical techniques that scientists use to study living systems."
Story Source:
The above story is reprinted from materials provided by Emory University. The original article was written by Carol Clark.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
1. Daniel R Stabley, Carol Jurchenko, Stephen S Marshall, Khalid S Salaita. Visualizing mechanical tension across membrane receptors with a fluorescent sensor. Nature Methods, 2011; DOI: 10.1038/nmeth.1747
http://www.sciencedaily.com/releases/2011/11/111109115818.htm
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« Reply #293 on Nov 13, 2011, 12:48am » | |
Brain Probe That Softens After Insertion Causes Less Scarring
ScienceDaily (Nov. 3, 2011) — A hard probe inserted in the cerebral cortex of a rat model turns nearly as pliable as the surrounding gray matter in minutes, and induces less of the tough scarring that walls off hard probes that do not change, researchers at Case Western Reserve University have found.
In the first test of the nanocomposite probe inspired by the dynamic skin of the sea cucumber, the immune response differed compared to that of a metal probe, and appeared to enable the brain to heal faster.
The findings, provide insights to the brain's responses to the mechanical mismatch between tissue and probe, are described in the online edition of the Journal of Neural Engineering.
Brain probes are used to study and treat neurological disorders. But, wires or silicon materials being used damage surrounding tissue over time and accumulate scarring, because they are far harder than brain matter.
In this test, "The scar wall is more diffuse; the nanocomposite probe is not completely isolated in the same way a traditional stiff probe is," said Dustin Tyler, a professor of biomedical engineering and leader of the experiment.
The result may prove beneficial. Studies by others in the field indicate the greater the isolation, the less effective the probe is at recording and relaying brain signals.
Tyler worked with James P. Harris, a graduate student in biomedical engineering and the lead author on the paper; Biomedical Engineering Professor Jeffery Capadona; Stuart J. Rowan, professor of macromolecular science and engineering, and former graduate student Kadhiravan Shanmuganathan; Robert H. Miller, professor of neurosciences at Case Western Reserve School of Medicine; Christoph Weder, formerly a professor of macromolecular science and engineering at Case Western Reserve and now at the University of Fribourg; and Harvard Neurology Professor and Research Fellow Brian C. Healy.
The new probe material is inspired by the skin of the sea cucumber, which is normally soft and flexible, but becomes rigid for its own defense within seconds of being touched. These changing mechanical properties may improve our interaction with our brain, Tyler said.
In the nanocomposite, short polymer chains are linked together in a network mesh to make the material rigid, which is necessary for insertion into the cortex. In the presence of water, the mesh begin unlinking in seconds, changing to a soft, rubbery material designed to cause less damage to surrounding brain tissue over time.
To test the effects of the changing mechanical properties, metal probes were coated in a think layer of nanocomposite materal. When both were implanted into the brain, the chemical properties as seen by the brain were these same, but the mechanical properties were very different.
Four weeks after implantation, the density of neuronal nuclei adjacent to the new probe was significantly higher than surrounding the traditional probe.
At eight weeks, the density of nuclei had increased around the wire probe to equal the density around the flexible probe, which remained unchanged.
"One hypothesis is that the soft material allows the brain to recover more quickly," Tyler said. "Both probes cause the same insult to the tissue when inserted."
But, testing for scar components at 8 weeks showed that although the thickness of scar surrounding the metal probe had shrunk, the scar was denser and more complete than that around the nanocomposite probe. This dense scar separated the stiff probe from the brain more than the loose tissue around the more flexible probe.
The researchers are now comparing the impacts of the two probes at longer time intervals and testing for more indicators of the immune response, Harris said. "We're trying to better understand the nuances regarding the response to the nanocomposite and how it would improve recordings."
Story Source:
The above story is reprinted from materials provided by Case Western Reserve University.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
1. J P Harris, J R Capadona, R H Miller, B C Healy, K Shanmuganathan, S J Rowan, C Weder, D J Tyler. Mechanically adaptive intracortical implants improve the proximity of neuronal cell bodies. Journal of Neural Engineering, 2011; 8 (6): 066011 DOI: 10.1088/1741-2560/8/6/066011
http://www.sciencedaily.com/releases/2011/11/111103120347.htm
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
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| | Re: MedTech IV: R & D
« Reply #294 on Nov 13, 2011, 12:50am » | |
Scientists Defuse the 'Vietnam Time Bomb': How Bacterial Pathogen Causes Deadly Tropical Disease Melioidosis
ScienceDaily (Nov. 10, 2011) — New findings are published on 10 November 2011 in the journal Science and show how a toxin produced by the bacterium Burkholderia pseudomallei kills cells by preventing protein synthesis. The study, led by the University of Sheffield, paves the way for the development of novel therapies to combat the bacterium which infects millions of people across South East Asia and Northern Australia.
Using intense X-rays at Diamond Light Source, the UK´s national synchrotron facility, and at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France, the research team solved the structure of a protein from Burkholderia, the function of which was initially unknown.
"The information gathered from the structure suggested that the protein was a previously unsuspected toxin and sparked a search for its mode of action. This eventually led to the discovery of how it prevents human cells from making proteins and helped us to understand how it causes cell death," says research lead Professor David Rice from the Department of Molecular Biology and Biotechnology at the University of Sheffield.
Melioidosis, along with HIV and tuberculosis, is one of the top three causes of death by infectious disease in parts of South East Asia and arises from infection by the bacterium which thrives in water and warm, moist soils and can enter the body through the lungs or through open wounds.
It causes either an acute form of the disease which presents immediately upon infection, or it can lay dormant in the body emerging many years, and often decades, later. In the acute form of the disease, even with a long course of treatment, mortality rates in endemic areas can be as high as 40 per cent. With a wide range of symptoms, melioidosis can be difficult to diagnose, hampering medical intervention.
"This disease is an everyday reality for many people living in the endemic areas and our findings will allow us to test if an inactivated toxin might be effective as a component of a vaccine," says Professor Rick Titball, a member of the team from the University of Exeter.
The delayed action of the bacteria has led to it being dubbed the `Vietnam time bomb´ following the recognition that many US military personnel who served in Vietnam have been infected. "Now that we know of the existence of this toxin it opens up opportunities for the development of novel drugs that could block its effects," says University of Sheffield Professor Stuart Wilson.
The study involved a consortium of UK scientists from the University of Sheffield, the University of Exeter, Diamond Light Source and the Defence Science and Technology Laboratory at Porton Down. European and international partners included: the European Synchrotron Radiation Facility (ESRF) in Grenoble, France; Universiti Kebangsaan Malaysia; the Malaysia Genome Institute; DSO National Laboratories, Singapore, and the Genome Institute of Singapore.
Kevin van Cauter, HE Advisor with the British Council, commented: "We are thrilled that PMI2 funding supported this international collaboration and are excited by the potential impact of the work."
These groups now plan to seek funding to continue the work and investigate potential applications of the toxin to fight other diseases, such as cancer, where it might usefully be employed in targeted therapies to prevent the proliferation of cancer cells.
Story Source:
The above story is reprinted from materials provided by University of Sheffield.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
1. A. Cruz-Migoni, G. M. Hautbergue, P. J. Artymiuk, P. J. Baker, M. Bokori-Brown, C.-T. Chang, M. J. Dickman, A. Essex-Lopresti, S. V. Harding, N. M. Mahadi, L. E. Marshall, G. W. Mobbs, R. Mohamed, S. Nathan, S. A. Ngugi, C. Ong, W. F. Ooi, L. J. Partridge, H. L. Phillips, M. F. Raih, S. Ruzheinikov, M. Sarkar-Tyson, S. E. Sedelnikova, S. J. Smither, P. Tan, R. W. Titball, S. A. Wilson, D. W. Rice. A Burkholderia pseudomallei Toxin Inhibits Helicase Activity of Translation Factor eIF4A. Science, 2011; 334 (6057): 821 DOI: 10.1126/science.1211915
http://www.sciencedaily.com/releases/2011/11/111110142052.htm
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
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Big Bunny
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| | Re: MedTech IV: R & D
« Reply #295 on Nov 13, 2011, 1:13am » | |
'Noise' Tunes Logic Circuit Made from Virus Genes
ScienceDaily (Nov. 8, 2011) — In the world of engineering, “noise” – random fluctuations from environmental sources such as heat – is generally a bad thing. In electronic circuits, it is unavoidable, and as circuits get smaller and smaller, noise has a greater and more detrimental effect on a circuit’s performance. Now some scientists are saying: if you can’t beat it, use it.
Engineers from Arizona State University in Tempe and the Space and Naval Warfare Systems Center (SPAWAR) in San Diego, Calif., are exploiting noise to control the basic element of a computer – a logic gate that can be switched back and forth between two different logic functions, such as AND\OR – using a genetically engineered system derived from virus DNA. In a paper accepted to the AIP’s journal Chaos, the team has demonstrated, theoretically, that by exploiting sources of external noise, they can make the network switch between different logic functions in a stable and reliable way.
The scientists focused on a single-gene network in a bacteriophage λ (lamda). The gene they use regulates the production of a particular protein in the virus. Normally, there are biological reactions that regulate the creation and destruction of this protein; upsetting that balance results in a protein concentration that is either too high or too low. The scientists assigned a “1” to one concentration and a “0” to the other. By manipulating the protein concentration, the team could encode the logic gate input values and obtain the desired output values.
Researchers modeled the system as two potential energy “wells” separated by a hump, corresponding to an energy barrier. In the presence of too much noise, the system never relaxes into one of the two wells, making the output unpredictable. Too little noise, on the other hand, does not provide the boost necessary for the system to reach a high enough protein concentration to overcome the energy barrier; in this case, there is also a high probability that the biological logic gate will fail to achieve its predicted computation. But an optimal amount of noise stabilizes the circuit, causing the system to jump into the “correct well” – and stay there.
This proof-of-concept work offers the possibility of exploiting noise in biologic circuits instead of regarding it as a laboratory curiosity or a nuisance, the researchers say.
Story Source:
The above story is reprinted from materials provided by American Institute of Physics.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
1. Anna Dari, Behnam Kia, Adi R. Bulsara, William L. Ditto. Logical stochastic resonance with correlated internal and external noises in a synthetic biological logic block. Chaos: An Interdisciplinary Journal of Nonlinear Science, 2011; (accepted)
http://www.sciencedaily.com/releases/2011/11/111108201544.htm
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
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Big Bunny
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| | Re: MedTech IV: R & D
« Reply #296 on Nov 14, 2011, 12:37am » | |
12 November 2011 Last updated at 02:43 GMT
Pre-eclampsia predicted using test during pregnancy
A test carried out during pregnancy could predict which women will develop a potentially fatal condition called pre-eclampsia, scientists say.
Presenting their study to the American Society of Nephrology, researchers said the test detected specific kidney cells in patients' urine.
Out of 15 women who developed pre-eclampsia, all tested positive for the cells.
Experts say a simple, predictive test during pregnancy would be valuable.
Warning sign
Pre-eclampsia is a disorder which appears in the late stages of pregnancy and is characterised by high blood pressure and excess protein in the urine.
Researchers at the Mayo Clinic, who presented their work to the annual meeting of the American Society of Nephrology, tested 300 women.
Dr Vesna Garovic assessed a test which detects the shedding of kidney cells called podocytes in the urine. The team had previously found podocytes present in patients with pre-eclampsia when they gave birth.
In this study, all the women who went on to develop pre-eclampsia had podocytes in their urine, while none of the 15 who went on to develop high blood pressure or the 44 healthy pregnant women did.
Although carried out on small numbers of women, the researchers say the test is highly accurate for predicting pre-eclampsia and could alert doctors early to the problem.
Ann Marie Barnard, chief executive of Action on Pre-Eclampsia, said an accurate test would help many women.
"A large number of the 1,500 women who call our helpline each year are terrified of becoming pregnant again because they have suffered pre-eclampsia, often with tragic results. Many do decide to go ahead with a new pregnancy anyway.
"Any test which can predict whether they are going to get it again has to be welcomed - while it cannot stop the disease occurring, it would enable services to be more closely focused on them and more alert to signs of the disease developing."
And Andrew Shennan, professor of obstetrics at St Thomas Hospital in London, said: "Being able to use a simple accurate test in pregnancy, such as from a urine sample, would be valuable in identifying those women to watch closely.
"Current tests are not reliable enough, and further work is needed to confirm these promising findings in larger groups."
http://www.bbc.co.uk/news/health-15694021
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
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Big Bunny
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| | Re: MedTech IV: R & D
« Reply #297 on Nov 14, 2011, 2:01am » | |
Tamoxifen Resistance -- And How to Defeat It
ScienceDaily (Nov. 13, 2011) — In the last three decades, thousands of women with breast cancer have taken the drug tamoxifen, only to discover that the therapy doesn't work, either because their tumors do not respond to the treatment at all, or because they develop resistance to it over time. Now researchers at the University of California, San Francisco (UCSF) have discovered the molecular basis for tamoxifen resistance and found a potential way to defeat it.
On Nov. 13, 2011, at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, UCSF oncologist Pamela Munster, MD, and her colleagues presented the results of clinical studies and laboratory experiments that show how some tumors resist tamoxifen and how this resistance can be overcome by administering a second class of drugs.
"Understanding the mechanism of tamoxifen resistance and how to defeat it may help a large number of women with hormone-resistant breast cancer," said Munster. "It may lead quickly to new, more effective treatment strategies and may help to identify biomarkers to help to gauge whether or not someone will respond to treatment in the first place."
Tamoxifen Resistance and Breast Cancer The National Cancer Institute estimates that more than 200,000 Americans are diagnosed with breast cancer every year. It is the second leading cause of cancer death among American women, claiming more than 40,000 lives in 2009 alone.
About 65 percent of women with breast cancer have tumors that, when examined in biopsies, show signs of co-opting a naturally occurring molecule in the human body called the estrogen receptor. This receptor helps to stimulate the proliferation and growth of cells -- something that is normally tightly controlled in the body.
Tumors can use the machinery of this receptor to stimulate the unregulated growth and proliferation of cancer cells. Doctors have known for decades that this is one of the main drivers of breast cancer, and elevated levels of estrogen receptor is something oncologists look for when they take tumor biopsies.
Tamoxifen, which blocks the estrogen receptor, is the front-line treatment for premenopausal women whose breast cancer biopsies show elevated levels of the receptor. It can be something of a wonder drug when it works, inhibiting cancer growth and shrinking tumors without the same side effects as chemotherapy.
However, tamoxifen only works in half the women to whom it is prescribed. It may not work in some women because they may have forms of cancer in which the estrogen receptor does not actually play a central role. However, many women taking tamoxifen acquire resistance to it. Their tumors respond to the treatment at first, but then the cancer rebounds and develops the ability to proliferate and grow even when the estrogen receptor is blocked.
While doctors have documented cases of tamoxifen resistance in the clinic for decades, nobody knew exactly how the cells were able to acquire resistance. Many scientists thought that genetics were to blame -- certain variations in one's DNA that would pass from parents to children and make one more likely to develop a tamoxifen-resistant form of breast cancer. According to Munster, that is not the case.
"We always thought that resistance was genetic," said Munster. "But now we have discovered that cells have a way of developing resistance by means of epigenetic modification."
Epigenetics is a general phenomenon in biology that explains how some cells, tissues, and whole organisms can acquire traits that go beyond mere genetic differences. Rather than genes being mutated or changed and then passed on to offspring, which is the domain of genetics, epigenetic changes are not in the genes themselves but in their levels of expression and activity.
Queen bees, for instance, are genetically identical to worker bees, but they are much larger and characteristically quite different. Genes don't account for these differences -- epigenetics does. Queens start out life the same as workers, but they are fed a steady diet of chemicals in their food that alter the levels of expression and activity of their genes, and over time these changes account for their queenly form.
According to the research Munster and her colleagues are presenting this week, it is a similar epigenetic story that accounts for tamoxifen resistance. They discovered that when cancer cells are fed tamoxifen, they sometimes respond by elevating expression of a gene known as AKT.
AKT is a "survival" gene that in normal situations helps to stimulate growth and proliferation of cells and prevent cells from dying. In breast cancer, however, it can become overactive and confer resistance by allowing the cancer cells to continue to use the estrogen receptor even in the presence of tamoxifen.
The good news clinically, said Munster, is that several existing compounds known as histone deacetylase inhibitors directly target AKT. Two of these are already approved by the U.S. Food and Drug Administration for treating a rare type of lymphoma. Several more are actively under development and at least one is in early clinical trials, said Munster.
She and her colleagues showed that when cells in the laboratory are fed these histone deacytalase inhibitors, their levels of AKT are knocked back. Giving the same cells tamoxifen at the same time dramatically curtails the ability of the cells to proliferate.
In clinical studies published earlier this year, Munster and her colleagues also showed that taking both drugs together can reverse tamoxifen resistance.
This approach will have to prove safe and effective in additional, large-scale clinical trials before it becomes generally available.
Story Source:
The above story is reprinted from materials provided by University of California - San Francisco, via Newswise.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
http://www.sciencedaily.com/releases/2011/11/111113141409.htm
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
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Big Bunny
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| | Re: MedTech IV: R & D
« Reply #298 on Nov 14, 2011, 2:04am » | |
Wearable Defibrillator Can Prevent Death in People With Arrhythmias, Research Finds
ScienceDaily (Nov. 13, 2011) — A wearable defibrillator can prevent sudden death in people with dangerous heart arrhythmias, according to research presented at the American Heart Association's Scientific Sessions 2011.
Wearable cardioverter defibrillators are used by people who may be at higher risk for sudden cardiac arrest, including those with weakened heart function, awaiting cardiac transplant or with a condition that prevents or delays them from receiving an implanted defibrillator.
The device monitors heart rhythm, emits alarms if a serious arrhythmia occurs, delivers an electric shock to the heart if needed and alerts bystanders to help if the heart's electrical activity has stopped.
About 5,000 patients are using wearable defibrillators at any one time, usually for about 60 days, said Vincent N. Mosesso Jr., M.D., professor of emergency medicine at the University of Pittsburgh School of Medicine and principal investigator of the study.
"In these patients, the wearable defibrillator is a non-invasive 'insurance policy' against sudden arrest during their vulnerable period," he said.
Researchers gathered heart rhythm records and calls about shocks from a registry of 14,475 patients with wearable defibrillators listed from 2007 through 2009. Of those, 185 (about 1 percent) received an appropriate shock and 91.6 percent survived one or more episodes of ventricular fibrillation or ventricular tachycardia, the most common abnormal rhythms during cardiac arrest.
Wearable defibrillators delivered 223 inappropriate shocks to 213 people who weren't experiencing ventricular fibrillation or ventricular tachycardia. However, no one died as a result. Researchers attribute the inappropriate shocks to signal noise, rapid non-VT rhythms, and rhythm misinterpretation.
Only about 7 percent of people in the United States who have sudden cardiac arrest outside the hospital survive to hospital discharge, and only about 21 percent who have them in the hospital survive to discharge.
"This study confirms the effectiveness of very early defibrillation as therapy for sudden cardiac arrest in high-risk patients when delivered by a wearable defibrillator," Mosesso said. "These defibrillators provide patients the critical advantage of not having to wait for a bystander or emergency responder to recognize the cardiac arrest and use an automated external defibrillator or manual defibrillator -- both of which can lead to delays in treatment and markedly worse survival rates."
Co-authors are: Jie Li, M.S.; Douglas Landsittel, Ph.D. and Leonard I. Ganz, M.D. Author disclosures are on the abstract.
ZOLL LifeCor of Pittsburgh, which makes the wearable defibrillator used in the study, funded the research.
Story Source:
The above story is reprinted from materials provided by American Heart Association.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
http://www.sciencedaily.com/releases/2011/11/111113141300.htm
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
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Big Bunny
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| | Re: MedTech IV: R & D
« Reply #299 on Nov 14, 2011, 2:06am » | |
New Strategy to Accelerate Blood Vessel Maturation Has Therapeutic Potentials for Ischemic Diseases
ScienceDaily (Oct. 10, 2011) — VIB-K.U.Leuven researchers describe a new mechanism to enhance the restoration of the blood flow in ischemic diseases, which are among the leading causes of death worldwide. The team of Massimiliano Mazzone demonstrates that blocking the protein PhD2 in white blood cells accelerates the maturation of blood vessels. This leads to a better blood perfusion to organs that had been deprived from blood -- and thus oxygen -- supply by ischemia. This might become a new therapeutic approach in ischemic diseases to prevent damage to the organs.
"Ischemic diseases can lead to serious damage to organs, for instance through a heart attack or stroke. It gives a good feeling to find possible new therapeutic strategies to restrict the following damage to a minimum," says Massimiliano Mazzone (VIB/K.U.Leuven).
Bypassing the occlusion
Mazzone has demonstrated that arteriogenesis (growth of pre-existing connections between distinct blood vessels into functional arteries) can be accelerated by blocking the function of the protein PhD2 in a particular class of white blood cells. This resulted in wider and functional vessels, which allows the blood to bypass the occlusion and thus offers better blood perfusion. The scientists want to investigate in further detail the therapeutic potential of blocking PhD2 for ischemic diseases.
Blood as supplier of vital substances
Every organ in our body needs enough oxygen and other vital substances in order to function properly. Our blood takes care of the transport throughout our body to the different organs. It also removes toxic products. A lower -- or no -- blood perfusion to a certain organ, e.g. through an occlusion of a blood vessel, endangers this organ and can cause irreversible damage after a while. This is what happens in ischemic diseases, which can lead to heart attacks and strokes. The challenge is to restore the blood flow as soon as possible to avoid damage of the organs.
Natural processes to prevent ischemic tissue damage include arteriogenesis. This is essential to obtain blood vessels that are wide and 'mature' enough for a good blood stream. Enhancing this process receives a lot of attention as a therapeutic approach to avoid tissue damage by ischemia.
Story Source:
The above story is reprinted from materials provided by VIB.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
1. Yukiji Takeda, Sandra Costa, Estelle Delamarre, Carmen Roncal, Rodrigo Leite de Oliveira, Mario Leonardo Squadrito, Veronica Finisguerra, Sofie Deschoemaeker, Françoise Bruyère, Mathias Wenes, Alexander Hamm, Jens Serneels, Julie Magat, Tapan Bhattacharyya, Andrey Anisimov, Benedicte F. Jordan, Kari Alitalo, Patrick Maxwell, Bernard Gallez, Zhen W. Zhuang, Yoshihiko Saito, Michael Simons, Michele De Palma, Massimiliano Mazzone. Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis. Nature, 2011; DOI: 10.1038/nature10507
http://www.sciencedaily.com/releases/2011/10/111010092856.htm
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"All truth passes through three stages. First, it is ridiculed, second it is violently opposed, and third, it is accepted as self-evident."
Arthur Schopenhauer, Philosopher, 1788-1860
"In the final analysis, our most basic common link is that we all inhabit this small planet, breathe the same air, and we all cherish our children’s future."
John F. Kennedy |
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