Dubai Cares And La Chaine De L’Espoir On Joint Gaza Emergency Mission
A joint Dubai Cares and La Chaine de L’Espoir mission is en route to the Gaza Strip, where a specialized surgical and medical team will treat children wounded in the ongoing war. The 4-member medical team includes Vascular surgeon Eric Cheysson, chest and cardiovascular surgeon Daniel Roux, Neurosurgeon Baris Turak and a logistician and is expected to enter Gaza today as an advance team to be followed by more specialties.
More than 750 people have been killed and more than 3100 injured in the fighting in Gaza, one of the most densely populated places in the world. According to the latest UN estimates, Palestinian children, who are dying at a heavy rate in this war, account for approximately one out of every three persons killed.
The mission follows an assessment of the needs of the civilian population in Gaza and a survey of local hospitals, which are struggling to cope with the high number of casualties amid limited specialized staff and diminishing levels of medical supplies.
HE Reem al Hashimy, Chairperson of Dubai Cares, said: “We continue to closely monitor events in Gaza and have been in contact with medical officials there in order to get an accurate reading of the situation. Officials at Al Shifa Hospital, Gaza’s largest hospital, are overwhelmed with the high number of casualties, especially among children, and have made an appeal for medical support. Dubai Cares’ joint mission with La Chaine de L’Espoir is our response to this appeal.”
The joint Dubai Cares-La Chaine de L’Espoir mission will provide specialized medical services not currently available in Gaza to perform life- and limb-saving operations on injured children. In the absence of these specialized surgeons, treatable limb injuries can result in amputations.
The medical team is headed by Dr. Eric Cheysson, Vascular Surgeon and Vice President of La Chaine de L’Espoir, who said: “This mission will support our colleagues in Gaza who have to cope with severe circumstances to treat children who continue to pay a heavy price in this conflict. With this specialized medical support, we hope to minimize the impact of these injuries on children and help them lead a normal life once the war is over.”
About La Chaine de l’Espoir
La Chaine de l’Espoir is a non-profit association engaged in facilitating access to medical care for the poorest children in developing countries. The association puts together high-level medical teams through its important network of French and best international specialists, surgeons, professional doctors and hospitals.
About Dubai Cares
Dubai Cares is the world’s largest charitable establishment solely devoted to improving primary education for underprivileged children. Its emergency interventions – which to date include interventions in Chad, Myanmar and Ethiopia – stems from its philosophy that guaranteeing the continuity of children’s education is as important as ensuring their physical well being.
Dubai Cares
Anticlotting Drug From Genetically Engineered Goats Is Safe Says FDA Panel
An expert panel that advises the US Food and Drug Adminstration (FDA) voted that the anti-clotting drug ATryn, which is made from the milk of
genetically engineered goats, is safe and effective and be approved for the treatment of people with a rare inherited disorder that makes them
susceptible to life-threatening blood clots. The drug, which is made by the biotechnology company GTC Biotherapeutics Inc based in Massachusetts,
is already approved in Europe.
ATryn is made from a human protein extracted from the milk of goats that have been genetically altered to produce it. If approved, the drug will be the
first commercially available pharmaceutical in the US to be made from “transgenic” animals, that is animals that have had genetic material from another
species (in this case from humans into goats) inserted in their DNA.
GTC is licensing the drug to OVATION, a biotech company based in Deerfield, Illinois who will be marketing the drug in the US. Both companies are
seeking FDA approval for ATryn in the “prevention and treatment of venous thromboembolism in hereditary antithrombin deficient patients
undergoing surgery or childbirth procedures”, said a recent statement from GTC.
A majority of the 19-member FDA Blood Products Advisory Committee voted that the drug was safe and effective after reviewing data supplied by
the manufacturer. The FDA does not have to follow the recommendation of its Advisory Committees but it usually does. Their decision is expected
by 7th of February.
The panel’s consumer representative, Dr Richard Colvin, who is a a clinical assistant in medicine at Massachusetts General Hospital, told the press that
this action “set a precedent for what will happen in the future”, reported Reuters.
Chairman and CEO of GTC, Dr Geoffrey F Cox said both companies were very pleased with the panel’s recommendation:
“ATryn is the first transgenically produced therapeutic to achieve approval in Europe and undergo review by the FDA.”
The new drug has the potential to provide ” an important new treatment option for patients with hereditary antithrombin deficiency,” he
explained.
President and CEO of OVATION, Jeffrey S Aronin said the panel’s decision meant they were a step closer to “making the drug available to people in
the US with hereditary antithrombin deficiency, a rare clotting disorder associated with severe complications for which there are few treatment
options”.
Antithrombin works as a natural blood clotter or anticoagulant by controlling thrombin, which is key to the formation of blood clots. ATryn is a
purified recombinant antithrombin with the same amino acid sequence as the antithrombin in human plasma, said a GTC statement.
People with hereditary antithrombin deficiency are more susceptible to venous blood clots, including pulmonary embolism and deep vein thrombosis
(DVT). About one in two to three thousand of the general population has the disorder, half of whom are likely to experience a thrombosis by the time
they are 25 years old, and according to one study cited by the GTC press statement, up to 85 per cent may experience an embolism before they are
51.
The drug is already approved for use in the European Union where the regulating authority is the European Medicines Agency (EMEA). The EMEA
approved label carries information about the most common adverse events that may occur from use of ATryn. These include: dizziness, nausea,
headache, bleeding, bleeding at the site of the injection, and increased bleeding during treatment.
GTC also warned that “as with any intravenous protein product, allergic type hypersensitivity reactions are possible”.
Sources: Reuters, GTC Biotherapeutics.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
National Oncologic PET Registry And Supporting Organizations, Including SNM, Continue To Advocate Cancer Coverage
The Centers for Medicare and Medicaid Services (CMS) have released a draft of their proposed positron emission tomography (PET) national coverage determination (NCD). This proposed legislation would allow for reimbursement of PET by the federal government for patients with all types of cancer. The proposed decision expands coverage to include cancer staging and restaging, in addition to initial diagnosis. Two important items in the CMS draft include a proposal to replace coverage for “diagnosis, staging and restaging and treatment” with “initial treatment” and “subsequent treatment.” A public comment period on these and other items will continue through Feb. 5. A final decision is expected in April 2009.
In concert with other nonprofit medical associations, SNM has worked closely with CMS over the past three years to increase access to these medically essential molecular imaging procedures used for the diagnosis, staging and restaging of cancer. Molecular imaging provides a rich portrait of exactly what is going on in a patient’s body, offering a wealth of useful information to help shape a treatment plan.
“We are highly encouraged by the CMS proposal to broaden reimbursement for PET for Medicare beneficiaries who are being treated for cancer,” said SNM President Robert W. Atcher, Ph.D., M.B.A. “Because PET is a minimally invasive imaging procedure that gives physicians critical information for patient care, expanded use of the technique in cancer diagnosis and treatment will help tailor the patient’s treatment to their current stage of the disease.”
In 2006, a nationwide study – the National Oncologic PET Registry (NOPR) – was established to collect data in response to a proposal from CMS to expand coverage for PET to include cancers and indications not presently eligible for Medicare reimbursement. Overwhelmingly, the data collected showed that PET has significant advantages for diagnosing, staging and restaging many types of cancer. According to a study published last year in The Journal of Clinical Oncology, PET resulted in a change in management of treatment in more than one-third of cancer patients, regardless of the type of cancer.
“This is a critical step in gaining access to critical molecular imaging and nuclear medicine tests for people nationwide with all forms of cancer,” added Atcher.
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Article adapted by Medical News Today from original press release.
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NOPR is sponsored by the Academy of Molecular Imaging (AMI), and managed by the American College of Radiology (ACR) and ACR Imaging Network (ACRIN). The registry received input from – and is endorsed by – ACR, the American Society for Clinical Oncology (ASCO) and SNM. The NOPR Working Group was chaired by Bruce Hillner, M.D., of Virginia Commonwealth University and co-chaired by Barry Siegel, M.D., Washington University; R. Edward Coleman, M.D., Duke University; and Anthony Shields, M.D., Wayne State University.
About SNM
SNM is an international scientific and medical organization dedicated to raising public awareness about what molecular imaging is and how it can help provide patients with the best health care possible. SNM members specialize in molecular imaging, a vital element of today’s medical practice that adds an additional dimension to diagnosis, changing the way common and devastating diseases are understood and treated.
SNM’s more than 17,000 members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings and leading advocacy on key issues that affect molecular imaging and therapy research and practice. For more information, visit http://www.snm.org/.
Source: Amy Shaw
Society of Nuclear Medicine
Hospital First In US To Treat Kidney Tumor With New Device Using Electrical Pulses
On Thursday, January 8, Rhode Island Hospital treated an inoperable kidney tumor using a new technology known as NanoKnife. Damian Dupuy, MD, director of ablation services at Rhode Island Hospital and a national pioneer in ablation treatment, performed the procedure — the first time it has been used on a kidney tumor in the United States.
NanoKnife is an image-guided device that uses “irreversible electroporation (IRE) technology” — pulses of electricity that selectively destroy tumor cells while sparing nearby nerves, blood vessels and other delicate structures within the body. While considered a form of ablation, it uses electricity rather than heat like other ablation techniques such as cryo-ablation, radiofrequency and microwave ablation.
The Food and Drug Administration has approved the device for general soft tissue ablation. It was first used in Australia for tumors in the lungs and lymph nodes, and has been used in a handful of other types of cases in the United States.
Dupuy, who is serving as an advisor on the IRE technology, used the new NanoKnife on a 70-year-old female with a kidney tumor. The patient is reported to be doing well. Dupuy says, “I’m excited about the continued advances in ablation technology that broaden the applications for patients with cancer. These new technologies are revolutionizing the way we are able to treat cancer, allowing us to minimize collateral damage to surrounding tissue while maximizing tumor kill.”
The NanoKnife is performed under sedation, however, little to no post-operative pain has been associated with the treatment to date. Because it is minimally invasive, Dupuy also notes that the new technology offers additional treatment options to patients who have no other alternatives or who have not responded to other forms of cancer treatment.
Prior forms of ablation treatment have been very successful in treating tumors in the past, and continue to provide new avenues of treatment for patients. Cryoablation, radiofrequency (RFA) and microwave ablation (MWA) all use intense heat or cold that destroys cells. The destroyed material may actually stay in the body for some time. The electrical fields used in the new IRE cause defects in cell membranes. Those cells within the targeted tissue then die within six hours of treatment, while the critical structures surrounding the targeted site are preserved and can then assist the body in removing the dead cells.
Damian Dupuy, MD, is a pioneer in image-guided ablation for the treatment of solid tumors, including RFA, MWA, cryoablation and now IRE. First approved by the FDA in 1997, RFA is a minimally invasive technique that uses heat to destroy tissue. A number of hospitals around the country have adopted the technique, most often to destroy liver tumors.
Dupuy, who is also a professor of diagnostic imaging at the Warren Alpert Medical School of Brown University, has broadened the applications of image-guided ablative therapies to successfully combat lung, kidney, adrenal, thyroid and bone cancer. Since 1997 more than 2,000 patients have undergone image-guided ablation at Rhode Island Hospital, the largest use of this technique in treating malignancy in North America. Other newer techniques such as combination therapies of ablation and external beam radiation or internal radiation seeds have been pioneered by Dupuy at Rhode Island Hospital. He is now leading National Cancer Institute-funded trials in the use of ablation for the treatment of tumors, and has published over 150 publications and given over 90 invited presentations nationally and internationally in the field of imaging and minimally invasive cancer therapies.
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Article adapted by Medical News Today from original press release.
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Founded in 1863, Rhode Island Hospital (http://www.rhodeislandhospital.org) in Providence, RI, is a private, not-for-profit hospital and is the largest teaching hospital of The Warren Alpert Medical School of Brown University. A major trauma center for southeastern New England, the hospital is dedicated to being on the cutting edge of medicine and research. Many of its physicians are recognized as leaders in their respective fields of cancer, cardiology, diabetes, emergency medicine and trauma, neuroscience, orthopedics, pediatrics, radiation oncology and surgery. Rhode Island Hospital ranks among the country’s leading independent hospitals that receive funding from the National Institutes of Health (NIH), with NIH research awards of nearly $27 million annually and nearly $46 million in total. It is home to Hasbro Children’s Hospital, the state’s only facility dedicated to pediatric care. Rhode Island Hospital is a founding member of the Lifespan health system.
Source: Nancy Cawley
Lifespan
Researchers First To “See” Reactive Oxygen Species In Vital Enzyme
Using two simultaneous light-based probing techniques at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory, a team of researchers has illuminated important details about a class of enzymes involved in everything from photosynthesis to the regulation of biological clocks.
The interdisciplinary team has a broad interest in flavoproteins, which were first discovered in the 1930s and derive from riboflavin, or vitamin B2. These proteins are now known to catalyze a wide range of biochemical reactions, including those that use molecular oxygen (O2) to help convert food into energy in animals, plants, fungi, and in some types of bacteria – a process known as oxygen activation.
Although scientists have determined more than 1,200 crystal structures of flavoproteins, they’ve been blind to exactly what oxygen activation looks like within these enzymes. Specifically, researchers have been unable to determine the structure of the flavoprotein’s reactive oxygen intermediate, a molecular complex that often forms halfway through important biochemical reactions. These intermediates possess high chemical potential energy, which is necessary to complete many critical but difficult-to-catalyze reactions in biology. Such intermediates typically have a lifetime of only a few milliseconds and are therefore very hard to observe using traditional synchrotron methods.
“Flavoproteins represent one of only a handful of ways that nature activates molecular oxygen, a process that’s important for all life on the planet,” said Brookhaven biophysicist Allen Orville. “We’ve determined structures of some oxygen intermediates involved in several important enzymes that assist in this process. But no one has ever seen an oxygen intermediate attached to the flavin. Until now.”
As reported in the January 9, 2009, online edition of Biochemistry, Orville and colleagues from Georgia State University, Georgia Institute of Technology, and the University of Miami have used a new facility at Brookhaven’s National Synchrotron Light Source (NSLS) to identify two possible oxygen intermediates in the flavoprotein, choline oxidase.
The researchers accomplished their work by combining two popular synchrotron techniques – x-ray diffraction and optical absorption spectroscopy – into one setup. By shining beams of powerful x-rays and visible light on the same region of the crystallized flavoprotein, two different but complementary sets of information are received. This allows the scientists to correlate the electronic structure of the enzyme – which gives details about chemical activities – with its three-dimensional atomic structure.
“The ability to collect multiple types of data from the same sample at the same time is a unique opportunity,” Orville said. “It takes less time and it means you never have to move the sample and risk altering it in any way. It also removes many potential ambiguities that either technique alone cannot resolve.”
To stabilize the flavoprotein intermediate, the researchers kept it at an extremely low temperature – about -280 degrees Fahrenheit. When exposed to the x-rays, the cold flavoprotein rapidly accepts electrons liberated in the sample by the x-ray beam. This starts the enzyme reaction, which progresses a bit further and then becomes trapped in its reactive intermediate state. Using the combined data, the group identified two possible intermediate structures. Further experiments will help determine which is the true intermediate.
Orville is installing additional complementary techniques at the NSLS. Planning also is underway for several beamlines with multiple complementary techniques at the National Synchrotron Light Source II, a new, proposed Brookhaven facility that will produce x-rays up to 10,000 times brighter than those at the NSLS. The hope is to provide a means for researchers to simultaneously obtain three or four different types of data from one sample.
This work was supported by DOE’s Office of Biological and Environmental Research, the National Institutes of Health, the National Science Foundation, the American Chemical Society, the American Heart Association, Georgia State University, and the U.S. Department of Education. The operation of the NSLS is supported by the Office of Basic Energy Sciences within the DOE’s Office of Science.
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Article adapted by Medical News Today from original press release.
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Source: Kendra Snyder
DOE/Brookhaven National Laboratory
First Examples Of RNA That Replicates Itself Indefinitely Developed By Scripps Scientists
Findings could inform biochemical questions about how life began#
Now, a pair of Scripps Research Institute scientists has taken a significant step toward answering that question. The scientists have synthesized for the first time RNA enzymes that can replicate themselves without the help of any proteins or other cellular components, and the process proceeds indefinitely.
The work was published on in Science Express, the advanced, online edition of the journal Science.
In the modern world, DNA carries the genetic sequence for advanced organisms, while RNA is dependent on DNA for performing its roles such as building proteins. But one prominent theory about the origins of life, called the RNA World model, postulates that because RNA can function as both a gene and an enzyme, RNA might have come before DNA and protein and acted as the ancestral molecule of life. However, the process of copying a genetic molecule, which is considered a basic qualification for life, appears to be exceedingly complex, involving many proteins and other cellular components.
For years, researchers have wondered whether there might be some simpler way to copy RNA, brought about by the RNA itself. Some tentative steps along this road had previously been taken by the Joyce lab and others, but no one could demonstrate that RNA replication could be self-propagating, that is, result in new copies of RNA that also could copy themselves.
In Vitro Evolution
A few years after Tracey Lincoln arrived at Scripps Research from Jamaica to pursue her Ph.D., she began exploring the RNA-only replication concept along with her advisor, Professor Gerald Joyce, M.D., Ph.D., who is also Dean of the Faculty at Scripps Research. Their work began with a method of forced adaptation known as in vitro evolution. The goal was to take one of the RNA enzymes already developed in the lab that could perform the basic chemistry of replication, and improve it to the point that it could drive efficient, perpetual self-replication.
Lincoln synthesized in the laboratory a large population of variants of the RNA enzyme that would be challenged to do the job, and carried out a test-tube evolution procedure to obtain those variants that were most adept at joining together pieces of RNA.
Ultimately, this process enabled the team to isolate an evolved version of the original enzyme that is a very efficient replicator, something that many research groups, including Joyce’s, had struggled for years to obtain. The improved enzyme fulfilled the primary goal of being able to undergo perpetual replication. “It kind of blew me away,” says Lincoln.
Immortalizing Molecular Information
The replicating system actually involves two enzymes, each composed of two subunits and each functioning as a catalyst that assembles the other. The replication process is cyclic, in that the first enzyme binds the two subunits that comprise the second enzyme and joins them to make a new copy of the second enzyme; while the second enzyme similarly binds and joins the two subunits that comprise the first enzyme. In this way the two enzymes assemble each other – what is termed cross-replication. To make the process proceed indefinitely requires only a small starting amount of the two enzymes and a steady supply of the subunits.
“This is the only case outside biology where molecular information has been immortalized,” says Joyce.
Not content to stop there, the researchers generated a variety of enzyme pairs with similar capabilities. They mixed 12 different cross-replicating pairs, together with all of their constituent subunits, and allowed them to compete in a molecular test of survival of the fittest. Most of the time the replicating enzymes would breed true, but on occasion an enzyme would make a mistake by binding one of the subunits from one of the other replicating enzymes. When such “mutations” occurred, the resulting recombinant enzymes also were capable of sustained replication, with the most fit replicators growing in number to dominate the mixture. “To me that’s actually the biggest result,” says Joyce.
The research shows that the system can sustain molecular information, a form of heritability, and give rise to variations of itself in a way akin to Darwinian evolution. So, says Lincoln, “What we have is non-living, but we’ve been able to show that it has some life-like properties, and that was extremely interesting.”
Knocking on the Door of Life
The group is pursuing potential applications of their discovery in the field of molecular diagnostics, but that work is tied to a research paper currently in review, so the researchers can’t yet discuss it.
But the main value of the work, according to Joyce, is at the basic research level. “What we’ve found could be relevant to how life begins, at that key moment when Darwinian evolution starts.” He is quick to point out that, while the self-replicating RNA enzyme systems share certain characteristics of life, they are not themselves a form of life.
The historical origin of life can never be recreated precisely, so without a reliable time machine, one must instead address the related question of whether life could ever be created in a laboratory. This could, of course, shed light on what the beginning of life might have looked like, at least in outline. “We’re not trying to play back the tape,” says Lincoln of their work, “but it might tell us how you go about starting the process of understanding the emergence of life in the lab.”
Joyce says that only when a system is developed in the lab that has the capability of evolving novel functions on its own can it be properly called life. “We’re knocking on that door,” he says, “But of course we haven’t achieved that.”
The subunits in the enzymes the team constructed each contain many nucleotides, so they are relatively complex and not something that would have been found floating in the primordial ooze. But, while the building blocks likely would have been simpler, the work does finally show that a simpler form of RNA-based life is at least possible, which should drive further research to explore the RNA World theory of life’s origins.
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Article adapted by Medical News Today from original press release.
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The paper is titled “Self-sustained Replication of an RNA Enzyme,” and the work was supported by NASA and the National Institutes of Health, and the Skaggs Institute for Chemical Biology.
About The Scripps Research Institute
The Scripps Research Institute is one of the world’s largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Scripps Florida is currently in the process of moving from temporary facilities to its permanent campus in Jupiter, Florida. Dedication ceremonies for the new campus will be held in February 2009.
Source: Keith McKeown
Scripps Research Institute
How Our Brain Works As A GPS Device
We’ve all experienced the feeling of not knowing where we are. Being disoriented is not pleasant, and it can even be scary, but luckily for most of us, this sensation is temporary. The brain employs a number of tricks to reorient us, keeping our confusion to a minimum and quickly pointing us in the right direction. Research has suggested that animals and young children mainly rely on geometric cues (e.g. lengths, distances, angles) to help them get reoriented. Human adults, however, can also make use of feature cues (e.g. color, texture, landmarks) in their surrounding area. But which method do we use more often? Psychologists Kristin R. Ratliff from the University of Chicago and Nora S. Newcombe from Temple University conducted a set of experiments investigating if human adults have a preference for using geometric or feature cues to become reoriented.
The first experiment took place in either a large or small white, rectangular room with a landmark (a big piece of colorful fabric) hanging on one wall. The study volunteers saw the researcher place a set of keys in a box in one of the corners. The volunteers were blindfolded and spun around, to become disoriented. After removing the blindfold, they had to point to the corner where the keys were. After a break, the volunteers were told the experiment would be repeated, although they wouldn’t watch the researcher hide the keys. Unbeknownst to them, during the break the researchers moved the landmark to an adjacent wall – this change forced the volunteers to use either geometric cues or feature cues, but not both, to reorient themselves and locate the keys. For the second experiment, the researchers used a similar method, except they switched room sizes (the volunteers moved from a larger room to a smaller room and vice versa) during the break.
The results, reported in Psychological Science, a journal of the Association for Psychological Science, reveal that the brain does not have a distinct preference for certain cues during reorientation. In the first experiment, volunteers reoriented themselves by using geometric cues in the smaller room but used feature cues in the larger room. However, the volunteers who went from the larger room to the smaller room in the second experiment also relied on feature cues, searching for the landmark to become reoriented.
During the second experiment, the researchers surmise, the volunteers had a positive experience using feature cues in the large room, so they kept on relying on the landmark in the smaller room to become reoriented. These findings indicate that the brain takes into account a number of factors, including the environment and our past experiences, while determining the best way to reorient us to our surroundings.
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Article adapted by Medical News Today from original press release.
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Psychological Science is ranked among the top 10 general psychology journals for impact by the Institute for Scientific Information.
Article “Reorienting When Cues Conflict”
Source: Barbara Isanski
Association for Psychological Science
A New Weapon To Fight Cholesterol Problems: Synthetic HDL
Buttery Christmas cookies, eggnog, juicy beef roast, rich gravy and creamy New York-style cheesecake. Happy holiday food unfortunately can send blood cholesterol levels sky high.
Northwestern University scientists now offer a promising new weapon — synthetic high-density lipoprotein (HDL), the “good” cholesterol — that could help fight chronically high cholesterol levels and the deadly heart disease that often results.
The researchers successfully designed synthetic HDL and show that their nanoparticle version is capable of irreversibly binding cholesterol. The synthetic HDL, based on gold nanoparticles, is similar in size to HDL and mimics HDL’s general surface composition.
The study is published online by the Journal of the American Chemical Society (JACS).
“We have designed and built a cholesterol sponge. The synthetic HDL features the basics of what a great cholesterol drug should be,” said Chad A. Mirkin, George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences, professor of medicine and professor of materials science and engineering. Mirkin and Shad Thaxton, M.D., assistant professor of urology in Northwestern’s Feinberg School of Medicine, led the study.
“Drugs that lower the bad cholesterol, LDL, are available, and you can lower LDL through your diet, but it is difficult to raise the good cholesterol, HDL,” said Mirkin. “I’ve taken niacin to try and raise my HDL, but the side effects are bad so I stopped. We are hopeful that our synthetic HDL will one day help fill this gap in useful therapeutics.”
In creating synthetic HDL the researchers started with a gold nanoparticle as the core. They then layered on a lipid that attaches to the gold surface, then another lipid and last a protein, called APOA1, the main protein component of naturally occurring HDL. The final high-density lipoprotein nanoparticles are each about 18 nanometers in diameter, a size similar to natural HDL.
“Cholesterol is essential to our cells, but chronic excess can lead to dangerous plaque formation in our arteries,” said Thaxton. “HDL transports cholesterol to the liver, which protects against atherosclerosis. Our hope is that, with further development, our synthetic form of HDL could be used to increase HDL levels and promote better health.”
“HDL is a natural nanoparticle, and we’ve successfully mimicked it,” said Mirkin, director of Northwestern’s International Institute for Nanotechnology. “Gold is an ideal scaffolding material — it’s size and shape can be tailored, and it can be easily functionalized. Using gold nanoparticles, which are non-toxic, for synthetic HDL bodes well for the development of a new therapeutic.”
The development of synthetic HDL is a result of a successful collaboration between scientists in Northwestern’s department of chemistry and the Feinberg School. Bringing these two groups together, says Mirkin, should lead to major advances in translational research. Their next step is to further study the synthetic HDL in biologically relevant conditions and measure and evaluate the cholesterol-binding properties.
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Article adapted by Medical News Today from original press release.
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In addition to Mirkin and Thaxton, other authors of the JACS paper, titled “Templated Spherical High Density Lipoprotein Nanoparticles,” are Weston L. Daniel, David A. Giljohann and Audrey D. Thomas, all from Northwestern.
Source: Marla Paul
Northwestern University
A Cell’s Inactive State Is Critical For Effectiveness Of Cancer Treatment
A new study sheds light on a little understood biological process called quiescence, which enables blood-forming stem cells to exist in a dormant or inactive state in which they are not growing or dividing. According to the study’s findings, researchers identified the genetic pathway used to maintain a cell’s quiescence, a state that allows bone marrow cells to escape the lethal effects of standard cancer treatments.
Researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) found elevated levels of the tumor suppressor protein p53 in hematopoietic stem cells (HSCs) – immature cells in the bone marrow that have the capacity to differentiate into all types of mature blood cells. They showed that when chemotherapy or radiation is delivered to a cell that lacks both p53 and a gene called MEF, the cell not only becomes less quiescent, but also becomes more susceptible to being killed. These findings are published in the January 9, 2009, issue of Cell Stem Cell.
“This is the first time that anyone has established that p53 has a role in defining a cell’s state of quiescence. Furthermore, it is surprising that some cells that lose p53 can actually be killed more readily than those that have p53 intact,” said the study’s senior author, Stephen Nimer, MD, Chief of the Hematology Service and Member of the Molecular Pharmacology and Chemistry Program at MSKCC. “Our findings have important implications for developing therapeutic strategies that could eliminate quiescent cancer stem cells.”
The study builds on previous research in which Dr. Nimer and colleagues first identified the MEF gene and showed its ability to control the state of quiescence of HSCs as well as its critical role in determining the sensitivity of normal bone marrow cells to chemotherapy and radiation. They have now identified p53 as the pathway that MEF utilizes to maintain this enhanced quiescence.
It is known that when a cell experiences DNA damage as a result of cancer treatment, p53 plays a critical role in guarding the genomic integrity of the cell by either triggering it to die or by causing cells to stop growing so they can repair their DNA successfully. However, p53 has additional functions during the process of blood cell formation in the body – a process called hematopoiesis.
In the current study, investigators set out to determine whether the increased amount of p53 and enhanced expression of p53 target genes might contribute to the quiescence of cells and their ability to resist chemotherapy. They examined the function of p53 during hematopoiesis and found an important interdependency between p53 and its target gene, MEF, on HSC quiescence.
“Our findings suggest that by targeting those specific genes that control quiescence in cancer cells, we may enhance the anticancer effects of chemotherapy and radiotherapy, thereby promoting their effectiveness,” said Dr. Nimer.
In addition, researchers identified two new targets of the p53 protein – Necdin and Gfi-1 – tumor growth suppressor genes that also regulate quiescence. Researchers lowered the expression of Necdin and Gfi-1 in hematopoietic stem cells lacking MEF and found a significant reduction in the quiescence of those cells. The results suggest that these p53 target genes are functionally responsible for the enhanced quiescence of HSCs in which MEF has been eliminated.
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Article adapted by Medical News Today from original press release.
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The study was supported by the Wally Yonamine Fund for Leukemia Research, and grants from the National Institutes of Health and the Marshall A. Lichtman Specialized Center of Research (SCOR) program of the Leukemia & Lymphoma Society.
The following investigators contributed to this research: Yan Liu, PhD, Shannon E. Elf, MS, Yasuhiko Miyata, MD, PhD, Goro Sashida, MD, PhD, Silvana Di Giandomenico, BS, Jennifer M. Lee, BS, Anthony Deblasio, MS, and Silvia Menendez, MS, of the Molecular Phamacology and Chemistry Program; Jack Antipin, PhD, and Boris Reva, PhD, of the Computational Biology Program; and Andrew Koff, PhD, of the Molecular Biology Program.
Memorial Sloan-Kettering Cancer Center is the world’s oldest and largest institution devoted to prevention, patient care, research, and education in cancer. Our scientists and clinicians generate innovative approaches to better understand, diagnose, and treat cancer. Our specialists are leaders in biomedical research and in translating the latest research to advance the standard of cancer care worldwide. For more information, go to http://www.mskcc.org/.
Source: Esther Napolitano
Memorial Sloan-Kettering Cancer Center
Switching Off Enzyme Prevents Obesity In Mice
A US study showed that switching off an enzyme that plays an important role in the breakdown of fat in mice helped them
to remain lean even when they ate a high-fat diet. They also showed switching off the enzyme in mice that had no appetite-suppressing hormone (this
normally signals when the body is full) had the same effect, the mice stayed lean.
The study was the work of lead investigator Dr Hei Sook Sul, University of California (UC) Berkeley professor of nutritional sciences and toxicology,
and colleagues, and is published in the 11 January issue of Nature Medicine.
Sul said:
“We have discovered a new enzyme within fat cells that is a key regulator of fat metabolism and body weight, making it a promising target in the
search for a treatment for human obesity.”
The enzyme, which is abundant only in fat tissue, is called adipose-specific phospholipase A2 (AdPLA), it is encoded by the gene Pla2g16, also called
HREV107. AdPLA triggers a sequence of events that increases prostaglandin E2 (PGE2), a signalling molecule that stops fat breaking down. Mice
that don’t have AdPLA have less PGE2 and a higher rate of fat breakdown.
Co-author Dr Robin Duncan, a post-doctoral fellow at UC Berkeley, explained:
“When levels of PGE2 are decreased because of the lack of AdPLA, fat breakdown proceeds unchecked, resulting in leanness even in animals that eat
all day long.”
For the study, Sul and her colleagues knocked out the gene that codes for AdPLA in one group of mice and compared them to a control group of
normal mice. When they reached 3 weeks old, the mice were weaned and given high-fat, tasty food, from which they could eat as much as they
wanted.
The researchers noted that knocking out AdPLA did not affect appetite because both groups ate similar amounts: they both gorged on the same high
fat food. But, as the mice got older, a gap appeared in their weight. When they reach their 64th week, toward the end of a lab mouse’s lifespan, the
mice that had no AdPLA averaged 39.1 grams in weight, while the control mice averaged 73.7 grams.
Sul and her colleagues also found that the mice without AdPLA still kept the same number of fat cells, but they just didn’t accumulate excess
fat.
In the next stage of the experiment, the researchers examined whether knocking out AdPLA could prevent genetic obesity in mice. Mice that don’t have
a hormone called leptin, which signals when the body is full, tend to eat two to three times more food than normal mice and become obese very
quickly. A normal mouse typically eats 2 to 3 grams of food a day.
The researchers compared two groups of mice: one (the controls) lacked leptin, and the other also lacked leptin and AdPLA. They found that the mice
without leptin ate an average of 5 grams of food a day, while the mice that lacked both leptin and AdPLA ate 7.5 grams. As they reached 17 weeks of
age, the mice that lacked leptin weighed an average of 75 grams, but the mice that lacked leptin and AdPLA weighed just less than 35 grams.
On studying AdPLA further, Sul and colleagues found it goes up after eating, which prevents fat breaking down, and it goes down during
fasting, which allows fat to break down. They also found that obese mice had higher levels of AdPLA.
Co-author Maryam Ahmadian, a graduate student at UC Berkeley said:
“This means that local signals in fat tissue allow fat cells to directly regulate fuel provision for the body, which changes our fundamental
understanding of how the body regulates fat breakdown.”
“”We found that mice deficient in AdPLA expend more energy than normal mice, and they also burn more fat directly within fat cells,” added
Ahmadian.
They also found that reducing AdPLA in the mice led to greater insulin resistance and their liver fat quadrupled, but when tested, their livers were
mostly normal.
A main function of fat tissue is to release fatty acids from stored fats so that other tissues can use them as an energy source. Before this discovery,
scientists believed that the endocrine system played the major role in controlling fat breakdown and body weight, where hormones would travel to fat
tissue from various organs and glands via the bloodstream and do their work there.
But this study shows that much of the work is done by agents already in the fat tissue, through the autocrine (signals acting in the same cell) and
paracrine (signals acting on neighbouring cells) actions of PGE2.
But Sul and her colleagues were also cautious to point out that findings about fat metabolism and appetite control in mice don’t always translate to
humans. Humans can have mutations of the gene that codes for AdPLA, but until we study them, we won’t know if they have the same effect as in the
mice.
However, they suggested that AdPLA may be a useful target for new obesity treatments, explaining that if you can get the excess fat to burn off before it
even leaves the fat cell, it can’t then travel to other organs like the heart and do damage there. As Duncan explained:
“We believe that the effects in the liver are due to the extremely high rate of fat breakdown and drastic leanness in these mice, so we are looking to see
if reducing rather than completely eliminating AdPLA can provide effective protection against obesity without secondary effects.”
The study was supported by grants from the US National Institutes of Health, the Natural Sciences and Engineering Research Council of Canada, and
the Canadian Institutes of Health Research.
“AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency.”
Kathy Jaworski, Maryam Ahmadian, Robin E Duncan, Eszter Sarkadi-Nagy, Krista A Varady, Marc K Hellerstein, Hui-Young Lee, Varman T Samuel,
Gerald I Shulman, Kee-Hong Kim, Sarah de Val, Chulho Kang, Hei Sook Sul.
Nature Medicine 11 Jan 2009.
DOI: 10.1038/nm.1904
Click here for
Abstract.
Sources: University of California Berkeley, journal abstract.
Written by: Catharine Paddock, PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
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