New compound could reverse loss of muscle mass in cancer, other diseases

Dec. 19, 2013 — A new antibody could dramatically boost strength and muscle mass in patients with cancer, chronic obstructive pulmonary disease (COPD), sporadic inclusion body myositis, and in elderly patients with sarcopenia according to research published ahead of print in the journal Molecular and Cellular Biology.

"Age-related loss of muscle mass is a major contributing factor to falls, broken bones, and the loss of mobility," says co-corresponding author David Glass of Novartis, Cambridge, MA, one of the compound's developers, along with first author Estelle Trifilieff, also of Novartis. "This study illustrates that we may have a powerful tool to prevent muscle wasting and promote growth."

The new compound (BYM338) acts to prevent muscle wasting by blocking a receptor that engages a cellular signaling system that exists to put the brakes on muscle development when appropriate. But sometimes those brakes are activated inappropriately, or are stuck on.

"Our goal was to release the brakes," says Glass.

A variety of signals can activate the receptor. Prior to development of BYM338, compounds developed to block these molecules were blunt instruments, either trapping all incoming signals (which stimulated muscle growth but also caused harmful side effects) or blocking just a single receptor activator (providing only tepid growth stimulation.) BYM338 was designed to be in the Goldilocks zone (just right.)

In the study the compound boosted muscle mass 25 to 50 percent and increased strength in animal models. Those gains were significantly superior to those of compounds that blocked a single receptor activator. Clinical trials are currently underway.

The conditions BYM338 is designed to treat are losses of skeletal muscle and fat, which are not reversed by simply eating more, and are known as cachexias when associated with certain chronic illnesses. Cancer cachexia develops in a majority of patients with advanced malignancy, and can interfere with the ability to undergo chemotherapy, says Glass. COPD afflicts an estimated 65 million people worldwide, and is predicted to become the third leading cause of death by 2020. As many as a quarter of COPD patients suffer from cachexia, which can worsen already dire respiratory difficulties.

Sarcopenia -- age-related loss of muscle and physical function -- afflicts 5-13% of 60-70 year olds, rising to 11-50% in individuals over 80 years old. These individuals become especially vulnerable to falling. Among older adults, falls are the leading cause of both fatal and non-fatal injuries, according to the Centers for Disease Control and Prevention.

Preliminary data on the antibody was promising enough to have it designated a breakthrough therapy by the US Food and Drug Administration for sporadic inclusion body myositis, a rare muscle wasting disease with no approved therapies.

"We need to be able to help people maintain productive and meaningful lives, and muscle function is a major part of the equation," says Glass. "It could be the difference between independent living and having to move into a nursing home."

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Key drug receptor: Atom-level simulation of a G protein-coupled receptor could lead to improved drug design

Dec. 20, 2013 — The successful atom-level simulation of a G protein-coupled receptor could lead to improved drug design, blazing the path for specialized scientific projects on cloud computer systems.

Roughly 40 percent of all medications act on cells' G protein-coupled receptors (GPCRs). One of these receptors, beta 2 adrenergic receptor site (B₂AR), naturally transforms between two base configurations; knowing the precise location of each of approximately 4,000 atoms is crucial for ensuring a snug fit between it and the drug.

Now, researchers at Stanford and Google have conducted an unprecedented, atom-scale simulation of the receptor site's transformation, a feat that could have significant impact on drug design.

This is the first scientific project to be completed using Google Exacycle's cloud computing platform, which allows scientists to crunch big data on Google's servers during periods of low network demand.

The study was published online in Nature Chemistry on Dec. 15.

As a type of GPCR, the B₂AR is a molecule that sits within the membrane of most cells. Various molecules in the body interact with the receptor's exterior, like two hands shaking, to trigger an action inside the cell.

"GPCRs are the gateway between the outside of the cell and the inside," said co-author Vijay Pande, a professor of chemistry and, by courtesy, of structural biology and computer science at Stanford. "They're so important for biology, and they're a natural, existing signaling pathway for drugs to tap into."

Roughly half of all known drugs -- including pharmaceuticals as well as natural molecules such as caffeine -- target some GPCR, and many new medications are being designed with these receptor sites in mind. The 2012 Nobel Prize in Chemistry was co-awarded to Brian Kobilka, a professor at the Stanford University School of Medicine, for his role in discovering and understanding GPCRs.

Traditionally, maps that detail each atom of GPCR, and other receptors, are created through a technique called X-ray crystallography. The technique is industry standard, but it can only visualize a molecule in its resting state; receptors naturally change configurations, and their intermediate forms might also have medical potential.

When developing a drug, scientists will often run a computer program, known as a docking program, that predicts how well the atomic structure of a proposed drug will fit into the known receptor.

In the case of GPCRs, for example, the X-ray crystallography techniques have detailed teceptors' "on" and "off" configurations; many medications have been specifically designed to fit into these sites. Scientists expect, however, that other fruitful configurations exist. Many drugs engage with GPCR sites, even though computational models suggest that they don't fit either of the two defined reaction site configurations.

Computer simulations of a GPCR's shape as it morphs from "on" to "off" could create a thicker catalog of reaction site profiles, Pande said, and provide scientists a better jumping-off point for computational drug design and more discoveries.

A cloud-based attack

To simulate the GPCR alternatives at the same atom-level accuracy of X-ray crystallography, however, would take too long using traditional computing methods.

"The computational burden of a model that is faithful to atomic details is very high," Pande said. "A very fast computer processor can compute a billionth of a second of this reaction in one computer day. So if you want to simulate a full reaction on a millisecond time scale, it's going to take millions of days."

Instead, Pande and his colleagues tapped the power of Google's Exacycle cloud computing system, which harnesses a distributed network of computers to process data in parallel.

The B₂AR simulation consists of almost 60,000 atoms. Each Exacycle system simulated tens of thousands of random trajectories that these atoms could take as the protein shifted its shape, generating about 250,000 molecular structures per simulated system.

The researchers then wrote algorithms to identify the most consistently generated configurations and to sift through that group for the states that are the most likely to actually exist given real-world constraints.

In total, the researchers simulated 2.5 milliseconds -- a virtual eternity in chemical reaction time, the authors said -- of the receptor shifting from "on" to "off," capturing every viable configuration of atoms in between. These intermediate structures can then be experimentally confirmed, Pande said, but even before that happens, they can guide more efficient drug design. In particular, the authors have shown that different classes of drugs are preferred by different intermediate GPCR states.

"There is some tension right now between doing this type of work with specialized hardware or with general commodity hardware, as we have done," Pande said. "Cloud resources are much more accessible to the general scientific community, and I think that we've shown here that, with the right method and algorithms, you can do the same quality of work."

The next "ridiculous" challenge

The work grew out of a key project from Simbios, the NIH Center for Biomedical Computation at Stanford, a decade-old collaboration between a broad group of bioengineering, chemistry, biology and computer science faculty from Stanford and the Stanford School of Medicine.

"This work really represents a capstone to the molecular types of calculations that a diverse group of people can tackle, and it's a challenge that I thought was really pushing the limits," Pande said. "Ten years ago I would have said this is ridiculous; even five years ago it felt a little bit out of reach.

"But we brought together people who are really at the top of their game, and being around people like that really pushes you to be the best that you can."

Asked to project the next insane step in this research, something that might take another 10 years to unfold, Pande said he'd really like to develop similar atomistic simulations of processes at the scale of an entire cell.

A key challenge of battling a disease like cancer, he said, is that the tumor cells are using normal proteins to conduct abnormal processes. Deciphering how the cells and proteins behave (or, rather, misbehave) at the molecular scale, he said, could help scientists design drugs that target specific molecular pathways to battle cancer.

"We will need to push the boundaries of both computers and algorithms," Pande said, " but the conceptual steps are there."

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Early stages breast cancer could soon be diagnosed from blood samples

Nov. 14, 2013 — What could someday be the first blood test for the early detection of breast cancer was shown in preliminary studies to successfully identify the presence of breast cancer cells from serum biomarkers, say the Houston Methodist Research Institute scientists who are developing the technology.

With a New York University Cancer Institute colleague, the researchers report in an upcoming Clinical Chemistry (now online) that the mixture of free-floating blood proteins created by the enzyme carboxypeptidase N accurately predicted the presence of early-stage breast cancer tissue in mice and in a small population of human patients.

"In this paper we link the catalytic activity of carboxypeptidase N to tumor progression in clinical samples from breast cancer patients and a breast cancer animal model," said biomedical engineer Tony Hu, Ph.D., who led the project. "Our results indicate that circulating peptides generated by CPN can serve as clear signatures of early disease onset and progression."

The technology is not yet available to the public, and may not be for years. More extensive clinical tests are needed, and those tests are expected to begin in early 2014.

There are currently no inexpensive laboratory tests for the early detection of breast cancer, providing the impetus for researchers around the world to invent them.

"What we are trying to create is a non-invasive test that profiles what's going on at a tissue site without having to do a biopsy or costly imaging," Hu said. "We think this could be better for patients and -- if we are successful -- a lot cheaper than the technology that exists. While there's more to the cost of administering a test than materials alone, right now those materials only cost about $10 per test."

CPN is an enzyme that modifies proteins after the proteins are first created. Past studies have only shown the enzyme is more active in lung cancer patients. The present report in Clinical Chemistry is the first to show CPN isn't merely more active in breast cancer patients, but there's more of it.

The technology being developed by Hu's group combines nanotechnology and advanced mass spectrometry to separate and detect extremely low levels of small proteins (peptides) created by CPN. These peptides are believed to originate in or near cancerous cells, eventually making their way into the bloodstream.

In animal models and human biopsies, Hu's group first determined the presence of breast cancer tissue, characterized each sample's stage of development, and looked at how much CPN was being expressed. Blood samples were also taken from each individual.

Blood serum proteins were separated on a nanoporous silica chip dotted with four nanometer holes, which captured and isolated smaller proteins for spectrographic analysis. Using MALDI-TOF mass spectrometry, the researchers analyzed what remained for the light signatures of six peptides known to be created by CPN.

The researchers compared the stages of breast cancer tissue development in previously diagnosed patients to the presence of CPN-created peptides in their blood. They found all six peptides were at detectably higher levels, as early as breast cancer's first pathologic stage. (That stage is defined as having cancerous cells and a tumor of 2 cm or smaller, or no tumor at all.) The researchers also found that CPN peptides were at detectably higher levels in the blood of mice, compared to controls, just two weeks after the introduction of breast cancer tissue.

Interestingly, CPN activity dropped significantly over time in mice over the eight week study period, suggesting the blood test as currently configured may not work as well in detecting later stages of breast cancer. Hu said he plans to investigate the phenomenon.

"Even at the eighth week, CPN activity was still significantly higher than baseline," Hu said. "However, we suspect the activity of different enzymes goes up and down as the disease progresses. We will be looking at how we might add known and future biomarkers to the blood test to increase its robustness and accuracy."

Current means for the early detection of breast cancer are expensive and are not generally recommend for prevention by the American Cancer Society. Rather, the society recommends healthy women age 40 and older have a mammogram every year and work with their doctors to assess their individual risks of developing the disease. Prior to age 40, the society recommends women have a clinical breast exam whenever they visit their doctors, or else every three years.

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What could possibly go wrong? A lot: Injuries from the Tough Mudder

Nov. 15, 2013 — The Tough Mudder, an extreme sports event that bills itself as "probably the toughest event on the planet," resulted in injuries ranging from multiple electrical burns to seizure-induced Todd's paralysis. A case series of serious injuries sustained by participants in one such race was reported online today in Annals of Emergency Medicine.

"No training on earth can adequately prepare participants for elements such as jumping from a nine-foot height or running through a field of electrical wires while wet and hot," said lead study author Marna Rayl Greenberg, DO MPH, of Lehigh Valley Hospital and Health Network in Allentown, Pa. "The volume and severity of injuries in the Tough Mudder race we studied was unusually high, possibly leading to some permanent disabilities. The 1.5 million people who are predicted to enter obstacle races like this in the next year should be well aware of the risks they are taking."

The Tough Mudder is a 10 to 12 mile endurance obstacle course known as "MOB (mud, obstacles, beer) runs." Dr. Greenberg and her team reported in depth on five patients injured at a 2-day event, who were treated (along with 33 other participants not included in the case series) at a local emergency department.

One patient, who had received 13 electrical shocks during the last obstacle in the Tough Mudder, had multiple burn marks from electrical injuries and inflammation of the heart muscle. After being treated in the emergency department, he was admitted to the hospital.

The second patient had sustained multiple electrical shocks to the head while running through water, which resulted in fainting and altered mental status. After being treated in the emergency department, he was admitted to the hospital.

The third patient, after completing 20 out of 22 obstacles, developed seizure-like activity and altered mental status. He was unable to move his entire right side. After treatment in the emergency department, he was admitted to the intensive care unit with Todd's paralysis and discharged from the hospital to a rehabilitation center 4 days later. Six months after the injury, he still had lower right leg disability.

Patient number four sustained face and head injuries after being struck by two electrical cords and landing face first in a hard mound of dirt. He was treated at the emergency department and discharged against medical advice.

A 25-year-old woman who sustained an electrical shock to the chest just before the finish line, after which she was given a beer to drink, was admitted to the hospital for dehydration and rhabdomyolsis, or muscle breakdown.

"In the past few years, obstacle racing has experienced a rate of growth that may be unprecedented in the history of participatory sports," said Dr. Greenberg. "Organizers, participants and local emergency services need to be prepared for a large number of diverse injuries at Tough Mudder and other similar obstacle races."

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Biomaterial-delivered chemotherapy could provide final blow to brain tumors

Nov. 12, 2013 — A polymer originally designed to help mend broken bones could be successful in delivering chemotherapy drugs directly to the brains of patients suffering from brain tumors, researchers at The University of Nottingham have discovered.

Their study, published in the journal PLOS ONE, shows that the biomaterial can be easily applied to the cavity created following brain cancer surgery and used to release chemotherapy drugs over several weeks.

The targeted nature of the therapy could also reduce the toxic effects of chemotherapy drugs on healthy parts of the body, potentially reducing the debilitating side-effects that many patients experience after cancer treatment.

Dr Ruman Rahman, of the University's Children's Brain Tumour Research Centre (CBTRC), who led the study, said: "Our system is an innovative method of drug delivery for the treatment of brain tumors and is intended to be administered immediately after surgery by the operating neurosurgeon."

"Ultimately, this method of drug delivery, in combination with existing therapies, may result in more effective treatment of brain tumors, prolonged patient survival and reduced morbidity."

Brain tumors are the major cause of cancer-related death in children and adults up to the age of 40. Most relapses occur when surgeons are unable to remove all of the cancerous cells during surgery -- something which can be particularly challenging in very young children and babies and by the very nature of a type of adult brain cancer called glioblastoma.

Although alternative systems for delivery of drugs directly to the brain have been developed, they are used infrequently because their success has been limited. This new drug delivery system is the first that can be molded to the shape of the brain tumor cavity and the first to deliver several different drugs over a clinically meaningful period of time.

The Nottingham polymer formulation is made from two types of micro-particles called PLGA and PEG and has been developed and patented by leading tissue engineer Professor Kevin Shakesheff, based in the University's School of Pharmacy. A powder at room temperature, it can be mixed to a toothpaste-like consistency with the addition of water.

The unique properties of the polymer lie in its ability to set into a rigid structure only when it reaches body temperature (37 degrees), a feature perfectly tailored for use in medical therapies. It was originally developed as a scaffold on to which new bone cells could be grown to speed up the knitting back together of broken bones.

Dr Ruman Rahman at the CBTRC and Dr Cheryl Rahman from the School of Pharmacy spotted the potential for the polymer to deliver chemotherapy drugs directly to patients' brain tumors. The work was performed at the CBTRC with neurosurgeon Mr Stuart Smith and neuro-oncologist Professor Richard Grundy. The cavity left by the removal of a tumor would be lined with the polymer while in paste form, which would start to solidify and gradually release the chemotherapy drugs after the incision has been closed. This would directly target any residual cells not initially removed during surgery.

In the lab, the Nottingham scientists were able to successfully demonstrate the slow-release properties of the material by placing paste loaded with three commonly used chemotherapy drugs into a solution of saline and measuring the quantities of the drugs given out by the material over time.

To establish whether the material itself is safe to use on patients in this form of therapy, they used it to create a 3D model onto which they were able to grow brain tumor cells and healthy brain blood vessel cells without any toxicity. They then simulated surgery on a sheep's brain from an abattoir by molding the paste around a brain cavity and warming the brain to human body temperature to harden the polymer.

The brain was then scanned using CT and MRI technology to demonstrate that it is still possible to distinguish the polymer from normal brain tissue on a routine brain scan, an aspect crucial for doctors when dealing with follow-up care for brain tumor patients who have undergone surgery.

The team also dealt with concerns that the material could disintegrate and release its chemotherapy contents too quickly during the subsequent radiotherapy which many cancer patients undergo following surgery. By placing the biomaterial loaded with chemotherapy drugs into a head cavity of a medical training dummy and subjecting it to the same duration and intensity of radiotherapy used for brain tumor patients they were able to successfully demonstrate the robust integrity of the structure.

Finally they showed that a chemotherapy drug called etoposide could be effective at killing brain cancer cells in a mouse when released from the polymer formulation. The next stage of the research will be to extend the study in mice with brain tumors to test whether animals with the drug-loaded polymers survive longer. The team are also investigating the release of other chemotherapeutic drugs that hold promise, supported by a recent grant award from Sparks.

As the research used a biomaterial and chemotherapy drugs already approved for medical use, many of the usual ethical approval hurdles to allow further investigation have already been cleared.

The first clinical test, anticipated in 3 years' time, will be to devise a multi-centre phase 0 clinical trial which would involve testing the therapy on a small number of patients for whom other clinical treatments have not been successful and would otherwise only be offered palliative care.

"This is a very exciting development and holds considerable promise for the treatment of malignant brain tumors in the near future" commented Professor Grundy, Co-Director of the CBTRC.

The study was funded by a grant from the Joseph Foote Trust, now part of the Brain Tumour Charity and a Nottingham Advanced Research Fellowship from The University of Nottingham.

Andy Foote, Chair of Trustees at The Brain Tumour Charity, said: "We are proud to have funded this research, which we hope will lead to an exciting new treatment in area where options are sorely lacking. Research into brain tumors receives a fraction of the funding than that of more common cancers and it is our priority to redress the balance. This is essential as figures show that advances in treatment, achieved through the dedicated work of committed researchers over the years such as Dr Rahman and all of the team at the CBTRC, have had a beneficial effect."

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Combining Chinese, Western medicine could lead to new cancer treatments

Sep. 28, 2013 — Combining traditional forms of Chinese and Western medicine could offer new hope for developing new treatments for liver, lung, colorectal cancers and osteosarcoma of the bones.

Experts from Cardiff University's School of Medicine have joined forces with Peking University in China to test the health benefits of a traditional Chinese medicine.

The team also set-out to examine how by combining it with more traditional methods like Chemotherapy could improve patient outcomes and potentially lead to the development of new cancer treatments and therapies.

"Traditional Chinese medicine where compounds are extracted from natural products or herbs has been practised for centuries in China, Korea, Japan and other countries in Asia," according to Professor Wen Jiang from Cardiff University's School of Medicine, who is the director of the Cardiff University-Peking University Joint Cancer Institute at Cardiff and led the research as part of a collaboration between Cardiff University and Peking University.

"Although a few successes, most of the traditional remedies are short of scientific explanation which has inevitably led to scepticism -- especially amongst traditionalists in the West.

"As a result, we set out to test the success of a Chinese medicine and then consider how combining it alongside traditional methods like Chemotherapy could result in positive outcome for patients," he adds.

Yangzheng Xiaoji is a traditional Chinese formula consisting of 14 herbs. The formula has been shown to be beneficial to cancer patients -- however, until now how it works has remained unknown.

Since 2012 the Team have investigated how the formula works, discovering that it works by blocking a pathway which stops the spread of cancer cells in the body.

"The formula has been shown to be beneficial to patients with certain solid tumours, when used alone and in conventional therapies, such as Chemotherapy.

"It suggests that combining the formula with conventional as well as new therapies could hold the key to developing new treatments for cancer patients.

"We are already looking to clinical trials in treatment of lung and other cancer types."

View the original article here

Tiny sensor used in smart phones could create urban seismic network

Sep. 29, 2013 — A tiny chip used in smart phones to adjust the orientation of the screen could serve to create a real-time urban seismic network, easily increasing the amount of strong motion data collected during a large earthquake, according to a new study published in the October issue of the Bulletin of the Seismological Society of America (BSSA).

Micro-Electro-Mechanical System (MEMS) accelerometers measure the rate of acceleration of ground motion and vibration of cars, buildings and installations. In the 1990s MEMS accelerometers revolutionized the automotive airbag industry and are found in many devices used daily, including smart phones, video games and laptops.

Antonino D'Alessandro and Giuseppe D'Anna, both seismologists at Istituto Nazionale di Geosifica e Vulcanologia in Italy, tested whether inexpensive MEMS accelerometers could reliably and accurately detect ground motion caused by earthquakes. They tested the LIS331DLH MEMS accelerometer installed in the iPhone mobile phone, comparing it to the earthquake sensor EpiSensor ES-T force balance accelerometer produced by Kinemetrics Inc.

The tests suggest that the MEMS accelerometers can detect moderate to strong earthquakes (greater than magnitude 5) when located near the epicenter. The device produces sufficient noise to prevent it from accurately detecting lesser quakes -- a limitation to its use in monitoring strong motion.

D'Alessandro and D'Anna note that the technology is rapidly evolving, and there will soon be MEMS sensors that are sensitive to quakes less than magnitude 5. The real advantage, say the authors, is the widespread use of mobile phones and laptops that include MEMS technology, making it possible to dramatically increase coverage when strong earthquakes occur.

The current state of the MEMS sensors, suggest the authors, could be used for the creation of an urban seismic network that could transmit in real-time ground motion data to a central location for assessment. The rich volume of data could help first responders identify areas of greatest potential damage, allowing them to allocate resources more effectively.

The article, "Suitability of low-cost three-axis MEMS accelerometers in strong-motion seismology: tests on the LIS331DLH (iPhone) accelerometer," is published in October issue of BSSA.

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Combining Chinese, Western medicine could lead to new cancer treatments

Sep. 28, 2013 — Combining traditional forms of Chinese and Western medicine could offer new hope for developing new treatments for liver, lung, colorectal cancers and osteosarcoma of the bones.

Experts from Cardiff University's School of Medicine have joined forces with Peking University in China to test the health benefits of a traditional Chinese medicine.

The team also set-out to examine how by combining it with more traditional methods like Chemotherapy could improve patient outcomes and potentially lead to the development of new cancer treatments and therapies.

"Traditional Chinese medicine where compounds are extracted from natural products or herbs has been practised for centuries in China, Korea, Japan and other countries in Asia," according to Professor Wen Jiang from Cardiff University's School of Medicine, who is the director of the Cardiff University-Peking University Joint Cancer Institute at Cardiff and led the research as part of a collaboration between Cardiff University and Peking University.

"Although a few successes, most of the traditional remedies are short of scientific explanation which has inevitably led to scepticism -- especially amongst traditionalists in the West.

"As a result, we set out to test the success of a Chinese medicine and then consider how combining it alongside traditional methods like Chemotherapy could result in positive outcome for patients," he adds.

Yangzheng Xiaoji is a traditional Chinese formula consisting of 14 herbs. The formula has been shown to be beneficial to cancer patients -- however, until now how it works has remained unknown.

Since 2012 the Team have investigated how the formula works, discovering that it works by blocking a pathway which stops the spread of cancer cells in the body.

"The formula has been shown to be beneficial to patients with certain solid tumours, when used alone and in conventional therapies, such as Chemotherapy.

"It suggests that combining the formula with conventional as well as new therapies could hold the key to developing new treatments for cancer patients.

"We are already looking to clinical trials in treatment of lung and other cancer types."

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Could Antidepressant Combat Lethal Lung Cancer?

Little-used depression drug shows early promise in lab, mice studies

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Could dog food additive prevent disabling chemo side effect?

Sep. 19, 2013 — Working with cells in test tubes and in mice, researchers at Johns Hopkins have discovered that a chemical commonly used as a dog food preservative may prevent the kind of painful nerve damage found in the hands and feet of four out of five cancer patients taking the chemotherapy drug Taxol.

The Food and Drug Administration-approved preservative, an antioxidant called ethoxyquin, was shown in experiments to bind to certain cell proteins in a way that limits their exposure to the damaging effects of Taxol, the researchers say.

The hope, they say, is to build on the protective effect of ethoxyquin's chemistry and develop a drug that could be given to cancer patients before taking Taxol, in much the same way that anti-nausea medication is given to stave off the nausea that commonly accompanies chemotherapy. While half of Taxol users recover from the pain damage, known as peripheral neuropathy, the other half continue to have often debilitating pain, numbness and tingling for the rest of their lives.

"Millions of people with breast cancer, ovarian cancer and other solid tumors get Taxol to treat their cancer and 80 percent of them will get peripheral neuropathy as a result," says Ahmet Hoke, M.D., Ph.D., a professor of neurology and neuroscience at the Johns Hopkins University School of Medicine and director of the Neuromuscular Division. "They're living longer thanks to the chemotherapy, but they are often miserable. Our goal is to prevent them from getting neuropathy in the first place."

A report on Hoke's research is published online in the Annals of Neurology.

Hoke and his team knew from previous experiments that adding Taxol to a nerve cell line growing in a petri dish would cause neurodegeneration. In a series of experiments, they set out to hunt for compounds that might interrupt the degenerative process by adding Taxol to nerve cells along with some 2,000 chemicals -- one at a time -- to see which, if any, could do that.

Ethoxyquin did so, Hoke says, apparently by making the cells resistant to the toxic effects of the Taxol.

Once they identified ethoxyquin's effects, they gave intravenous Taxol to mice, and saw nerves in their paws degenerate in a couple of weeks. But when they gave ethoxyquin to the mice at the same time as the Taxol, it prevented two-thirds of the nerve degeneration, which Hoke says would have a big impact on quality of life if the same effects were to occur in humans.

Specifically, Hoke and his team discovered that molecules of ethoxyquin were binding to Hsp90, one of the so-called heat shock proteins that cells defensively make more of whenever they are stressed. Hsp90 acts as a cell's quality control officer, determining whether a protein is properly formed before sending it out where it is needed. When ethoxyquin binds to Hsp90, two other proteins -- ataxin-2 and Sf3b2 -- can't bind to Hsp90. When they can't bind, the cell senses that these two proteins are flawed, so they are degraded and their levels in the cell diminished.

Hoke says his team is not certain why too much of those two proteins appears to have a negative effect on nerves, but reducing their levels clearly appears in their studies to make cells more resistant to Taxol toxicity.

Hoke and his colleagues are looking into whether this medication could also make nerves more resistant to damage in peripheral neuropathy caused by HIV and diabetes, two other major causes of the pain. A previous study, Hoke says, showed that ataxin-2 may cause degeneration in motor neurons in a rare form of ALS, commonly known as Lou Gehrig's disease, suggesting that ethoxyquin or some version of it might also benefit people with this disorder.

Twenty to 30 million Americans suffer from peripheral neuropathy. Hoke says it's a "huge public health issue" that doesn't get much attention because it is not fatal.

Hoke's team is hoping to conduct safety studies with ethoxyquin in animals in advance of possible testing in people. He says that while too much ethoxyquin is thought to be potentially harmful to dogs, the needed dose for humans would likely be 20-to-30-fold lower than what is found in dog food. Ethoxyquin was developed in the 1950s as an antioxidant, a compound to prevent pears and other foods from becoming discolored and spoiling.

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Colonoscopy screening every ten years could prevent 40% of colorectal cancers

Sep. 18, 2013 — According to a large, long-term study from Harvard School of Public Health (HSPH), 40% of all colorectal cancers might be prevented if people underwent regular colonoscopy screening. The new research also supports existing guidelines that recommend that people with an average risk of colorectal cancer should have a colonoscopy every 10 years.

The new study helps address previous uncertainty about the effectiveness of colonoscopy in reducing colorectal cancer incidence and mortality -- particularly among people with cancer that originates in the proximal, or upper part of the colon.

The study appears in the September 19, 2013 edition of the New England Journal of Medicine.

"Colonoscopy is the most commonly used screening test in the U.S. but there was insufficient evidence on how much it reduces the risk of proximal colon cancer and how often people should undergo the procedure," said Shuji Ogino, co-senior author and associate professor in the Department of Epidemiology at HSPH. "Our study provides strong evidence that colonoscopy is an effective technique for preventing cancers of both distal and proximal regions of the colorectum, while sigmoidoscopy alone is insufficient for preventing proximal cancer."

According to the most recent statistics from the Centers for Disease Control and Prevention, nearly 137,000 people in the U.S. were diagnosed with colorectal cancer in 2009, and nearly 52,000 died that year from the disease. Colorectal cancer is the second-leading cause of cancer-related death in the nation.

The researchers analyzed data from 88,902 participants in two long-term studies: the Nurses' Health Study and the Health Professionals Follow-up Study. Based on data from questionnaires that participants filled out every two years between 1988 and 2008, the researchers obtained information on colonoscopy and sigmoidoscopy procedures. They documented 1,815 cases of colorectal cancer and 474 deaths from the disease.

They found that both colonoscopy and sigmoidoscopy -- which screens for tumors in the distal, or lower part of the colorectum -- were associated with decreased risk of either getting colorectal cancer or dying from it. Only colonoscopy decreased the risk for cancers originating in the proximal colon, but not to the degree of its protective effect against distal colorectal cancers. The researchers suggested that colonoscopy's smaller effect in reducing risk for tumors in the proximal colon might be due in part to molecular or biological differences in those cancers.

Other findings include:

• The researchers estimated that if all participants in the study had undergone colonoscopies, 40% of colorectal cancers -- including 61% of distal cancers and 22% of proximal cancers -- would have been prevented.
• Sigmoidoscopy alone is likely insufficient for reducing the incidence or death risk of colorectal cancer that originates in the upper colon.
• People who get a clean bill of health after a colonoscopy have a significantly reduced risk of colorectal cancer for up to 15 years after the procedure, although the data support repeat screening at shorter intervals among individuals with a personal history of adenoma -- a benign tumor of glandular origin that can become malignant over time -- or a family history of colorectal cancer.
• Colorectal cancers diagnosed within five years of a colonoscopy had different molecular characteristics compared with cancers diagnosed more than five years after a colonoscopy, and they may be difficult to detect or completely remove.

"Each year, more than 1.2 million people are diagnosed with colorectal cancer worldwide. Our findings could help improve and strengthen the current guidelines for colorectal cancer screening," said Reiko Nishihara, lead author and research fellow in the Department of Nutrition at HSPH.

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New role for protein family could provide path to how crop traits are modified

Sep. 18, 2013 — Pioneering new research from a team of Indiana University Bloomington biologists has shown for the first time that a protein which has been long known to be critical for the initiation of protein synthesis in all organisms can also play a role in the regulation of gene expression in some bacteria, and probably land plants as well.

The protein, called translation initiation factor 3, or IF3, is one of three proteins that make up the core structure of the machinery needed to guide the joining of messenger RNAs and ribosomes as protein translation commences. These three proteins have been widely considered to simply operate in a constitutive manner and play little, if any, role in regulating the expression of genes.

The new findings, from the laboratory of David M. Kehoe, professor of biology in the Indiana University Bloomington College of Arts and Sciences, reveals that IF3, in addition to its well-accepted function during translation initiation, also regulates the expression of genes that encode components of the photosynthetic machinery in response to changes in the color of light in the surrounding environment, a process known as "chromatic acclimation."

These photosynthesis genes produce red-pigmented proteins called phycoerythrin in cyanobacteria when the cells are grown in green light and allow these organisms to efficiently absorb the predominant ambient light color for photosynthesis. The team uncovered the novel function of IF3 while searching for mutants that incorrectly regulated phycoerythrin. The discovery of this mutant was at first surprising, because in all other bacteria that have been examined, mutations in infC (the gene that encodes IF3) are lethal.

The team solved this puzzle by uncovering a second infC gene in Fremyella diplosiphon, the model organism for the study of light color responsiveness in cyanobacteria. While both IF3s, which have been named IF3a and IF3b, can act in the traditional role of translation initiation, only IF3a was found to also regulate photosynthetic gene expression.

By exploring the genomes of hundreds of prokaryotes and eukaryotes in collaboration with members of the laboratory of Indiana University Distinguished Professor and Class of 1955 Professor Jeffrey Palmer, the group identified a wide range of species whose genomes appear to have the potential to encode multiple IF3s, with one organism apparently encoding five distinct IF3 family members. And since almost none of these species are capable of chromatic acclimation, Kehoe believes that multiple IF3s must be used to regulate a wide range of environmental and perhaps developmental responses in both prokaryotes and eukaryotes.

"Particularly interesting was our finding that IF3 families exist in a number of plant species, including commercially important crops," Kehoe said. "This means that new approaches to the modification of traits in agriculturally significant plant species may be possible by manipulating the expression patterns of different IF3 family members."

The discovery has generated excitement for an additional reason. Historically, scientists have had a difficult time studying IF3 because it is so essential for translation initiation that it can not be altered without causing death. In fact, it remains one of the few proteins involved in translation for which no effective antibiotic has been developed. But the ability of the Kehoe team to delete either of the two infC genes in F. diplosiphon without causing lethality will allow the group to modify both IF3a and IF3b at will.

"Now that we know that F. diplosiphon contains two functionally different IF3s, and that each is nonessential, we have a unique opportunity to enhance our understanding of how the structural features of IF3 are related to its function," Kehoe said. "Advancing our understanding of the role of IF3 in translation is likely to provide opportunities to develop new antibiotics that are targeted to this class of proteins."

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New sensor could prolong the lifespan of high-temperature engines

Sep. 18, 2013 — A new, highly-accurate temperature sensor could save manufacturers millions in maintenance costs, lower fuel consumption, and prolong the lifespan of jet engines, nuclear reactors and other types of large gas turbine engines.

A temperature sensor developed by researchers at the University of Cambridge could improve the efficiency, control and safety of high-temperature engines. The sensor minimises drift -degradation of the sensor which results in faulty temperature readings and reduces the longevity of engine components.

The new sensor, or thermocouple, has been shown to reduce drift by 80 per cent at temperatures of 1200 degrees Celsius, and by 90 per cent at 1300 degrees Celsius, potentially doubling the lifespan of engine components. The results are published in the September issue of the Journal of Engineering for Gas Turbines and Power.

Generally, the hotter a jet engine burns, the more power it generates, improving fuel efficiency, range and thrust. However, an accurate temperature reading is critical, as when temperatures get too high, the mechanical integrity of engine components could be at risk. A temperature error of just ten degrees can trigger engine failure, which can be a huge blow to aircraft manufacturers, as seen in the 2010 recall of Rolls-Royce's Airbus A380 engines, which caused the company's share price to drop by a massive nine per cent.

Modern jet engines can reach temperatures as high as 1500 degrees, but drift in the nickel-based thermocouples used to measure temperature increases to unacceptable levels at temperatures above 1000 degrees. Therefore, the thermocouple is placed away from the hottest part of the engine, and the maximum temperature is extrapolated from that point.

The inaccuracy resulting from this form of measurement means that the engine temperature, and therefore efficiency, has to be set below maximum in order to leave a safety margin for the survival of engine components. Thermocouples with increased temperature capabilities can be placed closer to the combustion chamber, increasing the accuracy with which the peak temperature is estimated, and decreasing the required safety margin.

"A more stable temperature sensor provides several advantages -- a better estimation of temperature can increase the lifetime of engine components and decrease maintenance costs to manufacturers, without any reduction in safety," said Dr Michele Scervini, a postdoctoral researcher in the Department of Materials Science and Metallurgy, who developed the new thermocouple.

In its simplest form, a thermocouple consists of two bare wires of two different metals joined together at their ends, with a voltmeter incorporated into the circuit. The difference between the two ends of the thermocouple is measured by the voltmeter and used to determine the temperature. This type of thermocouple is not suitable for high-temperature applications as the elements oxidise above 800 degrees, increasing the amount of drift, so thermocouples sheathed in oxidation-resistant materials were introduced in the 1970s. While this configuration addressed the issue of oxidation, the sheath contaminated the wires at temperatures above 1000 degrees, increasing drift.

Scervini, along with Dr Cathie Rae, has developed a thermocouple which both withstands oxidisation and minimises any contamination to the wires from the metallic sheath. The thermocouple is made of an outer wall of a conventional oxidisation-resistant nickel alloy which can withstand high temperatures, and an inner wall of a different, impurity-free nickel alloy which prevents contamination while reducing drift.

Results from tests on a prototype device showed a significant reduction in drift at temperatures of 1200 and 1300 degrees, meaning that a double-walled thermocouple can be used at temperatures well above the current limitation of 1000 degrees.

There are platinum-based thermocouples which can withstand higher temperatures, but their extremely high cost means that they are not widely used. "Nickel is an ideal material for these applications as it is a good compromise between cost and performance, but there is a gap in the market for applications above 1000 degrees," said Scervini. "We believe our device could see widespread usage across a range of industries."

The team are currently commercialising their invention with the assistance of Cambridge Enterprise, the University's commercialisation arm, and have attracted interest from a range of industries. Tests on new prototypes are on-going.

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Could E. Coli Vaccine for Cows Cut Human Infections?

TUESDAY, Sept. 17 (HealthDay News) -- Vaccinating cattle against E. coli bacteria could cut the number of human infections by 85 percent, far higher than previous estimates, British scientists say.

The researchers reviewed the way that E. coli is transmitted from cattle to humans, noting that the risk of infection is particularly significant during the brief periods when cattle are "super-shedding" extremely large amounts of the bacteria in their feces.

"As far as we can assess, the major risk to humans is from those animals that are shedding the bug heavily," said Stuart Reid, senior study author and a principal at the Royal Veterinary College at the University of London. "If the vaccine has an impact on these animals at that time, the risk to humans is disproportionately reduced."

Previous research has predicted that vaccination of cattle could reduce E. coli risk by 50 percent, but those studies did not take into account the effect of vaccination on "super-shedding," the researchers said.

The new study of Scottish cattle appeared in the Sept. 16-20 issue of the journal Proceedings of the National Academy of Sciences.

E. coli infection causes severe gastrointestinal illness in humans, in some cases leading to death. It is spread by consuming contaminated food or water, most often ground beef.

Nearly 1,100 confirmed cases of E. coli infection occurred in the United States in 2012, according to the U.S. Centers for Disease Control and Prevention. They led to 275 hospitalizations and two deaths. The CDC said that for every reported case of E. coli, there are probably 26 more that go undiagnosed.

Vaccines against E. coli have been approved for cattle in the United States and Canada, but farmers have not shown much interest in using them, the study authors said.

Farmers aren't vaccinating cattle against E. coli because cattle don't get sick from the bacteria, said Mike Doyle, a distinguished professor of food microbiology and director of the Center for Food Safety at the University of Georgia.

"The farmer doesn't get any bang for the buck from a production perspective," Doyle said. "The vaccine doesn't help the animal grow more healthy."

Government intervention likely would be required for widespread vaccination to occur. "Unless all farmers were required to vaccinate by the government, it wouldn't be cost effective or cost competitive for them to do that," Doyle said.

Such intervention should be seriously considered, said lead study author Dr. Louise Matthews, a senior research fellow in the Institute of Biodiversity, Animal Health and Comparative Medicine at the University of Glasgow.

"Treating cattle in order to reduce the number of human cases [of E. Coli] certainly makes sense from a human health perspective, and, while more work is needed to calculate the cost of a vaccination program, the public health justification must be taken seriously," Matthews said.

The researchers started their work first by identifying the genetic marker associated with E. coli super-shedding in cattle. They then studied the relationship between cattle predisposed to super-shed E. coli and human outbreaks of the illness, concluding that the types of E. coli linked to super-shedding cause the vast majority of cases.

The researchers now are working to develop even more effective vaccines that would further reduce the risk of E. coli outbreaks.

Doyle warned against generalizing the Scottish results to the United States, however, noting that farming methods are very different between the two. For example, Scottish beef is mostly grass fed.

"You can't automatically extrapolate what they find over there to what we have here," he said. "There's probably more research that would need to be done to see how useful or relevant this information is to American farmers."

Dr. Georges Benjamin, executive director of the American Public Health Association, said the results are intriguing. He said, however, that he's concerned that a vaccine might reduce emphasis on the common-sense food-safety methods that now provide effective protection against foodborne illness.

"I do want to emphasize [that] it does not replace careful monitoring of animal health and surveillance of the food-safety process as animals move through the pipeline to become our food," Benjamin said. "It also doesn't replace good food safety. You're still going to have to wash your hands. You're still going to have to make sure your food is prepared properly."

More information

For more about foodborne pathogens, visit the U.S. Centers for Disease Control and Prevention.

Copyright c 2013?HealthDay. All rights reserved.

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Sanofi could acquire L'Oreal's stake, buy more of Regeneron

By Natalie Huet and Ben Hirschler

PARIS/LONDON (Reuters) - Repurchasing L'Oreal's 9 percent stake in Sanofi might make sense for the French drugmaker if the $12 billion holding is put up for sale, Sanofi's chief executive said on Friday.

Chris Viehbacher told an investor conference the group had the resources to do "opportunistic" share buybacks, as well as making bolt-on acquisitions and potentially increasing its stake in U.S. biotech firm Regeneron Pharmaceuticals.

Shares in Regeneron jumped more than 5 percent to an all-time high of $288.50 in New York after his comments, also buoyed by Lazard Capital Markets and RBC raising their price targets for the stock. Sanofi and L'Oreal shares were little changed.

Speculation over the fate of L'Oreal's stake in Sanofi has been fuelled by last month's comments from L'Oreal's CEO that the cosmetics company could buy back the 23-billion-euro ($30-billion) stake Nestle holds in it if L'Oreal in turn sold the 9-billion-euro stake it owns in Sanofi.

The comments have weighed on Sanofi shares, already dragged down by disappointing quarterly results, but some analysts say the drugmaker could use the opportunity to repurchase the shares with cheap debt, thereby boosting its earnings.

Asked about his potential interest in buying back L'Oreal's stake from next year, Viehbacher said it was difficult to comment because the issue was highly conditional.

"We certainly have cash flow to do some things," he told a Bank of America Merrill Lynch healthcare conference in London.

"Whether we would intervene in that or not is going to be a function of - if it does happen - what at that given point in time is the best use of capital. It may well be opportune to have a look at it."

Restrictions on Nestle selling its L'Oreal stake end in April.

More generally, Viehbacher said he did not exclude other share buybacks, but said these would depend on opportunities for acquisitions.

He said Sanofi could also look at raising its stake in Regeneron to as much as 30 percent. Sanofi holds about 16 percent of Regeneron and said in February it has the right to increase this to a maximum 30 percent under its decade-long partnership with Regeneron.

"The Regeneron relationship has become extremely productive for us," Viehbacher said. "Over time, it could well make sense to build our stake up to 30 percent. How fast we do that, whether or not we do that is a function of a number of different factors - but it is a bulky chunk of money to use."

Regeneron's market value is about $27 billion.

Regeneron is best known for its eye drug Eylea, co-marketed with Bayer. But it has also successfully developed the cancer treatment Zaltrap with Sanofi and is working with the French group on a new kind of cholesterol drug.

The drug, which is in late-stage trials, has cut levels of "bad" LDL cholesterol by 60 percent through a new mechanism - blocking a protein called PCSK9.

(Editing by Louise Ireland and Bob Burgdorfer)

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Test could identify which prostate cancers require treatment

Sep. 11, 2013 — The level of expression of three genes associated with aging can be used to predict whether seemingly low-risk prostate cancer will remain slow-growing, according to researchers at the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center. Use of this three-gene biomarker, in conjunction with existing cancer-staging tests, could help physicians better determine which men with early prostate cancer can be safely followed with "active surveillance" and spared the risks of prostate removal or other invasive treatment. The findings were published today in the online edition of Science Translational Medicine.

"Most of the 200,000 prostate cancers diagnosed each year in the U.S. are slow growing and will remain so, but the three-gene biomarker could take much of the guesswork out of the diagnostic process and ensure that patients are neither overtreated nor undertreated," said study leader Cory Abate-Shen, PhD, Michael and Stella Chernow Professor of Urological Oncology at CUMC.

"The problem with existing tests is that we cannot identify the small percentage of slow-growing tumors that will eventually become aggressive and spread beyond the prostate," said coauthor Mitchell C. Benson, MD, PhD, George F. Cahill Professor of Urology and chair of urology at CUMC.

In their search for a biomarker for slow-growing prostate cancer, Dr. Abate-Shen and her colleagues, including, coauthor Michael Shen, PhD, professor of medicine and of genetics and development, focused on genes related to aging, particularly those affected by cellular senescence, a natural phenomenon in which older cells cease to divide but remain metabolically active. Cellular senescence is known to play a critical role in tumor suppression in general and has been associated with benign prostate lesions in mouse models and in humans.

Using a technique called gene set enrichment analysis, the CUMC team, led by coauthor Andrea Califano, PhD, Clyde and Helen Wu Professor of Chemical Systems Biology and chair of systems biology, identified 19 genes that are enriched in a mouse model of prostate cancer in which the cancers are invariably indolent. They then used a decision-tree learning model, a type of computer algorithm, to identify three genes -- FGFR1, PMP22, and CDKN1A -- that together can accurately predict the outcome of seemingly low-risk tumors. Tumors that test negative for the biomarker are deemed aggressive.

In a blinded retrospective study, the researchers tested the prognostic accuracy of the three-gene panel on initial biopsy specimens from 43 patients who had been monitored for at least 10 years with active surveillance at CUMC. All the patients had first been diagnosed with low-risk prostate cancer (as defined by several measures, including a Gleason score of 6 or less). Of the 43 patients, 14 ultimately developed advanced prostate cancer. All 14 were correctly identified by the test.

"The bottom line is that, at least in our preliminary trial, we were able to accurately predict which patients with low-risk prostate cancer would develop advanced prostate cancer and which ones would not," said Dr. Abate-Shen.

The researchers plan to evaluate the test in a larger, prospective clinical trial, led by Dr. Benson and coauthor Sven Wenske, MD, assistant professor of urology at CUMC.

Physicians currently use several tests to diagnose prostate cancer and stage its aggressiveness. The process begins with a prostate-specific antigen (PSA) test, a digital rectal exam, or both. If these tests raise concerns, the patient is typically advised to undergo a biopsy, in which samples of prostate tissue are examined for the presence of cancer cells. If malignant cells are detected, the patient is given a Gleason score (ranging from 2 to 10), a measure of the severity of the cancer based on the cells' appearance. Patients with high Gleason scores (8 or above) are usually advised to undergo immediate treatment, while those with very low Gleason scores (5 or below) are usually advised to undergo active surveillance. "But it's not so clear what to do for patients with low (Gleason 6) or even intermediate (Gleason 7) scores," said Dr. Abate-Shen.

Men with seemingly low-risk prostate cancer currently have two basic choices. One is regular testing and monitoring, also known as active surveillance, which risks missing the window when the disease is localized and potentially curable. The other is aggressive treatment, which risks serious side effects such as urinary incontinence and impotence.

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Heart technique 'could save lives'

11 September 2013 Last updated at 10:07 GMT By Eleanor Bradford BBC Scotland Health Correspondent Every year 25,000 people in the UK have the kind of heart attack which is treated with an angioplasty A new, relatively simple way of treating heart attacks could save thousands of lives, according to specialists at a Clydebank hospital.

It involves clearing all narrowed arteries when someone is admitted with a heart attack, rather than just the one which is completely blocked.

A trial, involving the Golden Jubilee National Hospital, was so successful that the research was stopped early.

Jubilee heart specialist Prof Colin Berry said the results were "striking".

Fatty deposits

Another cardiologist, Prof Keith Oldroyd, said: "At the moment when patients come in with a heart attack they have an emergency angiogram and we usually only treat the artery that has caused the heart attack.

"Many of these patients have additional narrowings in other arteries. We're treating all the narrowed arteries at the same time to see if that confers additional benefit."

Every year 25,000 people in the UK have the kind of heart attack which is treated with an angioplasty.

This involves inserting a stent, or thin tube, to open an artery and restore the blood flow.

Arteries become narrowed by fatty deposits, so although a blood clot may have only blocked one artery, other narrowed arteries are common.

Current UK recommendations advise specialists only to treat the artery which is completely blocked.

"Most cardiologists thought it wasn't safe to treat a second or third artery at the same time as the first artery," Prof Oldroyd said.

"Sometimes the patients would be brought back several weeks later or sometimes only medication would be used. The results of this trial suggest that this recommendation should be revisited."

Reducing costs

The trial involved 465 patients in five specialist heart centres around the UK. In addition to the Golden Jubilee, they were the London Chest Hospital, Morriston Hospital in Swansea, Freeman Hospital in Newcastle, and Norfolk and Norwich University Hospital.

Half of the trial participants had all their arteries cleared, the rest were treated in the conventional way.

Prof Keith Oldroyd said most patients had narrowings in more than one artery

The researchers found that the new technique reduced the combined risk of dying, having another heart attack or being left with angina by two-thirds - such a significant finding that the trial was stopped early.

It also only added an average of 20 minutes to each treatment.

The results have been published in the New England Journal of Medicine and were presented at an international conference in Amsterdam earlier this month.

Prof Colin Berry, heart specialist at the Golden Jubilee and the University of Glasgow, said: "They were some of the most striking results for a treatment that I have ever seen. The results of this trial really challenge clinical practice."

Heart specialists are now keen that even larger studies get under way as quickly as possible.

In the past, it has taken a decade or more for the latest evidence to be adopted into frontline medical care.

Prof Berry added: "It's appealing because it's a form of usual care that can be readily adopted across the UK.

"On the other hand there are logistical considerations and cost considerations. However, we would argue that reducing the likelihood of further cardiac events, potentially reducing the heart failure admissions to hospital, is going to reduce costs overall and this should be implemented as soon as possible."

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Lung cancer drug could aid plight of ectopic pregnancy patients

Sep. 9, 2013 — Women with ectopic pregnancies could be spared surgery if they are treated with a lung cancer drug, a study suggests.

Researchers treated ectopic pregnancies -- where an embryo implants inside the Fallopian tube -- by combining an existing treatment with a lung cancer therapy.

They found that prescribing both drugs together was more effective at helping cure an ectopic pregnancy than the conventional drug alone.

Lung cancer drug

The lung cancer drug -- called gefitinib -- helps by blocking a protein that is known to encourage cell growth, and which was found to be present in high levels at the site of ectopic pregnancies.

Combining gefitinib with the conventional treatment, which is called methotrexate, could reduce the need to remove the Fallopian tube in a significant number of cases.

This would help the patient's level of fertility -- say researchers led by Dr Andrew Horne at the University of Edinburgh and Dr Stephen Tong at the University in Melbourne.

Ectopic pregnancies

Ectopic pregnancy can be treated with drugs in the early stages of development, but surgery is needed when it is more developed.

Researchers also found that the drug combination was able to shorten the time it took to successfully treat ectopic pregnancies in women who did not need surgery.

Around 12,000 women undergo an ectopic pregnancy in the UK each year, and the condition is responsible for up to eight per cent of pregnancy-related deaths.

The study, published in the journal Obstetrics and Gynaecology, involved a trial of 12 women with ectopic pregnancies. Researchers now plan to run a larger trial.

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Cutting Unneeded CT Scans in Kids Could Lower Future Cancer Risk

MONDAY, June 10 (HealthDay News) -- Reducing the number of unnecessary and high-dose CT scans given to children could cut their lifetime risk of associated cancers by as much as 62 percent, according to a new study.

CT (computed tomography), which uses X-rays to provide doctors with cross-sectional images of patients' bodies, is frequently used in young children who have suffered injuries.

Researchers concluded that the 4 million CT scans of the most commonly imaged organs conducted in children in the United States each year could lead to nearly 4,900 cancers in the future.

They also calculated that reducing the highest 25 percent of radiation doses could prevent nearly 2,100 (43 percent) of these future cancers, and that eliminating unnecessary CT scans could prevent about 3,000 (62 percent) of these future cancers.

The study was published online June 10 in the journal JAMA Pediatrics.

"There are potential harms from CT, meaning that there is a cancer risk -- albeit very small in individual children -- so it's important to reduce this risk in two ways," study lead author Diana Miglioretti, a professor of biostatistics in the department of public health sciences at the UC Davis Health System, in California, said in a health system news release.

"The first is to only do a CT when it's medically necessary, and use alternative imaging when possible," she said. "The second is to dose CT appropriately for children."

The researchers examined data on the use of CT in children at a number of health care systems in the United States between 1996 and 2010. Among children under 5 years old, CT use nearly doubled from 11 per 1,000 in 1996 to 20 per 1,000 between 2005 and 2007, and then decreased to about 16 per 1,000 in 2010.

Among children aged 5 to 14, CT use nearly tripled, from 10.5 per 1,000 in 1996 to a peak of 27 per 1,000 in 2005, before falling to about 24 per 1,000 in 2010.

Researchers examined 744 random CTs of the head, abdomen/pelvis, chest and spine conducted on children between 2001 and 2011 at five of the health systems to calculate radiation exposure levels and estimated cancer risk. These areas of the body account for more than 95 percent of all CT scans, the researchers said.

Head CT -- the most commonly performed CT in children -- poses the highest risk of radiation-induced leukemia and brain cancers, according to the study. Meanwhile, CTs of the abdomen and pelvis -- which had the most dramatic increase in use, especially among older children -- pose the highest risk of radiation-induced solid cancer. Leukemia and breast, thyroid and lung cancers account for 68 percent of estimated future cancers in girls who have had CTs, while leukemia and brain, lung and colon cancers account for 51 percent of future cancers in boys who have had CTs.

More information

The American College of Radiology/Radiological Society of North America has more about CT scans and children.

SOURCE: UC Davis Health System, news release, June 10, 2013

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New laser-based tool could dramatically improve the accuracy of brain tumor surgery

AppId is over the quota
AppId is over the quota

A new laser-based technology may make brain tumor surgery much more accurate, allowing surgeons to tell cancer tissue from normal brain at the microscopic level while they are operating, and avoid leaving behind cells that could spawn a new tumor. In a new paper, featured on the cover of the journal Science Translational Medicine, a team of scientists from the University of Michigan Medical School (home of the University of Michigan Comprehensive Cancer Center) and Harvard University (a component of the Dana-Farber Cancer Institute) researchers describes how the technique allows them to “see” the tiniest areas of tumor cells in brain tissue.

Click here to read full press release.?

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Among the research institutions NCI funds across the United States, it currently designates 68 as Cancer Centers. Largely based in research universities, these facilities are home to many of the NCI-supported scientists who conduct a wide range of intense, laboratory research into cancer’s origins and development. The Cancer Centers Program also focuses on trans-disciplinary research, including population science and clinical research. The centers’ research results are often at the forefront of studies in the cancer field.

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