The SOLITAIRE Flow Restoration Device is among an entirely new generation of devices designed to remove blood clots from blocked brain arteries in patients experiencing stroke. It has a self-expanding, stent-like design and, once inserted into a clot using a thin catheter tube, it compresses and traps the clot. The clot is then removed by withdrawing the device, thus reopening the blocked blood vessel.

In the first U.S. clinical trial of SOLITAIRE, the device opened blocked vessels without causing symptomatic bleeding in or around the brain in 61 percent of patients. The standard Food and Drug Administration–approved mechanical device — a corkscrew-type clot remover called the MERCI Retriever — was effective in 24 percent of cases.

The use of the new device also led to better survival three months after a stroke. There was a 17.2 percent mortality rate with the new device, compared with a 38.2 percent rate with the older one.

“This new device heralds a new era in acute stroke care,” said Saver, the study’s lead author and a professor of neurology at the David Geffen School of Medicine at UCLA. “We are going from our first generation of clot-removing procedures, which were only moderately good in reopening target arteries, to now having a highly effective tool. This really is a game-changing result.”

About 87 percent of all strokes are caused by blood clots blocking a blood vessel supplying the brain. The stroke treatment that has received the most study is the FDA–approved clot- busting drug known as tissue plasminogen activator, but this drug must be given within four-and-a-half hours after the onset of stroke symptoms, and even more quickly in older patients.

When clot-busting drugs cannot be used or are ineffective, the clot can sometimes be mechanically removed during, or beyond, the four-and-a-half–hour window. The current study, however, did not compare mechanical clot removal to drug treatment.

For the trial, called SOLITAIRE With the Intention for Thrombectomy (SWIFT), researchers randomly assigned 113 stroke patients at 18 hospitals to receive either SOLITAIRE or MERCI therapy within eight hours of stroke onset, between January 2010 and February 2011. The patients’ average age was 67, and 68 percent were male. The time from the beginning of stroke symptoms to the start of the clot-retriever treatment averaged 5.1 hours. Forty percent of the patients had not improved with standard clot-busting medication prior to the study, while the remainder had not received it.

At the suggestion of a safety monitoring committee, the trial was ended nearly a year earlier than planned due to significantly better outcomes with the experimental device.

Other statistically significant findings included:

• 2 percent of SOLITAIRE-treated patients had symptoms of bleeding in the brain, compared with 11 percent of MERCI patients. At the 90-day follow-up, overall adverse event rates, including bleeding in the brain, were similar for the two devices.
• 58 percent of SOLITAIRE-treated patients had good mental/motor functioning at 90 days, compared with 33 percent of MERCI patients.
• The SOLITARE device also opened more vessels when used as the first treatment approach, necessitating fewer subsequent attempts with other devices or drugs.

“Nearly a decade ago, our UCLA Stroke Center team invented the first stroke retrieval device — the MERCI Retriever — and now we are pleased to have helped develop and successfully test a superior, next-generation clot removing device,” said Dr. Reza Jahan, associate professor of radiology at UCLA and the study’s principal neurointerventional investigator, who also led the pre-clinical studies. “It is exciting to have a highly effective new tool that can improve the outcomes for more stroke patients.”

Additional co-authors included Dr. Elad Levy, Dr. Tudor G. Jovin, Dr. Blaise Baxter, Dr. Raul Nogueira, Dr. Wayne Clark, Dr. Ronald Budzik, Dr. Osama O. Zaidat and the SWIFT trial investigators.

Saver and Jahan received compensation from Covidien as scientific consultants for the design and conduct of the trial.

Covidien, the device manufacturer, funded the study. Although not yet approved in the United States, SOLITAIRE is used in Europe.

The UCLA Stroke Center, recognized as one of the world’s leading centers for the management of cerebral vascular disease, treats simple and complex vascular disorders by incorporating recent developments in emergency medicine, stroke neurology, microneurosurgery, interventional neuroradiology, stereotactic radiology, neurointensive care, neuroanesthesiology and rehabilitation neurology. The program is unique in its ability to integrate clinical and research activities across multiple disciplines and departments. Founded in 1994, the UCLA Stroke Center is designated as a certified Primary Stroke Center by the national Joint Commission on Accreditation of Healthcare Organizations.

Contact: Amy Albin
aalbin@mednet.ucla.edu
310-794-8672
University of California - Los Angeles Health Sciences

“It has been unclear whether multivitamin supplementation to cancer patients is helpful, has no effect, or is even detrimental during therapy,” commented Dr. Grant Pierce, Editor of CJPP. “This study is important because it gives some direction to cancer patients in desperate need of guidance on the value of multivitamins and minerals administered during cancer.”

The authors studied rats that were fed a high-fat diet (20% fat) over a 32 week period. The rats were divided into 6 groups, which were exposed to different combinations of supplements and carcinogens; the colon carcinogenisis induced in the study rats has characteristics that mimic human colon cancer. Rats fed a high-fat plus low-fibre diet and exposed to carcinogens developed pre-cancerous lesions; whereas, rats undergoing similar treatment, but provided with daily multivitamin and mineral supplements, showed a significant (84%) reduction in the formation of pre-cancerous lesions and did not develop tumours.

The authors conclude that “multivitamin and mineral supplements synergistically contribute to the cancer chemopreventative potential, and hence, regular supplements of multivitamins and minerals could reduce the risk of colon cancer.”

The study “Multivitamin and mineral supplementation in 1,2-dimethylhydrazine induced experimental colon carcinogenesis and evaluation of free radical status, antioxidant potential, and incidence of ACF” appears in the January issue of CJPP.

http://www.nrcresearchpress.com/cjpp

For more information contact:

Corresponding author: Ignacimuthu Savarimuthu (email: bhaskar_sci@yahoo.com)

Full Reference:

Arul, A.B., Savarimuthu, I., Alsaif, M.A., Al Numair, K.S. 2012. Multivitamin and mineral supplementation in 1,2-dimethylhydrazine induced experimental colon carcinogenesis and evaluation of free radical status, antioxidant potential, and indicence of ACF. Canadian Journal of Physiology and Pharmacology, 90: 45. [Available Open Access on the http://www.nrcresearchpress.com website.]

About the Publisher

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Canadian Science Publishing operates under the brand NRC Research Press but is not affiliated with the National Research Council Canada. Papers published by Canadian Science Publishing are peer-reviewed by experts in their field. The views of the authors in no way reflect the opinions of Canadian Science Publishing or the National Research Council of Canada. Requests for commentary about the contents of any study should be directed to the authors.

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Contact: Ignacimuthu Savarimuthu
bhaskar_sci@yahoo.com
Canadian Science Publishing (NRC Research Press)

In comparison to a previous generation of systems, the researchers state their test showed a significantly greater number of high-definition circulating tumour cells (HD-CTCs), in a higher proportion of patients, by using a computing-intensive method that enables them to look at millions of normal cells and find the rare cancer cells among them.

Their results, published today, Friday 3 February 2012, in IOP Publishing’s journal Physical Biology, could help reveal the mechanisms behind the spread of solid tumours from one organ or tissue to another – mechanisms that have, until now, remained a mystery.

Dr Jorge Nieva, an oncologist at Billings Clinic leading the study, said: “This technology will allow scientists to move away from mouse and cell culture systems and speed the delivery of cures for cancer in people. This is the technology we have been waiting for to solve the problem of resistance to chemotherapy drugs.”

Senior technology author of the study, Professor Peter Kuhn, said: “In the future, our fluid biopsy can effectively become the companion to the patient for life. If we can assess the disease in real time, we can make quantitative treatment decisions in real time. These decisions include predictive decisions about therapeutic response, diagnostic decisions and prognostic decisions about outcome.”

The researchers, based at the Scripps Physics Oncology Center in La Jolla, California, were able to find five or more CTCs in each milliliter of blood in 80% of the 20 patients they tested with prostate cancer; 70% in the 30 patients with breast cancer; and 50% in the 18 patients with pancreatic cancer.

The authors also report that their test showed significantly better results when compared with the commercial test, CellSearch®, which uses a slightly less accurate approach which effectively reduces the sample from approximately 50 million cells to just 5,000 before conducting fluorescent imaging, meaning important cells you wish to study could be lost.

In 7.5 mL of blood, the CellSearch® test found two or more CTCs in 5 out of the 15 patients tested whereas the new test found two or more CTCs in a single milliliter of blood in 14 out of the 15 patients tested.

The dyes used in this new approach contain antibodies that target, and then attach to, specific proteins that are expressed by the CTCs. Once attached, they fluoresce and allow the researchers to observe them. The result is a set of high resolution digital images that retain the intricate details of the cells and allow the researchers to effectively analyse them in the laboratory. Also striking is the quality of the images.

“The high definition method gives a detailed portrait of these elusive cells that are caught in the act of spreading around the body. It’s unprecedented – we’ve never been able to see them routinely and in high definition like this before,” says diagnostic pathologist Kelly Bethel, MD, the senior clinical investigator on Kuhn’s team.

“The science behind this approach, and the ability to obtain more detailed information about CTCs in a timely fashion, opens up opportunities to address some of the outstanding problems in cancer, such as drug-resistance. This is an example that bringing a physical sciences approach to a medical need has potential for profound consequences to greatly benefit cancer patients,” said Dr Larry Nagahara of the National Cancer Institute.

This paper is one of five to be published today in the journal Physical Biology by the research team at the Scripps Physics Oncology Center (http://4db.us) part of the signature initiative of the National Cancer Institute in Physical Sciences in Oncology (http://physics.cancer.gov). Participating clinics included the Billings Clinic, UCSD Moores Cancer Centre, USC and UCSF.

Notes to Editors

Contact

1. For further information, a full draft of the journal paper or contact with one of the researchers, contact IOP Publishing Press Officer,
Michael Bishop:
Tel: 0117-930-1032
E-mail: Michael.Bishop@iop.org

Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers

2. The published version of the paper “Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers” D Marrinucci et al 2012 Phys. Biol. 9 016003 will be freely available online from 3 February 2012. It will be available at http://iopscience.iop.org/1478-3975/9/1/016003

Physical Biology

3. Physical Biology publishes research on the quantitative characterization and understanding of biological systems at different levels of complexity.

IOP Publishing

4. IOP Publishing provides publications through which leading-edge scientific research is distributed worldwide. IOP Publishing is central to the Institute of Physics (IOP), a not-for-profit society. Any financial surplus earned by IOP Publishing goes to support science through the activities of IOP. Beyond our traditional journals programme, we make high-value scientific information easily accessible through an ever-evolving portfolio of community websites, magazines, conference proceedings and a multitude of electronic services. Focused on making the most of new technologies, we’re continually improving our electronic interfaces to make it easier for researchers to find exactly what they need, when they need it, in the format that suits them best. Go to http://ioppublishing.org/

The Institute of Physics

5. The Institute of Physics is a leading scientific society promoting physics and bringing physicists together for the benefit of all.

It has a worldwide membership of around 40 000 comprising physicists from all sectors, as well as those with an interest in physics. It works to advance physics research, application and education; and engages with policy makers and the public to develop awareness and understanding of physics. Its publishing company, IOP Publishing, is a world leader in professional scientific communications. Go to http://www.iop.org

Contact: Michael Bishop
michael.bishop@iop.org
01-179-301-032
Institute of Physics

“We have developed a procedure which can repair severed nerves within minutes so that the behavior they control can be partially restored within days and often largely restored within two to four weeks,” said Professor George Bittner from the University of Texas. “If further developed in clinical trials this approach would be a great advance on current procedures that usually imperfectly restore lost function within months at best.”

The team studied the mechanisms all animal cells use to repair damage to their membranes and focused on invertebrates, which have a superior ability to regenerate nerve axons compared to mammals. An axon is a long extension arising from a nerve cell body that communicates with other nerve cells or with muscles.

This research success arises from Bittner’s discovery that nerve axons of invertebrates which have been severed from their cell body do not degenerate within days, as happens with mammals, but can survive for months, or even years.

The severed proximal nerve axon in invertebrates can also reconnect with its surviving distal nerve axon to produce much quicker and much better restoration of behaviour than occurs in mammals.

“Severed invertebrate nerve axons can reconnect proximal and distal ends of severed nerve axons within seven days, allowing a rate of behavioural recovery that is far superior to mammals,” said Bittner. “In mammals the severed distal axonal stump degenerates within three days and it can take nerve growths from proximal axonal stumps months or years to regenerate and restore use of muscles or sensory areas, often with less accuracy and with much less function being restored.”

The team described their success in applying this process to rats in two research papers published today. The team were able to repair severed sciatic nerves in the upper thigh, with results showing the rats were able to use their limb within a week and had much function restored within 2 to 4 weeks, in some cases to almost full function.

“We used rats as an experimental model to demonstrate how severed nerve axons can be repaired. Without our procedure, the return of nearly full function rarely comes close to happening,” said Bittner. “The sciatic nerve controls all muscle movement of the leg of all mammals and this new approach to repairing nerve axons could almost-certainly be just as successful in humans.”

To explore the long term implications and medical uses of this procedure, MD’s and other scientist- collaborators at Harvard Medical School and Vanderbilt Medical School and Hospitals are conducting studies to obtain approval to begin clinical trials.

“We believe this procedure could produce a transformational change in the way nerve injuries are repaired,” concluded Bittner.

Contact: Ben Norman
Lifesciencenews@wiley.com
44-012-437-70375
Wiley-Blackwell

The study looked at 209 patients diagnosed with stage IV non-small cell lung cancer separated into four different molecular subgroups using testing performed by the University of Colorado Molecular Correlates Laboratory (CMOCO): those with epidermal growth factor receptor (EGFR) mutations, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements or a group without any of these abnormalities.

ALK positive lung cancer was strongly associated with cancers that spread to the linings around the heart and lungs (pericardial and pleural disease). Patients with ALK positive NSCLC were also predisposed to develop liver metastases as were those with an EGFR mutation when the different subgroups were compared.

“In the last few years we have been able to separate lung cancer into different molecular subtypes to help improve outcomes from specific targeted therapies. This study really confirms that these molecular subtypes are manifesting as different diseases in patients,” said Robert Doebele, MD, PhD, lead author of the study and CU Cancer Center investigator.

Another University of Colorado study published in the same edition of Cancer drills down on how some of these different molecular subtypes of lung cancer are detected in the first place. Specifically, the study examined the companion diagnostic test for detecting the ALK positive lung cancer cases, called a fluorescence in situ hybridization (FISH) test. This test is used to select patients for treatment with crizotinib, an ALK inhibitor drug. Now University of Colorado researchers have solved an unanswered question as to why patients who respond to crizotinib only appear to have the ALK change in a fraction of the cells in their cancers.

By looking in detail at the genetic changes present in the cancer cells they came to two major conclusions. First- cell counts below 100 percent in ALK positive tumors reflect the fact the assay misses a proportion of cells and not that the cells are truly missing the ALK change.

Second, the ALK change happens early in the development of the cancer and is likely to be a fundamental driver of the cancer’s growth. The study was conducted by D. Ross Camidge, MD, PhD, the director of the lung cancer clinical program at the CU Cancer Center and University of Colorado Hospital and Marileila Varella Garcia, PhD, professor of medicine, medical oncology and pathology at University of Colorado School of Medicine.

“Knowing that ALK changes are driving the cancer and that they are not actually missing from a significant proportion of the cancer reinforces our understanding of ALK positive lung cancer. It now makes sense why targeting these changes is going to affect a very large proportion of the tumor and explains the dramatic clinical responses seen with crizotinib.”

“In order to treat any disease successfully, you have to know what you are really treating,” said Camidge.” “It is only by understanding lung cancer better that we can hope to improve outcomes in the long term.”

Both studies were funded by the University of Colorado Lung specialized Program of Research Excellence.

The CU Cancer Center’s Thoracic Oncology Program is world renowned for its pioneering treatment of lung cancer. The program includes a multidisciplinary team of specialists and subspecialists working together to establish the best treatment plan for each patient. Advanced molecular profiling of a patient’s tumor, combined with an extensive array of standard and experimental treatments available through clinical trials has lead to major advances in patient outcomes in the last few years. The program’s one-year survival rates for advanced lung cancer consistently run twice as high as the national average. The survival rates at five years run four times higher than the national average.

CU Cancer Center is the lead site for the national Lung Cancer Mutation Consortium, the collaboration of 14 of the nation’s elite lung cancer programs. The consortium is profiling ten different molecular abnormalities in lung cancer and pairing them with specific experimental treatments over the next few years.

Please consider supporting the Lung Cancer Colorado Fund. This unique fund is overseen by the physicians and scientists and supports all aspects of the Center’s and University of Colorado Hospital’s combined fight against lung cancer.

For an appointment with a University of Colorado physician, please call Tiffany Caudill, intake coordinator for the lung cancer program at 720-848-0392 or email tiffany.caudill@uch.edu. To request physician interviews, please call Erika Matich at 303-524-2780 or email erika.matich@ucdenver.edu.

Contact: Erika Matich
erika.matich@ucdenver.edu
303-524-2780
University of Colorado Denver

Strokes involve the sudden loss of blood flow to an area of the brain. According to the U.S. Centers for Disease Control and Prevention, nearly 800,000 Americans suffer a stroke each year. Stroke is the third leading cause of death for both men and women in the United States, accounting for more than 140,000 deaths per year. Ischemic strokes, the type assessed in this study, account for more than eight in ten strokes over all and occur when blood clots obstruct blood vessels to the brain. Nearly three-quarters of all strokes occur in those over 65.

Abnormal levels of triglycerides and other so-called lipid biomarkers have long been associated with increased risk for heart disease and atherosclerosis (plaque buildup inside arteries). The study’s senior author, Sylvia Wassertheil-Smoller, Ph.D. , said that “until this study, researchers had not examined how these lipid biomarkers are independently related to stroke risk in a single group of people.” Dr. Smoller is head of the division of epidemiology, professor of epidemiology & population health, and the Dorothy and William Manealoff Foundation and Molly Rosen Chair in Social Medicine at Einstein.

The Einstein researchers analyzed data from the Hormones and Biomarkers Predicting Stroke (HaBPS) study, which consists of women enrolled in the Women’s Health Initiative (WHI), the landmark National Institutes of Health study that has monitored the health of more than 90,000 postmenopausal women nationwide over a period of 15 years. HaBPS is comprised of the first 972 women who experienced an ischemic stroke while participating in the WHI. These women were matched with a control group of 972 participants who had not had strokes. All the women had donated blood samples when they first enrolled in the WHI, and these samples were analyzed for lipid biomarkers. (Dr. Wassertheil-Smoller is principal investigator of WHI and HaBPS at Einstein.)

“It’s important to note, many of the traditional measures of cholesterol that physicians use including total cholesterol and LDL cholesterol were not associated with risk of ischemic stroke,” said lead author of the study, Jeffrey S. Berger, M.D., assistant professor of medicine at the NYU School of Medicine. “Currently, there is a lack of data that lowering triglyceride levels can help reduce the risk. We believe future studies of people with elevated triglyceride levels are warranted to show the reduction of ischemic stroke.”

Dr. Wassertheil-Smoller and her colleagues found that women in the highest quarter of baseline triglyceride levels were nearly twice as likely to have suffered an ischemic stroke as women in the lowest quarter of triglyceride values. Levels of total cholesterol and LDL (”bad”) cholesterol were not associated with stroke risk.

“The bottom line is that postmenopausal women and their physicians need to pay attention to triglyceride levels,” Dr. Wassertheil-Smoller said. “We already know that women with elevated levels of triglycerides face a greater risk for heart disease and heart attacks than men do. This study has underlined the importance of abnormal triglyceride levels by establishing them as an independent risk factor for stroke.” Elevated triglyceride levels can be triggered by genetic factors or behavioral habits but can be successfully treated with medication and dietary and lifestyle changes, Dr. Smoller pointed out.

The paper is titled “Lipid and Lipoprotein Biomarkers and the Risk of Ischemic Stroke in Postmenopausal Women.” Co-authors include lead author Jeffrey Berger, M.D., M.S., NYU School of Medicine; Aileen McGinn, Ph.D. and Robert Kaplan, Ph.D., Einstein; Barbara V. Howard, Ph.D., MedStar Research Institute, Washington, DC; Lewis Kuller, M.D., Dr.PH., University of Pittsburg, Pittsburgh, PA; JoAnn E. Manson, M.D., Dr.PH., Brigham and Women’s Hospital, Boston, MA; Jim Otvos, Ph.D., Liposcience, Inc, Raleigh, NC; J. David Curb, M.D., John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI; Charles B Eaton, M.D., Memorial Hospital of Rhode Island, Pawtucket, RI; John K. Lynch, D.O., M.P.H., National Institute of Neurological Disorders and Stroke, Section on Stroke Diagnostics and Therapeutics; Daniel M. Rosenbaum, M.D., SUNY Downstate, Brooklyn, NY. The WHI is funded by the National Lung, and Blood Institute and HaBPS is funded by the National Institute of Neurological Disorders and Stroke.

About Albert Einstein College of Medicine of Yeshiva University

Albert Einstein College of Medicine of Yeshiva University is one of the nation’s premier centers for research, medical education and clinical investigation. During the 2009-2010 academic year, Einstein is home to 724 M.D. students, 248 Ph.D.students, 117 students in the combined M.D./Ph.D. program, and 368 postdoctoral research fellows. The College of Medicine has 2,522 fulltime faculty members located on the main campus and at its clinical affiliates. 2011, Einstein received nearly $170 million in awards from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore Medical Center, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Through its extensive affiliation network involving Montefiore, Jacobi Medical Center – Einstein’s founding hospital, and five other hospital systems in the Bronx, Manhattan, Long Island and Brooklyn, Einstein runs one of the largest post-graduate medical training programs in the United States, offering approximately 155 residency programs to more than 2,200 physicians in training. For more information, please visit http://www.einstein.yu.edu/home/default.asp and follow us on Twitter @EinsteinMed.

Contact: Kim Newman
sciencenews@einstein.yu.edu
718-430-3101
Albert Einstein College of Medicine

Leishmaniasis is named after William Leishman, a Glasgwegian doctor serving with the British Army in India, who first identified the parasite in the early 1900s. The disease is the second biggest killer in Africa, Asia and Latin America after malaria, and affects 500,000 people, killing about 50-60,000 patients per year. Current drug treatments for the disease are unsatisfactory for reasons such as high cost, drug resistance or the need for hospitalisation.

Fexinidazole is already in phase 1 clinical trials for a related disease - African sleeping sickness – but a research team at Dundee including Dr Susan Wyllie, Professor Alan Fairlamb and colleagues has identified it as having potential in treating leishmaniasis.

Their research has been published by the journal Science Translational Medicine, and was funded by the Wellcome Trust.

Tests in mice showed that the drug has a greater than 98% rate of suppressing infection of leishmaniasis, comparable to current treatments such as miltefosine and Pentostam.

These and other existing treatment options all suffer from disadvantages; they are not always safe, effective or easy to administer. The only oral drug miltefosine cannot be given to women of child-bearing age due to a substantial risk of birth defects; other drugs are costly and have to be given by injection. Thus there is a continuing need for safe and cost-effective drugs suitable for use in resource-poor settings.

Professor Fairlamb said that fexinidazole has the potential to become a safe and effective oral drug therapy for treating the severest form of visceral leishmaniasis.

“Visceral leishmaniasis is a neglected disease of poverty which causes huge problems across Africa, Asia and Latin America, killing tens of thousands of people every year,” said Professor Fairlamb.

“The current treatments are far from ideal and we need to find better, cheaper and more easily delivered drugs to tackle the disease. Our research suggests that fexinidazole has strong potential to do that.

“Drugs for Neglected Diseases initiative have already established that fexinidazole is safe in early clinical trials for African sleeping sickness, so it is some way along the development path.

“This has been a great team effort and I would like to acknowledge the dedication and enthusiasm of the biologists, chemists and pharmacologists involved in this discovery.”

Professor Fairlamb and colleagues are based in the College of Life Sciences at Dundee, which houses the Drug Discovery Unit, formed in 2005 specifically to fill the void of research and development of drug targets for diseases of poverty like African sleeping sickness, leishmaniasis, and Chagas’ disease that afflict the developing world.

Professor Fairlamb cited the inspiration of the University’s former Chancellor, the Nobel prize-winning pharmacologist Sir James Black, in carrying out the research on fexinidazole.

“Sir James always liked to remind me that `the most fruitful basis for the discovery of a new drug is to start with an old drug’. This adage is particularly apt in the search for effective drugs to treat neglected tropical diseases such as visceral leishmaniasis,” said Professor Fairlamb. “Indeed, two of the existing anti-leishmanial drugs, miltefosine and amphotericin B, are examples of medicines originally developed for other purposes - anti-cancer and anti-fungal, respectively.

“Our hope is that fexinidazole can follow them and provide relief from a disease that is a major blight across the world.”

Notes to editors:

The University of Dundee is renowned for its academic contributions to tropical disease research. Many disciplines towards the discovery of new therapies for tropical diseases are combined, with 76 scientists working in and collaborating with the Drug Discovery Unit.

The Drug Discovery Unit (http://www.drugdiscovery.dundee.ac.uk) within the College of Life Sciences at Dundee has been created to respond to a lack of capacity in the UK for early stage drug discovery in the academic sector. The DDU’s aim is to translate basic science into lead compounds to validate putative drug targets, to use as tools to investigate disease pathways and, when appropriate, advance to pre-clinical drug candidates.

The drug discovery programme at the University matches the goals of the Drugs for Neglected Diseases Initiative (http://www.dndi.org), Medicines for Malaria Venture (http://www.mmv.org) and the UNICEF-UNDP-World Bank-WHO Special Programme for Research and Training in Tropical Diseases.

The complete project, from inception and including the construction and equipping of the new state-of-the-art laboratories, is expected to cost around £25 million to 2016.

Investors include the Wellcome Trust, the Scottish Funding Council, The Wolfson Foundation, The European Regional Development Fund, the Drugs for Neglected Diseases Initiative and the University itself.

Roddy Isles
Head of Press
University of Dundee
Nethergate, Dundee, DD1 4HN.
TEL: 01382-384910
MOBILE: 07800-581902
E-MAIL: r.isles@dundee.ac.uk

The University of Dundee is a Scottish Registered Charity, No. SC015096

Contact: Roddy Isles
r.isles@dundee.ac.uk
44-138-238-4910
University of Dundee

Results from the study at the University of Leeds, published in Dalton Transactions, show that particular silver compounds are as toxic to cancer cells as the platinum-based drug Cisplatin, which is widely used to treat a range of cancers.

But the crucial difference is that silver is thought to be much less toxic to healthy human cells, and in some cases, can be beneficial. Silver is currently used for its antiseptic and antibiotic properties, in bandages, wound dressings and water purification filters in the third world.

Nausea and vomiting, kidney damage and an increased risk of infection are common side effects of Cisplatin which is used to treat cancer of the lungs, breast, bladder, testicles, head and neck, ovaries and lymph nodes.

Dr Charlotte Willans who is leading the study said: “As many are unfortunately aware, chemotherapy can be a very gruelling experience for the patient. Finding effective, yet non-toxic drugs is an ongoing problem, but these preliminary results are an important step in solving it.”

“Our research has looked at the structure which surrounds a central silver atom. This ’shrubbery’ is what determines how reactive it is and what it will interact with. Our research has used different types of these ligands to see which is the most effective against cancer cells,” adds Dr Willans.

The research, still the first phase of drug development, involved exposing breast and colon cancer cells with different silver-based chemicals for six day periods. It has been shown that ligands which are co-ordinately bonded to the central silver atom through two sites are more effective than those coordinated through only one site. This may be due to the release of silver being much slower and make these compounds more effective over a longer period of time.

A major barrier to the continued development of these compounds is a lack of understanding of how they work. Over the next 12 months, research will focus on investigating how the compounds damage cancerous cells and what effects they have on healthy cells. This will establish whether these silver complexes are in fact less toxic to ordinary human tissue, and will help to design and develop the next-generation of chemotherapy drugs. This work is been carried out in collaboration with Dr. Roger Phillips at the University of Bradford and is funded by Yorkshire Cancer Research.

The paper Enhanced cytotoxicity of silver complexes bearing bidentate N-heterocyclic carbene ligands will be published in Dalton Transactions and can be found online here: http://pubs.rsc.org/en/content/articlelanding/2012/dt/c2dt12399a .

For more information

Contact Richard Mellor
Media Relations Assistant, University of Leeds
T: 0113-34-34031
E: r.d.mellor@leeds.ac.uk

Notes to Editor:

1. The 2008 Research Assessment Exercise showed the University of Leeds to be the UK’s eighth biggest research powerhouse. The University is one of the largest higher education institutions in the UK and a member of the Russell Group of research-intensive universities. The University’s vision is to secure a place among the world’s top 50 by 2015. www.leeds.ac.uk

Contact: Richard Mellor
r.d.mellor@leeds.ac.uk
44-011-334-34031
University of Leeds

Now Daniel Weiss at the Vermont Lung Center (Principal Investigator for this project) in collaboration with Cheryl Nickerson and her colleagues at the Biodesign Institute at Arizona State University are exploring a radically new approach for developing viable lung tissue suitable for transplantation. The technique is being developed under a $3.4 million grant from the NIH to Dr. Weiss, $1.2 million of which is going to Dr. Nickerson for these studies. If successful, it could ultimately provide a virtually limitless supply of donor lung tissue while avoiding the host rejection that has long plagued organ transplantation.

While some biological structures (including bladder and skin) may be grown in the laboratory, building a complex organ like a lung from scratch is outside the realm of current medical technologies. The method under study instead involves audacious new techniques of tissue engineering. An organ extracted from a cadaver is chemically stripped of cells—a process known as decellularization—leaving behind a delicate architecture of the extracellular matrix. This scaffold is then recellularized—that is, repopulated using stem cells drawn from the intended transplant recipient.

Though they occur in all multicellular organisms, stem cells are exceptional biological entities. Different types of stem cells are being investigated in this study for the successful repopulation of the decellularized lung scaffolds. These cell types include pluripotent and multipotent stem cells. As their name implies, ‘pluripotent’ cells have the remarkable ability to form virtually any cell type in the body, including cardiac, muscle, neuron and the variety of cell types making up a functioning lung. Multipotent stem cells can give rise to a more limited number of lineages than pluripotent stem cells, but they are easier to obtain from patients and involve less downstream risks.

The working hypothesis of this study is that when stem cells are applied to the decellularized lung scaffolding, they take up residence throughout the structure, differentiating into the appropriate tissue and vasculature of a normal lung. It is believed that subtle chemical as well as mechanical forces direct this metamorphosis.

As Nickerson explains, this process of stem cell differentiation and rebuilding is assisted by placing the cells in a rotating wall bioreactor—a device that gently circulates fluid and oxygen through the cells in such a way as to mimic conditions during fetal development. Nickerson hypothesizes that the decellularized scaffolding subjected to this environment will help guide the stem cells adhering to this template to multiply and mature into the cell types essential for a functioning lung. Because the replacement organ is constructed with the recipient’s own cells, issues of immune rejection are minimal.

As the lungs under study are recellularized, they can be carefully evaluated in terms of biomechanics, vascular perfusion and normal lung phenotype, including the production of surfactants—lipoproteins essential for proper functioning of pulmonary alveoli. To accomplish the ambitious goals of the project, Nickerson and research assistant scientists in her laboratory, Aurélie Crabbé and Shameema Sarker, are part of a multidisciplinary team, which includes experts in lung biology, stem cells and regenerative medicine, thoracic surgery and bioengineering.

In addition to the NIH grant, work related to the lung recellularization project was honored as a recipient of the 2010 ASU/Mayo Clinic Seed Grant program. A review committee, made up of physicians and researchers from ASU and the Mayo Clinic, Phoenix, selected the work as one of the most outstanding grant proposals to be awarded funding. “Our end goal is to build new lungs from patient’s own cells, overcoming the need for donor organs,” says researcher Crabbé. “I am thrilled to be part of this exciting effort.”

In addition to her appointment at the Biodesign Institute, Cheryl Nickerson is a professor in the College of Liberal Arts and Sciences, School of Life Sciences.

Written by: Richard Harth
Science Writer: The Biodesign Institute
richard.harth@asu.edu

Contact: Joseph Caspermeyer
Joseph.Caspermeyer@asu.edu
Arizona State University

Their study, published in the Feb. 1 issue of Neurosurgical Focus, suggests this tool, known as frontal near-infrared spectroscopy (NIRS), could offer hospital physicians a safe and cost-effective way to monitor patients who are being treated for a stroke, in real time.

“About one-third of stroke patients in the hospital suffer another stroke, and we have few options for constantly monitoring patients for such recurrences,” says the study’s senior investigator, neurocritical care specialist William Freeman, M.D., an associate professor of neurology at Mayo Clinic.

“This was a small pilot study initiated at Mayo Clinic’s campus in Florida, but we plan to study this device more extensively and hope that this bedside tool offers significant benefit to patients by helping physicians detect strokes earlier and manage recovery better,” he says.

Currently, at most hospitals nurses monitor patients for new strokes and, if one is suspected, patients must be moved to a hospital’s radiology unit for a test known as a CT perfusion scan, which is the standard way to measure blood flow and oxygenation. This scan requires that a contrast medium be used, and the entire procedure can sometimes cause side effects such as excess radiation exposure if repeated scans are required. Also, potential kidney and airway damage can result from the contrast medium.

Alternately, for the sickest patients, physicians can insert an oxygen probe inside the brain to measure blood and oxygen flow, but this procedure is invasive and measures only a limited brain region, Dr. Freeman says.

This NIRS device, which emits near-infrared light that penetrates the scalp and underlying brain tissue, has been used in animals to study brain blood, so the Mayo Clinic team thought that measuring the same parameters in stroke patients might be useful. They set up a study to compare measurements from NIRS with CT perfusion scanning in eight stroke patients.

The results show that both tests offer statistically similar results, although NIRS has a more limited field for measuring blood oxygen and flow. “That suggests that perhaps not all patients would benefit from this kind of monitoring,” he says.

The device sticks like an adhesive bandage onto each of the patient’s eyebrows and works like the pulse oximeter that is usually used on a patient’s finger to monitor health or brain perfusion during surgery.

If the device is successfully tested in upcoming studies and miniaturized, the NIRS might also be useful in military settings to assess and monitor blood functioning due to brain injuries, Dr. Freeman says.

Researchers from the University of South Florida College of Medicine and the University of North Florida College of Medicine participated in the study, along with several college students who were participating in Mayo Clinic’s Clinical Research Scholar Program (CRISP).

“This research could not have been accomplished without the dedication and assistance from our CRISP premedical student Brandon O’Neal, and vascular neurosurgery fellow Philipp Taussky, M.D.,” notes Dr. Freeman. “We are excited about the future possibilities in which this tool would be very useful.”

The study was approved by the Mayo Clinic IRB and not sponsored or funded by any company. The authors declare no conflicts of interest.

About Mayo Clinic
Mayo Clinic is a nonprofit worldwide leader in medical care, research and education for people from all walks of life. For more information, visit www.mayoclinic.org/about/ and www.mayoclinic.org/news2010-jax/5837.html.

Contact: Cindy N. Weiss
weiss.cynthia@mayo.edu
904-953-2299
Mayo Clinic