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Study shows blood markers can help choose best dose for antiangiogenic drugs

10-25-2007 · EurekAlert!

Scientists at Sunnybrook have new information that may help to improve the use of anti-cancer drugs designed to block the growth of new blood vessels in tumors, a process called angiogenesis that is critical to tumor growth. While these antiangiogenic drugs are effective, at present there are no reliable methods for determining whether they are working, if the right dose is used, or if a patient will benefit from treatment.

Keywords: study, shows, blood, markers, choose, dose, antiangiogenic, drugs, show, marker, drug

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Advance in understanding of blood pressure gene could lead to new treatments
02-04-2007 · EurekAlert!
Research by scientists at UCL (University College London) has clearly demonstrated for the first time the structure and function of a gene crucial to the regulation of blood pressure. The discovery could be important in the search for new treatments for illnesses such as heart disease, the UK's biggest killer. In a paper published online today in Nature Medicine, the team, led by Professor Patrick Vallance and Dr James Leiper, UCL Department of Medicine, reveal the role of the human gene dimethylarginine dimethylaminohydrolase (DDAH), showing that loss of DDAH activity disrupts nitric oxide (NO) production. NO is critical in the regulation of blood pressure, nervous system functions and the immune system. The role of DDAH is to break down modified amino acids (Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA)) that are produced by the body and have been shown to inhibit NO synthase. These molecules accumulate in various disease states including diabetes, renal failure and pulmonary and systemic hypertension, and their concentration in plasma (the fluid component of blood) is strongly predicative of cardiovascular disease and death. In a healthy human body, the majority of ADMA is eliminated through active metabolism by DDAH. Scientists have hypothesised that if DDAH function is impaired, NO production is reduced, and that this could be an important feature of increased cardiovascular risk. To examine this pathway in more detail, the researchers deleted the DDAH gene in mice. These mice went on to develop hypertension, or high blood pressure. They also designed specific inhibitors (small molecules) which bind to the active site of human DDAH. These small molecule inhibitors also induced hypertension in mice, confirming the importance of DDAH in the regulation of blood pressure. Dr Leiper, UCL Medicine, said: “These genetic and chemical approaches to disrupt DDAH showed remarkably consistent results, and provide compelling evidence that loss of DDAH function increases the concentration of ADMA and thereby disrupts vascular NO signalling. “There has been considerable scientific interest in this pathway and the role of ADMA as a novel risk factor, but so far there's been little evidence to support the idea that it's a cause of disease, rather than just a marker. Genes and their pathways are crucial to our understanding of cardiovascular disease and a better understanding of DDAH-1 could lead to important new treatments. “It could help us to establish if genetic variation predisposes certain people to these diseases, or whether environmental factors exert some of their effects through modulation of DDAH activity. “Our research also shows that this pathway could be harnessed therapeutically to limit production of NO in certain situations where too much nitric oxide is a bad thing; for example, hypotension and septic shock. These are some of the biggest problems in intensive care medicine and there is a huge unmet need for drug treatments.” The study, which was carried out at UCL's Rayne Institute, was funded by grants from the British Heart Foundation, the Wellcome Trust and the Medical Research Council. Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, said: "The unexpected finding in the 1980s that a simple gas, nitric oxide (NO), is made by cells in the blood vessel wall and is a powerful control of blood vessel relaxation led to the award of the Nobel Prize in 1998 to its discoverers. "More recently, there has been increasing evidence that impairment of NO production is likely to be an important factor in the development of heart and circulatory disease, but the mechanisms responsible are not fully understood. "This study suggests for the first time that the loss of the activity of the enzyme DDAH-1 leads to reduced NO production and may cause heart and circulatory disease. These findings are likely to be important in the search for new ways to optimise the health of our blood vessels." ### Notes for Editors 1. For more information, please contact Ruth Metcalfe in the UCL Media Relations Office on tel: +44 (0)20 7679 9739, mobile: +44 (0)7990 675 947, out of hours: +44 (0)7917 271 364, e-mail: r.metcalfe@ucl.ac.uk2. 'Disruption of methylarginine metabolism impairs vascular homeostasis' is published in the February issue of the journal Nature Medicine. Advance online publication is embargoed to 18.00 GMT (13.00 US Eastern) Sunday 4 February 2007. Journalists can obtain copies of the paper by contacting the UCL Media Relations Office.3. The study was funded by the British Heart Foundation, the Wellcome Trust and the Medical Research Council. About UCL Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government's most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence. UCL is the fourth-ranked UK university in the 2006 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Mahatma Gandhi (Laws 1889, Indian political and spiritual leader); Jonathan Dimbleby (Philosophy 1969, writer and television presenter); Junichiro Koizumi (Economics 1969, Prime Minister of Japan); Lord Woolf (Laws 1954, Lord Chief Justice of England & Wales); Alexander Graham Bell (Phonetics 1860s, inventor of the telephone), and members of the band Coldplay.
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Some drug studies more likely to have favorable conclusions
11-16-2007 · EurekAlert!
Previous work has shown that, when a drug study was funded by the company that made that drug, the results might be biased in favour of that drug because the methods or analyses were manipulated. New research published online today shows that, for blood pressure drugs, studies are now much less likely to have biased results but still tend to have overly positive conclusions favoring the company's products.
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Discovery of an HIV inhibitor in human blood points to new drug class
04-19-2007 · EurekAlert!
A new study has pinpointed a natural ingredient of human blood that effectively blocks HIV-1, the virus predominantly responsible for human AIDS, from infecting immune cells and multiplying. The virus blocker might play a role in the progression of HIV to full-blown AIDS and -- because it works in a different way than existing antiretroviral inhibitors -- could lead to the development of another class of drugs in the fight against the pandemic disease.
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Study finds drug spending caps cause some seniors to quit taking key medicines
09-11-2007 · EurekAlert!
Many seniors quit taking drugs for chronic illnesses such as diabetes and high blood pressure when they exceed their drug plan's yearly spending limits, according to a RAND Corp. study. The report, which examines the behavior of seniors enrolled in a private health plan, provides insight into how seniors may act under provisions of Medicare's new drug benefit plan that will leave about one-third of enrollees without drug coverage for some part of each benefit year.
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Plants can be used to study how and why people respond differently to drugs
09-26-2007 · EurekAlert!
While prescription medications work successfully to cure an ailment in some people, in others the same dose of the same drug can cause an adverse reaction or no response at all. According to a research team led by UC Riverside's Sean Cutler, such variation in drug responses can be analyzed by studying much simpler organisms -- like plants.
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Treatment extends survival in mouse model of spinal muscular atrophy
02-22-2007 · EurekAlert!
Drug therapy can extend survival and improve movement in a mouse model of spinal muscular atrophy (SMA), new research shows. The study, carried out at the NIH's National Institute of Neurological Disorders and Stroke (NINDS), suggests that similar drugs might one day be useful for treating human SMA.
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Bioabsorbable stent shows excellent performance
03-24-2007 · EurekAlert!
The use of slow-release drugs in stents (drug-eluting stents) has dramatically reduced restenosis rates after percutaneous coronary intervention. However, these permanent metal devices may impair coronary imaging, predispose patients to late stent thrombosis, prevent positive remodeling and hinder revascularization. A study presented today at the American College of Cardiology's Innovation in Intervention: i2Summit assesses the safety and performance of a bioabsorbable stent that, if effective, could eliminate several of the problems associated with metallic stents.
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Drug linked to increase in brain hemorrhage cases
01-08-2007 · EurekAlert!
The rate of brain hemorrhages associated with blood thinning drugs quintupled during the 1990s, according to a study published in the January 9, 2007, issue of Neurology, the scientific journal of the American Academy of Neurology. In people over age 80, the rate increased more than tenfold.
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Blood pressure drug telmisartan shows powerful activity against stroke
12-12-2007 · EurekAlert!
Telmisartan, a drug widely used to help control blood pressure, may have uniquely potent activity in preventing stroke, according to a new study conducted in an animal model.
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Pilot study shows withdrawal drug offers symptom relief to Crohn's sufferers
02-02-2007 · EurekAlert!
A Penn State College of Medicine pilot study suggests a low dose of naltrexone, a drug used to ease symptoms of alcohol and drug addiction, may also bring relief to people with Crohn's disease, a chronic inflammatory disorder of the intestine that affects an estimated 500,000 Americans. The study results were released online this week in an early edition of the American Journal of Gastroenterology.
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