More Progress in Use of Aspirin to Prevent Colon Cancer

from fiercebiotech.com

Aspirin has a shot at graduating from its long-term role as a headache fighter and impromptu blood thinner to a heady new role as an anti-cancer pill. The key: a little bit of gas.

Scientists at The City College of New York are developing a beefed-up aspirin that has helped reduce human colon cancer tumors implanted in mice by 85 percent, The U.K.'s The Telegraph, UPI, the Daily Mail and other news outlets report. What's also key here is that the aspirin didn't cause side effects that too much aspirin typically leave behind in humans--stomach ulcers and other digestive problems.

Lead researcher Khosrow Kashfi explained to UPI that the new compound, a unique formulation dubbed NOSH aspirin, is "very, very potent and yet it has minimal toxicity to the cells." The finding builds on previous research by Oxford University and others that showed 75 mg of aspirin a day can reduce the chance of developing some cancers by as much as 50 percent, but some patients faced stomach ulcers and other problems as a result, according to the media outlets' stories.

The City College of New York researchers added nitric oxide and hydrogen sulfide to beef up its effectiveness by helping to protect the stomach wall from damage and enhance aspirin's ability to fight cancer, respectively, the Daily Mail explains. The study, the article points out, made the NOSH-aspirin 100,000 times more potent than aspirin on its own just 24 hours after treating a cancer cell culture. That number grows, in vitro, to 250,000 times more potency.

The U.K. research and the stomach-ulcer fallout is something that should prevent you from running out to the drug store and picking up lots of aspirin to beat back or prevent cancer. You'd kill your stomach, for one thing, before you even come close to promising results, even if those consumer formulations were enough to do the job. The articles also note, however, that The City College of New York researchers are years away from testing their compound in humans for formal clinical trials.

If they're successful in larger scale animal trials and then testing the compound in people, the scientists believe that they could use the drug well beyond colon cancer to also treat lung, breast, prostate, pancreas and blood cancers.

Advil and Motrin Can Raise Risk of Crohn's

A new look at the 18-year-long Nurses' Health Study of more than 75,000 women confirms a link between the development of Crohn's and ulcerative Colitis and frequent use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as Motrin and Advil. The study, published in the Annals of Internal Medicine, found frequent use of NSAIDs, but not aspirin, was associated with increased incidence of the Inflammatory Bowel Diseases.

High doses of nonsteroidal anti-inflammatory drugs, longer duration of use, or greater frequency of use were all associated with an increased risk for Crohn's disease and ulcerative colitis, according to the study.

Compared with nonusers, women who used NSAIDs for more than 15 days a month faced a greater risk for Crohn's disease and ulcerative colitis. Women who used more than 5 tablets of NSAIDs per week also saw an elevated risk for Crohn's disease compared with women with more than 6 years of NSAID use.

Although significant advances have been made in understanding the genetics of Crohn's disease and ulcerative colitis, with up to 99 genetic variations associated with the 2 conditions, genetic changes explain only about one third of the risk for the diseases, suggesting that environment has a big influence on why someone gets either Crohn's disease or ulcerative colitis, said Dr. Ananthakrishnan, who was lead author on the study.

The researchers conducted a prospective cohort study of 76,814 women enrolled in the Nurses' Health Study (NHS). Since 1990, the NHS has captured data on aspirin and NSAID use. Gastroenterologists subsequently confirmed diagnoses of Crohn's disease or ulcerative colitis.

The data drew upon more than 18 years of data, including 123 confirmed incident cases of Crohn's disease and 117 cases of ulcerative colitis. The mean age of the cohort in 1990 was 57 years. The researchers used Cox proportional hazards models to examine the relative risks for Crohn's disease and ulcerative colitis after adjusting for possible confounders, including smoking, menopausal status, and hormone use. In all, 44% of women reported regular use of aspirin and 37% said they regularly used NSAIDs at baseline.

Dr. Ananthakrishnan cautioned against overinterpreting the results of the study. "It's very important to recognize you have to weigh the risks and benefits," he said. For someone who doesn't have Crohn's or ulcerative colitis, the absolute risk is fairly small. Perhaps 15 in 100,000 people risk getting the conditions.

More studies are needed to compare the safety of these agents, he said, noting that people are more likely to take high-dose NSAIDs and take NSAIDs more frequently for pain relief. Those who take aspirin for cardiac protection tend to take low doses. "We don't know if you take the same dose of NSAIDs or aspirin, if they are equally safe or equally dangerous," he said.

Bruce Sands, MD, MS, chief of the Division of Gastroenterology and Burrill B. Crohn professor of medicine at Mount Sinai Hospital in New York, New York, said he found the study "a very provocative, interesting, and well-done work."

Research Confirms Link Between Cardiovascular and Immune Systems

from medicalxpress.com

The findings suggest that the effects of chronic stress on cardiovascular health may be a side effect of having an immune system that can defend us from infection. The results also have potential implications for treating bothhigh blood pressure and anxiety disorders.

The results are published in the journal Biological Psychiatry.

"Chronic stress has long been known to have harmful effects on the immune system as well as being a risk factor for hypertension," says lead author Paul Marvar, a postdoctoral fellow at Emory University School of Medicine. "Our goal was to examine the role of T cells in stress-dependent hypertension."

Marvar began his research under the guidance of David Harrison, MD, who moved from Emory to Vanderbilt University in 2011. He completed his work in the laboratory of Kerry Ressler, MD, PhD. Ressler is a Howard Hughes Medical Institute investigator and professor of psychiatry and behavioral sciences at Emory, and maintains a laboratory at Yerkes National Primate Research Center.

In the current study, researchers subjected mice to psychological stress by confining them in a small space for one hour and then putting them in cages where other mice had already left their scents. Two hours of stress per day, for a week, results in a rise in blood pressure from around 115 to 125 mm Hg for normal mice.

However, mice that were genetically engineered to lack T cells did not display an increase in blood pressure under the same regimen. Introducing T cells into mice that lacked them made their blood pressure sensitive to stress again.

Harrison and his colleagues had previously shown that T cells are needed for the increase in blood pressure coming from high dietary salt or the hormone angiotensin, which regulates blood pressure.

Several studies in animals have suggested that medications now used to control blood pressure, such as angiotensin receptor blockers or ACE (angiotensin converting enzyme) inhibitors, may also be helpful in the reduction of stress and anxiety, Marvar says.

"Further understanding the mechanisms underlying these observations and determining whether they may benefit people with anxiety disorders, for example post-traumatic stress disorder (PTSD) is a current goal of my research," he says.

High blood pressure is a risk factor for heart attack and stroke, and many people take medications to reduce their blood pressure. Yet some find that medications are not effective in controlling their blood pressureRese, and researchers are investigating various alternative approaches.

"There are still many unanswered questions about clinical relevance and safety in treating hypertensive patients by targeting the immune system," Marvar says. "Understanding what triggers the immune response in hypertension will ultimately guide the feasibility of future clinical applications."

The Dream of Human Immortality Tonics Lives On--In Worms

from fiercebiotech.com

Drug developers have long dreamed of discovering a tonic to trip up the aging process, hunting for genetic clues and compounds that could provide a fountain of youth. U.K. researchers say they have found a recipe for immortality--in flatworms. But the worm study might shine a light on ways to prolong human life too, investigators said.

The University of Nottingham researchers dug deeper into the mechanisms that allow flatworms to regenerate tissue in a prolific manner. Chop one of these slimy planarians in half, and two complete worms will grow from the halves--and so on and so on until you end up with thousands of them. What the researchers found was that these worms maintain the length of a component of DNA known as telomeres, which are known for protecting chromosomes and maintaining cell functions, Reuters reported. Shortened telomeres, on the other hand, are markers of short lifespans.

Building on past telomere research that garnered a Nobel Prize in 2009, lead researcher Aziz Aboobaker and his team found that levels of telomerase, an enzyme associated with the telomere gene, rose as the worms were regenerating tissues. And the organism's ability to keep healthy supplies of the enzyme throughout life offers the potential for the worms to be immortal, according to The Telegraph's report on the findings.

"Our data satisfy one of the predictions about what it would take for an animal to be potentially immortal," said Aboobaker, as quoted by Reuters. "The next goals for us are to understand the mechanisms in more detail and to understand more about how you evolve an immortal animal."

The U.K. researcher isn't alone in his quest, and biotech companies have already trudged down the telomere trail, with little to show for it at this point. Harvard researchers have done some telomere tinkering in mice, showing they could activate growth of brains and testes in the critters. And former Geron scientist Bill Andrews, of course, has evangelized the promise of telomeres to lead to new anti-aging drugs, gaining lots of publicity for his views and fending off the naysayers who have tried to discredit him. 

No drugs from the research have yet arrived, but the telomere believers and the quest for new anti-aging remedies won't quit. 

Read more

With Help from Author Laura Hillenbrand, Drug Repurposing Comes to Chronic Fatigue Syndrome

from wsj.com

The CFIDS Association of America says that $2 million in funding — backed by individual gifts including a $250,000 donation from best-selling writer Laura Hillenbrand, who has chronic fatigue syndrome– is going to grants and projects designed to accelerate the development of treatments for CFS.

One of the new projects: an attempt at so-called drug repurposing, when already-approved drugs for one indication are tried in a different disease.

As the WSJ has reported, drug repurposing is getting a big push from a number of quarters, including the NIH, which is targeting repurposing efforts in rare diseases, and organizations such as the ALS Therapy Development Institute, which recently reported that an approved multiple sclerosis drug appeared to be effective in mice with ALS.

The high cost of developing new therapies has helped drive recent interest in drug repurposing. The concept is that a drug already approved for one condition will cost less and move faster into the clinic if it turns out to also work in a different disease. Nonetheless, at first glance, CFS might seem an unusual condition in which to try drug repurposing.

CFS has no known cause. Doctors usually make the diagnosis by ruling out other problems. Many of the symptoms — including muscle and joint pain, cognitive dysfunction, headaches, and unrefreshing sleep — are very difficult to treat. There is currently no FDA-approved drug for CFS.

read the story at wsj.com