New treatment for marfan syndrome shows promise

In continuation of my update on Losartan

The results are being presented Nov. 18 at the American Heart Association's annual meeting in Chicago and will appear online the same day in The New England Journal of Medicine.

"For years, standard medical therapy for Marfan syndrome consisted of giving patients beta blockers, which lower heart rate and blood pressure, reducing stress on the wall of the aorta," said study co-author Alan C. Braverman, MD, a cardiologist at Washington University School of Medicine in St. Louis. "This new study suggests that we have a second option for patients that appears to be as effective as standard treatment."

The second option is Losartan (see above structure) , an angiotensin receptor blocker. Past research in mice and smaller clinical trials suggested that this class of drugs might actually be superior to beta blocker treatment for Marfan syndrome. Angiotensin receptor blockers commonly are prescribed to treat high blood pressure.

People with Marfan syndrome have weak connective tissues and tend to develop unusually long arms, legs and fingers. In addition to heart problems, patients often develop problems with the eyes, lungs, bones and joints. Patients with the condition are at high risk of sudden death from a tear in the aorta, also called an aortic dissection.

Though there is no cure for Marfan syndrome, treatment with beta blockers and preventive surgery to replace the section of the aorta adjacent to the heart has increased lifespan to near normal. But physicians have continued to look for more effective therapies, especially since some patients on beta blockers experience side effects such as tiredness and nausea.

So investigators in the Pediatric Heart Network of the National Institutes of Health (NIH), including Braverman and senior author Ronald V. Lacro, MD, a cardiologist at Harvard Medical School and Boston Children's Hospital, conducted a clinical trial comparing the beta blocker Atenolol with Losartan.

The study included 608 patients with Marfan syndrome at 21 medical centers nationwide. Patients were ages 6 months to 25 years and had enlarged aortas. Half of these participants were randomly given Losartan, the investigational treatment, and the other half received Atenolol, the standard therapy, but in higher doses than physicians typically prescribe to see if this would increase the beta blocker's effectiveness.

After following participants for three years, the investigators reported no differences between the two groups in the growth rate of the aorta. They further observed similar rates of tears in the aorta, similar numbers of surgeries required to repair these tears and no difference in the number of deaths between the two groups.

New treatment for marfan syndrome shows promise  

New treatment for marfan syndrome shows promise

The results are being presented Nov. 18 at the American Heart Association's annual meeting in Chicago and will appear online the same day in The New England Journal of Medicine.

"For years, standard medical therapy for Marfan syndrome consisted of giving patients beta blockers, which lower heart rate and blood pressure, reducing stress on the wall of the aorta," said study co-author Alan C. Braverman, MD, a cardiologist at Washington University School of Medicine in St. Louis. "This new study suggests that we have a second option for patients that appears to be as effective as standard treatment."

The second option is Losartan, an angiotensin receptor blocker. Past research in mice and smaller clinical trials suggested that this class of drugs might actually be superior to beta blocker treatment for Marfan syndrome. Angiotensin receptor blockers commonly are prescribed to treat high blood pressure.

People with Marfan syndrome have weak connective tissues and tend to develop unusually long arms, legs and fingers. In addition to heart problems, patients often develop problems with the eyes, lungs, bones and joints. Patients with the condition are at high risk of sudden death from a tear in the aorta, also called an aortic dissection.

Though there is no cure for Marfan syndrome, treatment with beta blockers and preventive surgery to replace the section of the aorta adjacent to the heart has increased lifespan to near normal. But physicians have continued to look for more effective therapies, especially since some patients on beta blockers experience side effects such as tiredness and nausea.

So investigators in the Pediatric Heart Network of the National Institutes of Health (NIH), including Braverman and senior author Ronald V. Lacro, MD, a cardiologist at Harvard Medical School and Boston Children's Hospital, conducted a clinical trial comparing the beta blocker Atenolol with Losartan.

The study included 608 patients with Marfan syndrome at 21 medical centers nationwide. Patients were ages 6 months to 25 years and had enlarged aortas. Half of these participants were randomly given Losartan, the investigational treatment, and the other half received Atenolol, the standard therapy, but in higher doses than physicians typically prescribe to see if this would increase the beta blocker's effectiveness.

After following participants for three years, the investigators reported no differences between the two groups in the growth rate of the aorta. They further observed similar rates of tears in the aorta, similar numbers of surgeries required to repair these tears and no difference in the number of deaths between the two groups.

New treatment for marfan syndrome shows promise  

Chemical compound in coffee may help prevent damaging effects of obesity

In continuation of my update on chlorogenic acid

Researchers at the University of Georgia have discovered that a chemical compound commonly found in coffee may help prevent some of the damaging effects of obesity.

In a paper published recently in Pharmaceutical Research, scientists found that chlorogenic acid, or CGA, significantly reduced insulin resistance and accumulation of fat in the livers of mice who were fed a high-fat diet.

"Previous studies have shown that coffee consumption may lower the risk for chronic diseases like Type 2 diabetes and cardiovascular disease," said Yongjie Ma, a postdoctoral research associate in UGA's College of Pharmacy and lead author of the paper. "Our study expands on this research by looking at the benefits associated with this specific compound, which is found in great abundance in coffee, but also in other fruits and vegetables like apples, pears, tomatoes and blueberries."

During the past 20 years, there has been a dramatic increase in obesity in the United States. More than one-third of U.S. adults and approximately 17 percent of children are obese, according to the Centers for Disease Control and Prevention, and the annual medical cost of obesity is more than $147 billion.

Aside from weight gain, two common side effects of obesity are increased insulin resistance and the accumulation of fat in the liver. Left untreated, these disorders can lead to diabetes and poor liver function.

To test the therapeutic effects of CGA, researchers fed a group of mice a high-fat diet for 15 weeks while also injecting them with a CGA solution twice per week.

Chemical compound in coffee may help prevent damaging effects of obesity

Cholesterol-fighting statins inhibit uterine fibroid tumors that account for 50% of hysterectomies...

In continuation of my update on simvastatin

Researchers at the University of Texas Medical Branch at Galveston, in collaboration with The University of Texas Health Science Center at Houston (UTHealth), Baylor College of Medicine and the Georgia Regents University, report for the first time that the cholesterol-lowering drug simvastatin inhibits the growth of human uterine fibroid tumors. These new data are published online and scheduled to appear in the January print edition of the Journal of Biological Chemistry.

Statins, such as simvastatin, are commonly prescribed to lower high cholesterol levels. Statins work by blocking an early step in cholesterol production.

Beyond these well-known cholesterol-lowering abilities, statins also combat certain tumors. Statins have previously been shown to have anti-tumor effects on breast, ovarian, prostate, colon, leukemia and lung cancers. The effect of statins on uterine fibroids was unknown.

"Non-cancerous uterine fibroids are the most common type of tumor in the female reproductive system, accounting for half of the 600,000 hysterectomies done annually in the U.S. Their estimated annual cost is up to $34 billion in the U.S. alone," said UTMB's Dr. Mostafa Borahay, assistant professor in the department of obstetrics and gynecology and lead author. "Despite this, the exact cause of these tumors is not well understood, as there are several genetic, familial and hormonal abnormalities linked with their development."

Cholesterol-fighting statins inhibit uterine fibroid tumors that account for 50% of hysterectomies

Curcumin and tackling mesothelioma: an interview with Dr. Afshin Dowlati

 

In continuation of my update on Curcumin

Dr. Afshin DowlatiTHOUGHT LEADERS SERIES...insight from the world’s leading experts

Research focusing on mesothelioma

Curcumin and tackling mesothelioma: an interview with Dr. Afshin Dowlati

Chemotherapy drug combined with cancer-killing virus may treat recurrent ovarian cancer

In continuation of my update on doxorubicin

In six out of 10 cases, ovarian cancer is diagnosed when the disease is advanced and five-year survival is only 27 percent. A new study suggests that a cancer-killing virus combined with a chemotherapy drug might safely and effectively treat advanced or recurrent forms of the disease.

Researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James), led the cell and animal study. Reporting in the journal Clinical Cancer Research, the researchers showed that the oncolytic virus called 34.5ENVE has significant antitumor activity against ovarian cancer on its own, and that its activity is even greater when combined with the chemotherapy drug doxorubicin in an animal model of disseminated peritoneal ovarian cancer.

"Our findings suggest that this could be a promising therapy, and we believe it should be further developed for the treatment of recurrent or refractory ovarian cancer in humans," says principal investigator Balveen Kaur, PhD, professor of neurological surgery and an OSUCCC - James researcher.

Among women treated for ovarian cancer whose tumors regress, 70 percent experience recurrence. The recurrent tumors are thought to develop from reserves of cancer stem-like cells that are chemotherapy-resistant and survive therapy. Consequently, recurrent tumors also tend to be resistant to primary chemotherapy regimens, and lethal.

The oncolytic herpes simplex virus 34.5ENVE is engineered to target cancer cells that overexpress the protein nestin and to inhibit the growth of blood vessels to tumors.

Chemotherapy drug combined with cancer-killing virus may treat recurrent ovarian cancer

Cornerstone's CPI-613 drug candidate chosen as 2014 Top 10 Most Interesting Oncology Projects to Watch

We know that, CPI-613: CPI-613  is a racemic mixture of the enantiomers of a synthetic alpha-lipoic lipoic acid analogue with potential chemopreventive and antineoplastic activities. Although the exact mechanism of action is unknown, alpha-lipoic acid analogue CPI-613 has been shown to inhibit metabolic and regulatory processes required for cell growth in solid tumors. Both enantiomers in the racemic mixture exhibit antineoplastic activity. The mechanism-of-action of CPI-613 appears distinct from the current classes of anti-cancer agents used in the clinic. CPI-613 demonstrates both in vitro and in vivo anti-tumor activity.CPI-613 was known to strongly disrupt tumor mitochondrial metabolism. CPI-613 disruption of tumor mitochondrial metabolism is followed by efficient commitment to cell death by multiple, apparently redundant pathways, including apoptosis, in all tested cancer cell lines. Further, CPI-613 shows strong antitumor activity in vivo against human non-small cell lung and pancreatic cancers in xenograft models with low side-effect toxicity. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus). (last updated: 10/30/2014)

Now...........

Cornerstone Pharmaceuticals, Inc., a development stage company and leader in the growing field of cancer metabolism-based therapeutics, today announced that its lead compound CPI-613 has been chosen by Informa and Kantar Health as one of the 2014 Top 10 Most Interesting Oncology Projects to Watch.

Steve Carchedi, Chief Executive Officer of Cornerstone Pharmaceuticals, will present at Informa’s Therapeutic Area Partnerships meeting, taking place November 19-21, 2014 at the Hyatt Regency in Boston. Mr. Carchedi’s presentation will occur at 11:00 a.m. on November 20 within Track 3 (Oncology).

During the presentation, Mr. Carchedi will discuss differentiators of Cornerstone’s lead Altered Energy Metabolism Directed (AEMD) drug candidate, CPI-613, which is a first-in-class anticancer compound designed to disrupt the altered energy-production pathways in cancer cells by targeting mitochondrial metabolism.

Cornerstone's CPI-613 drug candidate chosen as 2014 Top 10 Most Interesting Oncology Projects to Watch

Alzheimer's drug may reduce addictive and impulsive behavior associated with binge eating

In continuation of my update on Memantine

The Alzheimer's drug memantine may perform double-duty helping binge eaters control their compulsion. Researchers have demonstrated that memantine, a neuroprotective drug, may reduce the addictive and impulsive behavior associated with binge eating.

The Boston University School of Medicine (BUSM) study, which appears online inNeuopsychopharmacology, also found that a specific area in the brain, the nucleus accumbens, which is responsible for addictive behaviors, facilitates the effects of memantine.

Binge-eating disorder is a prevalent illness in America, affecting more than 10 million people. It is characterized by periods of excessive uncontrolled consumption of food, followed by uncomfortable fullness and feelings of self-disgust. New evidence indicates that changes in brain chemistry reflecting the addictive nature of binge eating may parallel drug and alcohol addiction.

Using an experimental model to simulate binge-eating behavior, researchers were able to identify the area of the brain associated with binge-eating and then suppress the behavior by applying memantine directly into that area.

"We found that memantine, which blocks glutamate NMDA receptors, blocks binge eating of junk food, blocks the strength of cues associated with junk food and blocks the compulsivity associated with binge eating," explained senior author Pietro Cottone, PhD, an associate professor of pharmacology and psychiatry at BUSM and co-director of the Laboratory of Addictive Disorders.

This research opens new avenues for binge eating treatment especially since memantine is a drug already approved for other indications. "Individuals with binge eating disorder have a very poor quality of life and decreased lifespan. Our study gives a better understanding of the underpinning neurobiological mechanisms of the disorder," added coauthor Valentina Sabino, PhD, assistant professor of pharmacology and psychiatry at BUSM and co-director of the Laboratory of Addictive Disorders.

Alzheimer's drug may reduce addictive and impulsive behavior associated with binge eating

Oxytocin hormone inhibits fear center in brain, shows study

In continuation of my update on oxytocin...

Frightening experiences do not quickly fade from memory. A team of researchers under the guidance of the University of Bonn Hospital has now been able to demonstrate in a study that the bonding hormone oxytocin inhibits the fear center in the brain and allows fear stimuli to subside more easily. This basic research could also usher in a new era in the treatment of anxiety disorders. The study has already appeared in advance online in the journal "Biological Psychiatry". The print edition will be available in a few weeks.

Significant fear becomes deeply entrenched in memory. Following a car accident, for example, it is difficult to manage street traffic once again - even screeching tires can evoke significant anxiety. Scientists refer to this as "conditioning". Certain images or noises are very closely intertwined in the brain with the experience of pain or fear. Only gradually does one learn that not every screeching tire means danger. This active overwriting in the memory is known as "extinction". "In this process, however, the original contents of the memory are not erased but instead merely overlaid with positive experiences," explains Prof. Dr. Dr. René Hurlemann from the Department of Psychiatry and Psychotherapy of the University of Bonn Hospital. If there are dangerous situations once again, the fear, which was believed to have been already overcome, frequently flares up once more.

Extinction is often used in therapy for anxiety disorders. For example, a person suffering from a spider phobia will gradually and increasingly come face to face with spiders. First the patient has to view photos of spiders and then look at living examples until finally he holds a tarantula in his hand. When people with an anxiety disorder experience as frequently as possible the fact that they do not need to fear the trigger, their fear is reduced. "However, this can take a very long time, because this confrontation with the fearful situation frequently has to be experienced. In addition, there may be relapses because the original trace of fear is still anchored in the memory," reports Prof. Hurlemann. This is why therapists seek a possibility for "overwriting" the fearful memory in a faster and longer-lasting way.

Oxytocin hormone inhibits fear center in brain, shows study

New anti-cancer drug may protect normal cells against radiation

Although radiation treatments have become much more refined in recent years, it remains a challenge to both sufficiently dose the tumor while sparing the surrounding tissue. A new anti-cancer drug, already in clinical development, may help address this issue by protecting normal cells - but not the cancer - from the effects of radiation. The research, published November 14th in Molecular Cancer Therapeutics, further suggests this drug may also be useful in treating accidental exposure to radiation.

"It was a stroke of luck that the drug that most effectively protected normal cells and tissues against radiation also has anti-cancer properties, thus potentially increasing the therapeutic index of radiation therapy," says Ulrich Rodeck, M.D., Ph.D., Professor of Dermatology and Cutaneous Biology and Radiation Oncology at Thomas Jefferson University, and senior author on the study.

Together with first author Vitali Alexeev, Ph.D., Assistant Professor, Dermatology and Cutaneous Biology, Dr. Rodeck and colleagues tested five compounds that were shown to have radiation-protective properties in earlier studies. The researchers gave the mice one of the five compounds a day before and for several days after radiation treatment. A compound called RTA 408 emerged from this screen as a robust radiation protector and its effect was comparable to the only drug currently approved by the FDA for that purpose. (The approved drug, called amifostine, however, has a number side effects including severe nausea or vomiting that make it an unappealing choice for clinicians.) Sites that are usually most susceptible to radiation damage including the gut and blood cells in the bone marrow were both protected in mice treated with RTA 408.

Ref : http://mct.aacrjournals.org/content/early/2014/11/12/1535-7163.MCT-14-0354.abstract?sid=22fc8faf-65af-4c60-8a08-265701e2f6ad

New anti-cancer drug may protect normal cells against radiation

New active substance effectively combats Philadelphia chromosome-positive leukaemia

New active substance effectively combats Philadelphia chromosome-positive leukaemia

Bacterial protein flagellin can prevent and cure rotavirus infection

Activation of the innate immune system with the bacterial protein flagellin could prevent and cure rotavirus infection, which is among the most common causes of severe diarrhea, says a Georgia State University research team that described the method as a novel means to prevent and treat viral infection.

The team's findings are to be published in Science on Nov. 14.

Rotavirus is most problematic in infants and young children, who can become severely dehydrated and require hospitalization. Rotavirus causes about 500,000 deaths annually worldwide in children younger than five years of age, according to the Centers for Disease Control and Prevention.

The research, performed in mice, was led by Dr. Andrew Gewirtz and Dr. Benyue Zhang of the Institute for Biomedical Sciences at Georgia State, and included collaborators at Emory University School of Medicine, Baylor College of Medicine, Vanderbilt University School of Medicine, Genentech Inc. and the Pennsylvania State University.

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The researchers expect the specific method used in their work, using flagellin or the IL-22 and IL-18 proteins it elicits, might be effective against a range of chronic viral infections of the digestive system such as norovirus and hepatitis C virus. The team is now planning studies in humans to test this hypothesis. The general model of activating innate immunity to combat viral infection should prove an effective means of slowing down most any virus and could be a temporary means to deal with a broad range of viral infections until more specific solutions could be developed, Gewirtz said.

Bacterial protein flagellin can prevent and cure rotavirus infection

Smart drug Modafinil can impair cognitive performance in healthy students

It is claimed one in five students have taken the 'smart' drug Modafinil to boost their ability to study and improve their chances of exam success. But new research into the effects of Modafinil has shown that healthy students could find their performance impaired by the drug. 

The study carried out by Dr Ahmed Dahir Mohamed, in the School of Psychology at The University of Nottingham Malaysia Campus, and published today, Wednesday 12 November 2014, in the open access journal PLOS ONE, showed the drug had negative effects in healthy people.

Dr Mohamed said: "We looked at how the drug acted when you are required to respond accurately and in a timely manner. Our findings were completely opposite to the results we expected."

In a randomised double blind study, 'Modafinil increases the latency of response in the Hayling Sentence Completion Test in Healthy Volunteers: A Randomised Controlled Trial', they administered 32 participants with the drug and 32 with a placebo. All the participants were given a famous neuropsychological task known as the Hayling Sentence Completion Test in which they were asked to respond both quickly and accurately. Dr Mohamed found the drug slowed down reaction times, impaired their ability to respond in a timely manner and failed to improve their performance of the task.

Smart drug Modafinil can impair cognitive performance in healthy students

Breakthrough in flexible electronics enabled by inorganic-based laser lift-off

A research team led by Prof. Keon Jae Lee of KAIST provides an easier methodology  to  realize  high  performance flexible electronics by using the  Inorganic-based Laser  Lift-off  (ILLO),  which  enables    nanoscale processes  for   high   density   flexible   devices and    high temperature processes that were previously difficult to achieve on plastic substrates.

Breakthrough in flexible electronics enabled by inorganic-based laser lift-off  

Chaetocin synergistic with TKIs against CML cells

Chaetocin (structure below), a mycotoxin that increases oxidative stress, can complement the activity of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukaemia (CML) by overcoming innate resistance mediated by secreted bone marrow stromal cytokines and growth factors (BMSFs), researchers report.

The authors explain that CML–leukaemic stem cells (CML–LSCs), which exhibit innate resistance to TKIs, are crucial for the maintenance of CML. And add that BMSFs are implicated in this innate resistance, and are also known to increase the levels of reactive oxygen species (ROS).

“Higher ROS levels in CML-LSCs exposed to BMSFs might render them susceptible to ROS-mediated damage by exogenous ROS-generating agents”, hypothesises the team inOncogenesis.

Chaetocin significantly reduced the viability and colony forming capacity of CML–LSK cells, and increased apoptosis. These effects of chaetocin were enhanced in the presence of BMSFs.

Moreover, treatment with both chaetocin and imatinib overcame BMSF-mediated imatinib resistance, and resulted in increased cytotoxicity and apoptosis induction as well as a complete loss of colony formation.

Although treatment with either chaetocin or BMSFs resulted in increased ROS levels in CML–LSKs, when the two were used in combination, ROS levels were significantly higher than when either was used alone. Interestingly, chaetocin-mediated cytotoxicty was inhibited when the cells were pretreated with an antioxidant, N-acetyl-cysteine.

This “strongly suggested” that chaetocin activity against CML–LSKs, and its potentiation by BMSFs, was mediated by the increased ROS, say the researchers.

Chaetocin synergistic with TKIs against CML cells